Background: The purpose of this study was to assess if a computer-based multimedia education module (MEM) improved patients' comprehension when used as an adjunct to the standard verbal consent process for Morton's neuroma resection surgery. Methods: Nineteen patients (15 females and 4 males) considered candidates for Morton's neuroma resection surgery were prospectively recruited. A standardized verbal discussion was had with each patient regarding risks and benefits of surgery, alternative treatments, and the usual postoperative course. Patient understanding was then assessed with a questionnaire. Each patient subsequently viewed the MEM and the questionnaire was repeated. Patients also rated ease of understanding and satisfaction with both methods of patient education. Results: Patients answered a significantly greater proportion of correct answers after viewing the MEM module (85%), compared to verbal discussion alone (61%) (P = .002). Patients rated both the ease of understanding of the module and amount of information provided by the module as a mean of 9.3 cm on a 10 cm Visual Analog Scale (VAS). The majority of patients (76%) rated the multimedia tool as having answered their questions about surgery as well or better than the treating surgeon. Conclusion: An interactive multimedia educational tool was a useful adjunct to the informed consent process for patients considering Morton's neuroma resection surgery. Levels of Evidence: Level II, prospective cohort study.


Introduction: The study aimed to identify important interactions between Interleukin-6 and two single nucleotide polymorphisms of its gene expression (IL-6-174, IL-6-572) with some other factors including gender, age group, BMI, as while as blood concentration of sugar, lipids, and C-reactive protein, in association with hypertension. Methods: In this cross-sectional study, the data of first phase of the "Evaluation of Novel Risk Factors of NCD" project conducted in 2001by the Research Institute for Endocrine Sciences was used. To identify the interactions we used logic Features Selection approach. Analyses were done by logistic regression models using adjusted odds ratio (OR) to demonstrate the associations of interest. Results: Based on final selected model on data of 126 men and 208 women with age of 18 or more, significant regression coefficients were reported for individual variables including fasting blood sugar≥126mg/dl (P=0.001), body mass index>25 (P=0.03), and age>40 years of old (P 200 mg/dl+ age>40+ interloukin-6 >29+ fasting blood sugar<126mg/dl (P=0.003). Conclusion: Findings suggested that in addition to age, body mass index and fasting blood sugar, having high level of interleukin-6 besides high plasma concentration of total cholesterol in older adults with non diabetic fasting blood sugar can significantly increase hypertension prevalence, applying logic Features Selection approach.


Androgen deprivation therapy (ADT) is the preferred mode of treatment for patients with recurrence of prostate cancer (PC) following definitive treatment and locally advanced disease. With more men commencing ADT earlier in the treatment trajectory and for longer duration, the side effects of ADT are becoming more prevalent and of greater concern to clinicians. ADT can have serious adverse effects on bone mineral density (BMD) and metabolism, leading to the development of osteopenia or osteoporosis. This study was a cross-sectional investigation of dietary risk factors for bone loss, particularly calcium and vitamin D intakes, among men undergoing ADT for the treatment of non-metastatic PC (n = 12), hormone-naïve men with PC (n = 21) and healthy controls (n = 20). Outcome measures were dietary intake of calcium and vitamin D assessed by diet history questionnaire, as well as vitamin D status as assessed by serum 25-hydroxyvitamin D and parathyroid hormone levels. There were no between-group differences in calcium or vitamin D intake from food, supplements or both. When compared with the current Adequate Intake and treatment-specific guidelines, the majority of men did not meet current recommendations. Adherence to current dietary guidelines for the prevention of osteoporosis among men undergoing ADT was poor, with 91.7% falling short of the recommended 1500 mg of calcium per day, and no men meeting the treatment-specific recommendation of 20 mcg of daily vitamin D. In addition to inadequate calcium and vitamin D intakes, several additional dietary risk factors present among study participants further increase risk of bone loss and osteoporosis in this group ofmen. Vitamin D status was also not different among groups; however, serum values quantitated by the assays were well outside expected values, and it was concluded that the assays were likely not valid. The results of this study demonstrate the need for provision of nutrition information to these men at time of therapy commencement and on an ongoing basis throughout treatment, as a means of preventing or reducing the negative effects of ADT on nutritional status and quality of life.


The small glutamine-rich, tetratricopeptide repeat-containing protein alpha (SGTA) is an emerging player in the quality control of secretory and membrane proteins mislocalized to the cytosol, with established roles in tail-anchored (TA) membrane protein biogenesis. SGTA consists of three structural domains with individual functions, an N-terminal dimerization domain that assists protein sorting pathways, a central tetratricopeptide repeat (TPR) domain that mediates interactions with heat-shock proteins, proteasomal, and hormonal receptors, and viral proteins, and a C-terminal glutamine rich region that binds hydrophobic substrates. SGTA has been linked to viral lifecycles and hormone receptor signaling, with implications in the pathogenesis of various disease states. Thus far, a range of biophysical techniques have been employed to characterize SGTA structure in some detail, and to investigate its interactions with binding partners in different biological contexts. A complete description of SGTA structure, together with further investigation into its function as a co-chaperone involved quality control, could provide us with useful insights into its role in maintaining cellular proteostasis, and broaden our understanding of mechanisms underlying associated pathologies. This review describes how some structural features of SGTA have been elucidated, and what this has uncovered about its cellular functions. A brief background on the structure and function of SGTA is given, highlighting its importance to biomedicine and related fields. The current level of knowledge and what remains to be understood about the structure and function of SGTA is summarized, discussing the potential direction of future research.


In work was researched the composition and structure of high-alloyed aluminum cast iron ЧЮ22Ш. Crystalization of cast iron ЧЮ22Ш (ЧЮ22Ш standard cast iron) was researched by phase transformation, leaking upon its harden and cooling –down. High-alloyed materials are widely applied as the heat-resistant materials. Overall content of that reaches 30-50% and more. Previous performed researches allowed to optimize the content high-alloyed aluminum cast iron ЧЮ22Ш, to research its structure, casting and operational characteristics, to develop technological mode of melting, casting and thermal / heat treatment casts, to held its industrial examination and to determine perspective direction of its application. However, in present time ability of the aluminum cast iron ЧЮ22Ш is being used not sufficiently.


The time course of the concentration of radiocalcium was studied in the serum, skeleton, pelt, muscles, and pooled internal organs of 10-day-old rats. Within 10 hours of injection, the specific activity of the tissue groups exceeded the specific activity of the serum and remained above it during the period studied (120 hours). Chemical and autoradiographic analyses showed how rapidly most of the injected Ca45 found its way into the skeleton. A model was constructed with the assumption that the skeleton constitutes an essentially irreversible reservoir for the tracer in a multicompartment system in which the blood is the central or feeding compartment. The rate of transfer of the tracer from the soft tissue compartments to the serum was calculated from the equation See PDF for Equation in which C = concentration in serum (expressed as a series of exponential terms) C' = concentration in a given soft tissue Substitution in the integrated form of this equation yielded equations which had the major properties of the empirical equations fitted to the experimental points. The relative order of transfer constants (k' –1) was: organs ≥ pelt > muscle.


abstract The Dominion Observatory is carrying out a program to investigate the direction of faulting in large earthquakes through the study of first motion at distant stations. In this, the third paper of the series, solutions are obtained for fifteen earthquakes, with focal depths varying down to 600 km. For the first time, data from PP and P′ are used in obtaining solutions. Seven of the earthquakes considered lie in the North Pacific Ocean, four in South America, two in the southwest Pacific and two in central Asia. The two earthquakes in central Asia apparently occurred on steeply dipping normal faults, but most of the circum-Pacific shocks are due to transcurrent faulting. No attempt is made to correlate the results with structure. The attempt will be postponed until more earthquakes have been reduced.


This article investigates a previously neglected aspect of diplomatic relations between the Carolingians and the Umayyads of al-Andalus, the camels sent by Emir Muḥammad I to Charles the Bald, King of the West Franks, in 865. In addition to being placed within a diplomatic and historiographical context, the meaning of these animals needs to be understood within the traditions both of the donor and the recipient. The unusual nature of camels for both al-Andalus and Francia is explored. For both Muḥammad and Charles and their respective courts, camels would have been resonant of eastern monarchy, strengthening a claim to parity with other Islamic rulers for the former, while contributing to Charles's presentation of himself as a Solomonic king.


This paper develops and discusses the 1978-85 time trends in alternative measures of vehicle fuel economy. Nine alternative measures are presented ranging from ton-miles per gallon to menu-weighted performance adjusted miles per gallon. For each alternative measure, trends for important groups of manufacturers are presented. All of the trends in alternative measures are compared to the percent improvement implied by the original 1978 and 1985 passenger car average fuel economy standards (AFES).


We need a demonstrable evidentiary basis for understanding what works and what doesn't in international development, and to use that to guide programming decisions; the challenge is that some things are easier to measure than others, and so we tend to focus on the results and impacts that are easy to measure. Neither 'evidence' nor 'results' are limited to phenomena that are easily measurable, but we tend to lose track of this fact. We let the proxy of our limited definition of evidence stand in for what it was originally supposed to suggest, which is to say results. There is a related error that we often make, which focusing on the proxy of a static plan in place of focusing on actual dynamic implementation contexts and processes. Static plans are easier to develop and implement than dynamic ones, but – just as easily measurable evidence isn't necessarily the most important evidence – easily implemented static plans aren't the most effective ones. We need to develop methods for capturing and assessing and understanding the value we create by investing in learning, and this is what the KM Impact Challenge attempted to do for the field of knowledge management and learning for international development. Relatedly, to be more effective, we need to be more dynamic and adaptable in our strategy, design and implementation – and that in turn requires that we place more emphasis on sharing knowledge and learning about new technical learning, tacit/experiential knowledge, and contextual knowledge – in order that we and our implementing partners learn and adapt for maximum aid effectiveness.


Wind turbine is a device that converts kinetic energy of wind into electrical energy. Weak air pressure with an average of 2m/s to 4m/s makes wind turbine implementation in Malaysia becoming difficult and unrealistic. In order to produce a good power and torque, a quality air pressure is needed. Wind turbine performance depends on the incoming wind speed. Fluctuating and low quality air pressure are the significant challenges in wind turbine implementation. There are many types of mechanism and control but the production of output power is still considered low compared to the actual equipment. In a large building, Heat Ventilation Air Conditioning (HVAC) system is highly required to control the indoor temperature and consistent air pressure through ducting. The consistency of air pressure in ducting system make a drive for this research to proposed a wind turbine implementation in ducting system in order to produce electrical energy. In HVAC there are five parameters to be considered in order to identify the air pressure distribution in ducting system. These five parameters are input air pressure, ducting height, distance between blower to the pipe, total effective length and gap between trunk or run out.  In this paper, an analysis of air pressure  effect in a ducting system will be conducted via a development of air pressure prototype. Thousands of experiments are required with regards to a huge number of experiments to be considered. Spesifically a statistical analysis Taguchi Method is used to reduce a number of experiments. Without statistical analysis, 3125 experiments  shall be conducted to identify the air pressure distribution in the ducting system. However, these huge number of experiments are reduced to only 25 experiment by using Taguchi method based on the function of L25 in array orthogonal


The earliest examples of neurofibromatosis (in this case type 1, NF1) can be traced in the Ebers Papyrus (Ancient Egypt, 1.500 B.C.), in a Hellenistic statuette (Smyrna, 323 B.C.), in the coinage of the Parthians kings (247 B.C.) and in some 13th century monks' drawings. These earlier examples are somewhat less well defined as compared to the most recent better defined reports credited as having NF1 including an Inca child mummy (1480—1650 AD), Ulisse Aldrovandi's homuncio ("Monstrorum Historia", 1592 A.D.) with mosaic NF1 or the illustrations seen in the 18th century "Buffon's Histoire Naturelle" and "Cruveilhier's Anatomie Pathologique du Corps Human". The first English language report on NF1 was made by Akenside in 1768 and the first systematic review by Robert William Smith in 1849, while Virchow's pupil, Friedrich Daniel von Recklinghausen, in 1882, was the first to understand the origin of skin tumors and to name them neurofibromas. The touching story of Joseph C. Merrick (the "Elephant man," (who had Proteus syndrome and not NF1), in 1884, played an important role in the later misconception of NF1, as did the novel by Vicotr Hugo on the hunchback Quasimodo. The studies by van der Hoeve (1921), Yakovlev and Guthrie (1931), and Van Bogaert (1935), categorized "von Recklinghausen's" neurofibromatosis among the phakomatoses and the neurocutaneous syndromes. The first known mention of an acoustic neuroma (at autopsy) is attributed to Eduard Sandifort (1777 AD) while John H. Wishart made the earliest autoptic description of neurofibromatosis type 2 (NF2), in 1822, in a 21‐year‐old man with bilateral acoustic neuromas, who manifested signs since his infancy (Wishart subtype NF2). Smith likely described the first case of schwannomatosis in 1849. Older, Virchow, von Recklinghausen, and Verocay first classified "neuromas" and Masson and Penfield first used the word "schwannoma" taking it from Theodore Schwann's works. In 1903 Henneberg and Koch described NF2 in detail. Young, Eldridge, and Gardner, in the late '70, established NF2 as a distinct familial entity (Gardner subtype NF2). Schwannomatosis, the late entry of the different forms of neurofibromatosis, was credited in the middle '90.


Comparative studies of the application of monoammonium and diammonium phosphate for processing of fresh and aged manure litter from dairy cows were carried out with a view to decontamination. For this purpose changes in the quantities of pathogenic test strains of Proteus vulgaris, Pseudomonas aeruginosa and Staphylococcus epidermidis, differing in resistance to gentamicin and tetracycline antibiotics, were tracked. They were imported in the materials in quantities by 10 CFU/g of their total contents at the beginning of composting. It was found that in all investigated variants even after 2 weeks of the beginning of the experiments the quantities of test bacteria decreased to negligible levels (less than 2 lg). Complete decontamination of the studied composts in terms of pathogenic test bacteria was achieved in period of three weeks at temperature above 20°C. There were no significant differences of the antimicrobial effect between both nitrogen compounds tested (P>0.05), although diammonium phosphate showed slightly better results in this direction. Higher doses (600 ppm) also did not show statistically significant differences compared with smaller concentrations (200 ppm). In fresh and aged cattle manures without chemical treatment complete decontamination with respect to the introduced test strains was achieved for four weeks.


The main objective of this study was to investigate the influences of some personality traits, measured with the HEXACO model of personality, on the perceived ability to manage one's own affects. The results of the correlations and the linear regressions between the personality traits, measured by the HEXACO-60, and the perceived ability to manage affects, measured by the Regulatory Emotional Self-Efficacy Belief scale, support the idea that extraversion is more related to expressing positive affects, whereas emotionality is more related to managing negative affects, and conscientiousness is slightly related to some aspects of self-regulation of positive and negative affects. The results obtained in this study for the HEXACO are similar to those displayed for FFM in previous studies regarding personality traits and positive and negative affects.


Traditionally, studies of asthma have concentrated on interventions that were mainly pharmaceutical and outcomes that were usually based on pulmonary function testing. More recently, there has been increasing emphasis on organisational procedures that can enhance the delivery of effective care, and outcomes based more on the clinical than the physiological. Minimum length of stay is targeted as one outcome of benefit for patients and their families. The methods of decreasing hospital stay for asthmatic children which have been proposed and studied are reviewed.


This paper bring forward based on immune genetic algorithm to solve man on board automated storage and retrieval system optimized problem, immune genetic algorithm remains the characteristic which is not easy to plunge into local optimization and merge into the basic life immune theory, enhance overall searching efficiency, immune genetic algorithm has faster convergence velocity than traditional genetic algorithm. Experiment simulation result express: the result of immune genetic algorithm is better than traditional genetic algorithm in the circumstance of the same clusters and the same evolution generation. Immune genetic algorithm can shorten storage or retrieval distance in application, and enhance storage or retrieval efficiency.


We previously reported an efficient method for subtractive cDNA cloning using oligo(dT)30-Latex and polymerase chain reaction (PCR) (E. Hara et al., Nucleic Acids Res. 19, 7097-7104, 1991). The subtraction was performed by hybridization between mRNA of cell type B and the cDNA made from mRNA of cell type A using an oligo(dT)30 primer covalently linked to Latex particles in an Eppendorf tube. The mRNA common to both types of cells could be removed by a brief centrifugation. In the present paper, the method was improved by using the sense strand DNA instead of mRNA for hybridization to cDNA covalently linked to the particles to minimize mRNA degradation and by optimizing the hybridization condition. The sense strand DNA was made from cDNA-oligo(dT)30-Latex by asymmetric PCR. Using the improved method, a subtractive cDNA library with longer cDNA inserts was successfully constructed with higher probability than the original method.


BACKGROUND
Paracetamol, either alone or in combination with codeine or dihydrocodeine, is commonly used to treat chronic neuropathic pain. This review sought evidence for efficacy and harm from randomised double-blind studies.

OBJECTIVES
To assess the analgesic efficacy and adverse events of paracetamol with or without codeine or dihydrocodeine for chronic neuropathic pain in adults.

SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to July 2016, together with reference lists of retrieved papers and reviews, and two online study registries.

SELECTION CRITERIA
We included randomised, double-blind studies of two weeks' duration or longer, comparing paracetamol, alone or in combination with codeine or dihydrocodeine, with placebo or another active treatment in chronic neuropathic pain.

DATA COLLECTION AND ANALYSIS
Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE.

MAIN RESULTS
No study satisfied the inclusion criteria. Effects of interventions were not assessed as there were no included studies. We have only very low quality evidence and have no reliable indication of the likely effect.

AUTHORS' CONCLUSIONS
There is insufficient evidence to support or refute the suggestion that paracetamol alone, or in combination with codeine or dihydrocodeine, works in any neuropathic pain condition.


The growing concern over the depletion of hydrocarbon resources, and the adverse environmental effects associated with their use, has increased the demand for renewable energy sources. Thermoelectric (TE) power generation from waste heat has emerged as a renewable energy source that does not generate any pollutants. Recently, ink‐based processing for the preparation of TE materials has attracted tremendous attention because of the simplicity in design of power generators and the possibility of cost‐effective manufacturing. In this progress report, recent advances in the development of TE inks, processing techniques, and ink‐fabricated devices are reviewed. A summary of typical formulations of TE materials as inks is included, as well as a discussion on various ink‐based fabrication methods, with several examples of newly designed devices fabricated using these techniques. Finally, the prospects of this field with respect to the industrialization of TE power generation technology are presented.


In this study, we analyze Cluster observations of whistler-mode chorus and hiss waves during the event of August 19-21, 2006. Chorus is present outside the plasmasphere and hiss occurs inside the plasmasphere. Using a recently constructed plasma boundary layer model, we perform a ray-tracing study on the propagation of chorus. Numerical results show that chorus can penetrate into the plasmasphere through the plasma boundary layer, evolving into hiss. The current data analysis and modeling provide a further observational support for the previous findings that chorus is the origin of plasmaspheric hiss.


REQUASUD network (based in Wallonia, Belgium) consists of laboratories working directly with farmers, giving them soil fertility diagnostics and advice for a good management of soils and cultures. Therefore, the laboratories analyze, among others, available nutrients. But they need more information to correctly interpret the results and give fertility advice, like the cationic exchange capacity (CEC) and the clay content. However, analyzing CEC and clay content is expensive, time-consuming and requires the use of chemicals. To overpass this problem, the nearinfrared reflectance spectroscopy (NIRS) has been developed and is now used routinely in the laboratories. This method is rapid, non-destructive and allows the simultaneous estimation of soil characteristics. Nowadays, the REQUASUD NIR database performances for clay content are the followings : RPD = 2,22% for cultures and RPD = 1,72% for grasslands. This method of analysis can be used for other purposes than fertility advice.


BACKGROUND
Buerger's disease is a specific, idiopathic, recurrent, segmental, inflammatory, obliterative vascular disease involving medium-sized arteries and veins of the limbs. We performed omental transfer on a group of patients with Buerger's disease that had previously undergone lumbar sympathectomy and the results are described.

METHODS
Between January 1988 and December 1993, 100 cases of peripheral vascular disease (PVD) diagnosed as Buerger's Disease were subjected to femoral angiography. Fifty cases of angiographic intermediate/distal type blocks underwent omental transposition.

RESULTS
Of 50 patients subjected to omental transfer all had intermittent claudication, 40 had rest pain of whom 36 had non-healing ulcers, 8 had gangrene and 32 had bilateral lower limb involvement. Fifteen patients underwent bilateral omental transfer and posterior tibial artery biopsy was performed in 40. All patients showed improved skin temperature, rest pain decreased in 36 and claudication distance increased in 48. Ulcers healed in 32 of 36 patients and the line of demarcation receded in six of eight patients with gangrene.

CONCLUSIONS
Omental transfer improved skin and muscle microcirculation and forestalled the need for amputation by providing symptomatic relief and clinically arresting the progress of Buerger's disease. Omental transfer should be considered seriously as an alternative to other modalities of therapy to delay the ischaemic complications of Buerger's disease.


This study examines the settlement behaviour of the mytilids Mytilus galloprovincialis, Brachidontes
erosus, Brachidontes rostratus, and Trichomya hirsutus larvae in response to different substrata: which
were byssus threads of these four mussel species, coconut thread, and Polyvinyl chloride (PVC). The
number of settlers on different substrata in the laboratory was analysed separately for each species
using One-way ANOVA. A significant effect of substratum was found for all species tested. Larvae of T.
hirsutus and B. erosus settled preferentially on conspecific byssus threads, while B. rostratus and M.
galloprovincialis showed a similar trend. Settlement data from the field was analysed using two-way
ANOVA with species and substrata as the main effect. Settlement was effected by species, but not by
substrata. However, the overall settlement pattern indicated a conspecific preference with the lowest
number of settlers on PVC substratum. Small size of settlement larvae of B erosus comparing to
settlement larvae of T hirsutus, M galloprovinciallis, and B rostratus was observed.


The labor market is both a market and a "social institution". But what do we mean by that? In the first part of this article we analyze different interpretations of the labor market's "social" dimension, starting with the versions postulated by economists and ending with those that invoke solidarity as a criterion. In the second part, we analyze the functions of the institutions that embody the labor market's social dimension, both from the positive viewpoint - correcting market failures - and the negative viewpoint - creating and capturing rents. Discussion of the factors that explain how these institutions come into being and evolve allows us to identify a number of institutions that perform a dual function: correcting market failures, and also correcting failures in other institutions.


A two dimensional grating has been fabricated from hybrid polymer incorporated with organic dye-laser. The precursor hybrid polymers were synthesized from TMSPMA by sol-gel method. The precursor was mixed with photo-initiator to make sensitive with UV light. The photosensitive film was irradiated by laser interference of THG Nd-YAG laser (λ = 355 nm) yield 2D grating with hexagonal structure. The characteristic of lasing was investigated using strip-line excitation light of SHG Nd-YAG laser (λ = 532 nm). The lasing wavelengths are observed at 606 and 621 nm for grating period of 400 and 410 nm, respectively. The spectral width (FWHM) of lasing is about 3 nm at pumping power 14.88 mJ/pulse cm 2 .


Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA

Recent advances in improving outcome of locally advanced cervical cancer (LACC) were made by addition of cisplatin to radiotherapy. However, total 5-year survival rates are still ∼66%, underscoring the need for new therapy strategies.

Current therapeutic strategies in cervical cancer consist of cisplatin and radiotherapy, which exert their anti-cancer effects by inducing high levels of DNA lesions including DNA double strand breaks (DSBs), with the aim to induce cell death in tumor cells.

However, tumor cells can respond to these therapy-induced DNA lesions by activation of the DNA damage response (DDR). The DDR is a complex signalling network, consisting of multiple kinases and transcriptional programs that function in parallel to arrest ongoing cell cycle progression, which allows time for DNA repair. Effective DNA repair may thus counteracts therapy-induced cancer cell death.

Cervical cancers already have a partial dysfunction of the DDR due to frequent, human papilloma virus (HPV) infection. As a result, HPV-infected cervical tumors are thought to rely heavily on remaining DDR activity for their survival. We therefore hypothesize that the residual DDR activity may provide an 'Achilles heel' which could be exploited therapeutically using specific DDR inhibitors, to increase tumor cell sensitivity to cisplatin and ionizing radiation.

Firstly, we examined the expression and activation status of the key DDR components ATM, Chk2, ATR, Chk1, DNA-PK and MK2 in 375 cervical cancer patients using immunohistochemistry. We found that these DDR components were all abundantly expressed in cervical cancer tissues, underscoring the availability of these components for targeting by DDR inhibitors.

Subsequently, we tested chemo- or radiosensitization of specific chemical inhibitors against ATM (KU-55933), ATR (NU-6027), DNA-PK (KU-0060648), Chk1/2 (AZD7762) and MK2 (MK2-inhibitor III) using HPV-positive cervical cancer cell lines HeLa and SiHa. MTT-assay analyses showed that ATR, Chk1/2 and DNA-PK inhibition, sensitized cervical cancer cells to cisplatin. In contrast, clonogenic survival assays revealed that inhibition of ATM, DNA-PK and Chk1/2 caused radiosensitization. In order to uncover how DDR inactivation is most effective in a combined chemo-radiotherapy setting, we therefore optimised an in vitro 'combination therapy survival assay' reflecting the different DNA lesions given in clinical LACC therapy. We showed that targeting of ATM, ATR and Chk1/2 caused effective chemo-radiosensitization of cervical cancer cells.

Our data show that DDR components are abundantly expressed in cervical cancer. Furthermore, we show that targeting of individual DDR kinases has differential effects on chemo- or radiotherapy sensitivity. Finally, we show that ATM, ATR and Chk1/2 inhibition are promising strategies to further improve the efficacy of platinum-based chemoradiation.

Citation Format: Hylke W. Wieringa, Marieke Everts, G.Bea A. Wisman, Ate G.J. van der Zee, Elisabeth G.E. de Vries, Marcel A.T.M. van Vugt. Predictive and therapeutic impact of DNA damage response activation in locally advanced cervical cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2417. doi:10.1158/1538-7445.AM2014-2417


Abstract Democratic culture in the lives of villagers in Bali has some of the proceduralprinciples of a modern democracy. Some parameters are the rotation of power,open leadership recruitment systems, order management turnover, recognitionof appropriate manners, tolerance of differences of opinion, and accountabilityof power holders. Application of democratic culture clearly affects how desapakraman elaborates the concept of democracy as a power base andindependence. In addition, it also determines the shape and nature of relationsbetween the desa pakraman with desa dinas, this condition could be the basis ofprocedural democracy as one of the values of local wisdom in the development ofcultural tourism in Bali


Biliary excretion (BE) is a major elimination pathway, and its prediction is particularly important for optimization of systemic and/or target-site exposure of new molecular entities. The objective is to characterize the physicochemical space associated with hepatobiliary transport and rat BE and to develop in silico models. BE of 123 in-house compounds was obtained using the bile-duct cannulated rat model. Human and rat hepatic uptake transporters (hOATP1B1, hOATP1B3, hOATP2B1, and rOatp1b2) substrates (n = 183) were identified using transfected cells. Furthermore, the datasets were extended by adding BE of 163 compounds and 97 organic anion transporting polypeptide (OATP) substrates from the literature. Approximately 60% of compounds showing percentage of BE (%BE) ≥ 10 are anions, with mean BE of anions (36%) more than 3-fold higher than that of nonacids (11%). Compounds with %BE ≥ 10 are found to have high molecular mass, large polar surface area, more rotatable bonds, and high H-bond count, whereas the lipophilicity and passive membrane permeability are lower compared with compounds with %BE < 10. According to statistical analysis and principal component analysis, hOATPs and rOatp1b2 substrates showed physicochemical characteristics that were similar to those of the %BE ≥ 10 dataset. We further build categorical in silico models to predict rat BE, and the models (gradient boosting machine and scoring function) developed showed 80% predictability in identifying the rat BE bins (%BE ≥ 10 or < 10). In conclusion, the significant overlap of the property space of OATP substrates and rat BE suggests a predominant role of sinusoidal uptake transporters in biliary elimination. Categorical in silico models to predict rat BE were developed, and successful predictions were achieved.


In New Zealand, there are no liquid formulations of omeprazole commercially available, therefore suspensions must be extemporaneously compounded from solid dosage forms for patients with swallowing difficulties. The funding for solid dosage forms of omeprazole changes frequently, often every one to two years, without consideration of the impact this may have when extemporaneously compounded liquid dosage forms are required. This study examined suspensions compounded from various solid dosage forms of omeprazole with the purpose of identifying suitable quality formulations and evaluating their chemical and physical stability. Six different solid dosage forms of omeprazole that are available in New Zealand, including capsules, tablets, and powder, were used to prepare 2-mg/mL suspensions in 8.4% w/v sodium bicarbonate solution. The suspensions were then assessed visually for quality and by quantifying sedimentation rate over 120 minutes. Two products, stored in amber bottles at either 4°C or 25°C, demonstrated acceptable quality over a 30-day period whilst monitoring physical and chemical stability on day 0, 7, 14, 20, and 30. Four of the formulated suspensions were deemed to be of poor quality due to either a lack of uniformity or rapid sedimentation, attributes that could lead to inaccurate dosing. Acceptable quality suspensions were prepared from Losec and Dr. Reddy's brands of omeprazole 20-mg capsules. For both brands, a change in color was observed after 20 days and 7 days when stored at 4°C and 25°C, respectively. Chemical stability was determined using a stability-indicating high-performance liquid chromatographic method, with >90% of the active remaining for 30 days when kept at 4°C, and 20 days when stored at 25°C. Not all brands are suitable for extemporaneously compounding omeprazole suspensions. Losec and Dr. Reddy's brands of capsules were suitable to prepare quality omeprazole suspensions. Omeprazole suspensions compounded from these products are stable for 20 days if stored at 4°C and protected from light.


Through an aquarium-based study, we provide evidence that exposure to macroalgae (Dictyota spp.), seawater with reduced pH (7.6 vs 8.1), and elevated temperature (31.8 vs 28.8 °C) causes distinct and additive repercussions for larval settlement and condition (photochemical efficiency and oxidative stress). Larvae from the common Caribbean coral Porites astreoides (Lamarck, 1816) were provided settlement substrate and exposed to each factor for 72 hrs in isolation and combination under an orthogonal design. Largely, biotic and abiotic factors did not interact in their impact on coral planulae; instead, stressors independently affected the survival, condition, and settlement of P. astreoides. Dictyota spp. and low pH each individually reduced the survival of coral larvae. Furthermore, the presence of Dictyota spp. and elevated temperature distinctly inhibited larval settlement and photochemical efficiency, respectively. When combined, stressors additively increased cellular oxidative damage (lipid peroxidation) approximately four fold compared to larvae maintained under control conditions. The results indicate that each stressor independently impacts distinct and overlapping facets of coral settlement, and suggest that their combined effects could have severe collective consequences for coral demography.


Efficient DNA delivery is a prerequisite for the successful implementation of molecular antiviral strategies against chronic viral hepatitis and gene therapy in general. The cationic polymer polyethylenimine (PEI) has recently been explored as a gene transfer vector in various cell types in vitro and in vivo. In this study, we evaluated a linear PEI derivative (lPEI) as a vector for gene and oligodeoxynucleotide transfer into hepatocytes in vitro and in vivo. A simple protocol was developed that allowed transfection of up to 50% of primary hepatocytes in vitro. In addition, fluorescent oligodeoxynucleotides were efficiently delivered to the liver in vivo after intravenous injection into Pekin ducks. Thus, lPEI mediates highly efficient gene and oligodeoxynucleotide transfer into primary hepatocytes and is potentially useful for DNA delivery in vivo.


We present a new AI task - Embodied Question Answering(EmbodiedQA) - where an agent is spawned at a random location in a 3D environment and asked a question ('What color is the car?'). In order to answer, the agent must first intelligently navigate to explore the environment, gather necessary visual information through first-person (egocentric) vision, and then answer the question ('orange'). EmbodiedQA requires a range of AI skills - language understanding, visual recognition, active perception, goal-driven navigation, commonsense reasoning, long-term memory, and grounding language into actions. In this work, we develop a dataset of questions and answers in House3D environments [1], evaluation metrics, and a hierarchical model trained with imitation and reinforcement learning.


Improvements in cognitive flexibility during the preschool years have been linked to developments in both working memory and inhibitory control, though the precise contribution of each remains unclear. In the current study, one hundred and twenty 2‐, 3‐, and 4‐year‐olds completed two rule‐switching tasks. In one version, children switched rules in the presence of conflicting information, and in the other version, children switched rules in the presence of distracting information. Switching in the presence of conflict improved rapidly between the ages of 3 and 3.5 years, and was associated with better working memory. Conversely, switching in the presence of distraction developed significantly between the ages of 2 and 3 years, and was associated with better inhibitory control.


Chorionic villus biopsies made during the first trimester of pregnancy offer the advantage of earlier antenatal diagnoses than usual methods. This technic was introduced about 15 years ago but recently improved thanks to innovations in equipment and the contribution of echography. 75 biopsies were made using aspiration technic by echographic-guided catheter. These biopsies were carried out before elective abortion, 18 in an ambulatory setting one to three weeks before the abortion in order to test the social acceptability and tolerance of this method, as well as the inherent risks involved. The biopsy technic is described as well as preliminary results of chromosomic analyses of biopsied chorionic tissues. Drawing from a perspicacious review of the literature, the respective advantages of various biopsy technics and their uses (i.e. sex determination and chromosome analyses by culture and especially direct methods, study of fetal DNA, and enzyme assay) are examined. Finally, the risks of biopsy technic in the immediate and near future are discussed, and the indications today for this new technic are described.


Laws concerning the growing, selling, and consuming cannabis and its related products have been changing considerably over the last few years. The legalization of hemp in 2018 sparked an interest in Δ-9-tetrahydrocannabinol (Δ-9-THC) isomers and analogs that are derived from hemp and sold with minimal oversight. One example is Δ-8-tetrahydrocannabinol (Δ-8-THC). Although less potent than Δ-9-THC, Δ-8-THC is gaining popularity and can easily be found where cannabis-related products are sold. The forensic toxicology laboratory at the University of Florida routinely tests decedents for 11-nor-Δ-9-tetrahydrocannabinol-9-carboxylic acid (Δ-9-THC-acid), the primary metabolite of Δ-9-THC. Urine samples from approximately 900 decedents were received by the laboratory between mid-November 2021 to mid-March 2022 and subjected to CEDIA™ immunoassay testing. Subsequent confirmation of 194 presumptive positive samples was performed by gas chromatography-mass spectrometry (GC-MS). A peak eluting immediately after Δ-9-THC-acid was identified as 11-nor-Δ-8-tetrahydrocannabinol-9-carboxylic acid (Δ-8-THC-acid), a metabolite of Δ-8-THC, in 26 of those samples (13%). Six (6) of the Δ-8-THC-acid positive samples were positive for Δ-8-THC-acid only. Other toxicological findings were consistent with poly-drug use including fentanyl/fentanyl analogs, ethanol, cocaine, and methamphetamine. There has been an emergence of Δ-8-THC use as indicated by the presence of Δ-8-THC-acid in 26 of 194 presumptive positive cases during a four-month period. The majority of individuals were White males with a history of drug and/or alcohol use. Δ-9-THC-acid, as well as other drugs, were often present. Given the psychoactive potential and availability of Δ-8-THC, monitoring Δ-8-THC-acid in decedents is important to characterize risk and prevalence of Δ-8-THC use.


Abstract : Genetic epidemiological analysis provides convincing data that a significant portion of the liability for developing alcoholism is inherited. The identity and mechanism by which genes contribute to inherited susceptibility to alcoholism are unknown. If genes that affect susceptibility to alcoholism can be identified, they are logical targets for the development of pharmacological agents to modify susceptibility and treat alcoholism. Primarily, the meiotic gene mapping approach has been used in an effort to identify genes that affect susceptibility to alcoholism. This approach may be insensitive to genes that have common alleles with modest effects on susceptibility. An alternative approach, allelic association analysis, may be far more powerful for detecting these genes, but requires that analysis of individual candidate genes. This proposal examines a large number of genes implicated in the biology of alcoholism to see whether common alleles of these genes affect susceptibility. Two hundred and fifty polymorphisms, in 21 candidate genes were genotyped in 1200 subjects from the UCSF family study and 600 subjects in 120 families with nicotine dependence have been successfully genotyped. An additional 140 previously reported polymorphism were found not to be informative in these populations. The most promising observation are that a common haploytpe of the adenylate cyclase type 2 gene is associated with a series of addiction related phenotypes (p^0.001-0.00001).


The nitrilase AtNIT1 from Arabidopsis thaliana was overexpressed in Escherichia coli with an N-terminal His6 tag and purified by zinc chelate affinity chromatography in a single step almost to homogeneity in a 68% yield with a specific activity of 34.1 U.mg-1. The native enzyme (approximately 450 kDa) consists of 11-13 subunits (38 kDa). The temperature optimum was determined to be 35 degrees C and a pH optimum of 9 was found. Thus, recombinant AtNIT1 resembles in its properties the native enzyme and the nitrilase from Brassica napus. The stability of AtNIT1 could be significantly improved by the addition of dithiothreitol and EDTA. The substrate range of AtNIT1 differs considerably from those of bacterial nitrilases. Aliphatic nitriles are the most effective substrates, showing increasing rates of hydrolysis with increasing size of the residues, as demonstrated in the series butyronitrile, octanenitrile, phenylpropionitrile. In comparison with 3-indolylacetonitrile, the rate of hydrolysis of 3-phenylpropionitrile is increased by a factor of 330, and the Km value is reduced by a factor of 23. With the exception of fluoro, substituents in the alpha position to the nitrile function completely inhibit the hydrolysis.


Social Position and Dress in the Kiskunsag Region in the 18th - 19th Centuries - The a r- ticle gives a glimpse into the dress culture of the Kiskun District that existed from the late 17th century to 1876, located in the region between the Rivers Danube and Tisza. Drawing on research in archives, it examines the costumes worn by women and men in the different social strata and the regulations governing dress. The manner of dress that developed as a result of the bans and regul a- tions can be reconstructed from the documents of litigation, wills, inventories of estates and reports by the board of guardians. Using examples taken from this archive material the author presents se v- eral festive and everyday costumes, showing that dress had the function of indicating status. She concludes that the leaders of local society used the regulations on dress to support the preservation of external appearances reflecting social status.


Pseudomonas aeruginosa is an opportunistic pathogenic bacterium that causes acute and chronic infections in humans. The type VI secretion systems (T6SSs) have been shown to associate with chronic infections. ABSTRACT Pseudomonas aeruginosa possesses three type VI secretion systems (T6SSs) that are involved in interspecies competition, internalization into epithelial cells, and virulence. Host-derived mucin glycans regulate the T6SSs through RetS, and attacks from other species activate the H1-T6SS. However, other environmental signals that control the T6SSs remain to be explored. Previously, we determined PitA to be a constitutive phosphate transporter, whose mutation reduces the intracellular phosphate concentration. Here, we demonstrate that mutation in the pitA gene increases the expression of the H2- and H3-T6SS genes and enhances bacterial uptake by A549 cells. We further found that mutation of pitA results in activation of the quorum sensing (QS) systems, which contributes to the upregulation of the H2- and H3-T6SS genes. Overexpression of the phosphate transporter complex genes pstSCAB or knockdown of the phosphate starvation response regulator gene phoB in the ΔpitA mutant reduces the expression of the QS genes and subsequently the H2- and H3-T6SS genes and bacterial internalization. Furthermore, growth of wild-type PA14 in a low-phosphate medium results in upregulation of the QS and H2- and H3-T6SS genes and bacterial internalization compared to those in cells grown in a high-phosphate medium. Deletion of the phoB gene abolished the differences in the expression of the QS and T6SS genes as well as bacterial internalization in the low- and high- phosphate media. Overall, our results elucidate the mechanism of PitA-mediated regulation on the QS system and H2- and H3-T6SSs and reveal a novel pathway that regulates the T6SSs in response to phosphate starvation. IMPORTANCE Pseudomonas aeruginosa is an opportunistic pathogenic bacterium that causes acute and chronic infections in humans. The type VI secretion systems (T6SSs) have been shown to associate with chronic infections. Understanding the mechanism used by the bacteria to sense environmental signals and regulate virulence factors will provide clues for developing novel effective treatment strategies. Here, we demonstrate a relationship between a phosphate transporter and the T6SSs and reveal a novel regulatory pathway that senses phosphate limitation and controls bacterial virulence factors in P. aeruginosa.


The selective vulnerability of brain networks in individuals at risk for Alzheimer's disease (AD) may help differentiate pathological from normal aging at asymptomatic stages, allowing the implementation of more effective interventions. We used a sample of 72 people across the age span, enriched for the APOE4 genotype to reveal vulnerable networks associated with a composite AD risk factor including age, genotype, and sex. Sparse canonical correlation analysis (CCA) revealed a high weight associated with genotype, and subgraphs involving the cuneus, temporal, cingulate cortices, and cerebellum. Adding cognitive metrics to the risk factor revealed the highest cumulative degree of connectivity for the pericalcarine cortex, insula, banks of the superior sulcus, and the cerebellum. To enable scaling up our approach, we extended tensor network principal component analysis, introducing CCA components. We developed sparse regression predictive models with errors of 17% for genotype, 24% for family risk factor for AD, and 5 years for age. Age prediction in groups including cognitively impaired subjects revealed regions not found using only normal subjects, i.e. middle and transverse temporal, paracentral and superior banks of temporal sulcus, as well as the amygdala and parahippocampal gyrus. These modeling approaches represent stepping stones towards single subject prediction.


Background: Alcohol consumption is a potential trigger for inflammatory bowel disease (IBD) flare because of alcohol-induced oxidative stress and its deleterious effects on gut barrier function. Additionally, we have recently shown that alcohol consumption is associated with more symptoms in IBD. However, it is not known whether moderate daily alcohol consumption can modify IBD disease activity. To test what effects alcohol may have on patients with IBD, we evaluated the effect of moderate daily red wine for 1 week on two factors associated with recurrent IBD disease activity: intestinal permeability and stool calprotectin. Methods: To assess the effects of moderate daily alcohol consumption on intestinal permeability and inflammation, we recruited 21 patients: 8 with inactive ulcerative colitis (UC), 6 with inactive Crohn's disease (CD), and 7 healthy controls. All participants with IBD completed a validated questionnaire on disease activity (Crohn's disease activity index or ulcerative colitis clinical activity index), to confirm they had inactive disease. All subjects then underwent a baseline assessment that included a blood draw, urine collection after sugar challenge, and stool collection. Subjects then consumed 1–3 glasses of red wine a day for 1 week (approx. 0.4 g EtOH/kg), and repeated the three measures. Results: No subjects flared during the study. Moderate alcohol consumption did not significantly change either clinical disease activity scores or C-reactive protein. In contrast to healthy subjects, daily consumption of red wine significantly (1) decreased stool calprotectin in IBD subjects from baseline (p = 0.001) and (2) increased intestinal permeability as measured by urinary lactulose/mannitol excretion (marker of small bowel permeability) in CD (p = 0.028) or urinary sucralose secretion (marker of large bowel permeability) in UC (p = 0.012). Conclusions: One week of moderate consumption of red wine in inactive IBD was associated with a significant decrease in stool calprotectin and a significant increase in intestinal permeability. Our data suggests that patients with inactive IBD who drink red wine daily may be at an increased long-term risk for disease relapse.


The study of vitamin D(3) topical applications has begun at Osaka University after Morimoto S. reported a patient with senile osteoporosis whose psoriasis was cured after treatment with 1-alpha-hydroxyvitamin D(3) [1 alpha (OH) D(3)]. Another study of the first use of vitamin D(3) for psoriasis was reported in the same year in both Europe and the United States independently. Calcipotriol ointment came first onto the market for the treatment of psoriasis in Denmark in 1990. In Japan, where tacalcitol ointment was first approved in 1993, six kinds of topical vitamin D(3) applications are now available. Now new applications of vitamin D(3) are anticipated to replace therapeutic drugs currently in use for psoriasis and other skin diseases.


Uranium dioxide (UO2) is an important fuel material in the nuclear industry, and the behavior of the 5f electrons of uranium is one of the most interesting subjects about actinide elements and their compounds. Uranium dioxide is known to be a good insulator[1], and it is also known that the magnetic moment on uranium ions orders antiferromagnetically at temperatures below 30K.[2, 3], The structural and electronic properties of UO2 have been studied by using X-ray photoelectron spectroscopy (XPS) and Bremsstrahlung isochromat spectroscopy (BIS).[4, 5, 6] Theoretically, Kelly and Brooks[7] have performed density functional theory (DFT)[8, 9] calculations using the linear muffin-tin orbital (LMTO) method and the local density approximation (LDA)[10] to study the energy band structure of UO2. They found that the LDA calculations fail to describe UO2, predicting metallic behavior contrary to the observed insulating behavior. Petit et al. calculated the density of states and the cohesive properties of UO2 using the LMTO method in the atomic sphere approximation (ASA).[11] They obtained a smaller lattice constant, a smaller cohesive energy, and a larger bulk modulus than the experimental values. They also observed that the ground state of UO2 was still metallic. The failure of the conventional DFT has been attributed to the strong correlation of 5f electrons in UO2. Recently, theoretical calculations have been made that take into account this strong correlation. For instance, Dudarev et al.[12] obtained the correct insulating ground state of UO2 from the local spin density approximation (LSDA)+U calculations that were proposed by Anisimov et al.[13] In addition, Kudin et al. compared the results from DFT calculations using LSDA, a generalized gradient approximation (GGA),[14] and a hybrid DFT functional. They demonstrated that the hybrid DFT method successfully describes the electronic and the magnetic structure of UO2.[15] Very recently, Laskowski et al. investigated the magnetic structure of UO2 using the linear augmented plane wave method with spin-orbit coupling.[16] They compared different LDA+U schemes by calculating the uranium electric field gradients. In this work, we report on a comparative study of the conventional spin-polarized GGA (SP-GGA) and the SPGGA+U calculations for UO2. The ground state of UO2 was found to be insulating when the electronic correlation We have performed the density functional theory calculations of UO2 using the spin-polarized generalized gradient approximation (SP-GGA) and the SP-GGA+U approach. The SP-GGA+U approach correctly predicts the insulating electronic structure with antiferromagnetic ordering, but the SP-GGA calculations predict metallic behavior. The cohesive properties obtained from the SP-GGA+U calculations are in good agreement with the available experimental results and previous calculations. The spin-polarized local density of states shows that the antiferromagnetic ordering of UO2 is governed by 5f orbitals of uranium ion. Our calculations demonstrate that the strong correlation of U 5f electrons should be taken into account for a reliable description of UO2 physics.


The genetic basis of hybrid incompatibility in crosses between Drosophila mauritiana and D. simulans was investigated to gain insight into the evolutionary mechanisms of speciation. In this study, segments of the D. mauritiana third chromosome were introgressed into a D. simulans genetic background and tested as homozygotes for viability, male fertility, and female fertility. The entire third chromosome was covered with partially overlapping segments. Many segments were male sterile, while none were female sterile or lethal, confirming previous reports of the rapid evolution of hybrid male sterility (HMS). A statistical model was developed to quantify the HMS accumulation. In comparison with previous work on the X chromosome, we estimate that the X has approximately 2.5 times the density of HMS factors as the autosomes. We also estimate that the whole genome contains approximately 15 HMS "equivalents"-i.e., 15 times the minimum number of incompatibility factors necessary to cause complete sterility. Although some caveats for the quantitative estimate of a 2.5-fold density difference are described, this study supports the notion that the X chromosome plays a special role in the evolution of reproductive isolation. Possible mechanisms of a "large X" effect include selective fixation of new mutations that are recessive or partially recessive and the evolution of sex-ratio distortion systems.


Ameloblastic carcinoma is a rare and malignant odontogenic tumor. Approximately, 100 cases of ameloblastic carcinomas have been reported in the literature, with fewer than 10 reported cases of an even more rare variant with spindle-cell differentiation. Although it is presumed that most ameloblastic carcinomas arise de novo, it also appears capable of proliferating as carcinoma ex ameloblastoma. Without a full past history, the exact origin of these tumors can be unclear. The exact classification becomes further questionable when both an intraosseous and peripheral tumor exists. This currently reported case has been present for at least 4 years before the patient presenting for care. However, without prior biopsy, the etiology and category of this ameloblastic carcinoma is speculative. Our case represents a histologically unequivocal case of ameloblastic carcinoma. Based on tumor morphology, questions still remain, as to whether it arose de novo, or as carcinoma ex ameloblastoma. The possibility of categorizing the current lesion as a spindle cell variant also exists because of the presence of a prominent population of malignant epithelial spindled cells arranged in fascicles. The authors believe that this ameloblastic carcinoma would best be subclassified as a rare spindle cell variant, based on the prominent spindle cell component.


Monoamine transporters (MATs) carry out neurotransmitter reuptake from the synaptic cleft, a key step in neurotransmission, which is targeted in the treatment of neurological disorders. Cholesterol (CHOL), a major component of the synaptic plasma membrane, has been shown to exhibit a modulatory effect on MATs. Recent crystal structures of the dopamine transporter (DAT) revealed the presence of two conserved CHOL-like molecules, suggesting a functional protein-CHOL direct interaction. Here, we present extensive atomistic molecular dynamics (MD) simulations of DAT in an outward-facing conformation. In the absence of bound CHOL, DAT undergoes structural changes reflecting early events of dopamine transport: transition to an inward-facing conformation. In contrast, in the presence of bound CHOL, these conformational changes are inhibited, seemingly by an immobilization of the intracellular interface of transmembrane helix 1a and 5 by CHOL. We also provide evidence, from coarse grain MD simulations that the CHOL sites observed in the DAT crystal structures are preserved in all human monoamine transporters (dopamine, serotonin and norepinephrine), suggesting that our findings might extend to the entire family.


In many legal disputes, the selection of one body of law rather than another is outcome-determinative. The situation with targeted killings is no different. Although there are contrary impulses at the margins, in the main a human rights paradigm is more likely to restrict such operations while a law of war paradigm is more likely to sanction it. But the question is when each body of law applies, a question that is not explicitly addressed by either body. By looking at the underlying object and purpose of each body of law, however, an account of their respective spheres becomes apparent. This essay defends the claim that the dividing line is represented by a state acting as a sovereign as opposed to acting as a belligerent. In the former situation, the state acts as a ruler over its subjects and its activities are constrained by human rights law. In contrast, when the state acts as a belligerent during armed conflict, International Humanitarian Law regulates its actions. This essay provides a framework to determine when the state is acting in one mode rather than another: acting as a sovereign involves an unequal relationship (ruler-to-ruled), while belligerency is characterized by two, formally co-equal collectives facing each other in battle. At the closing stage of an armed conflict, the relationship of belligerency may give way to sovereignty, a transition point that is often characterized by the law of occupation. The argument is both normative and descriptive in the sense that the two bodies of law already embody these normative distinctions; therefore their respective application is currently delimited by these existing principles.


In the field of formal verification of real-time systems, major developments have been recorded in the last fifteen years. It is about logics, automata, process algebra, programming languages, etc. From the beginning, a formalism has played an important role: timed automata and their natural extension,hybrid automata. Those models allow the definition of real-time constraints using real-valued clocks, or more generally analog variables whose evolution is governed by differential equations. They generalize finite automata in that their semantics defines timed words where each symbol is associated with an occurrence timestamp.The decidability and algorithmic analysis of timed and hybrid automata have been intensively studied in the literature. The central result for timed automata is that they are positively decidable. This is not the case for hybrid automata, but semi-algorithmic methods are known when the dynamics is relatively simple, namely a linear relation between the derivatives of the variables.With the increasing complexity of nowadays systems, those models are however limited in their classical semantics, for modelling realistic implementations or dynamical systems.In this thesis, we study the algorithmics of complex semantics for timed and hybrid automata.On the one hand, we propose implementable semantics for timed automata and we study their computational properties: by contrast with other works, we identify a semantics that is implementable and that has decidable properties. On the other hand, we give new algorithmic approaches to the analysis of hybrid automata whose dynamics is given by an affine function of its variables.


This book contains all you need to know about Massive Open Online Courses (MOOC) for the world of business! It was written by academics and business experts from across Europe as part of the BizMOOC project (bizmooc.eu). Inside you will find a detailed analysis of key literature in this field along with a range of practical tips for designing, implementing, evaluating and improving online learning at scale. Use this guide to understand the MOOC potential for you and your organisation!BizMOOC (2016-9) was a Knowledge Alliance project funded by the European Union (Erasmus+ / Key Action 2 / Knowledge Alliance; 562286-EPP-1-2015-1-AT-EPPKA2-KA). The European Commission support for the production of this publication does not constitute an endorsement of the contents which reflects the views only of the authors, and the Commission cannot be held responsible for any use which may be made of the information contained therein.


This final project was dedicated to study some of the agreements that the In-ternational Maritime Organization approved over the past years. Concretely I decided to focus my efforts on the SOLAS conventions, all related with safety.
I also tried to explain what the IMO was and how all its different organisms worked. It was essential and interesting to learn what an international organi-zation meant, and therefore; understand how all the laws that were approved had a direct effect on the entire world fleet.
Since safety at sea is one of the most important issues related to the maritime sector, I thought that I needed to understand its evolution throughout the years. Because of different accidents that happened in the maritime world, a series of conventions were developed. After the sinking of the Titanic in 1912, a con-gress was organized in the United Kingdom to create the SOLAS. It covered and regulated the security on board of passenger ships and merchant marine. So, I asked myself, have all these measures worked?
The work method used all along the thesis, was analysing directly from the original texts of the IMO. By reading and summarizing the four SOLAS con-vention, I wrote the most important ideas that I considered. I checked the most part of the job that IMO did related to safety over the past years, and the goals for the future.
At the beginning, in 1914; the measures were really simple, and most of them were not even useful. Because of some historic facts like the sank of Titanic, the regulations became more strict and specific. Furthermore, technology and knowledge made a really high progress which allowed to make changes easily. The system established nowadays, is the result of these past years of work. However, our world is constantly evolving, and that is why organizations like IMO needs to be ready to face possible trouble


Background Accurate volumetric evaluation of donors' livers before surgery is crucial for successful living-donor liver transplantation. However, there are few studies on the volumetric evaluation in the recently popularized pure laparoscopic donor hepatectomy method, in contrast to the number of studies for conventional donor hepatectomy. We aimed to analyze the difference between estimated graft weight and actual graft weight in pure laparoscopic donor right hepatectomy (PLDRH) and conventional donor right hepatectomy (CDRH) procedures. Material/Methods The medical records of 612 donors who underwent right hepatectomy in living-donor liver transplantation between January 2014 and December 2020 were retrospectively reviewed. The CDRH group targeted patients from January 2014 to October 2015, and the PLDRH group targeted patients from March 2016 to December 2020. Results There were 119 and 376 donors who underwent CDRH and PLDRH, respectively. Although there was no significant difference in the estimated graft weights (P=0.994) and actual graft weights (P=0.489) between the groups, the estimated graft weights were significantly higher than the actual graft weights in both groups. However, the estimated graft weight and actual graft weight showed linear correlations in both the CDRH (r=0.81, P<0.001) and PLDRH (r=0.76, P<0.001) groups, with the CDRH group having greater linearity. Conclusions The estimates of graft weight were similar between the 2 groups. However, since the actual graft weight tended to be smaller in the PLDRH group, this should be considered before surgery.


Makgeolli is Korean traditional alcoholic beverage that has historically been brewed. In this study, we analyzed the profile of organic acids in makgeolli and also evaluated its physiological characteristics. Makgeolli contained excess lactic acid, which is produced by lactic acid bacteria (LAB). Anti-obesity effects of makgeolli were investigated in 3T3-L1 preadipocytes. Compared to the negative control, makgeolli inhibited the differentiation of preadipocyte as quantified by Oil red O dye. In particular, 100 μg/mL makgeolli reduced 40 to 70% of differentiation. To evaluate the anti-angiogenic and anti-inflammatory effects of makgeolli, we performed chorioallantoic membrane assay and measured nitric oxide production from lipopolysaccharide-induced RAW264.7 cells. Most makgeolli interrupted the formation of neo-vasculature and significantly inhibited NO production in a dose-dependent manner. Taken together, these findings suggest that commercial makgeolli has inhibitory activities against adipogenesis, neo-vascularization, and inflammation, and also they are influenced by second metabolites from nuruk microflora containing fungi and LAB.


Providing adaptive shared control for Brain-Computer Interfaces (BCIs) can result in better performance while reducing the user's mental workload. In this respect, online estimation of accuracy and speed of command delivery are important factors. This study aims at real-time differentiation between fast and slow trials in a motor imagery BCI. In our experiments, we refer to trials shorter than the median of trial lengths as "fast" trials and to those longer than the median as "slow" trials. We propose a classifier for real-time distinction between fast and slow trials based on estimates of the entropy rates for the first 2-3 s of the electroencephalogram (EEG). Results suggest that it can be predicted whether a trial is slow or fast well before a cutoff time. This is important for adaptive shared control especially because 55% to 75% of trials (for the five subjects in this study) are longer than that cutoff time.


We propose a unifying view of negation as failure, integrity constraints, and epistemic queries in nonmonotonic reasoning. Specii-cally, we study the relationship between satis-ability and logical implication in nonmono-tonic logics, showing that, in many nonmono-tonic formalisms, it is possible and easy to reduce logical implication to satissability. This result not only allows for establishing new complexity results for the satissability problem in nonmonotonic logics, but also establishes a clear relationship between the studies on epistemic queries and integrity constraints in monotonic knowledge bases with the work on negation by default in nonmonotonic reasoning and logic programming. From the perspective of the design of knowledge representation systems, such a reduction allows for deening both a simple method for answering epistemic queries in knowledge bases with nonmonotonic abilities, and a procedure for identifying integrity constraints in the knowledge base, which can be employed for optimizing reasoning in such systems.


Tularemia is a zoonotic infection which is caused by gram negative coccobacilli, Francisella tularensis. The disease occurs after contact with blood and body fluids of infected animals, bites and ingestion of infected food and water. Although it commonly presents with skin lesions, there may also be serious organ involvements. A55-year woman was consulted for presumptive diagnosis of tuberculosis. Multiple lymphadenopathy in right cervical area was present on physical examination. Pleural effusion on left side was detected with computed tomography. In detailed history, knowledge of a family member with the diagnosis of tularemia was obtained. Both of them had the history of contact with infected animals. Diagnosis of tularemia was confirmed with microagglutination test. With this patient who was initially presumptively diagnosed as tuberculosis, we aim to draw attention to diagnosis of tularemia in the presence of pleuropnemonia and peripheral lymphadenopathy and emphasize importance of detailed patient history.


Chalcopyrite copper indium gallium diselenide (Cu(In,Ga)Se2 or CIGS) solar cells have achieved the highest laboratory power conversion efficiency among thin film PV technologies, and have the potential to be manufactured cost-effectively at large scale. In this thesis, detailed studies on the growth of CIGS solar cells by means of a pilot scale inline co-evaporation system have been performed to explore the beneficial deposition techniques to successfully transfer the research achievements into costeffective industrial production. The work involved the development and optimisation of several new processes along with the design of the inline pilot scale system. Effects of the thin absorber layers (with thickness of ~1 μm) on material quality and the device performance have been investigated using (i) a two-step process with room temperature evaporated metal precursors, (ii) a three-stage process at constant substrate temperature and (iii) a three-stage process at varied substrate temperatures. Changing the copper and gallium compositions of the CIGS layers was observed to have a strong impact on the structural and electronic properties and hence on the performance of the solar cells. In one study, simple mechanical compression was employed on a batch of low quality porous CIGS films to significantly improve the surface morphological and the optoelectronic properties. Photoluminescence measurements revealed the band-to-tail defect-related recombination that was detrimental to the quality of as-grown and compressed films. In another study, rapid thermal processing (RTP) was applied to the low temperature Cu-In-Ga-Se precursor layers in an attempt to reduce the cost and optimise the reaction mechanism of the chalcopyrite material. After fine tuning of the process conditions, the CIGS layers with larger grain size exhibited power conversion efficiencies up to 10.8%. While these results are promising, the device performance was mainly limited by the low open circuit voltage and the low fill factor. It has been found that the Cu-In-Ga-Se precursors doped with low concentrations of sodium were beneficial for re-crystallisation of the CIGS films due to the reduced grain size and crystallinity of the precursors. An in-situ X-ray diffraction technique was used to investigate the phase evaluation in both Na-free and Na-doped Cu-In-Ga-Se precursor layers as a function of temperature. The results confirmed that the formation of both CIGS as well as secondary phases in the layer with the Na-doped precursors started at higher temperatures compared to Na-free precursors. It is therefore expected that further improvements in the solar cell efficiency might be achieved following this RTP and low-temperature precursor process. In Memory of My Dear Grandfather


To the Editor.— The June 1975 issue of theArchives(111:755-756, 1975) contains a report entitled "Pedunculated Malignant Melanoma." The authors describe one case and report on three others; they state: "To our knowledge these are the only ones reported in the English literature." We feel that this comment requires further clarification. In 1970, G. L. Beardmore et al reported 105 cases of fatal malignant melanoma; 36 (35%) of these were pedunculated ones. 1 In our own series, during the years 1955 to 1976, we examined 170 patients and found ten with pedunculated melanomas. Seven of these patients are alive. Five of them (two with metastases) have survived more than five years and two have survived almost two years. One patient died of an intermittent disease and two others of metastatic melanoma. Only in one of these patients (with more than five-years-survival) had the tumor infiltrated the reticular layer of


The physiological basis of auditory frequency selectivity was investigated by recording the temporal response patterns of single cochlear-nerve fibers in the cat. The characteristic frequency and sharpness of tuning was determined for low-frequency cochlear-nerve fibers with two-tone signals whose frequency components were of equal amplitude and starting phase. The measures were compared with those obtained with sinusoidal signals. The two-tone characteristic frequency (2TCF) is defined as the arithmetic-center frequency at which the fiber is synchronized to both signal frequencies in equal measure. The 2TCF closely corresponds to the characteristic frequency as determined by the frequency threshold curve. Moreover, the 2TCF changes relatively little (2%-12%) over a 60-dB intensity range. The 2TCF generally shifts upward with increasing intensity for cochlear-nerve fibers tuned to frequencies below 1 kHz and shifts downward as a function of intensity for units with characteristic frequencies (CF's) above 1 kHz. The shifts in the 2TCF are considerably smaller than those observed with sinusoidal signals. Filter functions were derived from the synchronization pattern to the two-tone signal by varying the frequency of one of the components over the fiber's response area while maintaining the other component at the 2TCF. The frequency selectivity of the two-tone filter function was determined by dividing the vector strength to the variable frequency signal by the vector strength to the CF tone. The filter function was measured 10 dB down from the peak (2T Q 10 dB) and compared with the Q 10 dB of the frequency threshold curve. The correlation between the two measures of frequency selectivity was 0.72. The 2T Q 10 dB does change as a function of intensity. The magnitude and direction of the change is dependent on the sharpness of tuning at low and moderate sound-pressure levels (SPL's). The selectivity of the more sharply tuned fibers (2T Q 10 dB greater than 3) diminishes at intensities above 60 dB SPL. However, the broadening of selectivity is relatively small in comparison to discharge rate-based measures of selectivity. The selectivity of the more broadly tuned units remains unchanged or improves slightly at similar intensity levels. The present data indicate that the frequency selectivity and tuning of low-frequency cochlear-nerve fibers are relatively stable over a 60-dB range of SPL's when measured in terms of their temporal discharge properties.


We examine the influence of daily variations in baseline ozone (O3) on urban air quality in the U.S. Pacific Northwest (PNW) during 2004 to 2010 through two analyses: (1) transport of free tropospheric (FT) O3 from Mount Bachelor Observatory (MBO) to Boise, Idaho; and (2) transport of marine boundary layer (MBL) O3 from Cheeka Peak (CP) to Enumclaw, Washington. Both Boise and Enumclaw experience days with maximum daily 8 hour averages of O3 (MDA8) exceeding U.S. standards. Backward trajectory cluster analyses identify days when FT and MBL O3 strongly influence MDA8 in Boise and Enumclaw. On these days, MBO and CP O3 observations explain 40% and 69% of the variations in Boise and Enumclaw MDA8, respectively. Bivariate regressions for Boise/MBO and Enumclaw/CP have slopes of 0.52 ± 0.16 and 1.04 ± 0.08, respectively, representing the differing interplay of O3 dilution, production, and loss during FT to boundary layer transport (Boise/MBO) and fast boundary layer transport (Enumclaw/CP). AIRPACT‐3/CMAQ (Air Indicator Report for Public Access and Community Tracking version 3/Community Multi‐scale Air Quality model) high‐resolution air‐quality simulation results demonstrate how transport of O3 from the FT above MBO contributes to elevated O3 at Boise. Average MDA8 O3 in Boise is higher than in Enumclaw due to site elevation and greater entrainment of FT air masses, a finding likely applicable to other PNW sites. Days with high baseline influence at Boise and Enumclaw have lower average MDA8 O3 than other days; however, some of these days would still exceed the U.S. standard if it is substantially tightened in 2013, highlighting the increasing importance of FT O3 influence on urban MDA8.


The ability of Powder Bed Fusion (PBF) to create complex geometries across a wide range of materials makes PBF a widely used powder-based metal additive manufacturing (AM) process in various industries for advanced applications. However, compared to conventional manufacturing processes, the metal parts printed by PBF exhibit lower surface quality due to soot and spatter particles arising from laser-powder interaction. To minimize spatter and soot generation during the build, PBF systems are equipped with cross-flow nozzles that are designed to flow inert gas across the build platform. It is desired that these gas flow systems have the ability to remove most of the spattered powder from the build chamber, but do not erode the freshly spread layer of powder on the to-be-printed surface to ensure high-quality manufactured parts. The onset of particle bed erosion can be characterized by the critical Shields number. Once the critical Shields number is known for the metal powders and system of interest, the flow of inert gas in the build chamber can be optimized to ensure the build process is efficient and clean.
 This work proposes a Shields number-based method for obtaining engineering design guidance for PBF gas flow systems to optimize the spatter removal process. A combined experimental and Computational Fluid Dynamics (CFD) study was performed to provide design guidance for these cross-flow systems. All experiments were conducted using a small, closed-loop wind tunnel, with built-in flexibility, capable of testing a number of cross-flow configurations. A high-speed camera captured the threshold of particle movement at a variety of operating conditions for various metal powders used in metal AM including aluminum alloy AlSi10Mg, nickel-based superalloy Inconel 718, titanium alloy Ti-6Al-4V, steel alloy 4340, and 316L stainless steel. Time-averaged flowfield measurements of the gas flow inside the test section were made using particle tracking velocimetry (PTV) and a hot-wire air flow meter at the same conditions. Using these experimental measurements and attendant CFD simulations, CFD predictions of wall shear stress can be used to calculate the Shields number at the condition of incipient movement as identified experimentally.


Tissue formation and maintenance is regulated by various factors, including biological, physiological and physical signals transmitted between cells as well as originating from cell-substrate interactions. In our study, the osteogenic potential of mesenchymal stromal/stem cells isolated from umbilical cord Wharton's jelly (UC-MSCs) was investigated in relation to the substrate rigidity on polyacrylamide hydrogel (PAAM). Osteogenic differentiation of UC-MSCs was enhanced on stiff substrate compared to soft substrates, illustrating that the mechanical environment can play a role in differentiation of this type of cells. These results show that substrate stiffness can regulate UC-MSCs differentiation, and hence may have significant implications for design of biomaterials with appropriate mechanical properties for regenerative medicine.


In 2020, law of the sea tribunals rendered one decision on jurisdiction and decided one case on the merits. First, the arbitral tribunal in the Azov Sea and Kerch Strait dispute dismissed the jurisdictional objections raised by the Russian Federation and thus will proceed to hear the merits of Ukraine's claims. Second, the arbitral tribunal in the Enrica Lexie Incident case found, after upholding its jurisdiction in relation to the dispute before it, that the Italian marines who had shot an Indian fisherman in India's Exclusive Economic Zone were entitled to immunity under international law and that Italy had breached certain provisions of the United Nations Convention on the Law of the Sea (UNCLOS). These two arbitral awards have confirmed and developed certain trends in the jurisprudence of law of the sea tribunals. In addition, a novelty in 2020 was the conclusion of a Model Agreement between Singapore and the International Tribunal for the Law of the Sea (ITLOS), for the latter to be able to discharge its judicial business in Singapore. Last, the Meeting of the States Parties to UNCLOS elected five new members of ITLOS and re-elected two.


Purpose: creation of working classification of morphologic variations of postoperative lens capsule opacity after Micro-Invasive cataract surgery. Material and methods. Morphologic study of the lens capsule (LC) has been conducted on 4 artiphakic cadaveric eyes. A specimen of an isolated anterior lens capsule, obtained during the repeated operation with changes characteristic for anterior capsular contraction syndrome has been studied too. The obtained specimens have been researched with the method of semithin sections. Results. The analysis of the morphologic cadaveric LC specimens revealed the polymorphism of secondary cataract (SC). Besides well known "classic" SC forms, which were caused by fibroplasias processes or pseudo-regeneration a new type of postoperative LC opacity not represented in the available literature before has been revealed. The given variant of opacities was called "pseudo-hyaloid" form and characterized by the absence of clear LC borders, changes of its normal structure, the appearance of loose fibrillar structure with microslit spaces and exfoliations, that possibly was the consequence of acustic cavitation, arising in the result of ultrasonic effect. As a result the LC lost characteristic for it the role of the dense bed and made impossible adhesion and migration on its changed surface the proliferative fibrocellular elements characteristic for "classic" SC forms. The microscopy results of the isolated anterior LC specimen in the area of capsulotomic aperture showed the presence of altered abundant loose fibrillar tissue with microporous structure and expressed forming of folds. Making layers of fibrous tissue exceeded the thickness of the normal anterior LC in 10 and more times and considerably reduced the diameter of capsulotomic aperture. Conclusion. The variety of postoperative LC opacities confirmed by the results of morphologic studies afforded to suggest a new working classification in which all possible morphologic variants and the stages of the secondary pathologic changes forming of anterior LC. The suggested classification is convenient for the understanding and must promote to make a right algorithm in the choice of optimal and safe technology of laser reconstructive interventions.


As more and more variable resources and demand response resources being integrated in the electric grid, the grid operation is experiencing increasing level of uncertainties. The decision making process under such environment becomes more challenging. This paper investigates the current risk management practices and proposes a risk management framework for the future grid operation. Under this framework, three risk management processes are proposed. The first process is the robust unit commitment for reliability, which focuses on the system capacity requirements using long-lead time units. The second process is the scenario-based look-ahead commitment for fast-start units, which concentrates on the system operability. The third process is the economic dispatch with corrective actions, which takes into account the trade-off between corrective actions and the system economics. The methodologies used to implement the proposed processes are also discussed in the paper.


This study investigated the relationship between the drying methods and the physicochemical properties of soybean during drying prior to converting it into flour. Three samples were prepared for each of Tax 1485 and mixed varieties. A sample for each variety was subjected to a drying method. The three drying methods used are roasting, oven and sun drying. The dried samples were converted to flour in attrition mill. Supplemented breads (5% soy + 95% wheat) were prepared from the flour for organoleptic evaluation; proximate analysis was also carried on the flour samples. The analyses were replicated thrice. The result of this study showed that oven drying method has highest acceptability levels when compared to the other two methods in both Tax 1485 and mixed variety; showing 58 and 64%, respectively. It was also established that oven drying method retained highest protein content of 40.54 and 33.7% for Tax 1485 and mixed variety, respectively, though there was no significant difference in the protein values. The results show that drying for a long period (as observed in sun drying) and with high temperature (as observed in roasting), to achieve safe moisture content, will defeat the purpose of using soy flour as supplement due to a significant reduction in the protein content and acceptability. Moderately high temperature of 60°C in oven as being investigated is therefore recommended. Key words : Roasting, boiling, oven drying, sun drying, quality.


Mounting evidence suggests that catechol metabolites of estradici may contribute to the development of estrogen-induced cancers. O-Methyla-tion, catalyzed by catechol-O-methyltransferase (COMT), inactivates cat echol estrogens. COMT is polymorphic in the human population, with 25% of Caucasians being homozygous for a low activity alà eleof the enzyme (COMT1-1-).We hypothesized that low activity COMT may be a risk factor for human breast cancer and designed a PCR-based RFLP assay to determine COMT genotype in a cohort of 112 matched, nested case-control samples. In the total study population, the odds ratios for the association of breast cancer risk with COMT"1' and COMT1-1-genotypes were 1.30 [confidence interval (CI), 0.66-2.58] and 1.45 (CI, 0.69-3.07), respectively. Postmenopausal COMT1'1-women had a greater than 2-fold increased risk of developing breast cancer [odds ratio (OR), 2.18; CI, 0.93-5.11]. The association of COMT1-1-with the development of postmenopausal breast cancer was stronger and statistically significant in those women with a body mass index >24.47 kg/m2 (OR, 3.58; CI, 1.07-11.98). When COMT1-1' was combined with either glutathione S-transferase (GST) Ml null or with GSTP1 Ile-105-Val/Val-105-Val (inter mediate/low activity, respectively) genotypes, the risk for developing postmenopausal breast cancer was also significantly increased. Our findings suggest that the alà eleencoding low activity COMT may be an important contributor to the postmenopausal development of breast cancer in cer tain women.


This study aimed to examine sex and age-level differences in preschool children with respect to walking times on acourse and on a balance beam with obstacles. Subjects were 324 healthy preschool children: 4-year-old boys (51) andgirls (51), 5-year-old boys (50) and girls (60), and 6-year-old boys (62) and girls (50). A 5- or 10-cm-high obstacle(depth, 11.5 cm; width, 23.5 cm) was set at the halfway point of a course (length, 200 cm; width, 10 cm) that wasdrawn on the floor and a balance beam (length, 200 cm; width, 10 cm; height 30 cm). The children walked to the endof the course and on a balance beam, and returned as quickly as possible under three conditions: no obstacle, lowobstacle, and high obstacle. In all obstacle conditions, children aged 4–4.5 years walked on the course and thebalance beam significantly slower than children aged 5 and 6 years, and children aged 4.5–5 years walked moreslowly than children aged 5.5–6 years and children aged 6 years. Both walking was significantly slower in childrenaged 5–5.5 years than children aged 6 years (course: aged 6.5–7 years) in the high-obstacle condition, and was lowerin the high-obstacle condition than in the no-obstacle condition in children aged 4 years. No significant sexdifference was found in children in either walking time in all obstacle conditions. The walking time on the courseshowed a significant curvilinear regression with age in boys except for the no- and low-obstacle conditions. Allbalance beam walking times showed a significant curvilinear regression with age in both sexes in all obstacleconditions.Finally, 4-year-old children walked more slowly than 5- and 6-year-old children on a course and on a balance beamregardless of the presence of the obstacles. Both walking abilities develop markedly in 4-year-old children, andchildren between 5.5 and 6 years walk at a similar speed. The two forms of walking, regardless of the presence of anobstacle, showed little difference based on sex in children aged 4–6 years. A 10-cm-high obstacle affects walking in4-year-old children, but not in children older than 5 years.


We present new algorithms to balance the computation of parallel hash joins over heterogeneous processors in the presence of data skew and external loads. Heterogeneity in our model consists of disparate computing elements, as well as general purpose computing ensembles that are subject to external loading. Data skew appears as significant nonuniformities in the distribution of attribute values of underlying relations that are involved in a join. We develop cost models and predictive dynamic load balancing protocols to detect imbalance during the computation of a single large join. Our algorithms can account for imbalance due to dates skew as well as heterogeneity in the computing environment. Significant performance gains are reported for a wide range of test cases on a prototype implementation of the system.<<ETX>>


Rapidly wedged, double cantilevered beam specimens have a critical bending moment as a propagating fracture criterion in the limit of Bernoulli-Euler beam theory. The magnitude of the critical bending moment is calculated from a fully dynamic analysis of crack propagation. The shear force, in the beam at the constant displacement rate end of the DCB specimen, multiplied by the square root of the loading time is related to the critical bending moment. Experimental measurements of the time dependence of the shear force were used to calculate the specific fracture surface energy versus crack velocity. The crack velocity in a single specimen decreases with increasing time, it varies by a factor of 5 and is typically 0.01 of ..sqrt..E/rho. Details of the experimental measurements for brittle and ductile fractures, including stress intensity values versus crack velocity are described.


Polte T, Foell J, Werner C, et al. J Clin Invest. 2006;116:1025–1036 PURPOSE OF THE STUDY. Allergen-specific CD4+ T-helper 2 (Th2) cells are thought to be at the center of asthma pathogenesis because of their ability to secrete cytokines such as interleukin 4 (IL-4), IL-5, and IL-13, which result in many of the features of allergic inflammation. CD4+ cells recognize the allergen-derived target presented with class II on antigen-presenting cells along with costimulatory signals. One recently described costimulatory molecule is CD137. Studies using murine disease models have shown that stimulation of CD137 on T cells can modulate the immune system in beneficial ways, such as promoting tumor regression and suppressing autoimmunity. The authors of this study investigated the effect of CD137 stimulation on a murine model of allergic asthma. METHODS. Allergic airway inflammation was induced in BALB/cByJ mice in the well-established manner involving systemic immunization to ovalbumin with alum followed by repeated aerosolized ovalbumin exposure. Control, nonspecific, antibody-treated mice were compared with mice treated with a single dose of agonistic anti-CD137 antibody given either before ovalbumin sensitization or after establishment of airway inflammation. Immunologic responses to ovalbumin were measured by ovalbumin-induced proliferation, in vitro cytokine production, and ovalbumin-specific immunoglobulin E and G1 titers. Changes in frequency of lymphocyte populations (CD4+, CD8+, CD19+, and CD4+CD25+) were measured by flow cytometry of total splenocytes. Adoptive transfer experiments were also conducted with CD4+ cells into severe combined immunodeficiency animals after control or anti-CD137 treatment. RESULTS. A single dose of anti-CD137 treatment was effective in prevention of ovalbumin-induced airway inflammation and in vitro recall responses to ovalbumin continued to show suppressed Th2 cytokine responses (IL-4, IL-5, IL-13) and elevated Th1 (interferon γ [IFN-γ]) even after chronic ovalbumin exposure. Anti-CD137 given as a single dose after establishment of airway inflammation induced significant reduction of inflammation, even when given at a time point associated with chronic inflammation (32 weeks). In vitro cytokine responses were modulated by anti-CD137 treatment, which resulted in lower levels of ovalbumin-induced Th2 cytokines and elevated levels of IFN-γ in both lung and spleen cells. Anti-CD137 treatment was also associated with an increase of CD8+ cells and a decrease of CD19+ cells. The anti-CD137 affect was not entirely accounted for by this increase in CD8+ or IFN-γ, because inhibition of either resulted in only a partial reversal of its effect. Consistent with this, adoptively transferred CD4+ cells from animals that had been treated with anti-CD137 induced lower levels of airway inflammation compared with control-treated CD4+ cells. CONCLUSIONS. CD137 is a potentially important target molecule for the modulation of Th2 inflammation. REVIEWER COMMENTS. Asthma morbidity continues to rise in the pediatric population. This was the first report of the potential importance of the CD137 costimulatory pathway in the pathogenesis of Th2-driven airway inflammation. CD137 activation has been shown to be associated with both promotion of Th1 and regulatory T-cell activity in various disease models, and clinical trials targeting this pathway are likely to come soon for tumor immunology. Much more study is required, but this may emerge as an important new target for suppressing allergic inflammation.