We demonstrate here that selective activation of endogenous members of the caspase family and cleavage of substrates responsible for the maintenance of nuclear functional and structural integrity are major effectors of antigen receptor (AgR)- and ionomycin-triggered apoptosis in Ramos-Burkitt lymphoma (Ramos-BL) B cells. Ramos-BL B cells express significant proenzyme levels of caspase-2, -3, -7 and -8, low levels of caspase-6 and are caspase-1-negative. However, while anti-IgM and ionomycin trigger for significant activation of caspase-3, -7 and -8 at 12-16 h and at 4 h post-stimulation respectively, both anti-IgM and ionomycin fail to activate caspase-2 indicating that AgR- and ionomycin-triggered Ramos-BL B cell apoptosis is mediated by the selective activation of, at least, caspase-3, -7 and -8. Anti-IgM triggers for cleavage of the resident nuclear proteins poly(ADP-ribose) polymerase (PARP) at 8 h, lamins B1 and B2 from 12 to 16 h; likewise, ionomycin triggers for degradation of PARP at 2 h, lamins B1 and B2 at 4 h. Signal transduction through CD40 rescues Ramos-BL B cells from AgR- and ionomycin-triggered apoptosis at a very early stage of the apoptotic process by inhibiting both the early cleavage of PARP as well as the activation of caspase-3, -7 and -8 and cleavage of lamin B1; CD40-mediated rescue occurs upstream of CD40-induced expression of Bcl-2 and increased expression of Bcl-xL. In such cellular populations subject to regulation through apoptosis, dysregulation of the apoptotic mechanisms can have devastating consequences by contributing to the pathogenesis of malignancy as well as to lymphoproliferative and autoantibody disorders. An understanding of the role played by caspases in the execution of apoptosis may provide insight into the pathogenesis of these disease states and thereby provide targets for novel therapeutic strategy.


Summary:Since 1950, marriage behavior in the United States has changed dramatically. Though most men and women still marry at some point in their lives, they now do so later and are more likely to divorce. Cohabitation has become commonplace as either a precursor or an alternative to marriage, and a growing fraction of births take place outside marriage.We've seen a retreat from marriage within all racial and ethnic groups and across the socioeconomic spectrum. But the decoupling of marriage and parenthood has been much less prevalent among college graduates. Why are college graduates such a prominent exception?Some scholars argue that marriage has declined furthest in low-income communities because men with less education have seen their economic prospects steadily diminish, and because welfare and other social programs have let women rear children on their own. Others contend that poor women have adopted middle-class aspirations for marriage, leading them to establish unrealistic economic prerequisites. The problem with these explanations, write Shelly Lundberg and Robert Pollak, is that they focus on barriers to marriage only in very poor communities. Yet we've seen a retreat from marriage among a much broader swath of the population.Lundberg and Pollak argue that the sources of gains from marriage have changed in such a way that families with high incomes and high levels of education have the greatest incentives to maintain long-term relationships. As women's educational attainment has overtaken that of men, and as the ratio of men's to women's wages has fallen, they write, traditional patterns of gender specialization in household and market work have weakened. The primary source of gains from marriage has shifted from production of household services to investment in children. For couples whose resources allow them to invest intensively in their children, marriage provides a commitment mechanism that supports such investment. For couples who lack the resources to invest intensively in their children, on the other hand, marriage may not be worth the cost of limited independence and potential mismatch.


Hydrogen may appear to be an attractive alternative fuel due to its obvious environmental and potentials of significant technical and economic advantages, the design and manufacture a safe and reliable hydrogen tank is the number one priority for development and deployment of hydrogen technology. Compared with aluminum-lined hydrogen tanks, composite tanks offer advantages of lightweight and conformability. Real life tank testing is very expensive and time consuming. In this study, a finite element analysis (FEA) tool has been developed to provide a more economical alternative for composite hydrogen tank analysis at operating pressures of 35 MPa, 45 MPa, and 70 MPa. It was found that the carbon-fiber/epoxy shell acts as the primary structural member, unlike an aluminum-lined tank where the liner acts performs this function. Critical portions of the tanks were found to be the top and bottom domes as well as the interaction between the liner and boss. Some slight plastic deformation was found to occur in the liner at 70 MPa, though under the 35 MPa and 45 MPa loads, the liner exhibited only elastic behavior. The shell elastically deformed in all loading cases, which results in very low residual stress and strain values following the load release. The results may help manufacturers improve tank safety in the design and manufacture of composite hydrogen.Copyright © 2007 by ASME


Background Fibromyalgia syndrome (FMS), a chronic widespread pain disorder, has been associated with various models of stress, including those that are workplace-related. In a previous study, we have documented the significantly increased prevalence of FMS among schoolteachers, as well as correlating symptoms with stressful workplace-related factors. In the current study, we have focused on the specific population of kindergarten teachers and attempted to document both the prevalence of FMS symptoms among this group and the association with stress and symptoms of posttrauma. Methods All participants in the study were working as kindergarten teachers in Israel at the time of the study. Participants responded to a questionnaire documenting FMS symptom, which included the widespread pain index (WPI) and symptom severity scale (SSS), which together constitute the suggested American College of Rheumatology (ACR) FMS diagnostic criteria. Additional items on the questionnaire documented work motivation and performance, the occurrence of workplace-related stressful events, and the presence of posttraumatic symptoms. Results 242 participants were recruited to the current study, including 239 (98.8%) females and 3 (1.2%) males. 62 individuals (25.6%) were found to fulfill ACR FMS criteria. Significant differences in work performance were found between teachers fulfilling FMS criteria compared with those not fulfilling criteria. Thus, FMS-positive teachers reported significantly higher rates of missing workdays, leaving work early, and a lower quality of interaction with children in the kindergarten and with peers and supervisors. Motivation to work was also significantly lower among these individuals. The widespread pain index (WPI) and symptom severity scale (SSS), which together constitute the components of the FMS diagnostic criteria, were positively correlated with both stress and posttraumatic symptoms. In addition, widespread pain, disordered sleep, difficulty with concentration, and other FMS symptoms were strongly correlated with many specific stressful factors at the workplace, including the number of children in the kindergarten, interaction with parents, lack of optimal physical conditions in the classrooms, and various demands on behalf of the educational system. Conclusion FMS symptoms were found to be highly prevalent among Israeli kindergarten teachers, at a rate that greatly exceeds the prevalence in the general Israeli population. Stressful work-related events appear to be positively associated with the occurrence of FMS symptoms and may serve as triggers for their development. Healthcare professionals treating individuals engaged in this occupation should be vigilant for the occurrence of symptoms that are clinically associated with FMS and overlapping functional disorders.


Before 1950, history of science did not exist as an independent academic branch, but was instead pursued by practitioners across various humanities and scientific disciplines. After professionalization, traces of its prehistory as a cross-disciplinary area of interest bound to an interdisciplinary, educational philosophy have remained. This essay outlines the development of history of science as an interdisciplinary academic field, and argues that it constitutes an obvious choice for inclusion in an interdisciplinary academic program, provided faculty and administrators learn how best to manage its advantages and pitfalls.


Research methods in sport and exercise psychology are embedded in the domain's network of methodological assumptions, historical traditions, and research themes. Sport and exercise psychology is a unique domain that derives and integrates concepts and terminologies from both psychology and kinesiology domains. Thus, research methods used to study the main concerns and interests of sport and exercise psychology represent the domain's intellectual properties.
 The main methods used in the sport and exercise psychology domain are: (a) experimental, (b) psychometric, (c) multivariate correlational, (d) meta-analytic, (e) idiosyncratic, and (f) qualitative approach. Each of these research methods tends to fulfill a distinguishable research purpose in the domain and thus enables the generation of evidence that is not readily gleaned through other methods. Although the six research methods represent a sufficient diversity of available methods in sport and exercise psychology, they must be viewed as a starting point for researchers interested in the domain. Other research methods (e.g., case study, Bayesian inferences, and psychophysiological approach) exist and bear potential to advance the domain of sport and exercise psychology.


Background: Rickets is one of the emerging diseases around the world and its records have been frequently increased among Saudi children.
 Objective: Our aim of the study was to discuss and improve the knowledge and the awareness of mothers in the Kingdom of Saudi Arabia about rickets disease and its environmental and nutritional risk factors. Methods: We conducted this cross-sectional retrospective Study at the maternal Children Hospital in Taif, Saudi Arabia. Data were collected using a pre-specified questionnaire after obtaining the patients consent. SPSS software was used to analyze the data.
 Results: We included 150 mothers with their children. There were 146 (97.3%) of the children with vitamin D deficiency.
 Conclusion: In Saudi Arabia, there is a need for campaigns that spread awareness among mothers and young adult females about the importance of vitamin D, diets containing adequate levels of it as well the risk factors that cause its deficiency.


Among throat swabs processed in the microbiology laboratory as back-up for negative rapid antigen detection test results, we found a significant increase in the proportion that tested positive for group A streptococci after changing from throat culture to a molecular test.For group A streptococcus testing, our hospital laboratory replaced throat cultures with a stand-alone molecular diagnostic test that takes no more than 1 hour to perform. The prevalence of positive laboratory test results increased significantly (P < .0001) after the change to molecular testing, probably because of the extreme sensitivity of the molecular test.


Abstract. Whilst hydrology is a Greek term, it was not in use in the Classical literature, but much later, during the Renaissance, in its
Latin form, hydrologia. On the other hand, Greek natural philosophers (or, in modern vocabulary, scientists) created robust knowledge in related
scientific areas, to which they gave names such as meteorology, climate and
hydraulics. These terms are now in common use internationally. Greek natural
philosophers laid the foundation for hydrological concepts and the hydrological cycle in its entirety. Knowledge development was brought about
by searches for technological solutions to practical problems as well as by scientific curiosity. While initial explanations belong to the sphere of
mythology, the rise of philosophy was accompanied by the quest for
scientific descriptions of the phenomena. It appears that the first
geophysical problem formulated in scientific terms was the explanation of
the flood regime of the Nile, then regarded as a paradox because of the
spectacular difference from the river flow regime in Greece, i.e. the fact that the Nile flooding occurs in summer when in most of the Mediterranean
the rainfall is very low. While the early attempts were unsuccessful,
Aristotle was able to formulate a correct hypothesis, which he tested
through what appears to be the first scientific expedition in history, in the transition from the Classical to Hellenistic periods. The Hellenistic period brought advances in all scientific fields including hydrology, an example of which is the definition and measurement of flow discharge by Heron of
Alexandria. These confirm the fact that the hydrological cycle was well
understood in Ancient Greece, yet it poses the question why correct explanations were not accepted and, instead, why ancient and modern mythical
views were preferred up to the 18th century.


The hallmark of Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) is inflammation-induced alveolar-vascular barrier destruction and neutrophilic infiltration that leads to the formation of cytokines and oxygen radicals. The objective of the study is to investigate the protective and toxicological effects of Antidesma bunius (L.) Spreng [Bignay] in murine model of Lipopolysaccharide E. coli (LPS)-induced ALI and compared with Fluticasone Propionate (FP), a synthetic corticosteroid. We showed that extracted Bignay fruits have high amount of phenols, steroids and flavonoids but insignificant amount of heavy metals and aflatoxins. BALB/c mice of either sex were divided into 4 groups in the ALI mouse model; Group 1: vehicle control; Group 2: LPS alone; Group 3: Bignay + LPS; and Group 4: FP + LPS. Bignay and FP were administered via intraperitoneal injection while LPS was given intra-tracheally. Biomarkers of ALI such as total lung inflammatory cell count, total lung protein content, lung edema and interleukin-6 (IL-6) secretion were measured 24 hrs after vehicle control or LPS treatment. Compared to vehicle controls, LPS caused significant increased in all measured biomarkers of ALI in samples collected from bronchoalveolar lavage fluid and were significantly attenuated by Bignay fruit extract or FP. Pulmonary vascular leakage caused by LPS was also evaluated after injection with Evans blue dye, an indication of lung injury. Extracted Bignay fruits or FP when given to mice 2 hrs after LPS administration substantially decreased the pulmonary vascular leak. Our findings are the first evidence demonstrating the preventive and non-toxic effects of extracted Bignay fruits in a murine model of LPS-induced ALI. The results could be attributed to the presence of active secondary metabolites such as flavonoids, phenols and steroids. It is also evident that extracted Bignay fruits are as effective as FP, well-established steroid, in blocking the biomarkers of ALI caused by LPS.


In this article I explore the challenges faced by First Nations language interpreters working in Australia's justice system in relation to the explicit requirement of impartiality/neutrality and the implicit expectation of invisibility in their day-to-day work. I interrogate the notion of (in)visibility and explore its potential to contribute to the marginalisation of First Nations interpreters in legal settings and beyond. In particular, I focus on the relationship between impartiality/neutrality and the visibility of First Nations interpreters. I argue that while impartiality is a stance that can be consciously adopted by professional interpreters, complete neutrality is an impossible and unfair requirement given how neutrality can be impacted by kinship relations, historical racial politics, community expectations, and the power differentials inherent to the justice system. The data analysed are drawn from fieldwork conducted between 2018 and 2019 in the Katherine region of Australia's Northern Territory. The data include field notes, court observations, as well as interviews with First Nations language interpreters, legal professionals, and judicial officers.


OBJECTIVE
Acute monocytic leukemia (AML)-M5 is the common type of acute myeloid leukemias in children. Studies have shown that there are abundant lipopolysaccharide (LPS) receptor (designated as CD14) molecules on the cell membrane of M5 cells and they play an important role in the diagnosis of M5, since they can be recognized and bound by mouse-anti-human CD14 monoclonal antibody (McAb). However, mouse-originated antibodies are largely not suitable for clinical application due to the severe side effects, thus "humanized antibody" is desired. As the first step for developing humanized antibody, the construction and expression of single chain antibody (scFv) with functional protein are necessary. The present study aimed to express ZCH-7-2F9 ScFv (scFv(2F9)) in eukaryotic cells and obtain the scFv(2F9) protein with a high biological activity.

METHODS
Four primers were synthesized to construct the eukaryotic expressional vector, which included SfiI and EcoRI enzyme cleaving site, 6 x His and stop code TGA sequences. scFv(2F9) gene was amplified through splicing by overlap extension (SOE) using the high fidelity Taq polymerase. Positive recombinants (pSectag2A/scFv(2F9)) were identified through enzyme cleaving and sequenced before expression and were transformed into Chinese hamster ovary (CHO) cells for expression. Western-Blot and flow cytometry (FCM) were carried out to determine the relative molecular mass (Mr) and binding activity of scFv(2F9).

RESULTS
The cloned scFv(2F9) gene was identified to be functional by sequencing and expressing. The interested protein could be detected in the culture supernatant of transformed CHO cells with an Mr of 31 000. The blocking test showed that the positive cell percentages, the mean fluorescence intensity (MFI) and the peak of channel (peak Ch) were reduced by 90.02%, 63.30% and 63.38%, respectively after blocking with scFv(2F9), while those were 4.55%, 10.09% and 5.02% after blockage using the supernatant from the CHO cells transfected with blanked vector pSectag2A.

CONCLUSIONS
The scFv(2F9) against human CD14 antigen was successfully expressed in eukaryotic cells and showed a high biological activity, which may be useful for the further studies on its humanized antibodies.


Considering the role of theory in ecology and evolution, we argue that scientific theorizing involves an interplay between narratives and models in which narratives play a key creative and organizing role. Specifically, as scientists, we reason through the use of narratives that explain biological phenomena by envisaging, or mentally simulating, causal paths leading from a plausible initial state to an outcome of interest. Within these narratives, some parts may appear clear, while others may appear puzzling. It is at these tenuous junctions—junctions where reasoning is made challenging by conflicting possible outcomes—that we often build mathematical models to support and extend, or reject and revise, our narratives. Accordingly, models, both analytical and computational, are framed by and interpreted within a narrative. We illustrate these points using case studies from population genetics. This perspective on scientific theorizing helps to clarify the nature of theoretical debates, which often arise from the narratives in which math is embedded, not from the math itself. Finally, this perspective helps place appropriate creative weight on the importance of developing, revising, and challenging narratives in the scientific enterprise.


ABSTRACT Recently, cobalt oxides attract a special attention mainly due to their excellent electrocatalytic activity towards various compounds. This study concerns with electrochemical preparation of cobalt oxide modified glassy carbon electrodes decorated with platinum nanoparticle in the pursuit of its catalytic applications. The parameters affecting the deposition conditions have been evaluated by monitoring oxygen reduction reaction (ORR) in pH 5.0 acetate buffer. Under optimal conditions, the composite film electrode surface was utilised as a platform forbiosensor development. Polyphenol oxidase enzyme was immobilised onto the electrode surface for phenol detection, and the influence of solution and operational parameters have been investigated. The medium pH and the enzyme amount have been optimised as pH 7.0 and 0.3 mg, respectively. Chronoamperograms were recorded for phenol detection in micromolar levels.


Metrics are proposed for quantifying the extent to which a transducer's polar radiation (or sensitivity) pattern is invariant with frequency. As there is currently no established measure of this quality (often called "controlled" or "constant directivity"), five metrics, each based on commonly-used criteria for constant directivity, are proposed: (1) a Fourier analysis of sensitivity contour lines (i.e., lines of constant sensitivity over frequency and angle), (2) the average of spectral distortions within a specified angular listening window, (3) the solid angle of the frontal region with distortions below a specified threshold, (4) the standard deviation of the directivity index, and (5) cross-correlations of polar responses. These metrics are computed for 10 loudspeakers that are ranked, from most constant-directive to least, according to each metric. The resulting values and rankings are compared and the suitability of each metric for comparing transducers in different applications is assessed. For critical listening applications in reflective or dynamic listening environments, metric 1 appears most suitable, while for such applications in acoustically-treated and static environments, metrics 2 and 3 may be preferable. Furthermore, for high-amplitude applications (e.g., live sound) in reflective or noisy environments, metrics 4 and 5 appear most suitable.


In this chapter the authors present a policy-based security engineering process for service oriented applications, developed in the SERENITY and MISTICO projects. Security and dependability (S&D) are considered as first-class citizens in the proposed engineering process, which is based on the precise description of reusable security and dependability solutions. The authors' process is based on the concept of S&D Pattern as the means to capture the specialized knowledge of security engineers and to make it available for automated processing, both in the development process (the focus of this chapter) and later at runtime. In particular, in this chapter they focus on the verification of the compliance with security policies, based on the formal specification of S&D Properties. The main advantages of the approach presented in this chapter are precisely that it allows us to define high-level policies and to verify that a secure oriented system complies with such policy (developed following the SERENITY approach). They also describe the application of the proposed approach to the verification of S&D properties in the web services (WS) environment. Concretely, the authors describe the use of SERENITY framework to facilitate the development of applications that use standard security mechanisms (such WS-Security, WS-Policy, WS-Security Policy, etc) and to ensure the correct application of these standard mechanisms, based on predefined policies. Finally, they show how to verify that the application complies with one or several S&D policies. Chapter 2.16 Policy-Based Security Engineering of Service Oriented Systems


The United Nations Climate Change Conference (COP21) held in Paris in 2015 and the follow-up conferences in Marrakesh (COP22) and very recently in Bonn (COP23) have established an unprecedented international agreement that during this century human society must break from its reliance on energy from fossil fuels to energy sources, which do not release greenhouse gases, particularly carbon dioxide. This is a very hard call. It will not only involve improving more efficient use of energy but also the establishment of new technologies and infrastructures for its generation and distribution. Among renewable energy resources able to tackle these challenges significantly are nuclear or those derived from solar radiation. However in the case of nuclear fusion, a technological breakthrough is required while nuclear fission is limited in the long run by the finite supply of uranium fuel. Here I focus on solar energy which is already contributing to the challenge of COP21. In particular, I discuss its capture and storage through the splitting of water to produce oxygen and hydrogen reducing equivalents, which is essentially the route taken by biology about 3 billion years ago. In so doing I will describe how Nature goes about achieving this fundamental energy converting reaction as a back drop to efforts to achieve the same goal using non-biological photo-electrochemical technology.


ABSTRACT Purpose: Three-dimensional (3D) virtual models have recently gained consideration in the partial nephrectomy (PN) field as useful tools since they may potentially improve preoperative surgical planning and thus contributing to maximizing postoperative outcomes (1-5). The aim of the present study was to describe our first experience with 3D virtual models as preoperative guidance for robot-assisted PN. Materials and methods: Data of patients with renal mass amenable to robotic PN were prospectively collected at our Institution from January to April 2020. Using a dedicated web-based platform, abdominal CT-scan images were processed by M3DICS (Turin, Italy) and used to obtain 3D virtual models. 2D CT images and 3D models were separately assessed by two different highly experienced urologists to assess the PADUA score and risk category and to forecast the surgical strategy of the single cases, accordingly. Results: Overall, 30 patients were included in the study. Median tumor size was 4.3cm (range 1.3-11). Interestingly, 8 (26.4%) cases had their PADUA score downgraded when switching from 2D CT-scan to 3D virtual model assessment and 4 (13.4%) cases had also lowered their PADUA risk category. Moreover, preoperative off-clamp, selective clamping strategy and enucleation resection strategy increased from CT-scan to 3D evaluation. Conclusion: 3D virtual models are promising tools as they showed to offer a reliable assessment of surgical planning. However, the advantages offered by the 3D reconstruction appeared to be more evident as the complexity of the mass raises. These tools may ultimately increase tumor's selection for PN, particularly in highly complex renal masses. Disclosure of potential conflicts of interest: The authors declare they do not have conflict of interests. Informed consent: Informed consent was obtained from all individual participants included in the study. All the procedures were in accordance with the ethical standards of the institutional and national research Committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


We report the emergence of the novel MEK1 V211D gatekeeper mutation in a patient with BRAF K601E colon cancer treated with the allosteric MEK inhibitor binimetinib and the anti-epidermal growth factor receptor (EGFR) antibody panitumumab. The MEK1 V211D mutation concurrently occurs in the same cell with BRAF K601E and leads to RAF-independent activity but remains regulated by RAF. The V211D mutation causes resistance to binimetinib by both increasing the catalytic activity of MEK1 and reducing its affinity for the drug. Moreover, the mutant exhibits reduced sensitivity to all the allosteric MEK inhibitors tested. Thus this mutation serves as a general resistance mutation for current MEK inhibitors; however, it is sensitive to a newly reported ATP-competitive MEK inhibitor, which therefore could be used to overcome drug resistance.


Future rotorcraft will require systems that allow carefree maneuvering. This has driven the need for advanced algorithms that predict the onset of structural limits and cue the pilot using tactile feedback. This paper presents a new method for the detection and avoidance of the main rotor hub moment limit. The dynamic nature of the hub moment limit makes it a challenging problem. An algorithm was developed which uses linear models to estimate constraints on longitudinal and lateral cyclic stick positions that ensure the transient response of hub moments remains bounded within prescribed limits. The system was tested using a high-fidelity non-linear simulation of a UH-60A helicopter. The simulation was run using prescribed force inputs and a pilot model to simulate maneuvers. The system was shown to be quite successful in constraining stick travel in multiple axes to prevent hub moment limit violations. The algorithm appeared to be relatively robust and could operate in real-time with a 10 ms time frame. The most critical conditions occurred during control reversals, at which point the system effectively imposed rate limits on the stick motion.


Porphyrins are photosensitizers and may be applicable in situations where viral inactivation is required, as for in vitro inactivation of nonenveloped viruses in blood components or in other aqueous media. No study has examined the efficacy of porphyrin inactivation on human pathogens such as hepatitis A virus (HAV) in plasma or other liquids. Experiments were conducted to evaluate the effect of synthetic porphyrins on HAV in porphyrin‐containing human plasma and phosphatebuffered saline exposed to long‐wavelength (365 nm) UV light. Inactivation of bacteriophage MS2 (MS2) also was determined in some trials. Solutions containing cationic, anionic or amphiphilic porphyrins irradiated with an average light dose of 4.3 J/cm2 for 90 min resulted in >3 log10 (>99.9%) to >4 log10 (>99.99%) inactivation of both HAV and MS2. Viral inactivation may have been greater than observed because the limits of detection of the assay had been reached. Under ambient lighting conditions, none of the porphyrins was mutagenic in the Ames assay and only the congener with the longest chain‐length, tetrakis (N‐[n‐hexadecyl]‐4‐pyridiniumyl) porphyrin, was appreciably toxic to mammalian cells. Disinfection by photoactivated synthetic porphyrins therefore can offer an effective and relatively safe approach to removal of nonenveloped viruses from aqueous media.


We consider a real production planning problem occurring in a glass container manufacturing company. The goal is to minimise the average stock level during a planning horizon of one year, maintaining customers satisfaction and keeping the production at its maximum rate. Besides the production capacity, the main constraints considered are related to the number of setup changes in machines, which is restricted in each factory. The main goal is to find the best balance between the number of setups and the average stock level. We propose a decomposition of the problem into two interrelated problems: a lot-sizing problem and a scheduling problem. For each problem we propose a mathematical model that can be solved using a commercial solver package. To be an efficient managerial tool, the method should provide quickly good solutions. Therefore we solve the lot-sizing problem through a relax-and-fix heuristic and discuss the results.


Although reports of Colletotrichum gloeosporioides (Penz.) Penz. & Sacc. in Penz. occurring as a hyperparasite of western hemlock dwarf mistletoe (Arceuthobium tsugense (Rosend.) G.N. Jones subsp. tsugense) have been previously published (1), there are no collection or herbarium records to support this finding (B. Geils, personal communication). Given this ambiguity, this report is the first record of C. gloeosporioides on A. tsugense subsp. tsugense based on voucher collections deposited at the Pacific Forestry Centre (DAVFP #25277). Western hemlock dwarf mistletoe is a parasitic plant that occurs on western hemlock (Tsuga heterophylla (Raf.) Sarg.), causing growth reduction, degradation of merchantable wood, and reduction in reproductive fitness of its host. Dwarf mistletoe infections result in significant reduction in volume of mature stands of T. heterophylla in coastal British Columbia (B.C.). Aside from traditional silvicultural control methods, a potentially important control includes the use of fungi deleterious to the growth of dwarf mistletoe. C. gloeosporioides has been identified as a hyperparasite of numerous Arceuthobium spp., including A.tsugense subsp. mertensiana Hawksworth & Nickrent (1). In October 1996 and May 1997, lesions were observed on shoots of A. tsugense subsp. tsugense collected from two field sites, Cowichan Lake (48°56'N, 124°23'W) and Duncan (48°45'N, 123°50'W), B.C. Acervuli containing masses of spores and dark setae were observed within lesions, and conidia from the acervuli produced pure cultures of C. gloeosporioides. The fungus was identified based on conidial and cultural characteristics (2). Conidia were cylindrical to elliptical in shape and measured 12.5 to 15.0 × 2.5 to 4.0 μm. On potato dextrose agar, colonies developed a white to patchy, dark gray mycelial mat with conidia produced in mycelia and in distinct salmon-colored masses. Colony growth occurred at 10 to 30°C, with optimum growth at 20°C, while maximum germination was observed at 30°C after 24 h, with germination occurring between 10 and 35°C. Branches with healthy mistletoe shoots were cut from western hemlock trees and placed in Hoagland's nutrient solution. A spore suspension (106 conidia per ml) was brushed onto mistletoe shoots at a rate of approximately 1 ml per replicate, with 8 to 10 replicate branches, each containing a cluster of >5 shoots. Controls were treated with sterile, distilled water and branches were incubated in the greenhouse with 55% relative humidity. The fungus was re-isolated from acervuli that developed on inoculated shoots after 14 days, and these results were repeated in a second experiment. The fungus was not isolated from the controls. Koch's postulates were fulfilled by inoculating shoots of A. tsugense subsp. tsugense and re-isolating the pathogen from symptomatic stems. C. gloeosporioides could be an important control measure for western hemlock dwarf mistletoe. References: (1) F. G. Hawksworth and D. Weins. 1996. Agric. Handb. 709, USDA, Forest Service, Washington, D.C. (2) B. C. Sutton. 1980. The Coelomycetes. Commonw. Mycol. Inst., Kew, England.


The mastermind behind Apple sheds his low profile and steps forward to tell his story for the first time. From the invention of the first personal computer to the rise of Apple as an industry giant, iWoz presents a no-holds-barred, rollicking, firsthand account of the humanist inventor who ignited the computer revolution.


Knowledge of iso-contours of the underwater terrain can be used to reconstruct it using interpolation. Identifying a set of isoclines can be more efficient and less time-intensive than sweeping a large area. In this paper, we propose a system where a small number of agile underwater vehicles cooperatively maintain a triangular formation on a plane above the terrain and use field values measured by the individual robots to implement the simplex optimization algorithm which has proven very useful for nonsmooth objective functions. In this paper, we propose general rules for implementing the reflection operation and extend it to reflexive motion over isoclines (areas of constant field value).


Besides the conventional D5h(8149)-C70 fullerene, there are a large number of C70 isomers that violate the isolated pentagon rule (IPR). However, these non-IPR C70 fullerenes have been less investigated owing to their low stabilities or high reactivities. In this study, we report for the first time the X-ray structure of an unconventional endohedral C70 fullerene, Sc2O@C2(7892)-C70. The combined study of geometrical analysis and computation further reveals the ionic and covalent interactions between the cluster and the cage, both of which contribute to the stabilization of this non-IPR C70 fullerene. In addition, a close structural relationship between the non-IPR C2(7892)-C70 and the IPR D5h(8149)-C70 has been demonstrated, which might provide an alternative explanation of the formation of non-IPR fullerenes.


The paper presents the experimental researches regarding the air pollution with sulfur dioxide (SO 2) to the steelmaking in the electric arc furnace. It presents a method for determining the sulfur dioxide (SO 2) concentrations from the steelmaking, the diagram variation of the sulfur dioxide (SO 2) concentrations over time during specific technological stages of the steelmaking process and the potential sources that generate the sulfur dioxide (SO 2) to steelmaking process in the electric arc furnaces. The air pollution during steelmaking in electric arc furnaces is manifested throughout this process, which includes the following technological stages: furnace charging, charge melting, refining, dephosphorization, desulphurization, deoxidizing, alloying and evacuation. Considering the stages of steelmaking in the electric arc furnace that have the potential to generate sulfur dioxide (SO 2), it was assessed its generation evolution for the following technological stages: melting, refining, desulphurization and deoxidizing. The experimental researches were performed on two electric arc furnaces with a capacity of 10 and 30 tons. The highest concentrations of sulfur dioxide (SO 2) were recorded during the desulfurization technological stage. After this stage, it has been recorded a significant reduction in sulfur dioxide (SO 2) concentrations. The sulfur dioxide (SO 2) concentrations from the electric arc furnace with the capacity of 30 tons are higher than those recorded in the furnace of 10 tons with 30-40%.


A low-lying country as The Netherland is prone to coastal flooding, and its risk may be enhanced by global-warming induced climate change. Sea level rise has been historically considered as the key factor in coastal retreat, but waves also play an important erosive role along the coast, which can also be affected by the changing climate. During the last years, important advances have been achieved in climate modeling, with a very detailed characterization of the different components of the climate system, for the present and for different future scenarios. However, characterization of future ocean waves is still a matter of discussion and ongoing research. In this thesis, a statistical downscaling methodology based on weather types has been chosen to model the present wave climate and explore potential changes in future waves. These changes are quantified in terms of the impact of these variations in the longshore sediment transport. The methodology is applied to Noordwijk, selected as a representative location of the central Dutch coast. The statistical downscaling methodology is based on a classification procedure of the predictor into similar atmospheric patterns over the wave generation areas, namely the weather types. Then, the wave data is grouped according to the occurrence of the weather types. The predictor is built from the sea level pressure fields (SLP) and the squared SLP gradients, while the predictant wave climate is characterized by significant wave height, wave peak period and mean wave direction of wind sea and swell components, resulting in unimodal or bimodal sea states. The chronology of the weather types is modeled using an autoregressive logistic model, which incorporates the seasonality, the interannual variability and the persistence observed from the historical data. For each weather type, wave parameters are modeled using the categorical distribution for the sea-state type, non-parametric kernel density functions for the central-mass regime and two generalized Pareto distributions for the lower and upper tails of wave height and wave period data. The statistical dependence between wave parameters for each sea state is included using a vine-copula approach, where the bivariate dependence of H_s and T_p is modeled using the AC skew t copula and the remaining relations are considered to be Gaussian. The effect of climate change is studied using SLP predictors from the global circulation model ACCESS1.0, under the RCP8.5 scenario and period 2070-2099. The statistical model is applied to identify changes in the occurrence probability of the weather types in the future. The importance of these changes are quantified in terms of the wave-induced longshore sediment transport using the process based model Unibest TC. The longshore sediment transport distribution for each weather type is computed and afterwards the changes in gross and net transports are estimated using the present and future probabilities of the weather types. In terms of the weather types, the results of this work suggest changes in the occurrence probability of the weather types in the future, with variations of ±60% with respect to present climate, and no relevant changes in the sequence of weather types, neither in terms of the transition probability matrix nor in terms of the persistence of each weather type. In terms of longshore sediment transport, significant changes are detected in the transport associated with some of the weather types. For the remaining weather types, the changes are in the order of the model uncertainty. Taking into account the contributions from all weather types, a net increase of the southward directed net longshore sediment transport with respect to the historical period is detected. This increase is driven by a decrease in northwards transport and a lower decrease in southwards transport. This result is in line with a poleward shift of the North Atlantic storm track reported in other studies. Most importantly, weather-type based climate classification has in this thesis been succesfully proven to be a reliable tool to analyze the wave climate at the location of interest. Furthermore, the statistical downscaling also provides a climate emulator that captures the climate dynamics at different time scales, which can be used for stochastic simulations of the atmospheric and wave climate, either for the recent past or future projections.


This paper presents an architecture and algorithms for optimizing the performance of Web services. For a given service, session-based admission control is combined with stage-wise request queuing, where the stages represent sub-tasks within sessions. The scheduling of requests is governed by generalized processor sharing. We present a performance model, relying on online estimation of parameters describing client-server interaction. A reward function corresponding to the service provider's objective is maximized using techniques for nonlinear optimization. In a case study, we model and optimize the resource sharing at a Web server hosting an electronic store. The performance advantages of our approach are quantified numerically, and the robustness to parameter estimation errors is assessed by sensitivity analysis.


We have examined the cell-to-substratum attachment surface of hamster fibroblasts with scanning EM, and describe the surface ultrastructure of focal contacts and microspikes during cellular attachment and spreading on fibronectin. Nil 8 fibroblasts were seeded onto fibronectin-coated glass coverslips in serum-free medium, fixed, and the fibroblast-fibronectin monolayer was separated from the glass and inverted for scanning electron microscopic (EM) analysis. Focal contact development was detected by interference reflection microscopy and correlated with the immunofluorescence microscopic distribution of fibronectin receptor antigens. The cell undersurface appeared smooth and featureless at 0.5 h when focal contacts were undetectable and fibronectin receptors were distributed diffusely. By 1-2 h, undersurface membrane impressions of focal contacts were detected with scanning EM; their size, shape and distribution matched that of focal contacts seen with interference reflection microscopy (IRM). These contacts had smooth external surfaces and were often arranged in chevron-shaped complexes. However, at 4-6 h, the surface texture of focal contacts became fibrous and the contact periphery was delineated with the orifices of membrane-associated vesicles. Development of this filamentous substructure is correlated with the maximum concentration of fibronectin receptors and fibronectin at focal contacts, suggesting that these molecules are involved in the maturation and stabilization of focal contacts.


Our studies on the thermal crosstalk of laser arrays with integrated thin-film heaters involved theoretical as well as experimental investigations. Comparing the effects of intentional geometrical variations of the device design, we found that the relative thermal crosstalk depends critically on the distance between the active area and the film heater. The most striking result is that a minimization of the thermal resistivity of the device does not always lead to a reduced thermal crosstalk. We demonstrate that an additional heat barrier close to the active region and/or an improved heat transfer between the submount and the heat sink may reduce the relative thermal crosstalk, a result completely unexpected from intuitive considerations.


Since depressive symptoms (SDS) are prevalent under-recognized and clinically important problems in patients with schizophrenia, the pattern of symptoms and associated features of depressive symptoms, as well, as inclusion of psychopathology and neurodynemic variations in personality structure of patients with chronic schizophrenia deserve more investigation. The aim of the research was to identify clinical and experimental-psychological features of post-schizophrenic depression. The longitudinal study has been designed to investigate patients with paranoid schizophrenia. As a result of the careful clinical and psychological analyses due to psychopathology we defined four types of depression. From which two types of depression--agitated and asthenic prevailed in active phase of schizophrenia and remained two hypochondriac and apathyc mainly occurred during stabilization. This finding would have prognostic value. The authors examined personality changes leaded by cognitive symptoms and specified psychopathological and neurodynamical input in alteration of personality structure with word association experiment by A.D. Zurabashvili. As the semantics of trigger words became more complex the qualitative impairment deepened. Lower pathological associations have overcome scanty logical thinking and fluctuation of latency time since thought blocking became prominent. SSRI (Fevarin, Rexetin) appeared especially effective in treatment of certain type of post-schizophrenic depression.


Heterotopic pancreas is a relatively common variant of foregut embryologic dystopia that can be described as pancreatic tissue found outside the normal anatomic location, being independent from vascular supply of normal pancreas. Having all features of pancreatic tissue except for the major duct structures, this ectopic tissue may be clinically recognized when pathologic changes take place. Inflammation, hemorrhagic or obstructive states, and eventually malignancy-related problems may become a diagnostic challenge for clinician and finally lead to consequences of misdiagnosis. In this article we will discuss a case of heterotopic pancreatic tissue located in gastric cardia, which was diagnosed preoperatively as gastrointestinal stromal tumor.


Most lawyers today self-publish, using the same word-processing software they use for composition, and letting their software's default settings determine their documents' typography. Those settings, however, are not optimized for legal writing. And lawyers who rely on software defaults, especially in documents submitted to courts, do so at their peril.This article explores one content-driven, context-specific way that typography might be used in legal briefs: to reinforce, complement, and independently create narrative meaning. Part I outlines those aspects of contemporary typography most germane to legal briefing. Part II offers six examples of how these principles might be used. The first few examples are "easy" cases - soft touches that are likely to be low risk, unlikely to offend, but mild in their potential impact - such as imitating Supreme Court typography or reflecting a law office's brand identity through typeface choice. The next cases explore how, in ways perhaps more meaningful to authoring lawyers and their clients than to the judges who read their briefs, typography might further outsider narratives or reflect character and point of view. The fifth case suggests ways that typography might augment a brief's narrative trajectory and help clothe a progressive legal argument in traditionalist clothing. The final example explores how typography might be used negatively (and perhaps inappropriately and unethically) to thwart an opposing party's narrative goals and obscure the meaning of inconvenient facts and law.


The authors gathered information on 1665 death-eligible cases nationwide for three years at decade intervals: 1994, 2004, and 2014. In 517 cases death sentences were imposed; in 311 cases sentencers spared the defendants from death sentences, and in 837 cases prosecutors spared defendants from death sentences. The Article proceeds in three Parts. Part I explains the methodology for unearthing relevant data and preparing it for analysis. Part II analyzes declines in death sentences due to decreasing death eligibility, that is, fewer murderers over time meeting the criteria that made death a sentencing option. Four reasons are examined: fewer death-eligible murders, the United States Supreme Court's exemptions of juveniles who were less than eighteen years of age at the time of the commission of the murder, and persons with intellectual disability (known to the law as the "mentally retarded"); and the abolition of the death penalty in several states. This Part concludes that about half of the decline in death sentences is attributable to decreased death-eligibility, mostly due to the steep decrease in the number of death-eligible murders. Part III examines increasingly narrower perceptions of death-worthiness, that is, the evolution in attitudes among prosecutors and sentencers toward deeming fewer among the many death-eligible defendants worthy of death sentences. This Part requires the most complicated analysis because unlike death-eligibility decisions, which are dictated by law, death-worthiness decisions emerge from an opaque brew of many factors, including, but not limited to, resource differentials among jurisdictions, prosecutorial attitudes, the wishes of the murder victim's survivors, defense counsel performance, public opinion, and sentencer reactions. But while death-worthiness decisions are often opaque in individual cases, each case generates empirical data from which patterns may be discerned. Part III uses such data to analyze ten questions and arrive at tentative answers:
• Did the advent of life-without-parole (hereinafter "LWOP") reduce death sentences in jurisdictions where it was added as an option? (only in Texas) • Did sentencers become more reluctant to return death sentences? (no) • Were death sentences decreasingly imposed in less aggravated cases and increasingly imposed in more aggravated cases? (to some extent) • Did presentation of greater numbers of mitigating factors conduce to fewer death sentences? (no) • Did robbery during a murder became a less powerful aggravator? (yes) • Did 18-to-20 year-olds benefit from a ripple effect from the exemption of juveniles? (yes) • Did death sentences become less common in multiple perpetrator cases? (yes) • Did low population counties increasingly drop out of death sentencing? (yes) • Did low revenue counties increasingly drop out of death sentencing? (no) and • Did a few traditionally high-volume death sentencing counties skew the figures by cutting back on the use of the death penalty due to local political factors? (yes)


The purpose of this study was to determine the test-retest reliability and construct validity of tools to assess how balance confidence (BC) and state anxiety (SA) change with progressively increasing walking speeds. Sixteen young adults and 15 older adults attended two sessions. Individuals began walking on a treadmill at 0.4 m/s Participants chose to continue increasing the treadmill speed (up to 2.0 m/s) or to discontinue the protocol while rating their BC and SA after completing each speed. BC at participants' fastest speed attempted demonstrated high and moderate test-retest reliability among young (intraclass correlation coefficient [ICC] = .908) and older adults (ICC = .704). SA for young adults and older adults was good (ICC = .833) and fair (ICC = .490), respectively. Our measures also correlated with measures of dynamic stability while walking for young (r = -.67, p = .008) and older adults (r = .54, p = .046). Our dynamic measures of BC and SA are valid and reliable in young and older adults.


Chronic lung diseases are complex, progressive disorders with increasing incidence and mortality. Chronic obstructive pulmonary disease (COPD), asthma and pulmonary fibrosis are examples of chronic lung conditions that can significantly impact the quality of life. Minimally-invasive diagnostic methods that eliminate bronchoscopic and surgical biopsy from patients are ideal; metabolomics therefore holds considerable promise for the discovery of biomarkers that can aid diagnosis and treatment with greater sensitivity, specificity and precision.

The main aim of this project was to employ ultra-performance liquid chromatography-quadrupole time-of-flight (UPLC-QTOF) high resolution mass spectrometry (HRMS) and matrix-assisted laser desorption ionisation (MALDI) mass spectral imaging (MSI) together with multivariate statistics-based metabolomics to identify and characterize potential lipid biomarkers of idiopathic pulmonary fibrosis (IPF). This dissertation consists of the following studies: (1) literature review of metabolomics in chronic lung diseases; (2) application of HRMS for untargeted metabolic profiling of chronic lung disease including COPD and IPF; (3) investigation of a novel data-independent acquisition (DIA) approach to augment untargeted approaches for lipid biomarker identification; (4) development of a novel matrix application technique to improve MALDI-MSI acquisitions of tissue sections whilst maintaining spatial localisation of endogenous metabolites; and (5) exploiting potassium adduct formation to resolve the spatial distribution of lipids in fibrotic tissues.

A total of 65 clinical plasma samples (from 20 healthy control subjects, 21 COPD and 24 IPF patients) were profiled using UHPLC-QTOF-MS. A fundamental challenge in using HRMS for untargeted profiling of complex, chronic lung diseases is the heterogeneity of the human samples. Various contaminations present in fibrotic tissues or adjacent non-fibrotic constituents can confound characterization and encumber the discovery of reliable biomarkers. The results of this study revealed significant correlation between COPD and IPF clinical phenotypes and plasma metabolite profiles. The unbiased metabolomics workflow and deconvolution pipeline provided end-to-end analysis from peak picking and annotation through to metabolite identification.

Subsequently, the ability of the UPLC-QTOF-MS method to discriminate between lipid species was enhanced by the application of a DIA method to distinguish between "stable versus progressor" IPF patients. This DIA method is known as SONAR and uses a wide, continuously sliding precursor window for fragmentation, thereby allowing correlation of precursor and fragment ions. SONAR lipid data were processed using Progenesis QI and searched against LIPID MAPS for structural elucidation and metabolite confirmation. The lipids identified were found to be intermediates of key metabolic pathways such as the glycolytic/TCA cycle, mitochondrial-beta oxidation and lipid metabolism and hold considerable promise as biomarkers of disease.

The matrix deposition step in MALDI-MSI is crucial for simultaneous extraction of metabolites from tissue sections as well as maintaining the spatial dimensionality of the endogenous metabolites. A novel, efficient and cost-effective preparative method referred to as the "freeze-spot" method was developed using wheat seed sections to demonstrate extraction efficiency and reliability, whilst maintaining the spatial resolution of the acquired MALDI-MSI images. The technique was also found to be simple and robust, forming fine matrix crystals that enabled efficient ionisation of surface metabolites, further eliminating the need for sophisticated matrix application approaches.

In the final study, 10 healthy and 10 fibrotic tissues were compared using MALDI-MSI. The MSI technique developed uses potassium adduct formation to improve spatial resolution and dimensionality of lipid species such as triglycerides (TG), ceramides, sphingolipids and glycerophospholipids. The results of this study showed changes in lipid composition of IPF tissues compared to healthy controls. This study identified lysophosphatidylcholine (LysoPC), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) as potential lipid biomarkers of the disease and requires further study as targets of intervention and treatment. Both SONAR and MSI successfully identified similar classes of lipids (TG, PE, LysoPC and PC) which may play a role in the pathophysiology of the IPF lipidome.

This project highlighted the complementarity of HRMS and MSI based metabolomics for the characterization of unique lipid features in fibrotic tissue and plasma samples. The study also demonstrated the discriminative power of the unbiased DIA approach for the identification of lipids via fragment ion patterns that were indicative of specific lipid classes. In addition, the application of chemometric principal component analysis (PCA) and orthogonal partial least-squares to latent structures-direct analysis (OPLS-DA) proved useful for the identification of statistically significant lipids. This statistical approach allowed for the assessment of covariance and correlation between lipids and the modelled lung diseases, and further illustrated lipid compositional changes in chronic lung diseases.

Taken together, the experimental work presented in this thesis show the large potential for mass spectrometry-based metabolomics as a tool for discovery. The specificity of the novel methods outlined will be highly beneficial for compound identification and further confirmation of disease biomarkers.


This paper presents an experimental study on environment recognition and movement control for multi-agent robotic soccer using wheeled mobile robots. A color image segmentation method based on YUV color information of each pixel of the color image is applied to the object recognition. The color image segmentation is performed using the tables that transform each value in a pixel to membership in several color classes, where the lower and higher threshold values of Y, U, and V are determined and described for the sample color markers. The position of objects on the field is efficiently and accurately calculated using a monocular camera. A common image processing method is used to detect landmarks such as corners/edges in the environment. A movement control algorithm is implemented based on the distance and orientation to the target. Experimental results of real-time movement control are also presented.


One of the first things a cancer cell does is move around some of its genes, Meaburn and Misteli show.

Cells rearrange their DNA during certain diseases. In neurons from people with epilepsy, for instance, the X chromosome tends to be closer to the middle of the nucleus than in neurons from nonepileptics. Researchers have also observed chromosomal relocation in the few cancers they have examined. However, these observations involved late-stage disease, and no one knew what happened early in tumor development.

Meaburn and Misteli scrutinized mammary cells that they had coaxed to grow abnormally. When the researchers pinpointed 11 genes, they found that four—including the antiapoptotic gene BCL2—were in different positions in the cancer cells than in normal cells. Three of the genes were closer to the edge of the nucleus in the tumor cells, and one was closer to the center.

Some studies suggest that active genes tend to shift into the interior of the nucleus, whereas inactive genes are marginalized. But the team determined that the location of a particular gene in the nucleus didn't depend on its expression level. For example, activity of the gene for the extracellular matrix protein MMP1 shot up in the cancerous cells, but the gene remained in place. The researchers conclude that early in tumor formation, cancer cells reposition certain genes. Why the cells go to the trouble is a mystery, but the discovery might lead to new diagnostic tests.

Reference:

Meaburn, K.J., and T. Misteli. 2008. J. Cell Biol. 180:39–50. [PubMed]


A description of the tutorial: The design of hardware platforms has to meet several constraints such as execution time, energy consumption and system cost. In the recent years, Moore's Law has made many innovative architectural designs a reality, resulting in increasingly complex and heterogeneous target systems, and soaring programming costs. To keep up with this situation, today's compilers must handle whole applications, redefine functional boundaries regardless of the APIs used, and target different processors simultaneously, yet their development cost must remain under control. The PIPS compiler framework was designed in 1988 at MINES ParisTech to research interprocedural parallelization. It was based on core ideas that are still relevant today. The PIPS framework: * has been used to generate automatic code distribution, OpenMP-to-MPI code translation, HPF Compiler, automatic C and Fortran to CUDA translation, code modelization for graphic IDEs, genetic algorithm-based optimizations, SIMD (SSE, AVX...) portable code generation and code optimization for FPGA-based accelerators. * provides a flexible and scriptable pass manager; * Supports entire Fortran 77 and C applications, while handling call sites, function definitions and missing library source code; * is easily extensible, via text declarations of all analyses, transformations and key data structures; * ensures global consistency of the various analyses and transformations thanks to these declarations; * uses dynamic typing to support automatic consistency check, allocation / deallocation, copy, iterators and persistance for any object, however complex (the NewGen tool and runtime with XML back-end); * uses sparse linear algebra as a powerful underlying proof mechanism. After 20 years of development and constant improvement, PIPS is a robust source-to-source compiler, providing a large set of program analyses and transformations with around 300 phases. Instead of reimplementing a source-to-source compiler instrastructure from scratch whenever a new programming technology appears, we focused on refactoring libraries, while taking advantage of PIPS extensible consistency manager, Pipsmake, to add new functionalities over time. Moreover, thanks to the source-to-source approach, transformations and analyses can be combined in any way for new purposes, and newcomers to PIPS immediately benefit from past contributions. Recent developments in PIPS have focused on the inlining of library functions, outlining of key code parts and automatic generation of data communications and now all standard program and loop transformations are available. Former activities include interprocedural parallelization, property instrumentation (aliasing, uninitialized variable and buffer overflow detection), code refactoring, etc. PIPS is written mainly in C, has around 15 active contributors and its source code (456 KLOC) is available under the GPL v3 license. It can be downloaded from http://pips4u.org. *This tutorial aims to: * Illustrate usage of PIPS analyses and passes to generate hardware accelerator code in an interactive demo. * briefly survey the functionalities available in PIPS, using examples; * describe key internal data structures; * show how to declare a new transformation within pipsmake; * present how to implement this transformation within the PIPS infrastructure using only a few lines of C code, thanks to Newgen-based data structures and iterators, and existing PIPS libraries. This presentation is based on the real-life experience of people having used PIPS for less than a year, using SVN to contribute from several different geographical locations, as well as source code documentation generated by Doxygen.


Orofacial clefts are one of the most common congenital anomalies worldwide; however, morphopathogenesis of the clefts is not yet completely understood. Taking the importance of innate immunity into account, the aim of this work was to examine the appearance and distribution of macrophages (M) 1, M2, and TNF-α, as well as to deduce any possible intercorrelations between the three factors in cleft affected lip tissue samples. Twenty samples of soft tissue were collected from children during plastic surgery. Fourteen control tissue samples were obtained during labial frenectomy. Tissues were immunohistochemically stained, analysed by light microscopy using a semi-quantitative method, and the Mann–Whitney U and Spearman's tests were used to evaluate statistical differences and correlations. A statistically significant difference in the distribution was observed only in regard to M1. A weak correlation was observed between M2 and TNF-α but a moderate one between M1 and M2 as well as M1 and TNF-α. However, only the correlation between M1 and M2 was statistically important. The rise in M1, alongside the positive correlation between M1 and TNF-α, suggested a more pro-inflammatory/inflammatory environment in the cleft affected lip tissue. The moderate positive correlation between M1 and M2 indicated an intensification of the protective mechanisms.


Background The majority of COVID-19 cases are asymptomatic, or minimally symptomatic with management in the home. Little is known about the frequency of specific symptoms in the general population, and how symptoms predict the magnitude of antibody response to SARS-CoV-2 infection. Methods We quantified IgG antibodies against the SARS-CoV-2 receptor binding domain (RBD) in home-collected dried blood spot samples from 3,365 adults participating in a community-based seroprevalence study in the city of Chicago, USA, collected between June 24 and November 11, 2020. Results 17.8% of the sample was seropositive for SARS-CoV-2. A cluster of symptoms (loss of sense of smell or taste, fever, shortness of breath, muscle or body aches, cough, fatigue, diarrhea, headache) was associated with stronger anti-RBD IgG responses among the seropositives. 39.2% of infections were asymptomatic, and 2 or fewer symptoms were reported for 66.7% of infections. Total number of symptoms was positively but weakly associated with IgG response: Median anti-RBD IgG was 0.95 ug/mL for individuals with 3 or more symptoms, in comparison with 0.61 ug/mL for asymptomatic infections. Conclusion We document high rates of asymptomatic and mild infection in a large community-based cohort, and relatively low levels of anti-SARS-CoV-2 IgG antibody in the general population of previously exposed individuals.


Two and one-half years ago (see Science, 28 June 1993) Science launched a campaign to expand its international operations. The intent, fully endorsed by the AAAS Board of Directors, was to reach out to readers in Europe and Asia. Feedback received from readers, reviewers, and Science journalists in both regions during my visits there over the past 4 months indicates that our campaign is clearly gaining momentum, as emphasized by several recent changes. Before our U.K. office in Cambridge was opened, approximately 7% of Science Reports had a majority of European authors. As of this month, that figure has reached 25%. Over the same period, the number of Europe- and Japan-based members of our Board of Reviewing Editors has increased from 0 out of 45 to 18 out of 74, with comparable increases in non-U.S. peer reviewers. These reasonably satisfying early results have been achieved without any geographic quotas, through fair and equal competition among submittals. Our intention is to provide a rapid and fair review system conducted by an accessible editorial staff. Meanwhile, Science has also expanded its international cadre of science journalists. Two full-time European reporters are now working out of the Cambridge office and another in Tokyo, with regular correspondents in Paris, Berlin, Heidelberg, Moscow, and Beijing. The result has been well over 100 pages per year of European news coverage and about double that amount of overall non-U.S. coverage. For example, this issue examines the special research support made possible in Germany by the Max Planck Institutes (two of whose researchers won Nobel Prizes this year) and includes an interview with the newly appointed head of the Max Planck Society. All this is, of course, just a beginning. As demonstrated in London and Paris last week to European scientists and science journalists, our World Wide Web offerings have allowed us since June 1995 to inform connected readers throughout the world of our contents on the day of publication (see Science, 23 June 1995). In the past 5 months, the number of unique computer addresses that visit us weekly has grown to over 8000. As other journals join in this alternative means of communication, scientists everywhere will be all the better informed. The exploration of enhancements to our printed media is only beginning. Like other diligent editors, we have been actively soliciting reader feedback. The next version of our "Science On-Line" Web pages will debut shortly, offering many of the features our browsers have most often requested. We want more than simply to quell readers' curiosity until their mailed copies arrive. Our "Beyond the Printed Page" section has already shown data on genomes, computer simulations, and molecular structures that enhance what print readers can see, and our forums for the ongoing discussion of critical policy issues in science have provided an avenue for direct reader-to-reader feedback in full public view. Speaking of our blossoming Web pages (and of science journalists), beginning today, browsers of "Science's Next Wave" will be able to explore the pros and cons of pursuing innovative alternatives to the traditional academic research career. The first of a series of features on alternative careers focuses on science journalism. Later we will present discussions of careers in industry, patent law, science policy-making, environmental work, teaching, and many more. Like all the rest in this series, the focus on science journalism will provide both resources (descriptions of the top U.S. science journalism programs, with contact information) and role models (access to a group of carefully selected journalists and scientists, most of whom were Ph.D.'s before making the transition to journalism). Readers will be able to interact directly with these career role models at our Web site. They will tell you how they made the transition and what you will need to know to make it yourself, if you choose. This effort is designed to help our young scientists and their increasingly beleaguered advisers keep up to date on careers that do not depend on yet more government grants, by answering such questions as, What in fact are the options? How does one make the right preparations? Where are the jobs? In the near future, both "Science's Next Wave" and Science will be expanding their international offerings, with a special concentration on Asia. We think the need for such expansion—both internationally and into the new media of communication—is very real. Let us know your views.


The presence of electrolytes in aqueous solutions has long been recognized as contributing to significant departures from thermodynamic ideality. The presence of ions in process streams can greatly add to the difficulty of predicting process behavior. The difficulties are increased as temperatures and pressures within a process are elevated. Because many chemical companies now model their processes with chemical process simulators it is important that such codes be able to accurately model electrolyte behavior under a variety of conditions. Here the authors examine the electrolyte modeling capability of ASPEN PLUS{trademark}, a widely used simulator. Specifically, efforts to model alkali metal halide and sulfate systems are presented. The authors show conditions for which the models within the code work adequately and how they might be improved for conditions where the simulator models fail.


Electro Hydraulic Brake (EHB) system plays an important role for improving vehicle active safety. In this paper, the dynamic behavior of EHB system is discussed. From its working principle, a dynamic model of quarter EHB system is established based on AMESim and Matlab. To analyze performance of the proposed EHB system, the strategy of Single-Neuron PID regulation is presented and a typical numerical case is given. The results show that this strategy can obtain good performance and proper parameters can improve the dynamic characteristics of EHB system effectively.


Externally observing the experience of a participant in a virtual environment is generally accomplished by viewing an egocentric perspective. Monitoring this view can often be difficult for others to watch due to unwanted camera motions that appear unnatural and unmotivated. We present a novel method for reducing the unnaturalness of these camera motions by minimizing camera movement while maintaining the context of the participant's observations. For each time-step, we compare the parts of the scene viewed by the virtual participant to the parts of the scene viewed by the camera. Based on the similarity of these two viewpoints we next determine how the camera should be adjusted. We present two means of adjustment, one which continuously adjusts the camera and a second which attempts to stop camera movement when possible. Empirical evaluation shows that our method can produce paths that have substantially shorter travel distances, are easier to watch and maintain the original observations of the participant's virtual experience.


Background: Chronic systemic hypoxia is severe environmental stress for the heart and might lead to the development of heart failure. Apelin is an endogenous peptide that has been shown to have various beneficial effects on cardiac function. Apelin appears to have a role to play in the ventricular dysfunction and maintaining the performance of the heart.
Objectives: In the present study we want to investigate the adaptive response of heart tissue to chronic systemic hypoxia and the correlation with apelin expression and oxidative stress in rat.
Methods: An experimental study was performed using 28 Sprague-Dawley male rats, 8 weeks of age. Rats were divided into 7 groups 4 each, namely control group; normoxia (O2 atmosphere) and the treatment group of hypoxia (8% O2) for 6 hours; 1;3;5;7 and 14 days respectively. Body weight and heart weight were measured at each treatment. Ventricular thickness was measured by caliper, Apelin mRNA was measured using real-time qRT-PCR with Livak formula and malondialdehyde (MDA) level was used to assess oxidative stress due to cardiac tissue hypoxia.
Results: Macroscopic exams showed hypertrophy at day 7th. The relative expression of Apelin mRNA in hypoxic heart is decreased at the beginning and then increased, starting from day-7 to day-14. The MDA levels were significantly increased from day-7 and were strongly correlated with relative expression Apelin.
Conclusion:  It is concluded that the increase of Apelin expression is related to oxidative stress in heart tissue of rats during chronic systemic hypoxia.


Erythrocytosis (an increase in the total red cell mass)* in childhood is usually secondary to cyanotic congenital heart disease. Occasionally it occurs with pulmonary disease, methemoglobinemia, brain tumors, Cushing's disease, or renal adenoma. When there is an accompanying increase of white blood cells and platelets, the condition is termed polycythemia vera; this is extremely rare in children. Occasionally the condition may be familial with no elevation of white blood cell or platelet count and with no underlying cause or associated condition discernable. It is the purpose of this paper to present a case of primary erythrocytosis in a 6-year-old child whom we have been able to investigate. Report of Case The patient, a 6-year-old boy, was first seen in the Congenital Heart Disease Clinic of the University of Colorado Medical Center on Jan. 22, 1957. He had been referred because of cyanosis and decreasing tolerance for exercise. Pregnancy and delivery


Interleaved memories are essential in pipelined computers to attain high memory bandwidth. As a memory bank is accessed, a reservation is placed on the bank for the duration of the memory cycle, which is often considerably longer than the processor cycle time. This additional parameter, namely, the bank reservation time or the bank busy time, adds to the complexity of the memory model. For Markov models, exact solutions are not feasible even without this additional parameter due to the very large state space of the Markov chain. The authors develop a Markov model which explicitly tracks the bank reservation time. Because only one processor and the requested bank are modeled, the transition probabilities are not known and have to be approximated. The performance predicted by the model is in close agreement with simulation results. >


The proliferation of T-lymphocytes is dependent upon their ability to synthesize and secrete the cytokine, interleukin-2, and to express cell surface receptors for interleukin-2 and transferrin. We have previously reported that certain fatty acids inhibit mitogen-stimulated T-lymphocyte proliferation. We now report that unsaturated fatty acids decrease the concentration of interleukin-2 in the culture medium of such cells by up to 45%. This suggests that unsaturated fatty acids inhibit lymphocyte proliferation by suppressing interleukin-2 production. However, lymphocyte proliferation was only partially restored by addition of exogenous interleukin-2 to cell culture medium in the presence of unsaturated fatty acids, indicating that these fatty acids also affect other processes involved in the control of proliferation. Saturated fatty acids, which also inhibit lymphocyte proliferation, did not affect the interleukin-2 concentration in the culture medium suggesting a different mechanism for their action. Neither saturated nor unsaturated fatty acids affected the expression of the interleukin-2 receptor by mitogenstimulated lymphocytes. In contrast, unsaturated fatty acids decreased expression of the transferrin receptor by up to 50%. These observations suggest that the mechanism by which unsaturated fatty acids inhibit lymphocyte proliferation involves suppression of interleukin-2 production and of transferrin receptor expression. The mechanism for the inhibitory action of saturated fatty acids is not clear.


Several intermediates in the reaction of 2-methylglutamate with glutamate decarboxylase from Escherichia coli were detected by stopped-flow spectrophotometry and by rapid-scanning spectrophotometry after conventional mixing. Structures were assigned to intermediates on the basis of kinetic and spectral evidence. In the early stages of the reaction an intermediate with the properties expected of a geminal diamine accumulated significantly. Changes consistent with the conversion of this species into the external aldimine were also observed. The course of product formation was determined and linked with spectral changes taking place in the bound coenzyme. The effect of the minor decarboxylation-dependent transamination that accompanies the major reaction was analysed.


Quality management systems in public organizations influence the quality of service delivery outputs. The purpose of this study was to determine the quality of service delivery at Community Service Centres (CSC) of the South African Police Service (SAPS) in the Western Cape, South Africa. A mixed-method research approach was employed to gather data for the study. Both a survey questionnaire and in-depth interviews were used to collect the data. The sample data set contacted 300 respondents from three policing areas situated in the Western Cape Metropolis. The main findings indicated that clients were satisfied with the level of service they received from the SAPS. However, the main area of concern was the absence of service delivery initatives at three police stations. Nicolette Daniels (South Africa), Rozenda Hendrickse (South Africa) BUSINESS PERSPECTIVES LLC "СPС "Business Perspectives" Hryhorii Skovoroda lane, 10, Sumy, 40022, Ukraine www.businessperspectives.org THE STATUS OF QUALITY MANAGEMENT IN SELECTED COMMUNITY SERVICE CENTRES IN THE WESTERN CAPE,


The importance of agile methods increased in recent years due to the need of being more flexible due to unstable requirements and high competitive pressure. Therefore, recent empirical studies have been conducted identifying a number of issues and advantages of incremental and agile methods. However, the majority of studies focused on one model (Extreme Programming) and small projects. Thus, in order to draw more general conclusions there is a need to also study large scale implementations of agile and incremental practices. Therefore, this paper 1) investigates a large-scale implementation of agile and incremental practices and identified issues and advantages and 2) compares them with the findings of previous studies mainly focusing on small-scale agile implementations.


Background: Leptospirosis is considered the most widespread zoonosis worldwide, occurring more frequently in tropical and developing regions. The aim of the present study was to detect the presence of Leptospiraspp. in different primate tissues, using immunohistochemical (IHC) assays, taking advantage of the considerable number of necropsies compatible with a diagnosis of leptospirosis in neotropical primates at the Animal Pathology Laboratory (APL) of the University of Passo Fundo (UPF) in the northern region of Rio Grande do Sul. Materials, Methods & Results: Paraffin-embedded primate tissue samples were selected from necropsy examinations and subjected to IHC. The streptavidin-biotin-peroxidase method was used with diaminobenzidine chromogen (DAB) to verify immunostaining. Of the101 primates tested for Leptospira spp., 51.48% were positive; taining was distributed between lung (76.92%), liver (44.23%), and kidney (32.69%) tissue. Analysis of the combined anatomopathological verification data of the studied organs revealed a high frequency of lesions commonly observed in the tissues of animals exposed to the pathogen. For complementary diagnosis, an anti-Leptospira spp. antibody test was performed in primates at the UPF-Zoo, from which a population of the necropsied animals originated. The microscopic agglutination test (MAT) was utilized, which demonstrated 90.47% positivity in 21 individuals; sejroe and panama were the most frequent serovars. Discussion: Different intensities of tissue immunostaining were observed. Areas of fragmented or diffuse staining were considered to indicate equal positivity to that indicated by areas of staining with preserved morphology. Of 52 Leptospira-positive primates, most presented some degree of staining in lung samples, which shows a high level of involvement for this organ in primate leptospirosis. Conventional pathological diagnostic methods do not allow fort issue antigen recognition, thus making the IHC technique important to facilitate conclusive antigen sample verification. In the liver, leptospires were detected mostly between the sinusoids, hepatocytes, and Kupffer cells. In kidney tissues, staining indicated small agglomerates in the tubular lumen, interstitium, and glomeruli. All these forms of presentation have been previously reported. Considering that we detected the highest number of positive samples in lung tissue, followed by those from liver and kidney tissue, we argue that the IHC technique, when applied to samples of these three tissues, decreases the chance of false negatives. Anatomopathological studies of primate leptospirosis are scarce. In dogs, renal lesions are characterized by the necrosis and degeneration of tubular epithelium, cellular debris, and hyaline cylinders. In the liver, hepatocyte cord dissociation and biliary pigment accumulation within the canaliculi and hepatocellular necrosis are observed. These findings are similar to those from our study. In the lung, diffuse alveolar lesions are reported, with hemorrhage and edema, in addition to capillaritis. The high frequency of Leptospira-positive animals determined by serological examination was consistent with the IHC findings, thus confirming the pathogen's high prevalence in neotropical primate populations in the studied region. Serological surveys on primate populations have already been carried out and have revealed frequency and serovar variations between regions. Immunohistochemical examination allows the detection of leptospires in various tissues and should be used based on the characteristics of the investigated case.


Thoracic aortic endovascular repair (TEVAR) is increasingly preferred as a treatment of choice in thoracic aortic diseases. Intravascular foreign body is one of the TEVAR-related complications similar to the other endovascular operations. Here, to the our best knowledge for the first time in the English literature, this report presents an extremely rare complication of a broken and stuck tip part of aortic stent-graft in the intravascular space and successful removal by using the coaxial technique. Thoracic aortic endovascular repair (TEVAR) has been increasingly preferred as the treatment of choice in thoracic aortic diseases (1). Endovascular treatment has been gaining popularity compared with open surgery due to its less invasive approach and rapid application, and allows the patient to easily return to daily life (2). However, TEVAR is associated with several specific complications including paraplegia, stroke, vascular injuries and local complications. These complications depend on vascular or nonvascular comorbidities, vascular anatomy, equipment, and experience of the provider (3-6). Intravascular foreign body could be among TEVAR-related complications similar to other endovascular operations (7). Several types of equipment, including guidewire, vascular sheath, or suboptimally uncoiled stents may get stuck in the intravascular space, causing complications (8). Herein, to the best of our knowledge, we present the first report in the English literature of broken and stuck tip part of an aortic stent-graft in the intravascular space and its successful removal using the coaxial technique.


We analyze a simple random process in which a token is moved in the
 interval $A={0,dots,n$: Fix a probability distribution $mu$
 over ${1,dots,n$. Initially, the token is placed in a random
 position in $A$. In round $t$, a random value $d$ is chosen
 according to $mu$. If the token is in position $ageq d$, then it
 is moved to position $a-d$. Otherwise it stays put. Let $T$ be
 the number of rounds until the token reaches position 0. We show
 tight bounds for the expectation of $T$ for the optimal
 distribution $mu$. More precisely, we show that
 $min_mu{E_mu(T)=Thetaleft((log n)^2
ight)$. For the
 proof, a novel potential function argument is introduced. The
 research is motivated by the problem of approximating the minimum
 of a continuous function over $[0,1]$ with a ``blind'' optimization
 strategy.


Since the end of World War II, the freeing of trade has been most visible in reciprocal liberalization agreements negotiated under the General Agreement on Tariffs and Trade, or GATT, and through increasing bilateral and plurilateral agreements. There has also, however, been a significant, if less visible, unilateral freeing of trade by several nations. This book, based on a research project directed by Jagdish Bhagwati, examines the experiences with such unilateral trade liberalization. Part 1 considers historical experiences, following Britain's unilateral embrace of free trade. Part 2 discusses recent examples, and Part 3 discusses unilateral liberalization in specific sectors. The substantive introduction provides a synthesis of the findings as well as theoretical support. It argues that although unilateral freeing of trade is generally less beneficial than reciprocity, it can trigger "sequential" reciprocity through example or by encouraging lobbies abroad to favor trade expansion.


OBJECTIVES:Patients with inflammatory bowel disease (IBD) have an increased risk of thrombotic complications. Moreover, a hypercoagulable state has been hypothesized as a contributing factor in the pathogenesis of IBD. Recently, a growing amount of interest has focused on mild-to-moderate hyperhomocysteinemia as a risk factor for thromboembolic disease. We aimed to evaluate the prevalence of hyperhomocysteinemia in patients with IBD and to investigate the contribution of genetic defects in the enzymes involved in homocysteine (Hcy) metabolism and vitamin status in determining increased levels of plasma total Hcy (tHcy).METHODS:The concentrations of tHcy, folate, and vitamin B12 as well as the prevalence of methylenetetrahydrofolate reductase (MTHFR) 677C to T mutation and the 68-bp insertion at exon 8 of cystathionine β-synthase (CBS) were measured in patients with IBD and healthy controls.RESULTS:In all, 17 out of 64 IBD patients (26.5%) and four out of 121 (3.3%) controls had hyperhomocysteinemia with a statistically significant difference (p < 0.0001). No significant difference was found between IBD patients and controls with regard to the prevalence of homozygotes for the C677T variant (TT) of MTHFR or the prevalence of heterozygotes for the CBS-gene mutation (IN). Among the IBD patients the only independent factor significantly associated with hyperhomocysteinemia was folate deficiency (p = 0.0002), regardless of the MTHFR or the CBS genotype.CONCLUSIONS:IBD patients have a higher prevalence of hyperhomocysteinemia than do healthy controls. Folate deficiency is the only independent risk factor in developing hyperhomocysteinemia.


Changes in dynamic psychological structures are often a treatment goal in psychotherapy. The present study aimed at creating a typology of self-representations among young women and men in psychoanalytic psychotherapy, to study longitudinal changes in self-representations, and to compare self-representations in the clinical sample with those of a nonclinical group. Twenty-five women and sixteen men were interviewed according to Blatt's Object Relations Inventory pretreatment, at termination, and at a 1.5-year follow-up. In the comparison group, eleven women and nine men were interviewed at baseline, 1.5 years, and three years later. Typologies of the 123 self-descriptions in the clinical group and 60 in the nonclinical group were constructed by means of ideal-type analysis for men and women separately. Clusters of self-representations could be depicted on a two-dimensional matrix with the axes Relatedness-Self-definition and Integration-Nonintegration. In most cases, the self-descriptions changed over time in terms of belonging to different ideal-type clusters. In the clinical group, there was a movement toward increased integration in self-representations, but above all toward a better balance between relatedness and self-definition. The changes continued after termination, paralleled by reduced symptoms, improved functioning, and higher developmental levels of representations. No corresponding tendency could be observed in the nonclinical group.


Within global education policy, the role of multilateral agencies in pushing cross-national policy borrowing is increasingly being complemented by efforts from private international networks within civil society, such as Teach For All. This introductory article summarizes the scarce extant literature on Teach For All, highlighting the contributions to this growing area of inquiry within this special issue. Especially provocative and fruitful lines of further inquiry surrounding Teach For All and similar policy networks are also highlighted and explored.


Streptococcus pyogenes is one of the most common bacteria infecting humans. One of the factors contributing to the disease-causing properties is the secreted streptococcal cysteine proteinase, SpeB, which degrades several host proteins in connective tissue and circulation. SpeB activity depends on the transformation from an inactive precursor, zymogen, into a mature proteinase. We show that the important cell wall-anchored M protein is involved in the unfolding and maturation of SpeB. An engineered strain lacking M protein secreted the SpeB zymogen in a conformational state that did not allow the maturation to proceed normally. Furthermore, we identified genes that were regulated by environmental changes using RNA fingerprinting. One of the identified glucose-induced genes encodes a phosphotransferase system that could be involved in the signaling leading to down-regulation of virulence genes in response to the nutritional status. Moreover, a novel secreted endoglycosidase, EndoS, has been identified. Purified EndoS removes the glycan from native human immunoglobulin G (IgG).This glycan is known to be important for IgG effector functions such as complement activation and binding to Fc receptors on phagocytic cells. Furthermore, it was discovered that SpeB cleaves the heavy chain of IgG resulting in distinct fragments separating the antigen-binding Fab portions from the effector-triggering Fc portion. SpeB also degrades the heavy chains of IgA, IgM, IgD and IgE. Finally, it was shown that both these enzymatic activities on human IgG have functional consequences with significantly impaired antibody-mediated killing of S. pyogenes in an ex vivo model. (Less)


The five-phased process for building Web sites in the classroom may be useful in helping educators facilitate the process of integrating computer technology and the Internet into instruction and curriculum design. The method described is a synthesis of a personal process of discovery, teaching, and learning that has come from practical experience with teachers and students. To effectively utilize this five-phased approach, the instructor must ascertain the final goal, whether it is a curriculum product, Web site, oral presentation, or some other form of demonstration of learning. The identified phases are a set of guiding principles that at any time may be revisited depending on the progress of the teaching and learning. In this approach, the instructor truly facilitates the learning process, no longer standing in the front of the room as the expert, but working alongside each learner to assist them in learning moments that are meaningful and timely in their delivery.


The success of international business relationships depends on effective business negotiations. Negotiators need to be well prepared. Understanding how to achieve international business negotiation outcomes and the factors relevant to the process will allow negotiators to be more successful. Based on theories of negotiation with a cultural focus, this study focuses on the dimensions of negotiating outcomes and process as perceived by Thai and International business negotiators related to past cross-cultural international business negotiations. From a review of negotiation practices a questionnaire focusing on positive retrospective negotiation experiences was developed and sent to executives working in Thailand. The results indicate that the important outcomes for successful cross-cultural negotiators are future-oriented prospects and performance. An information focus and a relationship orientation are the dominant keys to success identified by both Thai and International negotiators. Tactics and protocol are much less emphasized in successful experiences. International business negotiators significantly emphasize a specific time orientation more than their Thai counterparts.


There is a high international priority attached to activities which reduce NOx in the atmosphere. The current level of permitted emissions is typically between 50 µmol/mol and 100 µmol/mol, but lower values are expected in the future. Currently, ambient air quality monitoring regulations also require the measurement of NOx mole fractions as low as 0.2 µmol/mol. The production of accurate standards at these levels of mole fractions requires either dilution of a stable higher concentration gas standard or production by a dynamic technique, for example one based on permeation tubes. The CCQM-K74 key comparison was designed to evaluate the level of comparability of National Metrology Institutes' measurement capabilities and standards for nitrogen dioxide (NO2) at a nominal mole fraction of 10 µmol/mol. The measurements of this key comparison took place from June 2009 to May 2010. Seventeen laboratories took part in this comparison coordinated by the BIPM and VSL. The key comparison reference value was based on BIPM measurement results, and the standard measurement uncertainty of the reference value was 0.042 µmol/mol. This key comparison demonstrated that the results of the majority of the participants agreed within limits of ±3% relative to the reference value. The results of only one laboratory lay significantly outside these limits. Likewise this comparison made clear that a full interpretation of the results of the comparison needed to take into account the presence of nitric acid (in the range 100 nmol/mol to 350 nmol/mol) in the cylinders circulated as part of the comparison, as well as the possible presence of nitric acid in the primary standards used by participating laboratories. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).