The interaction behaviours of successful, high-achieving learners when using a Learning Management System (LMS) are different than the behaviours of learners who are having more difficulty mastering the course material. This paper explores the idea that conventional Learning Management Systems can exploit data mining techniques to predict the success or failure of students without requiring the results of formal assessments. This paper describes a study with a second semester computer science class that shows that the success or failure of a learner can be predicted using information about learner interactions with course materials and learner self-reports of subject matter confidence.


We investigate the dynamics in the logarithmic galactic potential with an analytical approach. The phase-space structure of the real system is approximated with resonant detuned normal forms constructed with the method based on the Lie transform. Attention is focused on the properties of the axial periodic orbits and of low-order "boxlets" that play an important role in galactic models. Using energy and ellipticity as parameters, we find analytical expressions of several useful indicators, such as stability-instability thresholds, bifurcations, and phase-space fractions of some orbit families, and compare them with numerical results available in the literature.


Fossil vertebrate remains are found throughout the Lower Oxford Clay (Callovian, Middle Jurassic) in the Peterborough (Cambridgeshire) area, but occur more frequently in the Jason Zone at the base of the sequence. Five types of vertebrate preservation can be distinguished, most of which are lithologically restricted. Predation, scavenging and bacterial decomposition are responsible for the break-up of corpses. Current activity, storm events, firmness of substrate and oxygen content of sediment pore waters are factors affecting preservation.


Many Areas in Science and industrial applications requires huge computation power that is must achieve the desired level of computation. The field of distributed computing covers all aspects of computing and information access across multiple processing elements connected by any form of communication network. In this paper we investigate the design and implementation of a grid based system depending on an Intranet based on Windows operating system. The proposed Virtual Grid-Based Parallel Computer (VGBPC) system was written using C# and .NET 3.5 framework. The system uses the remote computer as a node to accomplish the execution task. The Grid Manger system was built to be initiated on the server of the Intranet which responsible of partitioning the task and assigning each partition to Grid thread that is transmitted to the Grid Executer. The Grid Executer implemented in this work responsible of receiving the threads from the Grid manger, executing them and resending them back to the Grid Manager. The proposed system was used to accomplish parallel Prime Number Checker to investigate the (VGBPC) capabilities.


Abstract. Patterns of distinct preferential pathways for fluid flow and solute transport are ubiquitous in heterogeneous, saturated and partially saturated porous media. Yet, the underlying reasons for their emergence, and their characterization and quantification, remain enigmatic. Here we analyze simulations of steady state fluid flow and solute transport in two-dimensional, heterogeneous saturated porous media with a relatively short correlation length. We demonstrate that the downstream concentration of solutes in preferential pathways implies a downstream declining entropy in the transverse distribution of solute transport pathways. This reflects the associated formation and downstream steepening of a concentration gradient transversal to the main flow direction. With an increasing variance of the hydraulic conductivity field, stronger transversal concentration gradients emerge, which is reflected in an even smaller entropy of the transversal distribution of transport pathways. By defining "self-organization" through a reduction in entropy (compared to its maximum), our findings suggest that a higher variance and thus randomness of the hydraulic conductivity coincides with stronger macroscale self-organization of transport pathways. While this finding appears at first sight striking, it can be explained by recognizing that emergence of spatial self-organization requires, in light of the second law of thermodynamics, that work be performed to establish transversal concentration gradients. The emergence of steeper concentration gradients requires that even more work be performed, with an even higher energy input into an open system. Consistently, we find that the energy input necessary to sustain steady-state fluid flow and tracer transport grows with the variance of the hydraulic conductivity field as well. Solute particles prefer to move through pathways of very high power, and these pathways pass through bottlenecks of low hydraulic conductivity. This is because power depends on the squared spatial head gradient, which is in these simulations largest in regions of low hydraulic conductivity.


Endothelial dysfunction is considered to be an initial step of arteriosclerosis [R. Ross: N. Engl. J. Med. 340 (2004) 115]. For the assessment of the endothelium function, brachial artery flow-mediated dilation (FMD) caused by increased blood flow has been evaluated with ultrasonic diagnostic equipment. In the case of conventional methods, the change in artery diameter caused by FMD is measured [M. Hashimoto et al.: Circulation 92 (1995) 3431]. Although the arterial wall has a layered structure (intima, media, and adventitia), such a structure is not taken into account in conventional methods because the change in diameter depends on the characteristic of the entire wall. However, smooth muscle present only in the media contributes to FMD, whereas the collagen-rich hard adventitia does not contribute. In this study, we measure the change in elasticity of only the intima–media region including smooth muscle using the phased tracking method [H. Kanai et al.: IEEE Trans. Ultrason. Ferroelectr. Freq. Control 43 (1996) 791]. From the change in elasticity, FMD measured only for the intima–media region by our proposed method was found to be more sensitive than that measured for the entire wall by the conventional method.


Human granulocytic anaplasomsis and human monocytic ehrlichiosis are tick-borne emerging infectious diseases which are caused by Anaplasma phagocytophilum and Ehrlichia chaffeensis. These bacteria are obligatory intracellular parasites with tropism for hematopoietic cells. Here, we introduced analysis of protein expression profiles of HL-60 host cells in the response to infection with those bacteria by proteomic approach using fluorescence-prelabeled two dimensional difference gel electrophoresis to clarify the molecular mechanisms of the intracellular parasitism. Three experiments were designed for this purpose: differential analysis of infection at late (i) or early (iii) stages, and time-course analysis postinfection (ii). The detailed technical approaches, advantage of this procedure, and technical improvements desired were described and discussed.


Impacts of climate change were simulated over five summer seasons in a high arctic polar semi-desert at Ny Alesund, Svalbard, by using polythene tents to increase temperature, and by increasing precipitation and soil nutrient (NPK) availability. The effects of these treatments on vegetation cover were assessed at the start of the 1991, 1993, and 1995 field seasons, and at peak biomass in the same years. Over the first season of the experiment (1991), changes in percentage total living vegetation cover were significantly greater, and changes in dead vegetation cover significantly lower, in the tented treatments. In subsequent seasons, changes in total living cover were also greater under treatments simulating climate change, although the significant factors and interactions were year- specific. Between years, at both the early and mid-season sampling periods, the fertilizer application had the strongest effect on changes in plant cover, significantly decreasing cover of living Dryas octopetala, Saxifraga oppositifolia, and bare ground between 1991 and 1995, while increasing cover of bryophytes, Salix Polaris, Polygonum viviparum, and total dead vegetation. Although cover of D. octopetala was greater during the first three years of fertilizer addition, marked winter injury occurred in this species on fertilized plots during winter 1993-1994. This resulted in reductions in total live cover and D. octopetala cover and an increase in total dead cover (by up to 22%) in watered and fertilized plots between 1991 and 1995. Seedlings of nitrophilous "immigrant" species were established naturally on bare ground in fertilized plots in the third year of the study and subsequently increased in number, so that after five seasons the community tended more toward bird-cliff vegetation rather than polar semi-desert vegetation. The tent treatment and the simulated increase in summer precipitation had little effect between seasons on the plant community, in com- parison with the fertilizer treatment.


Summary.  It is common practice that some or all animals in a group of animals, e.g. a herd, are tested for their health status by using a diagnostic test to investigate whether the herd is infected by a disease. Several obstacles complicate the estimation of herd prevalence on the basis of test results of the animals. First, diagnostic tests are often imperfect, resulting in a misclassification of the animal's disease status. It is well known how to correct the animal's apparent prevalence by using the diagnostic sensitivity and specificity of the animal test, but the effects on herd prevalence are less clear. Second, in practice, a herd is often defined as positive when at least one sampled animal tested positively. This definition is ambiguous and is also different from the herd prevalence that is based on having at least one diseased animal in the herd. The paper provides a discussion of these aspects and proposes a method to estimate the true herd prevalence on the basis of the health status of (all or a sample of) animals within a herd corrected for the sensitivity and specificity of the individual test, the number of animals that are tested in the herd and the uncertainty of the diagnostic test characteristics.


A retro-detection technique is introduced for simultaneous optical retroreflection, detection, and control in bidirectional sensor links. An architecture with three orthogonal photodiodes (PDs) is used to retroreflect incident light and sample the incident optical signals. Such a system establishes a two-way (bidirectional) optical link. Moreover, the three photocurrent signals can be used in differential combinations for active control and optimization of the alignment. The theory and methodology for the optical retroreflection, detection, and control characteristics are presented, and the technique is verified experimentally with a silicon PD retro-detection prototype. The active remote sensing capabilities of the retrodetector are found to be successful.


Fishing operations by drift nets were in vogue off
the Malabar region on a medium scale since the beginn.
ing of this century. Four types of drift nets operated
aboard the canoes or non-mechanised boats were extant
since that time ; they were : (1) a thick large-meshed
and heavy (325 mm mesh size) hemp drift net locally
called ' Sraavu vala' (shark nets) employed for the
apture of large sharks, sawfish, billfishes, etc. from
deep waters, (2) a thin big-meshed (12-20 cm mesh)
hemp drift net called ' Thirandi vala' (Rayfish net)
used mainly for the capture of rayfishes, skates and
sawfish from the nearshore waters, (3) a small-meshed
(7-8.5 cm) cotton-made or hemp drift net called
' Kandadi vala' used for the capture of smaU sized
cybiids, Chirocentrus, pomfrets, sharks, sawfish, tachysurids,
large carangids and mackerel and, (4) a
slightly bigger meshed hemp drift net called ' Odu vala'
(9-12 cm mesh) used for the capture of big-sized fishes
such as cybiids, tunas, tachysurids, pomfrets, Chirocentrus,
carangids, chorinemids, Rachycentron, sphyraenids,
and medium-sized sharks.


Abstract. The NCAR Whole Atmosphere Community Climate Model with thermosphere and ionosphere eXtension (WACCM-X) v2.1 has been developed to include the neutral and ion-molecule chemistry and dynamics of three metals (Mg, Na, and Fe), which are injected into the upper mesosphere/lower thermosphere by meteoric ablation. Here we focus on the self-consistent electrodynamical transport of metallic ions in both the E and F regions. The model with full ion transport significantly improves the simulation of global distribution and seasonal variations of Mg+. Near the magnetic equator, the diurnal variation in upward and downward transport of Mg+ is generally consistent with the ''ionosphere fountain effect''. The thermospheric distribution of Fe is shown to be closely coupled to the transport of Fe+. The effect of ion mass on ion transport is also examined: the lighter ions (Mg+ and Na+) are transported above 150 km more easily than the heavy Fe+. We also examine the impact of the transport of major molecular ions, NO+ and O2+, on the distribution of metallic ions.


During breast cancer progression, transforming growth factor-β (TGF-β) switches from a tumor suppressor to a pro-metastatic molecule. Several recent studies suggest that this conversion in TGF-β function depends upon fundamental changes in the TGF-β signaling system. We show here that these changes in TGF-β signaling are concomitant with aberrant expression of the focal adhesion protein, p130Cas. Indeed, elevating expression of either the full-length (FL) or just the carboxyl terminus (CT) of p130Cas in mammary epithelial cells (MECs) diminished the ability of TGF-β1 to activate Smad2/3, but increased its coupling to p38 MAPK. This shift in TGF-β signaling evoked (i) resistance to TGF-β-induced growth arrest, and (ii) acinar filling upon three-dimensional organotypic cultures of p130Cas-FL or -CT expressing MECs. Furthermore, rendering metastatic MECs deficient in p130Cas enhanced TGF-β-stimulated Smad2/3 activity, which restored TGF-β-induced growth inhibition both in vitro and in mammary tumors produced in mice. Additionally, whereas elevating TβR-II expression in metastatic MECs had no affect on their phosphorylation of Smad2/3, this event markedly enhanced their activation of p38 MAPK, leading to increased MEC invasion and metastasis. Importantly, depleting p130Cas expression in TβR-II-expressing metastatic MECs significantly increased their activation of Smad2/3, which (i) reestablished the physiologic balance between canonical and noncanonical TGF-β signaling, and (ii) reversed cellular invasion and early mammary tumor cell dissemination stimulated by TGF-β. Collectively, our findings identify p130Cas as a molecular rheostat that regulates the delicate balance between canonical and noncanonical TGF-β signaling, a balance that is critical to maintaining the tumor suppressor function of TGF-β during breast cancer progression.


Food texture remains a key sensory attribute for food enjoyment, with the potential to modulate food intake, particularly in individuals with limited oral processing capabilities (OPC) such as the elderly, dysphagia, and head and neck cancer (HNC) patients. However, information relating to the textural quality of foods for these consumers is limited. Unsuitable food textures can cause food aspiration, lower meal enjoyment, reduce food/nutrient intake, and potentially lead to malnutrition. The objective of this review was to critically examine the state-of-the-art scientific literature on the textural properties of foods for individuals with limited OPC, identify existing gaps in research, and appraise the rheological-sensory textural design of optimal foods for individuals with limited OPC to improve eating safety, food intake, and nutritional status. Depending on the food type and nature of oral hypofunction, many foods for individuals with limited OPC have very low or too high viscosity, with low cohesiveness and high values for hardness, thickness, firmness, adhesiveness, stickiness, and slipperiness. Fragmented stakeholder approaches, the non-Newtonian nature of foods, the complexity of in vivo, objective food oral processing evaluation, suboptimal application of sensory science and psycho rheology, and research methodological weaknesses are some of the obstacles to addressing texture-related dietary challenges for individuals with limited OPC. There is a need to explore various multidisciplinary strategies for food texture optimization and interventions to improve food intake and nutritional status amongst people with limited OPC.


Optimizing horizontal well placement is often not limited to identifying the most favorable reservoir, but also identifying the ideal target window within that reservoir. In unconventional reservoirs, the ideal target window must have both appropriate reservoir quality and the mechanical rock properties conducive to effective hydraulic fracturing. This paper presents two case studies from the Permian Basin. The first study directly compares wireline logs and core data with drilling vibration analysis. Analyzing drill bit vibrations, one can process mechanical rock property data. This process is called drill bit geomechanics. These high-resolution drill-bit-derived data were first calibrated to wireline and core data, then applied to target future landing zones. The second case study compares drill bit geomechanics data across three neighboring 10,000-ft horizontal wells, all of which landed in the same target zone. Based on the drill bit geomechanics data, the three wells showed notable differences in mechanical rock quality. The operator found the three wells' production responses also differed.
 High frequency measurements of drilling-induced vibrations were recorded through several producing Permian reservoirs. In the pilot well, the recording tool was run behind a coring assembly to obtain mechanical data at in-situ pressure and temperature. Elastic stress-strain relationships were used to solve for the stiffness coefficients and determine relative values of mechanical properties (i.e., Young's Modulus (YM) and Poisson's Ratio (PR)). The resulting mechanical data were compared directly to core analysis, wireline dipole sonic logs, and wireline image logs.
 In general, the mechanical rock properties derived from drilling vibrations compared well with those from the sonic log and core analysis. One can attribute differences between the datasets to fluid effects and differences in resolution. The drill-bit-derived mechanical properties showed fine-scale changes and thinly-bedded intervals that were not identified by the sonic log. Using sonic measurements to determine in-situ mechanical properties can have non-uniqueness. Analyzing cores also includes challenges of translating exhumed core properties to those of in-situ conditions. Combining the in-situ measurement of mechanical properties from drilling vibrations with the traditional sonic log and core analysis minimized uncertainties. Increased understanding of mechanical properties in the pilot well informed the landing zone target intervals for the horizontal well development plan. Understanding mechanical properties is also critical to effective hydraulic fracture stimulation design and execution. Even within a landing zone, mechanical properties can vary laterally. Measuring and understanding these variations in mechanical properties can improve completions and lead to increased well productivity.
 Gathering drill bit geomechanics data provides a lower cost and lower risk method to acquire mechanical rock properties in long, horizontal wellbores. These near-wellbore variations in mechanical rock properties are ideal for use in identifying target landing zones for horizontal wells. One can use the data to create high-resolution, laterally variable fracture simulation and reservoir models. By integrating these data sets with mechanical rock properties recorded while drilling, operators can have significantly higher confidence in choosing a target landing zone and improving completions.


There is a variety of mechanical prosthetic valves that can be applied to blood pumps, and one can be selective about those particular characteristics tailored to each blood pump and its application. These devices have become extremely reliable, particularly since, in the experience of this laboratory, the dp/dt generated in the ventricle of the pneumatically powered artificial heart is successfully lowered. Future modifications of the valves, such as the Medtronic-Hall monostrut valve and the Medtronic-Hall tubular valve, are expected.


ABSTRACT Molecular networks governing responses to targeted therapies in cancer cells are complex dynamic systems that demonstrate non-intuitive behaviors. We applied a novel computational strategy to decipher causal relationships between signaling network components. Gene networks were constructed MEK from global gene expression profiles to model G1-S cell cycle arrest as a consequence of inhibition of MEK, a key component of the oncogenic RAF-MEK-ERK signal transduction pathway. Through forward-simulation of reverse-engineered networks candidate MEK-dependent regulators of the cell cycle were identified. The potential of the approach to infer causality is demonstrated by confirmed predictions of differential effects of two early-response transcription factors, IER2 and EGR1. Conventional linear regression analysis shows strong correlation of expression of both with MEK inhibition and cell cycle distribution, while only IER2 is predicted by our model and experimentally validated to have a causal effect on G1-S transition. Furthermore, we identify TRIB1 (tribbles homologue 1 drosophila) as a potent and novel cell cycle regulator. TRIB1 also mediates cross-talk to the NFkB pathway by enhancing p100 and IkBa-phosphorylation and degradation thus regulating cell survival and expression of cytokines crucial for tumor-stroma interaction. In agreement with this, knock-down of TRIB1 results in induction of apoptosis and sensitizes cells to cell killing induced by the death-receptor agonist TRAIL via upregulation of TRAIL receptor, DR5. Thus TRIB1 is a central regulator of cell cycle and survival and represents a potential therapeutic target. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 986. doi:1538-7445.AM2012-986


ABSTRACT Urban and town life, which has begun to disappear due to globalization, has been replaced by megacities, people's lifestyles are changing day by day, food culture, daily social activities, and many other areas are under the influence of speed. The slow city movement has emerged as a new movement against this speed and uniformity. The primary purpose of this research is to develop a scale to determine the perceived slowness level of slow cities from the tourist perspective. It is also aimed to analyze the level of slowness perceived by tourists regarding slow cities and the variance of these evaluations according to their willingness to adopt a voluntarily simple life and environmental sensitivities, in the case of Seferihisar, Turkey. It has been revealed that the perceived slowness level of Seferihisar is high, and there is a positive relationship between the slowness perceptions of the tourists and their voluntary simplicity (VS) lifestyles and environmental sensitivities. Also, it has been determined that the profiles of people who have different perceptions of slowness levels differ in their VS levels, environmental sensitivity, and socio-demographic characteristics. Determining the slowness levels of slow cities from the tourists' eyes will help reveal the cities' deficiencies and successes.


The work was based on the results of studying the potential ability and outcomes of endovascular interventions (balloon angioplasty, stenting) in treatment of patients presenting with occlusive and stenotic lesions of the arteries of the popliteal-tibial segment at the stage of chronic ischaemia of lower limbs, in whom surgical reconstruction was impossible due to the type of the lesion or severity of concomitant pathology. The study was carried out in one hundred and four patients. On a total of 108 extremities involved, we carried out 174 endovascular interventions, including 29 stenting procedures and 145 balloon angioplasties. The following parameters were studied: dynamics of the clinical status, indices of the peripheral blood flow, immediate technical outcome, limb salvage rate, as well as short- and long-term (up to 2 years) patients' survival. It was proved that endovascular treatment of patients presenting with lesions of arteries of the popliteal-tibial segment is an efficient therapeutic method to relieve chronic ischaemia of lower extremities. For patients suffering from critical ischaemia of the lower limbs and diabetic angiopathy, this technique is sometimes the only method of surgical correction of the disordered blood flow. This method makes it possible not only to save the limb involved but also to improve the patient's quality of life.


Since the beta function of the electron beam within the undulator has a great influence on the power gain of the free electron laser (FEL), optimization of the undulator lattice becomes important. In this paper, the transfer matrix of the planar undulator is obtained from differential equations of the electron motion. Based on this, the lattice function of the planar undulator in a terahertz FEL oscillator proposed by Huazhong University of Science and Technology (HUST-FEL) is optimized and the expressions of the average beta function are derived. The accuracy of the optimization result was confirmed well by the numerical method. The application range of this analytical method is given as well. At last, the emittance growth in the horizontal direction due to the attenuation of the magnetic field is discussed.


Objectives: Many of the mortality cases we see today especially in rural and remote areas are due to lack of proper medical facilities in emergency cases and lack of genuine information about hospital infrastructure and facilities i.e. whether the treatment for particular disease is available in the hospital they choose to go. In order to aid the decision making in choosing the correct hospital, a methodology based on Decision Tree Induction is adopted. Methods: It is based on the recent statistics about staff and infrastructure of hospitals. The core idea of "Decision Tree Induction Methodology" is to provide ranking for the hospitals based on the facilities available in the hospital. The methodology is applied on a set of hospitals in a location. Findings: The medical statistics and ranking plays a key role in the functioning of the methodology adopted. The data about facilities is gathered and fed to a trained paradigm which predicts the rank of a specific hospital. The representatives grasp the information from the GUI built for this methodology. Application: The result can be fed to all the possible medical centers so that public can get correct guidance from the representatives present there.


Abstract Soluble extracts of Gigantocotyle explanatum, isolated from the liver of buffalo Bubalus bubalis were fractionated on Sephadex G-200 columns. Nine major fractions referred to as F1, F2, F3, F4, F5, F6, F7, F8 and F9 were separated. Each fraction was tested by ELISA for antigenicity using sera from G. explanatum-infected field buffaloes. Fractions F1 and F2 were highly antigenic, F3, F4, F6 and F7 were moderately antigenic and F5, F8 and F9 were poorly antigenic. Analyses by SDS–PAGE revealed that each fraction comprised several polypeptide(s) in the molecular weight range of <29 to >205 kDa. Results of Western blotting indicated that not all polypeptides which appeared in the SDS–PAGE were antigenic. The antigenic molecules of each fraction were mostly in the low molecular weight range of <14 to >94 kDa with the polypeptides in the range of >14, 14, 18, 21–25 and 34–36 kDa.


Mobile communication networks are using signaling protocols to allow mobile users to communicate using short messages, phone calls and mobile data. Signaling protocols are also used to manage billing for operators and much more. The design flaws that signaling inherits made them vulnerable to attacks such as location tracking of subscriber, fraud, calls and SMS interception. With the high rate of these emerging attacks on telecommunication protocols there is a need to create a comprehensive penetration testing framework for signaling. In this paper, we propose a framework called Sigploit that takes into consideration the following protocols: SS7, GTP, Diameter and SIP.


Mucins are bottlebrush biopolymers that are glycoproteins on the surfaces of cells and as hydrogels secreted inside and outside the body. Mucin function in biology includes cell-cell recognition, signaling, protection, adhesion, and lubrication. Because of their attractive and diverse properties, mucins have recently become the focus of synthetic efforts by researchers who hope to understand and emulate these biomaterials. This review is focused on the development of methodologies for preparing mucin-inspired synthetic oligomers and glycopolymers, including solid-phase synthesis, polymerization of glycosylated monomers, and post-polymerization grafting of glycans to polymer chains. How these synthetic mucins have been used in health applications is discussed. Natural mucins are formed from a conserved set of monomers that are combined into chains of different sequences and lengths to achieve materials with widely diverse properties. Adopting this design paradigm from natural mucins could lead to next-generation bioinspired synthetic materials.


A new subgenus [Allograpta (Costarica Mengual & Thompson), type Allograpta zumbadoi Thompson], and one new species [Allograpta (Costarica) nishida Mengual & Thompson; type-locality: Costa Rica, type-depository: Instituto Nacional de Biodiversidad de Costa Rica] of flower flies (Diptera: Syrphidae) are described from the Neotropical biotic region. A checklist of the world species of Allograpta including synonyms is provided, and a key to and diagnoses of the subgenera are also supplied. The phylogenetic relationships among Allograpta species, representing all hitherto detected morphological diversity of the genus, and related genera were studied under parsimony based on morphological characters.


In situ neutron diffraction experiments during tension-compression deformation were performed on five Fe–Cr–Ni alloys with the volume fraction of ferrite (α) ranging from 0.0 to 100 %. Tensile deformation was applied in a step by step manner up to a strain of 1.3–2.0 % followed by compressive deformation, and neutron diffraction spectra were recorded during temporary stops of a deformation machine with fixed crosshead. (111) reflection of austenite and (110) of ferrite, respectively, were measured simultaneously by using a position sensitive detector. Elastic lattice strains in both constituent phases were evaluated from measured diffraction spectra as a function of external load. Based on these experimental results, heterogeneous deformation behavior in the α–γ dual phase alloys is discussed considering the Bauschinger effect. It is concluded that large compressive residual lattice strains detected in the γ phase after tensile pre-strain-ing, causes the large Bauschinger effect in α–γ dual phase alloys.


Endometriosis is an ectopic occurrence of tissue morphologically and functionally resembling endometrial tissue outside the uterine cavity. Vulva is one of the rarest location of extrapelvic endometriozis. We report a case of a 44-year-old multiparous woman, referred to our clinic with the complaints of having a vulvar mass and cyclic swelling of the mass during menstruation. She had a history of 2 previous cesarean delivery and no history of previous vulvar or vaginal surgery. The mass was 3-4cm in diameter and localized on the upper-portion of the right labium minus. Complete surgical excision was performed with the suspicion of endometriosis. Final histopathology report confirmed the diagnosis of endometriosis. Three weeks after surgery there was no evidence of endometriosis. In conclusion whether or not having a history of a previous vulvar surgery, vulvar endometriosis should be considered as a part of differential diagnosis in evaluation of vulvar masses.


The sialic acid content of the mouse erythrocyte was compared with that of the Ehrlich ascites carcinoma cell. Neuraminidase treatment of intact tumor cells yielded 36 times more sialic acid than was released from the erythrocyte on a per cell basis. If this were all located on the surface, it may be calculated that the density of sialic acid on the Ehrlich ascites carcinoma cell is about 4 times greater than that on the erythrocyte. Trypsin released a sialic acid-containing fragment from both types of cells, the sialic acid being in the "bound" form. The sialic acid released by trypsin treatment of Ehrlich ascites tumor cells was only about one-sixth of that released by neuraminidase. By contrast, approximately equal amounts were liberated from the erythrocytes by these two enzymes. The erythrocyte sialic acid-containing substance was nondialyzable and was not precipitated by trichloroacetic acid. N -acetylneuraminic acid constituted approximately 70 per cent and N -glycolyneuraminic acid the remaining 30 per cent of the sialic acid of the tumor cell as determined by paper chromatography. In the erythrocyte N -acetylneuraminic acid constituted almost all the sialic acid, N -glycolylneuraminic acid being undetectable in this cell.


Adenylosuccinate synthetase (PurA) is an enzyme responsible for the nitrogen addition to inosine monophosphate (IMP) by aspartate in the purine nucleotide biosynthetic pathway. And after which the fumarate is removed by adenylosuccinate lyase (PurB), leaving an amino group. There are two other enzymes that catalyze aspartate addition reactions similar to PurA, one in the purine nucleotide biosynthetic pathway (SAICAR synthetase, PurC) and the other in the arginine biosynthetic pathway (argininosuccinate sythetase, ArgG). To investigate the origin of these nitrogen-adding enzymes, PurA from Thermus thermophilus HB8 (TtPurA) was purified and crystallized, and crystal structure complexed with IMP was determined with a resolution of 2.10 Å. TtPurA has a homodimeric structure, and at the dimer interface, Arg135 of one subunit interacts with the IMP bound to the other subunit, suggesting that IMP binding contributes to dimer stability. The different conformation of His41 side chain in TtPurA and EcPurA suggests that side chain flipping of the His41might play an important role in orienting γ-phosphate of GTP close to oxygen at position 6 of IMP, to receive the nucleophilic attack. Moreover, through comparison of the three-dimensional structures and active sites of PurA, PurC, and ArgG, it was suggested that the active sites of PurA and PurC converged to similar structures for performing similar reactions.


Pregnancy as an notion used in both, positive and negative meaning, has the great importance in the human sexual education and as an consequence influences on possibility of conception and pregnancy development in adult women as an natural obligation of human being delivery.


The aim of this research was to use qualitative research to investigate temple management for religious tourism at Tham Khao Roop Chang temple, which is situated on the Thai-Malaysian border and supervised by a foreign abbot. Data were collected from related documents and from the field through participant observation and in-depth interviews with 16 key informants consisting of monks, nuns, workers, local residents, the temple committee members, and tourists who were selected using purposive sampling. Specifically, the informants were selected from amongst those who gave the most information and participated in the rituals and activities at the temple or who had been seen in the temple for more than 3 years. Triangulation was a way of assuring the validity of data and conclusions were drawn from a descriptive analysis. It was noted that the temple has beautiful architecture and caves; therefore, its administrative plan emphasizes the maintenance of the environment along with human development based on the principle that humans are the mechanism driving social development. Staff work collaboratively without a fixed management structure, Tasks are assigned to monks, nuns, and workers. The abbot plays an important role as a facilitator and provides Buddhist teaching to heal people's minds. Direction is traditionally manipulated; no dictatorial power is exercised to control the temple. Only motivation-building strategies are used to encourage people to appreciate the value of Buddhism. Coordination with internal and external parties is maintained through merit makers in the locality and a social network of religious tourists has been created by word of mouth and through social media channels. The abbot applies his Singaporean characteristics to manage the temple focusing on cleanliness and tidiness to maintain the landscape and culture with the aim of making the temple one of the most prominent religious tourist attractions in the region.


In this paper, we provide a detailed review of development of a highly-efficient high-power nanosecond pulse CO2 laser using transverse-flow radio-frequency (RF)-exited laser amplifiers, which is for extreme ultraviolet (EUV) light source of a next generation of nano-lithography. High-density excited high-power transverse-flow CO2 lasers were designed and built for the application of laser produced plasma (LPP) EUV source. We carried out an amplification test of the transverse-flow CO2 laser seeded by a nanosecond pulse CO2 laser. A four-amplifier system generated an average output power of 21 kW with an electrical input power of 400 kW for discharges. The electrical-to-optical efficiency was 5.2%. The input pulse laser had an average power of 46 W, the repetition rate was 100 kHz, and the pulse duration was 15 ns. The transverse-flow CO2 laser has strong points in high gain and availability of the multi-fold optical path. A highly-efficient amplification was experimentally proved characterized by transverse-flow CO2 laser amplifiers even with low-power seed. A transverse-flow CO2 laser is a promising candidate for an amplifier in the LPP EUV light source.


Genetic differentiation among shiny cowbird (Molothrus bonariensis) females that use different hosts indicates that in this brood parasite, host use is not random at an individual level. We tested whether there exist differences in morphology and coloration between eggs of shiny cowbirds laid in the nests of two different hosts, the chalk-browed mockingbird (Mimus saturninus) and the house wren (Troglodytes aedon). We took morphometric measures of shiny cowbird eggs found in nests of mockingbirds and wrens and analysed their coloration using digital photography and reflectance spectrometry. We found that shiny cowbird eggs found in mockingbird nests were wider and more asymmetric than those found in wren nests. In addition, cowbird eggs coming from mockingbird nests were brighter and had higher relative red reflectance than those coming from wren nests. Our results show that shiny cowbird eggs laid in nests of two different hosts vary in shape and background colour, but not in spotting pattern.


Regional cerebral blood flow and oxygen utilisation can be measured using positron emission tomography and the continuous inhalation of 13O-labelled carbon dioxide and molecular oxygen. However, there is concern about the propagation of errors in this technique. This arises from statistical uncertainties, inherent in the transmission and emission scans, being amplified in the steady state model used for calculating the physiological parameters. The magnitude of this effect has been studied using a series of repeat transmission and emission phantom measurements in which pixel count densities equivalent to those seen in the clinical data were recorded. These measurements have been used to determine the final propagated errors that occur in the calculated values of regional cerebral blood flow, oxygen extraction fraction, and oxygen utilisation rate.


It is often highly desirable to know not only where species are likely to occur (i.e. occupancy) but also how many individuals are supported by a given habitat (i.e. density). For many animals, occupancy and density may be determined by distinct ecological processes. Here we develop a novel abundance model as the product of landscape‐scale occupancy probability and habitat‐scale density given occupancy. One can conceptualize our model as fully packing a landscape with home ranges or territories based on habitat quality, and then subtracting territories based on a probabilistic process that accounts for the fact that species rarely exhibit full occupancy across heterogeneous landscapes. The model is designed to predict abundance at fine spatial scales, using resolutions equal to or smaller than a single home range or territory. We demonstrate this model on the Black‐backed Woodpecker (Picoides arcticus), a species of management concern linked to post‐fire forests. Occupancy is derived from a regional monitoring effort, while density given occupancy comes from a telemetry study of variation in territory size. A Bayesian framework is used to combine independent occupancy and home‐range size models and predict abundance of Black‐backed Woodpeckers at 4 fires that burned in 2012 or 2013. Predictions are evaluated with independently collected survey data, showing that the model is successful at predicting both absolute abundance at fires as well as relative abundance within and among fires. The conceptual model presents a promising new framework for fine‐scale modelling of density and abundance for other territorial yet elusive species. Telemetry and occupancy data are widely collected for many species, but rarely utilized in combination, and the ecological exploration of the factors that determine occurrence versus home‐range size may provide useful biological insight. As applied to the Black‐backed Woodpecker, the model provides a tool for resource managers to explore trade‐offs in retaining burned forest habitat versus managing for other post‐fire goals, such as salvage logging or reforestation efforts that require snag removal.


Summary Matrix metalloproteinases (MMPs) areagroup of proteases containing Zn ions asacofactor, which are involved in degrading ofalarge number of extracellular matrix proteins, and bioactive molecules. They also playamajor role in processes such as cell proliferation, cell migration, differentiation and apoptosis. Very little is known about the expression and function of MMPs in the male reproductive tract. Occurrence of MMP-2 and MMP-9 activity in human seminal plasma has been previously reported but their origin and function are still not fully understood. The aim of this study was to examine the presence of MMP-2 and MMP-9 in normal and abnormal human sperm samples and find if any correlation existed between the levels of expression of MMPs and fertilization potential of the spermatozoa. Human spermsamples were examined for the presence of MMP-2 and MMP-9 by gel zymography and western blot analysis. A DNAfragmentation test was performed. The samples were divided into two groups - samples with normozoospermia and teratozoospermia. The gelatin zymography showed gelatinolytic bands with molecular weight 64 and 72 k Da corresponding to active and inactive form of MMP-2. MMP-9 was not detected. The MMP-2 enzymatic activity appeared to be much higher in samples with compromised sperm morphology as compared to the normozoospermic samples. The mean DNAfragmentation index (DFI) of the group with teratozoospermia was relatively higher (22.16%) and over the upper reference limits, compared to the normozoospermic group, in which it was within the normal range (17.26%).


One of the public services that is always attempted to be improved by the government is administration service. Public services are involved in such problems as the duration of the management of documents and infrastructure facilities are not adequate in serving the community. Disdukcapil Kabupaten Pati as one of civil registration provider in Pati regency has many problem accordin to Ombudsman's Reports. This study aims to discover on how the quality of civil registration service and what factors are supporting and obstructing. The method used in this study is qualitative descriptive method. The data source in this study was obtained from interviews, observations, and documentation. Informant selection techniques are done using purposive sampling and accidental sampling. The quality of service is measured using five dimensions of Zeithaml theory, namely, tangible, reliability, responsiveness, assurance, and empathy. The measurement quality of service is also influenced by the supporting factors / obstructing (Moenir). This study obtained the results, there are four dimensions tangible, reliability, responsiveness, and assurance that have not run well, there is only one dimension of empathy has been run well. The results of the study can be explained that there are four of six factors that initiative the quality civil registration services (awareness, rules / procedures, organization, and income). On the other hand proportional to the factors that become obstacles such as, the ability / appearance factors of officers who are still requiring training, monitoring, and evaluation periodically as well as the factors of supporting service facilities the main support service that is less in terms of quantity and quality.


We studied the development and spatial organization of vertically arranged pyramidal dendritic and axonal bundles in the visual cortex of the rat by using extracellular biocytin injections into frontal brain slice preparations. Vertical bundles of intracortical axons could be clearly observed at time of birth with a initial center-to-center distance of 18 microns +/- 3.1 microns. At the same time a clustering of pyramidal cell apical dendrites was completely absent. Dendritic bundles were demonstrated for the first time at postnatal day 5 when the supragranular layer 2/3 begins to differentiate. In the following weeks both axonal as well as dendritic bundles grew continuously and completely in parallel with regard to their center-to-center distances, diameters and number of elements up to their adult values at around postnatal day 90. At adulthood both types of bundles showed a center-to-center distance of 50.1 microns +/- 20.1 microns (axons) and 52.6 microns +/- 18.1 microns (dendrites), respectively. Our results demonstrate that axonal and dendritic bundles originating from the same neurons in the visual cortex of the rat correspond very well with regard to their size and distances. Developing neurons migrating along radial glia fibers group their axons together in fascicles before the lamination of the cortex is completely matured. After all layers have been developed, the apical dendrites of pyramidal cells with aggregated axons also group in clusters. The following development of axonal and dendritic bundles is presumably concerned with the volume increase of the maturating neocortex. Evidence for activity dependent plasticity after eye opening could not be found.


Generating compressive stresses in aerospace materials is an important consideration for enhancing fatigue life. Shot peening and cold expansion of holes are two techniques for imparting beneficial compressive stresses. X-ray diffraction is a direct method for measuring elastic strains. Diffraction peak widths are an indication of plastic strain. Elastic and plastic strains can be used to better assess the true condition of a component. This paper presents elastic and plastic strain information from shot peened and cold expanded aerospace materials. Examination of surface data showed which shot peened samples had the deeper layer of compressive stresses. Likewise, elastic and plastic strain data enabled successful ranking of the holes in terms of the maximum amount of cold working.


Background Transcatheter arterial chemoembolization LIHC, Liver hepatocellular carcinoma; (TACE) is a valid therapeutic method for hepatocellular carcinoma (HCC). However, many patients respond poorly to TACE, thus leading to an adverse outcome. Therefore, finding new biomarkers for forecasting TACE refractoriness occurrence and prognosis becomes one of the current research priorities in the field of HCC treatment. Materials and Methods Based on microarray datasets and a high-throughput sequencing dataset, the TACE refractoriness–related genes (TRGs) were identified by differential expression analysis. LASSO and Cox regression were applied to construct TACE refractoriness diagnostic score (TRD score) and prognostic score (TRP score) and validated their accuracy in external datasets. Functional correlation of TRP score was analyzed by gene set variation analysis and Gene Ontology. CIBERSORT and IMMUNCELL AI algorithms were performed to understand the correlation between the two scores and immune activity. We further carried out the efficacy analysis of immunotherapy and targeted drugs in the different TRP score groups. Furthermore, a nomogram was built by integrating various independent prognostic factors and validated its effectiveness in different datasets. Results We identified 487 TRGs combined with GSE104580 and TCGA datasets. Then four novel TRGs (TTK, EPO, SLC7A11, and PON1) were screened out to construct TRD score and TRP score models, and both two scores had good predictive ability in external datasets. Tumors with high TRP score show an immunosuppressive phenotype with more infiltrations of regulatory T cells and macrophages. Immunotherapy and chemotherapy response evaluation revealed patients with a high TRP score demonstrated well reactions to immune checkpoint inhibitors (ICIs) and sorafenib. TRP score, TNM stage, and cancer type were brought into the combined nomogram with optimum prediction. Conclusions Our research provided dependable and simplified methods for patients with HCC to assess tumors' susceptibility to TACE refractoriness and prognosis and guide patients' clinical therapy choices.


Insulin, C-peptide and proinsulin were measured in peripheral blood of 11 patients suffering from different types of hormone-producing pancreatic B-cell tumours. While proinsulin was elevated in 10/11 patients during prolonged fasting, C-peptide and insulin levels were found within the reference range in 5/11 and 3/5 cases respectively. A rapid insulin assay performed during surgery was helpful for localisation and identification of the respective tumours.


This paper presents an analysis, design of system parts, and practical development of an ultrasonic cleaning system based on a pulse-density modulation converter. The use of the pulse-density modulation control method makes it possible to achieve a significant reduction in switching losses and increase the converter efficiency under various loads and with a wide range of power control. And the use of a separate filter for each transducer makes it easy to assemble the converter for a wide power range without the need to modify filter components. A prototype ultrasonic cleaning unit has been implemented, and the experiments demonstrated the operability of the proposed system. The developed unit operates at a frequency close to 41.8 kHz with a maximum output power of 200 W.


Background: An assessment of the germination of African oil bean seeds as affected by crude oil pollution of soil was carried out in Asaba, Nigeria in 2008. Six (0.0, 1.4, 2.8, 5.3, 11.2 and 22.4% by weight per 1.6kg of weight of soil sample) crude oil concentrations in soil served as the treatments. A randomized complete block design was adopted with four replications. Results: The results showed that no significant differences (P>0.05) existed between the Pentaclethra macrophylla seeds sown in the unpolluted (0.0%) and those planted in the 1.4% level of oil pollution as regards percentage germination, days to germination and rate of germination. Significant differences (P≤0.05) were however observed in the germination characteristics of P. macrophylla seeds sown in soils as the concentration of oil in soils increased. Conclusion: The study has established that crude oil pollution of soil has a significant effect of reducing the viability of Pentaclethra macrophylla seeds. It is also demonstrated in the study that crude oil application to soil significantly delayed and reduced the rate of germination of Pentaclethra macrophylla seeds while the minimum (critical) level of crude oil pollution that Pentaclethra macrophylla seeds can tolerate with respect to germination is 1.4% wet weight.


One of the main problems of the integrated processing of sea, groundwater or mine water when receiving drinking water is their high salinity, as well as mineral and biological deposits in the pro-cesses of demineralization. Several methods for demineralization of water: evaporation, reagents, membranes (reverse osmosis), ion exchange, electrodialysis, etc. have been developed. Each of these methods has both positive and negative qualities and is used within certain concentration limits. New developments offer complex multistage mine water treatment schemes with concentrated brine processing. The reduction of CO32-, SO42-, Cl- ions from 25000 to 1000 mg/dm3 is the most sophisticated component of salt extraction technology. These processes are very time consuming and energy intensive. In addition, methods such as electrodialysis, reverse osmosis, sodium cationization are economically feasible to apply with mineralization of 1000-100 mg/dm3 and below. The urgent task is to create an apparatus for primary demineralization of highly mineralized mine water with minimization of energy costs. The method of unipolar electrochemical activation in the purification and desalination of water provides a short-term state of the aqueous solution, when the cathode and anode electrolysis process-es have changed its composition, and the processes of mutual neutralization of electrolysis products are artificially restrained by the presence of permeable membranes-partitions, which are temporarily electrodeparticles. At the cathode, a concentration gradient of hydroxyl ions is observed:2 H2O + 2 e → 2 OH- + H2. At the anode acidification of the electrolyte occurs: 2 H2O - 4 e → 2 H + + 2O2. In the cathode space, due to the increased concentration of free hydroxyl ions, secondary processes of fixation of hydroxides of a number of metals, the cations of which form OH-insoluble bases and basic salts, are observed. The article deals with the methods of groundwater treatment – their advantages and disadvantages. The investigations carried out experimentally have proved the versatility of the method of electrochemical activation of water, which allows to reach the required desalination standards in one process, while reducing the content of organic compounds and (due to the synthesis of ClO- ions) to produce metered water chlorination. The catholyte and anolyte, after pre-extracting the precipitates formed, are mixed for another demineralization step (e.g. reverse osmosis). It is found that the unipolar electrical activation method is effective for mineralized waters con-taining carbonates, sulfates and chlorides of calcium, magnesium, iron and other heavy metals. Chlorine ion, as shown by the experiments on the treatment of sodium chloride solution, leads to the for-mation of water desirable ClO- and ClO3- ions, which prevent the clogging and biofouling of membranes. Several semi-industrial devices have been developed and studies of the efficiency of the method of electroactivation have been carried out, dependences of parameters of electrochemical influence on the composition of highly mineralized and groundwater have been determined. Graphic dependences of the degree of water purification on various parameters (current, voltage, distance between electrodes, time of electro-activation, volume of acid water sampling during electro-activation) are obtained, their analysis is made and conclusions are drawn regarding the use of electrochemical activation process for the preparation of water supplied to stage of membrane desalting.


Retinoic Acid-Related Orphan Receptor Beta (RORβ) is a transcription factor (TF) and marker of layer 4 (L4) neurons, which are distinctive both in transcriptional identity and the ability to form aggregates such as barrels in rodent somatosensory cortex. However, the relationship between transcriptional identity and L4 cytoarchitecture is largely unknown. We find RORβ is required in the cortex for L4 aggregation into barrels and thalamocortical afferent (TCA) segregation. Interestingly, barrel organization also degrades with age. Loss of RORβ delays excitatory input and disrupts gene expression and chromatin accessibility, with downregulation of L4 and upregulation of L5 genes, suggesting a shift in cellular identity. Expression and binding site accessibility change for many other TFs, including closure of neurodevelopmental TF binding sites and increased expression and binding capacity of activity-regulated TFs. Lastly, a putative target of RORβ, Thsd7a, is downregulated without RORβ, and Thsd7a knockout alone disrupts TCA organization in adult barrels.


The triglyph problem which arose at the corners of a Doric building, and was held by Vitruvius to be responsible for the disuse of the Doric order in Roman times, has for many years been discussed by archaeologists. The best short explanation of the difficulties involved is probably that by Robertson. The much more complex problems which are met at a re-entrant angle in the Doric order, have, on the other hand, received little attention, for such angles do not occur in temples, the type of building which has been studied most thoroughly. They do, however, appear fairly frequently in more utilitarian buildings such as stoas and palaistras, and various treatments of them were evolved.


In order to understand the process of band-offset modification by the introduction of interlayers at semiconductor heterojunctions, the authors performed self-consistent ab initio pseudopotential calculations on the Si/Ge interface with In and Sb interlayers. The results of the calculations show a substantial reduction in the valence band offset with the Sb interlayer compared with no interlayer but no change when In is introduced. They suggest a possible reason for these different results.


Stress-driven formation of nanograin chains - groups of two or more elongated nanograins - in nanocrystalline (NC) and ultrafine-grained (UFG) materials is theoretically de- scribed. Within the suggested theoretical description, stress-driven formation of new nanograins is enhanced at previously generated nanograins with disclinations at their grain boundary junc- tions. The formation process occurs through splitting transformations of grain boundaries (con- taining disclination dipoles) into immobile and mobile grain boundaries. Stress-driven migra- tion of mobile grain boundaries serves as a plastic flow mode at the nanograin level and results in formation of nanograin chains. It is shown that the transformations under consideration are energetically favorable in mechanically loaded nanoceramics � -Al 2 O 3 (sapphire) and NC/UFG Al (aluminum) in certain ranges of their parameters.


In many parts of the world, the case-fatality rate of Chromobacterium violaceum infection approaches 60%. To evaluate the spectrum of disease associated with C. violaceum in Far North Queensland (FNQ), Australia, we reviewed all culture-confirmed isolates from 1997 to 2017. There were 28 isolates, 15 represented infection, 11 were contaminants, and two charts were destroyed preventing detailed evaluation of these cases. The most common sites of infection were the skin and soft tissue and the urinary tract; there were two cases of bacteremia without focus. There were no deaths attributable to C. violaceum during the study period and only two cases required intensive care unit support, although in both patients this was not for the C. violaceum infection, but for the management of other health issues. Globally, C. violaceum has a reputation as a deadly pathogen, but in FNQ, Australia, infections usually follow a relatively benign course.


We present single-epoch black hole mass ( ) calibrations based on the rest-frame ultraviolet (UV) and optical measurements of Mg ii 2798 Å and Hβ 4861 Å lines and the active galactic nucleus (AGN) continuum, using a sample of 52 moderate-luminosity AGNs at z ∼ 0.4 and z ∼ 0.6 with high-quality Keck spectra. We combine this sample with a large number of luminous AGNs from the Sloan Digital Sky Survey to increase the dynamic range for a better comparison of UV and optical velocity and luminosity measurements. With respect to the reference based on the line dispersion of Hβ and continuum luminosity at 5100 Å, we calibrate the UV and optical mass estimators by determining the best-fit values of the coefficients in the mass equation. By investigating whether the UV estimators show a systematic trend with Eddington ratio, FWHM of Hβ, Fe ii strength, or UV/optical slope, we find no significant bias except for the slope. By fitting the systematic difference of Mg ii-based and Hβ-based masses with the L3000/L5100 ratio, we provide a correction term as a function of the spectral index as ΔC = 0.24 (1 + αλ) + 0.17, which can be added to the Mg ii-based mass estimators if the spectral slope can be well determined. The derived UV mass estimators typically show >∼0.2 dex intrinsic scatter with respect to the Hβ-based , suggesting that the UV-based mass has an additional uncertainty of ∼0.2 dex, even if high-quality rest-frame UV spectra are available.


What are the major political, economic, technological, environmental, and social changes confronting the world today, and what risks do they pose? Given what we know about these changes and risks, what adjustments will have to be undertaken to make the world as peaceful and stable as possible? Drawing on over 30 years' research, the eminent European scholar Mihaly Simai combines a global systems approach with a hard-headed appreciation of political realities as he seeks answers to these two overarching questions.This volume is at once richly informative and profoundly challenging. Unflinching in its diagnosis of the past failures and present inadequacies of global governance, pragmatic in its prescriptions for more effective multilateral cooperation, Simai's work dissects the dimensions and dangers of a world in transition.


The purpose of this study was to investigate the possibility that some artifactual high signals produced in CSF with fluid-attenuated inversion-recovery MR sequences could be due to inhomogeneity in the amplitude of the initial inversion pulse, and that this problem could be reduced or eliminated by the use of adiabatic inversion pulses. Studies with four volunteers showed dependence of high CSF signals in the posterior fossa on radiofrequency pulse amplitudes and that these signals could be eliminated by the use of adiabatic inversion pulses. Two illustrative clinical cases are included.


BACKGROUND
Correct assessment of the severity and activity of ulcerative colitis (UC) is necessary for determining effective treatment and predicting prognosis. The correlation between histologic activity and endoscopic activity, however, has not yet been determined by using a quantitative scoring system.

STUDY AIMS
To compare the endoscopic activity index (EAI), detected during colonoscopy, with the histologic activity index (HAI) detected in biopsy samples taken from the same colon segments of UC patients in order to determine the degree of agreement between both assessments.

PATIENTS AND METHODS
Ninety-six UC patients participated in this prospective study. EAIs and HAIs were obtained by summing the scores given for each mucosal/histological change to produce a total score between 1 and 12. The correlation between EAI and HAI was calculated.

RESULTS
There was a positive correlation between HAI and EAI (r = 0.78; p < 0.001). There was no statistical inconsistency between the EAI and HAI results (p = 0.625, using the McNemar test). The whole group kappa coefficient was 0.607 (p < 0.001).

CONCLUSION
Endoscopic and histologic activity of mucosal disease in patients with UC are generally consistent. Measuring both histologic and endoscopic activity with a quantitative scoring system during patient follow-up would be a more accurate method for monitoring UC patients.


We read with interest the article by Edén et al.1 assessing the CSF biomarkers of intrathecal inflammation (CSF white blood cell counts, neopterin, β2-microglobulin [β2M], and immunoglobulin G index), blood-brain barrier integrity (albumin ratio), and axonal injury (CSF neurofilament light chain protein [NfL]) in COVID-19 patients with neurologic symptoms. The results illustrate evidence of significant CSF inflammation with raised soluble markers without any cellular response, unlike other viral CNS infections. As far as intrathecal markers such as neopterin and β2M are concerned, these are nonspecific and are produced by macrophages during the activation of cell-mediated immune response. These are often found significantly raised in various conditions such as HIV infection,2 relapsing-remitting or chronic progressive multiple sclerosis,3 and head trauma,4 putting forth questions about its value as a disease-specific marker.


This thesis is concerned with the detection, identification and estimation of drugs and their metabolites in body fluids. The principal drugs studied were the halogenated drugs chlorbutanol and chloral hydrate. One widely used technique for the detection of chloral hydrate and its metabolite, trichloroacetic acid, is the Fujiwara test. This test was also known to be capable of detecting chlorbutanol. The reaction conditions were studied to determine the optimum conditions for the detection of chlorbutanol. As part of the investigation into the optimum conditions an investigation was carried out into the mechanism of the Fujiwara reaction. Previously this test was thought to detect only a series of halogenated compounds. This investigation showed, however, that this is not correct. A positive reaction can be obtained if the reaction conditions lead to the attachment of an electrophilic group to the nitrogen atom of a pyridine ring if this group, in the presence of base, gives rise to a conjugated system which can give rise to an ionised species. A modification of this test was also used for quantitative estimation of the metabolites of chloral hydrate. For the identification of the drugs in body fluids gas chromatography was found to be the most suitable technique. A number of possible systems were investigated and the most suitable chosen for the routine identification and estimation of these drugs. This technique was preferred to the Fujiwara test for estimations as more than one drug can be readily estimated in the same sample. The Fujiwara test was used to study the excretion of chlorbutanol by racing greyhounds, in conjunction with a comprehensive study designed to assess all aspects of the drug's effects on these animals. A similar study was carried out using phenobarbitone. The gas chromatographic technique was used to investigate the effectiveness of the Fujiwara technique developed, and also a number of aspects relating to the handling of samples thought to contain chlorbutanol. Both the Fujiwara and gas chromatographic techniques were employed in the routine analysis of samples. A study was also carried out into the rapid detection of phenylbutazone and contraceptive steroids. Existing techniques were found to be satisfactory for the detection of phenylbutazone and its metabolites, and these substances were characterised using these techniques. However a simple, speedy technique is not practical for the detection of contraceptive steroids in urine samples. The technique of gas chromatography was also used to identify and estimate a number of volatile materials. This was originally carried out to detect contaminants in the reagents used for the Fujiwara test, but also found an application in a post-mortem analysis. One of the column packings found to be unsuitable for the identification of chlorbutanol was found to be capable of separating a wide range of volatile materials. This range included ethanol and trials were carried out in conjunction with a test of the effect of orally administered fructose upon ethanol metabolism. This column packing was found to be a useful supplement to the standard packing used for the determination of blood and urine ethanol concentrations.


Abstract
Social network sites are gaining increasing importance in tourism business and marketing. They have become a rich source of information by creating virtual destination environments that offer pictures, videos, and other opportunities for sharing tourism experiences. These are significant electronic means that affect intentions of potential tourists to visit a destination. This chapter discusses how social network sites provide a great opportunity for individuals to virtually experience destinations prior to their potential journeys. This may, in turn, influence their expectations and satisfaction levels during their actual visits, followed by reinterpretation after the trip.


PURPOSE
To compare the radiobiological effect on large tumors and surrounding normal tissues from single fraction SRS, multi-fractionated SRT, and multi-staged SRS treatment.

METHODS
An anthropomorphic head phantom with a centrally located large volume target (18.2 cm3 ) was scanned using a 16 slice large bore CT simulator. Scans were imported to the Multiplan treatment planning system where a total prescription dose of 20Gy was used for a single, three staged and three fractionated treatment. Cyber Knife treatment plans were inversely optimized for the target volume to achieve at least 95% coverage of the prescription dose. For the multistage plan, the target was segmented into three subtargets having similar volume and shape. Staged plans for individual subtargets were generated based on a planning technique where the beam MUs of the original plan on the total target volume are changed by weighting the MUs based on projected beam lengths within each subtarget. Dose matrices for each plan were export in DICOM format and used to calculate equivalent dose distributions in 2Gy fractions using an alpha beta ratio of 10 for the target and 3 for normal tissue.

RESULTS
Singe fraction SRS, multi-stage plan and multi-fractionated SRT plans had an average 2Gy dose equivalent to the target of 62.89Gy, 37.91Gy and 33.68Gy, respectively. The normal tissue within 12Gy physical dose region had an average 2Gy dose equivalent of 29.55Gy, 16.08Gy and 13.93Gy, respectively.

CONCLUSION
The single fraction SRS plan had the largest predicted biological effect for the target and the surrounding normal tissue. The multi-stage treatment provided for a more potent biologically effect on target compared to the multi-fraction SRT treatments with less biological normal tissue than single-fraction SRS treatment.


The aim of this study was to compare the plantar pressures and forces recorded from both feet of two groups of javelin throwers of different performance levels, in order to investigate differences between skill levels. The study was carried out using an EMED insole system on a Tartan javelin runway at the University of Innsbruck, Austria. Most of the differences (at p < .01) between the two groups were found in the two foot contacts during the delivery stride. Higher maximum total forces (forces on the whole foot) and maximum pressures were recorded for the more skilled or club throwers during the right foot contact at the beginning of this stride. For the left foot landing before release, the club throwers exhibited higher overall maximum forces and overall pressures (the largest forces and pressures recorded on any of the different foot regions) than the novices. The differences between the groups in the medial forefoot region contributed significantly to this result.


Exposure to atmospheric fine particulate matter (PM(2.5)) is a modifiable risk factor of cardiovascular disease. Ultrafine particles (UFP, diameter <0.1 μm), a subfraction of PM(2.5), promote vascular oxidative stress and inflammatory responses. Epidemiologic studies suggest that PM exposure promotes vascular calcification. Here, we assessed whether UFP exposure promotes vascular calcification via NF-κB signaling. UFP exposure at 50 μg/ml increased alkaline phosphatase (ALP) activity by 4.4 ± 0.2-fold on day 3 (n = 3, P < 0.001) and matrix calcification by 3.5 ± 1.7-fold on day 10 (n = 4, P < 0.05) in calcifying vascular cells (CVC), a subpopulation of vascular smooth muscle cells with osteoblastic potential. Treatment of CVC with conditioned media derived from UFP-treated macrophages (UFP-CM) also led to an increase in ALP activities and matrix calcification. Furthermore, both UFP and UFP-CM significantly increased NF-κB activity, and cotreatment with an NF-κB inhibitor, JSH23, attenuated both UFP- and UFP-CM-induced ALP activity and calcification. When low-density lipoprotein receptor-null mice were exposed to UFP at 359.5 μg/m(3) for 10 wk, NF-κB activation and vascular calcification were detected in the regions of aortic roots compared with control filtered air-exposed mice. These findings suggest that UFP promotes vascular calcification via activating NF-κB signaling.


The aim of this study was to validate the Multidimensional Territorial Sense of Community Scale (MTSOCS), a new theory-driven sense of community scale referred to the geographical community. Starting from McMillan and Chavis' theoretical dimensions, five subscales (Membership, Shared Influence, Social Climate and Bonds, Help in Case of Need, and Needs Fulfillment) were proposed. The MTSOCS, a sociodemographic questionnaire, and several other instruments were administered to three groups of adults (for a total of 781 participants). Confirmatory factor analysis of all participants' data showed that the five subscales were good from a statistical point of view. Tests of factorial invariance showed that the five-factor model of the MTSOCS is basically the same across different-sized territorial communities: small towns, cities and metropolis neighborhoods. The total score of the scale and the five subscales showed good construct validity. A positive relationship emerged between total MTSOCS score and participation in groups/associations, cohabitation, community identification, life satisfaction, perceived social support, interpersonal trust and trust in local government. More complex relationships emerged between the five subscales and the other variables, confirming the usefulness of also having the single subscale scores. © 2009 Wiley Periodicals, Inc.


Alfalfa (Medicago sativa L.) can provide many economic and environmental benefits to crop rotations. Our objectives were to quantify alfalfa stand lengths, identify the two crops following alfalfa, and determine the soil and temporal factors affecting them. The USDA-National Agricultural Statistics Service (NASS) Cropland Data Layers (CDLs) for 2006 to 2012 and USDA-NRCS soil survey layers for North Dakota, South Dakota, Nebraska, Minnesota, Iowa, and Wisconsin were combined and used to meet these objectives. Location and soil textural class generally determined stand length, with alfalfa being kept in production longer outside the major Corn Belt area of this region. Soil textural class effects on stand length varied by state. Corn (Zea mays L.) was the most common crop planted during the first- and second-year following alfalfa (79 and 61%, respectively), except in North Dakota (35% both years). Soybean [Glycine max (L.) Merr.] was grown in 11 and 28% of cases, respectively. Small grains were planted as the first-year crop in 29% of cases in the Dakotas and 6% of cases in the other four states. As a second-year crop, small grains occurred in 26% of cases in North Dakota and 5% of cases in the other five states. Stand length, soil textural class, state, and year significantly influenced grower choice of both following crops. These geographic assessments will guide research and extension education designed to increase use of perennials for economic and environmental benefits. Similar methods can be applied to other crop rotations or U.S. regions.


Bidirectional communication between the immune system and the brain and the implications of this communication are emerging concepts in pain research. Although representing a small portion of the disc degeneration syndromes, lumbar herniated discs can cause significant symptoms that may persist even after surgical interventions. Evolving evidence demonstrates that proinflammatory cytokines are a key mediator in the process of disc degeneration as well as in the pain experienced by those afflicted with lumbar herniated discs. Activated immune cells release proinflammatory cytokines, which signal the brain through humoral and neural routes. The brain responds by altering neural activity and promoting further production of proinflammatory cytokines within the brain and spinal cord. Increased local cytokine production by disc tissue irritates spinal nerve roots, resulting in pain and functional changes in neural activity. This review of the current literature explores the importance of cytokine production within the context of lumbar disc degeneration and lumbar spine pain. Furthermore, the significance of the neural-immune interaction will be examined as it relates to pain management and to patient treatment.


The mechanical behavior of polymer materials is strongly dependent on polymer structure and morphology of the material. The latter is determined mainly by processing and thermal history. Temperature-dependent on-line X-ray scattering during deformation enables the investigation of deformation processes, fatigue and failure of polymers. As an example, investigations on polypropylene are presented. By on-line X-ray scattering with synchrotron radiation, a time resolution in the order of seconds and a spatial resolution in the order of microns can be achieved. The characterization of the crystalline and amorphous phases as well as the study of cavitation processes were performed by simultaneous SAXS and WAXS. The results of scattering experiments are complemented by DSC measurements and SEM investigations. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 1574–1586, 2010


OBJECTIVE
IGFBP3 immunoreactivity may appear elevated in patients with chronic kidney disease (CKD), in part due to accumulation of low molecular fragments. The importance of these IGFBP3 variants for binding and inactivation of IGF1 and their relevance for the impaired growth of uremic children are unclear. Nevertheless, IGFBP3, measured as total (t-)IGFBP3, is frequently used as a diagnostic parameter in pediatric CKD patients. A new assay for functional (f-)IGFBP3 exclusively detects IGFBP3 capable of IGF binding. The aim of the study was to evaluate the significance of f-IGFBP3 measurements for the assessment of uremic abnormalities of the GH/IGF1 axis.

DESIGN
Prospective cross-sectional study.

METHODS
t-IGFBP3, f-IGFBP3, and IGF1 were measured in pediatric CKD patients, including patients with CKD stage 3-4 not on dialysis (CKD, n=33), on dialysis treatment (DT, n=26), patients after renal transplantation (RTx, n=89), healthy children (n=29), children with GH deficiency (GHD, n=42), and small for gestational age (SGA) children (SGA, n=34).

RESULTS
Mean t-IGFBP3 SDS was elevated in CKD, DT, and RTx children compared with controls and GHD patients (P≤0.0004). Highest values were reached in DT (P<0.0001 vs all groups). In contrast, mean f-IGFBP3 was similar in all groups (P=0.30).

CONCLUSIONS
Pediatric CKD patients displayed elevated serum concentrations of t-IGFBP3 but not f-IGFBP3, supporting the hypothesis that IGFBP3 fragments not binding IGF1 accumulate during uremia. f-IGFBP3 is an indicator of IGFBP3 fragmentation and seems to reflect IGF1 binding in CKD better than t-IGFBP3. However, the role of f-IGFBP3 for the diagnosis of disturbances of the GH/IGF hormonal axis appears to be limited.


Although innate immunity is crucial to pulmonary host defense and can initiate immune and inflammatory responses independent of adaptive immunity, it remains unstudied in the context of transplant rejection. To investigate the role of innate immunity in the development of allograft rejection, we assessed the impact of two functional polymorphisms in the toll-like receptor 4 (TLR4) associated with endotoxin hyporesponsiveness on the development of acute rejection after human lung transplantation. Patients and donors were screened for the TLR4 Asp299Gly and Thr399Ile polymorphisms by polymerase chain reaction using sequence-specific primers. The rate of acute rejection at 6 months was significantly reduced in recipients, but not in donors, with the Asp299Gly or Thr399Ile alleles as compared with wild type (29 vs. 56%, respectively, p = 0.05). This association was confirmed in Cox proportional hazards and multivariate logistic regression models. Our results suggest activation of innate immunity in lung transplant recipients through TLR4 contributes to the development acute rejection after lung transplantation. Therapies directed at inhibition of innate immune responses mediated by TLR4 may represent a novel and effective means to prevent acute rejection after lung transplantation.


Tetracycline-resistant organisms isolated from six patients with periodontal disease included Bacteroides spp., Eubacterium spp., Fusobacterium nucleatum, Neisseria perflava-N. sicca, Peptostreptococcus anaerobius, Veillonella parvula, and facultative streptococci. All but the Bacteroides spp. and Eubacterium spp. hybridized with the TetM determinant. An additional 417 bacterial strains were screened, and 4% of both the oral streptococci and the Fusobacterium spp. hybridized with the TetM probe.


While the organization We Need Diverse Books has increased the number of high-quality LGBTQ books being published by mainstream publishers, it hasn't gotten easier for teens to find them on library shelves. They often don't know the books exist and aren't comfortable asking for assistance from library staff. In order to bridge this gap, librarians working with teens need to be more proactive in designing collections and spaces that improve access to LGBTQ resources. In this article, we outline how Oregon City Public Library worked with a local group of LGBTQ teens to develop a Teen LGBTQ collection. By sharing our experiences and the resources we utilized, we hope to provide other libraries with a process they can use to meet the unique needs of teens in their communities. While a dedicated LGBTQ collection was the best choice for us, something different might work better for you.


Financial theory and resource-based theory are often used to explain syndication practice among venture capital (VC) firms (Lockett & Wright, 2001; Manigart et al., 2006). While extending this diverse set of theoretical frameworks, we investigate the propensity of VC firms to syndicate to provide new insights on the syndicate size, duration and the number of financing rounds of VC firms. While the existing research has focused on the entire VC entity within syndication or on the sole leader of the syndicate, our study considers both parties within the syndicate, the leader and the other syndicate members. Using a longitudinal and unique data set of 196 venture backed companies over a 19-year period, financed through syndicated investments in France, this research highlights a number of key findings. At first, our empirical study supports earlier work on syndication in Europe. The propensity to syndicate is driven by finance considerations, alongside to financial corporate governance arguments. Particularly, the higher representation of VC firms at the board is significantly and positively correlated with the propensity of investors to syndicate their deals and to the number of financing rounds. We also show that VC firms are motivated by resource based arguments, especially the lead investors whose propensity to syndicate depends on their complementary of skills with minority VC firms. At second, our study provides further evidence that the syndicate size and duration mainly relate also to resource-based considerations. VC firms co-invest on a longer period of time when the lead and non-lead investors are highly experienced. More complementary of skills among investors is associated with a greater number of members in the syndicate and a higher number of financing rounds. Lastly, we find support that the industry sector of the investee firm, especially when defined as a sector of high level of specific knowledge also relates to the number of financing rounds.


Senior population health often is underrepresented in curricula for medical and allied health students. Furthermore, entrenched and dense curricular schedules preclude interprofessional teams from clinical experiences related to senior population health. Community service learning potentially offers the opportunity to engage interprofessional students with a panel of older adults to assess health promotion metrics over time. To test this educational concept, we created Health Ambassador Teams for Seniors, also known as HATS. Utilizing a telehealth platform, interprofessional student teams were tasked with older adult wellness promotion. The annual Medicare wellness exam served as a template for patient encounters which was enhanced with key elements of geriatric assessment such as gait and balance, cognition, and functional evaluations. The objective was to have dyads of interprofessional students conduct telehealth visits and gather healthcare data to be used for serial patient encounters and track functional trajectories over time. As a proof of concept, pilot telehealth encounters with medical, physical therapy, nursing and occupational therapy students revealed that data on older adult functional performances such as gait speed, Timed Up and Go test (TUG), and Mini-Cog test could be acquired through telehealth. Equally importantly, trainees received diverse feedback from faculty, peers and volunteer patients. A Research Electronic Data Capture (REDCap) data repository allows trainees to track patient trends relative to their health promotion recommendations as well as handoff their patient panel to the next set of trainees. The HATS program promises to strengthen the Geriatric Workforce, especially with senior population health.


A 4Mbit nonvolatile memory with a Carbon Nanotube (CNT) storage element has been manufactured in a 0.25 µm CMOS process at a production fab. The CNT storage element is integrated in BEOL, requires minimal additional processing steps, and only a single additional mask. The memory can be RESET in 50 nanoseconds and SET in 500 nanoseconds. Demonstrated read access time of the development vehicle is 50 nanoseconds. Write endurance is in excess of 10,000 cycles, and robust data retention has been demonstrated. The CNT storage element is scalable to <5 nm, and voltage and current consumption during write operations are low. As intrinsic NRAM SET & RESET times are < 1 nanosecond, improvements in performance are anticipated.


Background Gene transfer using a nanoparticle vector is a promising new approach for the safe delivery of therapeutic genes in human disease. The Tat peptide-decorated gelatin-siloxane (Tat-GS) nanoparticle has been demonstrated to be biocompatible as a vector, and to have enhanced gene transfection efficiency compared with the commercial reagent. This study investigated whether intracisternal administration of Tat-GS nanoparticles carrying the calcitonin gene-related peptide (CGRP) gene can attenuate cerebral vasospasm and improve neurological outcomes in a rat model of subarachnoid hemorrhage. Method A series of gelatin-siloxane nanoparticles with controlled size and surface charge was synthesized by a two-step sol-gel process, and then modified with the Tat peptide. The efficiency of Tat-GS nanoparticle-mediated gene transfer of pLXSN-CGRP was investigated in vitro using brain capillary endothelial cells and in vivo using a double-hemorrhage rat model. For in vivo analysis, we delivered Tat-GS nanoparticles encapsulating pLXSN-CGRP intracisternally using a double-hemorrhage rat model. Results In vitro, Tat-GS nanoparticles encapsulating pLXSN-CGRP showed 1.71 times higher sustained CGRP expression in endothelial cells than gelatin-siloxane nanoparticles encapsulating pLXSN-CGRP, and 6.92 times higher CGRP expression than naked pLXSN-CGRP. However, there were no significant differences in pLXSN-CGRP entrapment efficiency and cellular uptake between the Tat-GS nanoparticles and gelatin-siloxane nanoparticles. On day 7 of the in vivo experiment, the data indicated better neurological outcomes and reduced vasospasm in the subarachnoid hemorrhage group that received Tat-GS nanoparticles encapsulating pLXSN-CGRP than in the group receiving Tat-GS nanoparticles encapsulating pLXSN alone because of enhanced vasodilatory CGRP expression in cerebrospinal fluid. Conclusion Overexpression of CGRP attenuated vasospasm and improved neurological outcomes in an experimental rat model of subarachnoid hemorrhage. Tat-GS nanoparticle-mediated CGRP gene delivery could be an innovative strategy for treatment of cerebral vasospasm after subarachnoid hemorrhage.


Neurologic toxicity has been observed with anti-CD19 chimeric antigen receptor (CAR) T cells and the anti-CD19 BiTE blinatumomab. Both focal (e.g., cranial nerve palsy) and global (e.g., generalized seizures) abnormalities have been reported, often associated with systemic cytokine release syndrome (CRS) but also observed after recovery from or in absence of CRS. CART-BCMA consists of expanded autologous T cells transduced with a 4-1BB:CD3-zeta-based CAR specific for B Cell Maturation Antigen. Here, we report clinical features and management of a severe neurotoxicity observed on a phase 1 trial of CART-BCMA for multiple myeloma (MM) ([NCT02546167][1]).

The subject is a 55-year-old female with high-risk IgA lambda MM. At time of CART-BCMA infusion, her MM manifestations included cytopenias and plasmacytomas of the pleura and paravertebral muscles. Bone marrow (BM) was >95% BCMA+ plasma cells. Pre-treatment brain MRI showed pachymeningeal thickening and enhancement over the left cerebral convexity, possibly due to extension of calvarial MM lesions. There was no evidence of CNS MM on a neurologist's exam or by CSF cytology.

The subject received 2x108 CART-BCMA cells, 40% of the planned dose, over two consecutive days, without lymphodepleting chemotherapy; a third planned infusion was held due to fevers. Over the next 4 days, fevers persisted, hypoxia and delirium developed, and cytopenias worsened. Brain MRI and lumbar puncture on day 4 showed no new abnormalities. Evaluation for infection was negative. These symptoms coincided with rise in serum IL-6 (nl range <5 pg/ml) and other CRS biomarkers. On day 6, tocilizumab was administered, which led to resolution of fevers and hypoxia; IL-6 transiently rose and then declined but remained above normal (Figure, orange & black lines).

On day 8, the subject became obtunded. She was intubated, and methylprednisolone 1000mg was administered followed by hydrocortisone 100mg q8h. By day 11, she was more alert, permitting extubation and cessation of steroids, but remained slow to respond. On day 12 she developed a generalized seizure, was re-intubated for airway protection, and received antiepileptic drugs (AED). She again improved and was extubated but, on day 15, developed status epilepticus that required five AEDs to control. Repeat MRI showed new diffuse sulcal, cortical, and subcortical T2/FLAIR signal abnormalities involving the bilateral frontal, parietal, occipital, posterior temporal, and cerebellar hemispheres, with sulcal effacement concerning for cerebral edema. This deterioration was not associated with fevers, other features of systemic CRS, or hypertension, but it coincided with rise in circulating CAR T cell frequency to one of the highest levels observed on our CAR trials (Figure, red line). CRS-related cytokines continued to decrease in serum, but CSF on day 16 showed marked elevation in IL-6, IL-8, and other CRS-related cytokines compared to day-16 serum and day-4 CSF (Figure, green line). CART-BCMA cells were detected in CSF. High-dose methylprednisolone was restarted without improvement. On day 17, cyclophosphamide 1.5 g/m2 was administered to reduce CART-BCMA cells. Beginning on day 18, mental status improved substantially, and she was extubated on day 20. Steroids were gradually tapered. MRI on day 23 showed near-resolution of signal abnormalities, which were completely resolved on MRI 4 weeks later. Neurologic signs and symptoms resolved; the last symptom to recover was mild difficulty processing visual information. Despite cyclophosphamide and a prolonged steroid course, CART-BCMA cells remained detectable in both blood and BM at last evaluation, 164 days after infusion, and the subject achieved a five-month VGPR.

Conclusions: Given the rapid reversibility and MRI appearance, this neurologic syndrome was felt to be most consistent with posterior reversible encephalopathy syndrome (PRES), possibly due to high CSF levels of CRS-related cytokines, as opposed to encephalitis from direct CART-BCMA cytotoxicity against neuronal tissue. PRES developed amidst improvement of systemic CRS, suggesting a CNS-localized CRS, possibly due to occult CNS MM encountered by expanding CART-BCMA cells and/or failure of tocilizumab to block IL-6 receptor in the CNS. Cyclophosphamide may effectively reverse life-threatening, steroid-refractory CAR T cell neurotoxicity while retaining some CAR T cell efficacy and long-term persistence.

![Figure][2]

Figure

Disclosures Garfall: Medimmune: Consultancy; Bioinvent: Research Funding; Novartis: Consultancy, Research Funding. Lancaster: Grifols, Inc.: Other: Teaching courses; Medimmune, Inc.: Consultancy; Janssen: Consultancy. Stadtmauer: Teva: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Amgen: Consultancy; Takada: Consultancy; Celgene: Consultancy. Lacey: Novartis: Research Funding. Ambrose: Novartis: Research Funding. Chen: Novartis: Research Funding. Kulikovskaya: Novartis: Research Funding. Vogl: Acetylon: Research Funding; GSK: Research Funding; Calithera: Research Funding; Teva: Consultancy; Celgene: Consultancy; Constellation: Research Funding; Takeda: Consultancy, Research Funding; Karyopharm: Consultancy. Plesa: Novartis: Patents & Royalties, Research Funding. Weiss: Novartis: Consultancy. Richardson: Novartis: Employment, Patents & Royalties, Research Funding. Melenhorst: Novartis: Patents & Royalties: Novartis, Research Funding. Levine: Novartis: Patents & Royalties, Research Funding; GE Healthcare Bio-Sciences: Consultancy. June: Novartis: Honoraria, Patents & Royalties, Research Funding; Celldex: Consultancy, Equity Ownership; Immune Design: Consultancy, Equity Ownership; Tmunity Therapeutics: Equity Ownership; Johnson & Johnson: Honoraria; Novartis: Honoraria, Patents & Royalties, Research Funding; Pfizer: Honoraria. Milone: Novartis: Patents & Royalties, Research Funding. Cohen: Janssen: Consultancy; Bristol-Meyers Squibb: Consultancy, Research Funding.

 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02546167&atom=%2Fbloodjournal%2F128%2F22%2F5702.atom
 [2]: pending:yes


A thin transition sublayer between the ferromagnetic and the nonmagnetic sublayers is introduced for describing the interface roughness and/or the interface alloying. Based on the Kubo formalism in the real spaces, the giant magnetoresistance effects for both the cases of the structures with and without the transition sublayers at the interfaces are discussed. The numerical results show that the transition sublayers induce a phase shift on the curves of magnetoresistance (MR) vs the thicknesses of the ferromagnetic and the nonmagnetic sublayers, and there exists a critical thickness dc of the ferromagnetic sublayer, the ratio of the MR values for the structures with and without the transition sublayers at the interfaces changes at the critical thickness.


A rapid and novel procedure using the liquid chromatography coupled to an electrospray ionization ion trap mass spectrometry technique was applied for the profiling of isovalertatin-family aminooligosaccharides in the extract from the culture filtrate of Streptomyces luteogriseus. The aminooligosaccharides were separated on a C-8 reversed-phase column with an acetonitrile-alkaline water gradient. The desired homologues were detected using the multiple reaction monitoring mode, and the chemical structures were confirmed by analyzing the characteristic fragment ions in their collision-induced dissociation spectra. This facile procedure led to the identification of all the five known aminooligosaccharides, isovalertatins M03, M13, M23, D03, and D23, in addition to the characterization of at least 41 novel isovalertatins, the molecular weights of which ranged from 729 to 2,793. This kind of assay should be intended as a simple and convenient way for the high-throughput analysis of screening aminooligosaccharides and potentially other structural families of natural products.