cssi/SciSciGPT-SciSciNet huggingface dataset:
Autoregulatory mechanism for dynactin control of processive and diffusive dynein transport

Dynactin is the longest known cytoplasmic dynein regulator, with roles in dynein recruitment to subcellular cargo and in stimulating processive dynein movement. The latter function was thought to involve the N-terminal microtubule-binding region of the major dynactin polypeptide p150(Glued), although recent results disputed this. To understand how dynactin regulates dynein we generated recombinant fragments of the N-terminal half of p150(Glued). We find that the dynein-binding coiled-coil α-helical domain CC1B is sufficient to stimulate dynein processivity, which it accomplishes by increasing average dynein step size and forward-step frequency, while decreasing lateral stepping and microtubule detachment. In contrast, the immediate upstream coiled-coil domain, CC1A, activates a surprising diffusive dynein state. CC1A interacts physically with CC1B and interferes with its effect on dynein processivity. We also identify a role for the N-terminal portion of p150(Glued) in coordinating these activities. Our results reveal an unexpected form of long-range allosteric control of dynein motor function by internal p150(Glued) sequences, and evidence for p150(Glued) autoregulation.
Four-dimensional dynamics of MAPK information-processing systems

Mitogen activated protein kinase (MAPK) cascades process a myriad of stimuli received by cell-surface receptors and generate precise spatio-temporal guidance for multiple target proteins, dictating receptor-specific cellular outcomes. Computational modelling reveals that the intrinsic topology of MAPK cascades enables them to amplify signal sensitivity and amplitude, reduce noise and display intricate dynamic properties, which include toggle switches, excitation pulses and oscillations. Specificity of signaling responses can be brought about by signal-induced feedback and feedforward wiring imposed on the MAPK cascade backbone. Intracellular gradients of protein activities arise from the spatial separation of opposing reactions in kinase-phosphatase cycles. The membrane confinement of the initiating kinase in MAPK cascades and cytosolic localization of phosphatases can result in precipitous gradients of phosphorylated signal-transducers if they spread solely by diffusion. Endocytotic trafficking of active kinases driven by molecular motors and traveling waves of protein phosphorylation can propagate phosphorylation signals from the plasma membrane to the nucleus, especially in large cells, such as Xenopus eggs.
Intra-Axonal Translation of RhoA Promotes Axon Growth Inhibition by CSPG

Chondroitin sulfate proteoglycans (CSPGs) are a major component of the glial scar that contributes to the limited regeneration of the CNS after axonal injury. However, the intracellular mechanisms that mediate the effects of CSPGs are not fully understood. Here we show that axonal growth inhibition mediated by CSPGs requires intra-axonal protein synthesis. Application of CSPGs to postnatal rat dorsal root ganglia axons results in an increase in the axonal levels of phosphorylated 4E-BP1, a marker of increased protein translation. Axons grown in media containing CSPGs exhibit markedly reduced growth rates, which can be restored by the selective application of protein synthesis inhibitors to distal axons. We show that these axons contain transcripts encoding RhoA, a regulator of the cytoskeleton that is commonly used by the signaling pathways activated by many inhibitors of axon growth. We also show that selective application of CSPGs to axons results in increased intra-axonal synthesis of RhoA and that depletion of RhoA transcripts from axons results in enhanced growth of axons in the presence of CSPGs. These data identify local translation as an effector pathway of CSPGs and demonstrate that local translation of RhoA contributes to the axon growth inhibitory effect of CSPGs.
Partner-Killing by Women in Cohabiting Relationships and Marital Relationships

Using a national-level U.S. database that includes more than 400,000 homicides committed from 1976 to 1994, the author calculated rates of partner-killing by women by relationship type (cohabiting or marital), by partner ages, and by the age difference between partners. Men in cohabiting relationships are 10 times more likely to be killed by their partners than are married men. Within marriages, the risk of being killed by a partner decreases with a man's age. Within cohabiting relationships, in contrast, middle-aged men are at greatest risk of being killed by their partners. The risk that a man will be killed by his partner generally increases with greater age difference between partners. These findings provide the first national-level replications of risk patterns reported for a national-level Canadian sample. Discussion highlights future research directions, including identifying why men in cohabiting relationships incur greater risk of being killed by their partners than do married men.
Mössbauer Investigation on Phase Transformation in Rapidly Solidified (RS) Al-Fe-V-Si-Nd Nanoalloy

The dynamics and mechanism of phase transformation in rapidly solidified (RS) Al-Fe-V-Si-Nd nano-alloy annealed at 633K, 648K, 663K were investigated by Mossbauer spectroscopy, X-ray diffraction and DSC analyses. The results indicated that the metastable Al 8 Fe 4 Nd phase transformed to α-Al 13 (Fe, V) 3 Si phase when heated. The kinetics of this process were estimated by the Avrami equation: X= 1- exp (-Kt n ). The activation energy was E,= 2.48± 0.09ev when the concentration of α-Al 13 (Fe,V) 3 Si was taken into consideration. As to Al 8 Fe 4 Nd, E 2 = 1.61±0.12eV It is to say that the transformation of Al 8 Fe 4 Nd to α-Al 13 (Fe,V) 3 Si phase was controlled by atomic volume diffusion, together with interface diffusion during the temperature range.
Deciphering the Function of Neurexins at Cellular Junctions

The mechanisms that allow the nervous system of animals to interpret and respond to their environment requires an astonishing complexity of neuronal connections and signaling pathways. The past decade has seen the emergence of a common theme in the mechanisms mediating these seemingly complex tasks
Single-beam homodyne SPIDER for multiphoton microscopy

We report a new version of spectral phase interferometry for direct electric field reconstruction (SPIDER) requiring only a single phase-shaped laser beam. A narrowband probe pulse is selected out of a broadband ultrafast laser pulse by a phase pulse-shaping technique and mixed with the original broadband pulse to generate a second-harmonic generation (SHG) signal. Using another SHG signal solely generated by the broadband pulse as a local oscillator, the spectral phase of the broadband laser pulse can be analytically retrieved by a combination of double-quadrature spectral interferometry and homodyne optical technique for SPIDER (HOT SPIDER). An arbitrary spectral phase at the sample position of a microscope can be compensated with a precision of 0.05 rad over the FWHM of the laser spectrum. It is readily applicable to a nonlinear microscopy technique with a phase-controlled broadband laser pulse.
Texture-Based Visualization of Unsteady 3D Flow by Real-Time Advection and Volumetric Illumination

This paper presents an interactive technique for the dense texture-based visualization of unsteady 3D flow, taking into account issues of computational efficiency and visual perception. High efficiency is achieved by a 3D graphics processing unit (GPU)-based texture advection mechanism that implements logical 3D grid structures by physical memory in the form of 2D textures. This approach results in fast read and write access to physical memory, independent of GPU architecture. Slice-based direct volume rendering is used for the final display. We investigate two alternative methods for the volumetric illumination of the result of texture advection: First, gradient-based illumination that employs a real-time computation of gradients, and, second, line-based lighting based on illumination in codimension 2. In addition to the Phong model, perception-guided rendering methods are considered, such as cool/warm shading, halo rendering, or color-based depth cueing. The problems of clutter and occlusion are addressed by supporting a volumetric importance function that enhances features of the flow and reduces visual complexity in less interesting regions. GPU implementation aspects, performance measurements, and a discussion of results are included to demonstrate our visualization approach.
Affect circumplex redux: the discussion on its utility as a measurement framework in exercise psychology continues

It has been suggested that the circumplex model could be a useful conceptual and measurement framework for investigating the effects of exercise on affect. This paper reviews three critical issues pertaining to this model, namely (a) the fit of the circumplex model to self-reported affective data, (b) the notion that postulated separable neural substrates of pleasure and displeasure challenge the principle of a bipolar relationship between these states, and (c) the idea that assessments of perceived activation are problematic. For each criticism, the evidence is reviewed and caveats that must be taken into account in evaluating the data and conceptual arguments are identified. The circumplex model has both considerable strengths and important limitations. For the application of the model in exercise psychology to be fruitful, researchers should recognize both aspects of this model.
Offshore Software Projects: Assessing the Effect of Knowledge Transfer Requirements and ISD Capability

The risks and challenges faced by client companies involved in offshore project development are many. Clients impose a range of control mechanisms to mitigate such challenges. Building on prior research utilizing control theory, we investigate the effect of knowledge transfer requirements and client ISD capability in shaping the choice of control modes, choice of offshore model and relationships in offshore application development projects. We utilize a grounded theory approach to examine four offshore application development projects. Results indicate that formal controls and pure-offshore models predominate in projects involving low knowledge transfer requirements, while a portfolio of control modes and hybrid models are preferred in projects involving high knowledge transfer requirements. Partner relationships are preferred in projects having high client ISD capability, while one-off relationships are favored in low ISD capability projects.
The vector field histogram-fast obstacle avoidance for mobile robots

A real-time obstacle avoidance method for mobile robots which has been developed and implemented is described. This method, named the vector field histogram (VFH), permits the detection of unknown obstacles and avoids collisions while simultaneously steering the mobile robot toward the target. The VFH method uses a two-dimensional Cartesian histogram grid as a world model. This world model is updated continuously with range data sampled by onboard range sensors. The VFH method subsequently uses a two-stage data-reduction process to compute the desired control commands for the vehicle. Experimental results from a mobile robot traversing densely cluttered obstacle courses in smooth and continuous motion and at an average speed of 0.6-0.7 m/s are shown. A comparison of the VFN method to earlier methods is given. >
Evaluation of the Effect of Host Immune Status on Short-Term Yersinia pestis Infection in Fleas With Implications for the Enzootic Host Model for Maintenance of Y. pestis During Interepizootic Periods

Plague, a primarily flea-borne disease caused by Yersinia pestis, is characterized by rapidly spreading epizootics separated by periods of quiescence. Little is known about how and where Y. pestis persists between epizootics. It is commonly proposed, however, that Y pestis is maintained during interepizootic periods in enzootic cycles involving flea vectors and relatively resistant host populations. According to this model, while susceptible individuals serve as infectious sources for feeding fleas and subsequently die of infection, resistant hosts survive infection, develop antibodies to the plague bacterium, and continue to provide bloodmeals to infected fleas. For Y. pestis to persist under this scenario, fleas must remain infected after feeding on hosts carrying antibodies to Y. pestis. Studies of other vector-borne pathogens suggest that host immunity may negatively impact pathogen survival in the vector. Here, we report infection rates and bacterial loads for fleas (both Xenopsylla cheopis (Rothschild) and Oropsylla montana (Baker)) that consumed an infectious bloodmeal and subsequently fed on an immunized or age-matched naive mouse. We demonstrate that neither the proportion of infected fleas nor the bacterial loads in infected fleas were significantly lower within 3 d of feeding on immunized versus naive mice. Our findings thus provide support for one assumption underlying the enzootic host model of interepizootic maintenance of Y. pestis.
BOTHRIOLEPIS VIRGINIENSIS, A VALID SPECIES OF PLACODERM FISH SEPARABLE FROM BOTHRIOLEPIS NITIDA

(2004). Bothriolepis virginiensis, a valid species of placoderm fish separable from Bothriolepis nitida. Journal of Vertebrate Paleontology: Vol. 24, No. 1, pp. 245-250.
The crisis of reason in contemporary thought: Some reflections on the arguments of postmodernism

Many recent thinkers imagine that a new way of life, or a new kind of thinking, is beginning to unfold on the basis of the discovery that reason is an outmoded concept and that the projects of Western philosophy are defunct. Postmodernist thinkers, in particular, have tried to describe the way things look from a post‐philosophical, post‐rational point of view. Jean‐Francois Lyotard's The Postmodern Condition argues against the possibility of a comprehensive understanding of contemporary social and intellectual activities, while most of the essays in Literature and the Question of Philosophy (ed. Anthony J. Cascardi) also reject the idea that there can be a valid comprehension of the elements found in textual or in ethical and political phenomena. Yet in every instance, the effort to establish a post‐philosophical, post‐rational way of looking at things involves an unwitting exercise of the rational power to conceive of a situation in terms of the relative disposition of its elements. Furthermore, the them...
Behavior Analysis in Special Education White Rabbit or White Elephant

The extensive and multi-faceted contributions of behavior analysis to the field of special education have been documented in numerous research studies and review articles. However, this literature is widely scattered and comes from different orientations within the general discipline of behavior analysis. These circumstances have contributed to some confusion on the part of those persons who only sample limited facets of the behavior analysis literature, and have resulted in criticisms that behavioral technology is narrow in scope. The present review attempts to organize the diverse data base pertaining to behavior analysis, and offers support for the contention that while the impact of behavioral technology on special education research and practice has been considerable, its potential has yet to be fully realized.
In silico Driven Redesign of a Clinically Relevant Antibody for the Treatment of GD2 Positive Tumors.

Ganglioside GD2 is a cell surface glycolipid that is highly expressed on cancer cells of neuroectodermal origin, including neuroblastoma, retinoblastoma, melanoma, sarcomas, brain tumors and small cell lung cancer. Monoclonal antibodies (MoAb) that target GD2 have shown clinical efficacy in the treatment of GD2 expressing tumors, and are expected to be the new standard of care for the treatment of pediatric neuroblastoma. In this study, the crystal structure of anti-GD2 murine MoAb 3F8 was solved to 1.65 A resolution and used as a template for molecular docking simulations of its antigen, the penta-saccharide head group of GD2. Molecular docking revealed a binding motif composed of 12 key interacting amino acid side-chains, involving an extensive network of interactions involving main-chain and side-chain hydrogen bonding, two Pi – CH interactions, and an important charged interaction between Arg95 of the H3 loop with the penultimate sialic acid residue of GD2. Based on in silico scanning mutagenesis of the 12 interacting amino acids from the docked 3F8:GD2 model, a single point mutation (Heavy Chain: Gly54Ile) was engineered into a humanized 3F8 (hu3F8) MoAb and found to have a 6–9 fold enhancement in antibody-dependent cell-mediated cytotoxicity of neuroblastoma and melanoma cell lines. With enhanced tumor-killing properties, the re-engineered hu3F8 has the potential be a more effective antibody for the treatment of GD2-positive tumors.
High-level modeling and analysis of the traffic alert and collision avoidance system (TCAS)

We demonstrate a high-level approach to modeling, analyzing, and verifying complex safety-critical systems through a case study on the traffic alert and collision avoidance system (TCAS); an avionics system that detects and resolves aircraft collision threats. Due to the complexity of the TCAS software and the hybrid nature of the closed-loop system, the traditional testing technique of exhaustive simulation does not constitute a viable verification approach. Moreover, the detailed specification of the system software employed to date as a means toward analysis and verification neither helps in intuitively understanding the behavior of the system nor enables the analysis of the closed-loop system behavior. We advocate defining high-level hybrid system models that capture the behavior not only of the software but also of the airplanes, sensors, pilots, etc. In particular, we show how the core components of TCAS can be captured by relatively simple hybrid I/O automata, which are amenable to format analysis. We then outline a methodology for establishing conditions under which TCAS guarantees sufficient separation in altitude for aircraft involved in collision threats. The contributions of the paper are the high-level models of the closed-loop TCAS system and the demonstration of the usefulness of high-level modeling, analysis, and verification techniques.
Update on the status of pathogen inactivation methods

Background Improvements in donor selection criteria and donor testing have reduced the risks of transfusion-transmitted diseases to remarkably low levels in developed countries. Residual risk remains because of window period donations and the potential for error. Developing countries may not have implemented all these safety measures fully, however. In all countries, tests with limited sensitivity (e.g. for detection of bacterial contamination) and ‘emerging’ pathogens, for which accurate tests have not been developed, pose continued threats to recipients. Results Pathogen inactivation (PI) has brought a welcome level of safety to plasma derivatives, and an increasing number of techniques are available for labile blood components. The toxicity profile of these techniques appears acceptable. Although the processes inevitably cause a reduction in the content or efficacy of the component, transfusions of the inactivated components appear to provide clinically useful outcomes. Transfusion of pathogen-inactivated plasma components is in widest use across multiple countries, and an increasing number of centres in multiple countries are adopting PI of platelet units as well. Development of techniques applicable to red cell units continues and preliminary success has been claimed. Not all reports of clinical use of PI platelets and plasma have been positive, however. Differences in bleeding rates may be attributable to different approaches to patient evaluation. Some regulatory agencies continue to place emphasis on the potential for pulmonary complications, although reanalysis of previous data indicates no increased risk of pulmonary toxicity. Multiple cost-effectiveness analyses have demonstrated that currently available PI techniques will likely reduce the residual risk of known pathogens by only a small amount and thus have marginal cost-effectiveness ratios in the range of $500 000–1 500 000/QALY (this is worse than for most commonly accepted medical procedures but not out-of-line in comparison to other blood safety interventions). The presumed effectiveness of current bacterial detection approaches is central to these analyses as bacteria remain the most frequently transmitted pathogen with culture detecting only 30–50% of contaminated units. An analysis of residual risk indicates that while techniques applicable across all components will be necessary to achieve the desired maximal effect of PI, implementing PI for plasma and platelets with currently available technology would reduce transmissions of both acute and chronic emerging disease agents by 40%. Conclusions The decision whether to implement PI is a complex one with ethical, societal and financial aspects. The ability to improve the safety of transfusion for recipients, particularly with respect to bacteria and emerging threats, is an important augmentation to our commitment to patients.
Health care lobbying: time to make patients the special interest.

s i h e q c m n this issue of The American Journal of Medicine, Landers and Sehgal (1) address the important issue of health care lobbying. Lobbying describes acts perormed to influence or sway an individual toward a deired action (2). Political lobbying in the United States ncludes communicating with legislators (through indiidual meetings, letter writing campaigns, and press reeases) and making financial contributions to politicians or their discretionary use on political campaigns. Using public records (3) made available through the obbying Disclosure Act of 1995 (4), Landers and Sehgal etermined that health care expenditures accounted for 5% of all federal lobbying and represented the most ommon form of lobbying in the federal government. hey note that lobbying expenditures by pharmaceutical nd health product corporations were twice those of phyicians and other health professional groups and that the ate of growth of lobbying was also considerably higher y pharmaceutical and health product interest groups han by health professions. Financial figures from the obbying Disclosure Act do not include expenditures on rassroots lobbying (e.g., media campaigns urging perons to write their legislators), lobbying of state or local uthorities, or campaign contributions. It is not entirely surprising that healthcare lobbying as whole accounts for 15% of all lobbying expenditures; ealthcare’s growing segment of the Gross Domestic roduct is estimated to be approximately the same size 5). The disproportionate rise in pharmaceutical lobbyng between 1997 and 2000 should not surprise us either, s this segment of the health care marketplace experinced the greatest degree of inflationary cost increases uring this time period. Dramatic increases in health care pending for pharmaceutical products received widepread media attention during this time as members of ongress began to debate whether price controls were ecessary. For some, growth in pharmaceutical spending ndicated a health care improvement in the form of a roader range of treatments, whereas for others it repreented a potential access to care barrier for consumers. his concern was particularly pertinent for the elderly, ho not only have the greatest burden of disease but who lso are predominantly insured by Medicare, a health in-
Test Bed for Analyzing High Frame-Rate Detector Devices with Reprogrammable Capabilities

This paper describes the capabilities being developed by The Aerospace Corporation to emulate and test "smart detectors" for use in pointing, acquisition, and tracking systems. A smart detector is defined as a device in which a significant processing capability exists within an integrated and dedicated processing sub-system rather than resident within an external or "host" general purpose computer. A detailed discussion of the Reprogrammable Array Detector (R.A.D.) test bed design, and its capabilities, is presented. The approach represents a flexible system architecture with the emphasis placed upon the array detector processing algorithm implementation and flexible hardware interconnectivity. The focus of this effort is to systematically analyze the bottlenecks, performance options, and hardware trades associated with high frame-rate array detector devices with region-of-interest (ROI) capability. Three approaches currently under study include separate implementations of a Digital Signal Processor (DSP), a Field Programmable Gate Array (FPGA), and a commercial off the shelf (COTS) detector system connected to a focal plane array (FPA) operating in the visible spectrum.
SUCCESSFUL MANAGEMENT OF CHYLOUS ASCITES AFTER LAPAROSCOPIC PRESACRAL NEURECTOMY

Laparoscopic presacral neurectomy is a safe, effective, and well-established surgical procedure to relieve intractable dysmenorrhea and chronic pelvic pain. In one woman, substantial lymphatic leakage occurred due to damaged lymphatic vessels. Adequate exposure and coagulation of the presacral lymphatic zone through the laparoscope resolved the problem, and a substantial amount of chylous ascites was removed. The patient fully recovered after the intervention.
Neuropsychological and neuropsychiatric prediction of global cognitive status among older Spanish-speaking Hispanics and English-speaking whites

Background:Neuropsychological and depression measures have been found to predict cognitive functioning. We compared these associations among whites and Spanish-speaking Hispanics.Methods:Fifty-two ...
Physician Complicity in Misrepresentation and Omission of Evidence of Torture in Postdetention Medical Examinations in Turkey

Between June 1994 and October 1995, representatives of Physicians for Human Rights studied the problem of physician complicity in torture (ie, misrepresentation and omission of medical evidence in postdetention examinations of detainees) in Turkey. The research consisted of a survey of forensic documentation of torture, interviews with individual physicians who examine detainees, analyses of official medical reports of detainees, and interviews with survivors of torture. Results from the survey, interviews, and medical report analyses provide evidence that torture of political and criminal detainees continues to occur in Turkey and that Turkish physicians are coerced to ignore, misrepresent, and omit evidence of torture in their examinations of detainees to certify that there are no physical signs of torture.
Differential effects of sleep stage on coronary hemodynamic function

The sleep-wake cycle results in distinctive patterns of autonomic nervous system activity. The present study examined the effects of rapid eye movement and slow-wave sleep on coronary hemodynamic function in chronically instrumented dogs. Mean arterial blood pressure was measured via a catheter in the aorta, and coronary blood flow was determined with Doppler probes placed around the left circumflex and right coronary artery. Identification of sleep stages was accomplished by means of electrodes implanted via the frontal sinus to record electro-oculogram, electromyogram, and electroencephalogram. Results indicated that during slow-wave sleep there were moderate but significant reductions in heart rate, 9% decreases in left coronary blood flow, and increases in coronary vascular resistance. In rapid-eye-movement sleep, the circumflex coronary blood flow base line returned to awake levels, and there were pronounced, phasic 35% increases in heart rate and 35% increases in coronary blood flow lasting 15-20 s. These surges were eliminated by stellectomy, indicating that they were mediated by the sympathetic nervous system.
Which patients need critical care intervention after total joint arthroplasty? : a prospective study of factors associated with the need for intensive care following surgery.

Older patients with multiple medical co-morbidities are increasingly being offered and undergoing total joint arthroplasty (TJA). These patients are more likely to require intensive care support, following surgery. We prospectively evaluated the need for intensive care admission and intervention in a consecutive series of 738 patients undergoing elective hip and knee arthroplasty procedures. The mean age was 60.6 years (18 to 91; 440 women, 298 men. Risk factors, correlating with the need for critical care intervention, according to published guidelines, were analysed to identify high-risk patients who would benefit from post-operative critical care monitoring. A total of 50 patients (6.7%) in our series required critical care level interventions during their hospital stay. Six independent multivariate clinical predictors were identified (p 1000 mL (OR 17.36, 95% CI 5.36 to 56.19), chronic obstructive pulmonary disease (13.90, 95% CI 4.78 to 40.36), intra-operative use of vasopressors (OR 8.10, 95% CI 3.23 to 20.27), revision hip arthroplasty (OR 2.71, 95% CI 1.04 to 7.04) and body mass index > 35 kg/m(2) (OR 2.70, 95% CI 123 to 5.94). The model was then validated against an independent, previously published data set of 1594 consecutive patients. The use of this risk stratification model can be helpful in predicting which high-risk patients would benefit from a higher level of monitoring and care after elective TJA and aid hospitals in allocating precious critical care resources.
Abstract T P79: Molecular Disorganization of Axons Adjacent to Subcortical Stroke in Hereditary Endotheliopathy With Retinopathy, Nephropathy, and Stroke; an Imaging to Molecular Neuropathology Correlation

White matter stroke secondary to microvascular injury is common yet the molecular changes that accompany ischemic damage to white matter are poorly understood. MRI imaging studies suggest that abnormalities exist within the white matter adjacent to lacunar infarcts and this may lead to infarct progression through a functional disruption of adjacent axons. Hereditary subcortical stroke syndromes provide a unique opportunity to study the molecular mechanisms of cerebral microvascular disease and its effect on white matter. Here, we examined two autopsy cases of hereditary endotheliopathy with retinopathy, nephropathy and stroke (HERNS) syndrome with severe microvascular ischemic disease in the cerebral white matter to determine the molecular organization of myelin and axons within the cerebral white matter adjacent to lacunar infarcts in these patients. MRI imaging was used to identify regions of prior lacunar infarction or FLAIR hyperintensity. Serial paraffin-embedded sections within these regions were immunolabeled for markers of nodes of Ranvier and paranodes as well as neurofilaments and myelin basic protein and compared to normal-appearing white matter and non-diseased controls. Compared to controls, HERNS cases demonstrate lengthening of paranodes and disrupted nodal staining patterns consistent with a loss of normal axon-oligodendrocyte molecular interactions. These abnormalities of axonal microdomains are present beyond the region of infarction suggested by MRI and H&E sections and occur in areas of FLAIR hyperintensity without frank lacunar infarction. These results indicate there is a peri-infarct in white matter stroke marked by molecular disruption of axons surrounding the infarct that may serve as a new therapeutic target for this currently untreatable form of ischemic stroke.
Changes in Body Mass Related to the Initiation of Disease-Modifying Therapies in Rheumatoid Arthritis.

Objective Unintentional weight loss is important and can be predictive of long-term outcomes in patients with rheumatoid arthritis (RA). This study was undertaken to assess how primary therapies for RA may influence changes in body mass index (BMI) in RA patients from a large administrative database. Methods Unique dispensing episodes of methotrexate, prednisone, leflunomide, and tumor necrosis factor inhibitors (TNFi) administered to RA patients were identified from the US Department of Veterans Affairs pharmacy databases. Values for C-reactive protein (CRP) level and BMI closest to the time point within 30 days of the treatment course start date and at follow-up time points were linked. Missing laboratory values were imputed. Weight loss was defined as a decrease in BMI of >1 kg/m2. Regression models were used to evaluate changes in BMI during each drug treatment as compared to treatment with methotrexate. To assess the impact of confounding by indication, propensity scores for use of each drug were incorporated in analyses using matched-weighting techniques. Results In total, 52,662 treatment courses in 32,859 RA patients were identified. At 6 months from the date of prescription fill, weight gain was seen among patients taking methotrexate, those taking prednisone, and those taking TNFi. On average, compared to methotrexate-treated patients, prednisone-treated patients had significantly more weight gain, while leflunomide-treated patients demonstrated weight loss. In multivariable models, more weight loss (β = −0.41 kg/m2, 95% confidence interval [95% CI] −0.46, −0.36; P < 0.001) and a greater risk of weight loss (odds ratio 1.73, 95% CI 1.55, 1.79; P < 0.001) were evident among those receiving leflunomide compared to those receiving methotrexate. Treatment with prednisone was associated with greater weight gain (β = 0.072 kg/m2, 95% CI 0.042, 0.10; P < 0.001). These associations persisted in analyses adjusted for propensity scores and in sensitivity analyses. Conclusion Leflunomide is associated with significantly more, but modest, weight loss, while prednisone is associated with greater weight gain compared to other therapies for RA.
SIMULATION OF A F/A-18 E/F DROP MODEL USING THE LaSRS++ FRAMEWORK

A simulation of a 22% dynamically scaled F/A18 E/F Drop Model was successfully developed within the Langley Standard Real-Time Simulation in C++ (LaSRS++) framework. Development in the LaSRS++ framework is done using object-oriented analysis, design and programming techniques. Common software design patterns are also used. Development using the LaSRS++ framework promotes the development of a simulation which is inherently maintainable, extensible, reliable and computationally efficient.
Ranking the parameters of deep neural networks using the fisher information

The large number of parameters in deep neural networks (DNNs) often makes them prohibitive for low-power devices, such as field-programmable gate arrays (FPGA). In this paper, we propose a method to determine the relative importance of all network parameters by measuring the amount of information that the network output carries about each of the parameters — the Fisher Information. Based on the importance ranking, we design a complexity reduction scheme that discards unimportant parameters and assigns more quantization bits to more important parameters. For evaluation, we construct a deep autoencoder and learn a non-linear dimensionality reduction scheme for accelerometer data measuring the gait of individuals with Parkinson's disease. Experimental results confirm that the proposed ranking method can help reduce the complexity of the network with minimal impact on performance.
DCC expression is altered by multiple mechanisms in brain tumours

The DCC (deleted in colorectal cancer) candidate tumor suppressor gene spans greater than 1350 kilobases at chromosomes 18q21.1 and encodes a transmembrane protein of unknown function. Although DCC is expressed in a number of adult tissues, its expression is highest in the brain and we have, therefore, undertaken studies to determine if DCC inactivation might contribute to tumors arising there. Decreased or absent DCC protein expression was noted in more than 50% of the thirty brain tumors studied. Although specific mutations in the DCC gene were not identified, a variety of mechanisms appeared to contribute to the altered DCC expression, including allelic loss, aberrant splicing of transcripts and allele-specific loss of transcripts. In total, the data suggest that DCC inactivation may be important in brain tumor pathogenesis.
Passing the Baton--Harnessing the Full Value of Older Scientists

Funding for older scientists represents an increasingly large proportion of NIH dollars awarded, a trend with important consequences for the scientific workforce. But we can more actively encourage the transfer of knowledge and resources between generations.
Protein and fiber digestion by steers grazing winter annuals and supplemented with ruminal escape protein.

Six abomasally cannulated Hereford steers (12 mo of age, 300 +/- 10 kg) grazing annual ryegrass (Lolium multiflorum Lam.) paddocks were used in a replicated 3 x 3 Latin square design to determine effects of ruminal escape protein (EP) supplementation on forage intake, fiber digestion, and protein flow to the intestine. Steers were fed one of three isoenergetic supplements: high ruminal escape protein (HEP), low ruminal escape protein (LEP), or corn, which supplied an estimated .25, .125, or 0 kg of EP/d in addition to EP supplied by corn. Fish meal (FM) and distiller's dried grains with solubles (DDGS) were sources of EP; FM provided 66.7% and DDGS provided 33.3% of estimated EP. Steers were adjusted to each supplement for 7 d before a 4-d collection period. Both total and forage DMI responded quadratically (P less than .03 and P less than .07, respectively) to EP supplementation. Total tract DM digestion tended (P less than .13) to increase linearly with EP supplementation. Abomasal total CP flow increased linearly (P less than .10) as supplemental EP increased. Crude protein flow in steers receiving HEP, LEP, and corn was 1,137, 1,027, and 844 g/d, respectively. Likewise, abomasal nonammonia N (NAN) tended to be greater (P less than .15, linear) for steers receiving HEP. Nonammonia N flows were 1,044, 955, and 771 g/d for steers receiving HEP, LEP, and corn, respectively. Abomasal ammonia flow did not differ (P less than .20) among treatments, nor did reticuloruminal fiber digestion (P less than .20). These data indicate that EP can increase postruminal protein flow and will not negatively affect fiber digestion in steers grazing annual ryegrass pastures.
Medical Research Participation as “Ethical Intercorporeality”: Caring for Bio–Social Bodies in a Mexican Human Papillomavirus (HPV) Study

While medical research ethics guidelines frame participants as individual and autonomous, anthropologists emphasize the relational nature of health research participation. I analyze interviews with Mexican male HPV study participants and their wives to examine how research participants themselves focus on relationships when imagining research-related benefits. I argue that couples incorporated the local trope of the Mexican citizenry as a biologically homogeneous national body, which individual members help or harm through their gendered health behavior to understand these benefits. I use the concept of "ethical intercorporeality" to discuss spouses' understandings of themselves as parts of bio-social wholes-the couple, family, and society-that they believed men's research participation could aid both physically and socially. This finding extends the insight that focusing on relationships rather than individuals is necessary for understanding the consequences of medical research by showing how participants themselves might apply this perspective in context-specific ways.
Higher Education and the Labour Market

Today almost 50 per cent of all American youths attend institutions of higher learning, and almost 36 per cent of all Japanese high school graduates proceed to higher education (US Department of Education, 1982; Monbusho, 1982a, 1982b). These two countries along with Canada are among the leading countries in the Western world in terms of the number of students enrolled in institutions of higher learning and the proportion of college-educated population (Monbusho, 1983). With such a large number of the youth population now proceeding to higher education, two important consequences related to the process of socioeconomic attainment can be expected. The first is that the socioeconomic returns to higher education may decline due to a larger supply of the college-educated population. The second is that stratification in higher education may have a significant impact on labour market outcomes.
Antifungals, Antimalarials, and Antivirals

This chapter includes a discussion of antifungal, antimalarial, and antiviral drugs. Similarities and differences of these with antibacterial antibiotics are discussed. Drugs presented include amphotericin B, nystatin, azoles, allylamines, morpholines, fluoropyrimidines, DDT, quinine, chloroquine, pyrimethamine, artemisinin, proguanil, amantadine, acyclovir, lamivudine, zidovudine, and HIV protease and neuraminidase inhibitors. Mechanisms of action of the drugs and resistance development against them are discussed. PCR method for detection of point mutations is also discussed.
Modeling phase changes in multistream heat exchangers

Abstract A new method for modeling phase changes in multistream heat exchangers (MHEXs) is presented. In many industrially relevant applications, streams in MHEXs will undergo phase changes between their inlet and outlet. In this model, nonsmooth equations are formulated which properly account for the existence or nonexistence of phases in heat integration, flash and physical property calculations in a MHEX. These new equations are used in conjunction with a recently developed nonsmooth model for MHEXs to create a compact equation system which can be used for the simulation and design of complex processes. Notably, this formulation does not involve the solution of a difficult optimization problem, since it avoids the use of either disjunctive or complementarity constraints. The robustness and functionality of the new formulation is illustrated through several simulations of the well-known Poly Refrigerant Integrated Cycle Operations (PRICO) process for liquefied natural gas production.
Graph Programming Interface (GPI): A Linear Algebra Programming Model for Large Scale Graph Computations

Graph processing is becoming a crucial component for analyzing big data arising in many application domains such as social and biological networks, fraud detection, and sentiment analysis. As a result, a number of computational models for graph analytics have been proposed in the literature to help users write efficient large scale graph algorithms. In this paper we present an alternative model for implementing graph algorithms using a linear algebra based specification. We first specify a set of linear algebra primitives that allows users to express graph algorithms by composition of linear algebra operations. We then describe a high performance implementation of these primitives using C $$++$$ and subsequently its integration with the Spark framework to achieve the scalability we need for large systems. We provide an overview of our implementation and also compare and contrast the expressiveness and performance of various algorithms implemented with our approach with that of the current Spark GraphX implementation of those algorithms.
In patients with proteinuric IgA nephropathy, benefits of methylprednisolone were offset by harms

Source Citation Lv J, Zhang H, Wong MG, et al; TESTING Study Group. Effect of oral methylprednisolone on clinical outcomes in patients with IgA nephropathy: The TESTING randomized clinical trial. J...
Technology, Culture, and Values: Implications for Enactment of Technological Tools in Precollege Science Classrooms

This chapter explores the culture of technology and the impact of technology on culture and values in the context of precollege science classrooms that implement (or aim to implement) technology-supported inquiry environments. We adopt perspectives of technology that at its core emphasize context and the artifact and its associated activity. These perspectives inform how notions of technology, culture, and values are intertwined in complex interactions of agents (designer, developer, or educational researcher and/or teacher educator, teacher, or student), and context of practice (science classroom), and mediated by associated knowledge and skills. Toward explicating how these interactions are realized in practice, first, we explore conceptualizations of technology that leverage human activity associated with design, development, implementation, use, and sustainability of technological tools. Second, we draw on Pacey’s (The culture of technology. MIT Press, Cambridge, MA, 1983) technology-practice framework to elucidate how cultural, organizational, and technical aspects of technology must be part and parcel of any analysis of the culture of technology implementation in precollege science classrooms. Third, we explicate how understandings of the nature of technology (NoT) undergird the role of context and associated culture and values of science teaching and learning. Dimensions of NoT (notions of technological progression, technology as part of systems, technological diffusion, technology as a fix and expertise) highlight how culture and values are influenced by various factors at different stages of technology adoption and implementation. Fourth, we examine empirical investigations of the enactment of technology-supported inquiry environments to identify (a) conceptualizations of technology, (b) how dimensions of NoT are manifested, and (c) how the presence or absence of these dimensions reflect key aspects of culture and values within science classrooms. We conclude that understandings of culture and values have implications for (a) conceptualizing technological tools in the context of precollege science classrooms, (b) transference of technologies across contexts (including requisite transference of habits of mind, practices, and expertise), and (c) implementing, enacting, and reappropriating technologies in science classrooms.
Reading and Phonological Processing

To clarify the special role of phonological processes in reading and learning to read, this article explains how language structures are incorporated into writing systems. All writing is based on speech, hence all writing somehow exploits phonology. Alphabetic writing does so by symbolizing meaningless particles of spoken words and consonant and vowel phonemes. Awareness of phonemic segmentation of words is key to learning to read alphabetic writing, but attaining it is often difficult for beginners, leading to difficulties in mapping. Dyslexia is interpreted as a deficit in phonological processing that permanently impairs learning to decode written words. Genetic studies and brain science have confirmed the phonological basis of dyslexia and reading differences.
Tests of Higher Cognitive Function

The Porteus Maze Test is a series of increasingly difficult mazes, which the manual states are designed to examine the ability to use “planning capacity, prudence, and mental alertness in a new situation of a concrete nature” (Golden, 1978b). The manual also asserts that performance on the test is affected by “impulsiveness, suggestibility, irresolution, and excitability” (p. 1). The user is told to expect practice effects, but not to worry about their presence because practice is built into the test. The Porteus has held fascination for clinical neuropsychologists for a long time. It has often been used as a dependent measure in experimental and clinical investigation, but its diagnostic utility is largely unknown.
Endometriosis Manifesting as a Urachal Tumor

ABSTRACT:Endometriosis of abdominal wall scars is rare, especially in the postmenopausal woman. However, it must be considered as a possible cause of any abdominal wall mass in a woman who has had previous pelvic surgery and who is of reproductive age or taking exogenous hormones.