cssi/SciSciGPT-SciSciNet huggingface dataset:
Preparation of Substituted Pyridines Via Regiocontrolled [4 + 2] Cycloadditions of Oximinosulfonates: Methyl 5‐Methylpyridine‐2‐Carboxylate

Methyl 5-methylpyridine-2-carboxylate 5(Tosyloxyimino)-2,2-dimethyl-1,3-dioxane-4,6-dione Meldrum's acid N-Chlorosuccinimide p-Toluenesulfonyl chloride Keywords: pyridines; cycloadditions; regiocontrolled; oximinosulfonates; pyridine rings; Diels-Alder reaction; cycloadducts; pyridine annulations
The politics of presidential illness. Ronald Reagan and the Iran-Contra Scandal.

This paper assesses the likelihood that the Iran-Contra scandal was shaped heavily by the effects of Ronald Reagan's cancer surgery in summer, 1985. During the President's hospitalization and in the period soon after, he took several actions—which he apparently did not remember—that launched a policy that was unwise, counterproductive, and a failure. These damaged both his Administration and his standing in history. The 25th Amendment afforded Reagan the means by which his involvement in these events could easily have been avoided. However, the President and his aides determined that he would resume the powers and duties of the presidency only hours after undergoing extensive cancer surgery. This decision contributed materially to the most damaging episode of Reagan's eight-year presidency.
Medial nucleus tractus solitarius oxytocin receptor signaling and food intake control: the role of gastrointestinal satiation signal processing

Central oxytocin (OT) administration reduces food intake and its effects are mediated, in part, by hindbrain oxytocin receptor (OT-R) signaling. The neural substrate and mechanisms mediating the intake inhibitory effects of hindbrain OT-R signaling are undefined. We examined the hypothesis that hindbrain OT-R-mediated feeding inhibition results from an interaction between medial nucleus tractus solitarius (mNTS) OT-R signaling and the processing of gastrointestinal (GI) satiation signals by neurons of the mNTS. Here, we demonstrated that mNTS or fourth ventricle (4V) microinjections of OT in rats reduced chow intake in a dose-dependent manner. To examine whether the intake suppressive effects of mNTS OT-R signaling is mediated by GI signal processing, rats were injected with OT to the 4V (1 μg) or mNTS (0.3 μg), followed by self-ingestion of a nutrient preload, where either treatment was designed to be without effect on chow intake. Results showed that the combination of mNTS OT-R signaling and GI signaling processing by preload ingestion reduced chow intake significantly and to a greater extent than either stimulus alone. Using enzyme immunoassay, endogenous OT content in mNTS-enriched dorsal vagal complex (DVC) in response to ingestion of nutrient preload was measured. Results revealed that preload ingestion significantly elevated endogenous DVC OT content. Taken together, these findings provide evidence that mNTS neurons are a site of action for hindbrain OT-R signaling in food intake control and that the intake inhibitory effects of hindbrain mNTS OT-R signaling are mediated by interactions with GI satiation signal processing by mNTS neurons.
Drug–Vitamin D Interactions A Systematic Review of the Literature

Extensive media coverage of the potential health benefits of vitamin D supplementation has translated into substantial increases in supplement sales over recent years. Yet, the potential for drug-vitamin D interactions is rarely considered. This systematic review of the literature was conducted to evaluate the extent to which drugs affect vitamin D status or supplementation alters drug effectiveness or toxicity in humans. Electronic databases were used to identify eligible peer-reviewed studies published through September 1, 2010. Study characteristics and findings were abstracted, and quality was assessed for each study. A total of 109 unique reports met the inclusion criteria. The majority of eligible studies were classified as class C (nonrandomized trials, case-control studies, or time series) or D (cross-sectional, trend, case report/series, or before-and-after studies). Only 2 class C and 3 class D studies were of positive quality. Insufficient evidence was available to determine whether lipase inhibitors, antimicrobial agents, antiepileptic drugs, highly active antiretroviral agents, or H2 receptor antagonists alter serum 25(OH)D concentrations. Atorvastatin appears to increase 25(OH)D concentrations, whereas concurrent vitamin D supplementation decreases concentrations of atorvastatin. Use of thiazide diuretics in combination with calcium and vitamin D supplements may cause hypercalcemia in the elderly or those with compromised renal function or hyperparathyroidism. Larger studies with stronger study designs are needed to clarify potential drug-vitamin D interactions, especially for drugs metabolized by cytochrome P450 3A4 (CYP3A4). Healthcare providers should be aware of the potential for drug-vitamin D interactions.
BRACE for a New Interventionist Economics

The Great Recession seems to be creating a New Interventionist Economics characterized by bubbles, radical uncertainty, animal spirits, complexity dynamics, and extra-market control. When placed in that order, these characteristic create the acronym BRACE. We review some evidence and literature pointing to BRACE economics and briefly suggest some avenues to challenge the new interventionists.
Differences in regional brain activation patterns assessed by functional magnetic resonance imaging in patients with systemic lupus erythematosus stratified by disease duration.

The mediators of tissue damage in systemic lupus erythematosus (SLE) such as antibodies, cytokines and activated immune cells have direct access to most organs in the body but must penetrate the blood-brain barrier (BBB) to gain access to brain tissue. We hypothesized that compromise of the BBB occurs episodically such that the brain will acquire tissue damage slowly and not at the same rate as other organs. On the basis of these assumptions, we wished to determine if duration of disease correlated with brain injury, as measured with functional magnetic resonance imaging (fMRI), and if this was independent of degree of tissue damage in other organs. We investigated differences in brain activation patterns using fMRI in 13 SLE patients stratified by disease duration of ≤2 years (short-term [ST]) or ≥10 years (long-term [LT]). Two fMRI paradigms were selected to measure working memory and emotional response (fearful faces task). Performance in the working memory task was significantly better in the ST group for one and two shape recall; however, both groups did poorly with three shape recall. Imaging studies demonstrated significantly increased cortical activation in the ST group in regions associated with cognition during the two shape retention phase of the working memory task (P < 0.001) and increased amygdala (P < 0.05) and superior parietal (P < 0.01) activation in response to the fearful faces paradigm. In conclusion, analysis of activation patterns stratified by performance accuracy, differences in comorbid disease, corticosteroid doses or disease activity suggests that these observed differences are attributable to SLE effects on the central nervous system exclusive of vascular disease or other confounding influences. Our hypothesis is further supported by the lack of correlation between regional brain abnormalities on fMRI and the Systemic Lupus International Collaborating Clinics (SLICC) damage index.
A look back at 50 years of lens designs from the Tropel attic: Do improvements in computer optimization overcome the current restrictions of available glass materials?

A historical collection of Corning Tropel optical systems was analyzed with the primary goal of organizing and archiving the designs in a searchable computer database. The analysis of these systems was two-fold: the system data and documented design procedure were examined from both a technical as well as a historical viewpoint. Items of historical interest included letters and handwritten comments from various well-known designers, computer print outs from early lens design programs, and aberration plots and pictures of the system drawn painstakingly by hand. The technical analysis involved entering the system data into a modern day computer analysis package (CODE V) and comparing the performance (in the form of MTFs, field and distortion curves, etc.) with the original performance claimed by each system. One of the most significant findings was the ability to consistently replace obsolete glasses with current glasses, without sacrificing performance. In some cases, it was even possible to reoptimize the system and improve the performance.
Effects of l-methamphetamine treatment on cocaine- and food-maintained behavior in rhesus monkeys

Monoamine releasers with prominent dopaminergic actions, e.g., d-methamphetamine (d-MA), significantly reduce cocaine use and craving in clinical and preclinical laboratory studies. However, D-MA and related drugs also display high abuse potential, which limits their acceptability as agonist replacement medications for the management of Cocaine Use Disorder. The l-isomer of methamphetamine (l-MA), unlike d-MA, has preferential noradrenergic actions and is used medicinally with low, if any, abuse liability. The present study was conducted to determine whether l-MA could serve as an agonist replacement medication by both mimicking interoceptive effects of cocaine and decreasing intravenous (IV) cocaine self-administration. Separate groups (N = 4–5) of rhesus monkeys were studied to determine whether l-MA could (1) substitute for cocaine in subjects that discriminated intramuscular (IM) cocaine (0.4 mg/kg) from saline and (2) decrease IV cocaine self-administration under a second-order FR2(VR16:S) schedule of reinforcement. l-MA, like d-MA but with approximately 5-fold lesser potency, substituted for cocaine in drug discrimination experiments in a dose-dependent manner. In IV self-administration studies, 5–10-day treatments with continuously infused l-MA (0.032–0.32 mg/kg/h, IV) dose-dependently decreased cocaine-maintained responding; the highest dosage reduced cocaine intake to levels of saline self-administration without appreciable effects on food-maintained responding. These results indicate that l-MA both shares discriminative stimulus effects with cocaine and reduces cocaine self-administration in a behaviorally selective manner. l-MA and other compounds with a similar pharmacological profile deserve further evaluation for the management of Cocaine Use Disorder.
Regulation of Neuronal Gene Transcription by Ethanol

Much of the pathology caused by alcoholism can be attributed to the continued use of large quantities of ethanol. Alcoholics can expose themselves to extraordinarily large concentrations of ethanol due to an acquired resistance to the drug, termed tolerance. Resistance to ethanol can occur as dispositional (pharmacokinetic) or functional (pharmacodynamic) tolerance (Jaffe, 1985). Dispositional tolerance refers to an alteration in the rate of metabolism, absorption, distribution, or secretion. Functional tolerance refers to adaptive changes that occur within the central nervous system upon chronic ethanol exposure.
The Prevalence and Predictors of Low-Cost Generic Program Use in a Nationally Representative Uninsured Population

The uninsured population has much to gain from affordable sources of prescription medications. No prior studies have assessed the prevalence and predictors of low-cost generic drug programs (LCGP) use in the uninsured population in the United States. A cross-sectional study was conducted using data from the Medical Expenditure Panel Survey (MEPS) during 2007–2012 including individuals aged 18 and older who were uninsured for the entire 2-year period they were in MEPS. The proportions of LCGP fills and users was tracked each year and logistic regression was used to assess significant factors associated with LCGP use. A total of 8.3 million uninsured individuals were represented by the sample and 39.9% of these used an LCGP. Differences between users and non-users included higher age, gender, year of participation, and number of medications filled. The proportion of fills and users via LCGPs increased over the 2007–2012 study period. Healthcare providers, especially pharmacists, should make uninsured patients aware of this source of affordable medications.
Innovations to Address Global Drug Counterfeiting: Implications for Urbanization and Health

The recent rise in counterfeits has now extended from basic consumer goods and electronics to pharmaceuticals, jeopardizing the health of millions across the globe.
The Existence of Multiplicative Inverses

1. E. R. Berlekamp, J. H. Conway, and R. K. Guy, Winning Ways for Your Mathematical Plays, A. K. Peters, 2001. 2. M. Bezzel (using pseudonym “Schachfreund”), Berliner Schachzeitung 3 (1848) 363. 3. P. J. Campbell, Gauss and the eight queens problem: A study in miniature of the propagation of historical error, Historia Mathematica 4 (1977) 397–404. 4. J. Giusburg, Gauss’s arithmetization of the problem of 8 queens, Scripta Mathematica 5 (1939) 63–66. 5. P. M. Grundy, Mathematics and games, Eureka 2 (1939) 6–8; reprinted Eureka 27 (1967) 9–11. 6. G. Schrage, The eight queens problem as a strategy game, Int. J. Math. Educ. Sci. Technol. 17 (1989) 143–148. 7. R. P. Sprague, Uber mathematische Kampfspiele, Tohoku Math. J. 41 (1935–36) 438–444.
Characterization of Thin Film Dielectrics by FTIRS

The silicon-oxygen chemical bond is the key building block for many of the dielectric thin films used in silicon MOS technology. High quality thermal silicon oxides serve as gate dieletrics. CVD silicon oxides, produced by a variety of deposition processes, are used as interlayer dielectrics and as passivating layers. These films may be stoichiometric or nonstoichiometric, or doped with boron and/or phosphorus to provide the most desirable film properties. Bandshape analysis of the Fourier Transform Infrared (FTIR) spectra of these films can provide information on the chemical bond strength, the homogeneity, and the optical dielectric function of various glasses. Spectral features are found to change characteristically, depending upon deposition conditions, subsequent processing (densification), the influence of dopants, stress, and the effects of overlying films. In comparing films [Bposited under different conditions, the primary Si-O stretching mode peak position shifts over a 30cm−1 range and has a FWHM that varies by as much as 50%. The FTIR technique can routinely resolve peak shifts in glasses as small as 2 cm−1, sufficient to detect the differences observed due to deposition or processing.
Role of alpha-adrenergic mechanisms on responses to area postrema stimulation and circulating vasopressin

This study evaluated the role of catecholamines in the nucleus tractus solitarius (NTS) on the inhibition of renal sympathetic nerve activity (RSNA) due to direct electrical stimulation of the area postrema. In addition, the effects of catecholaminergic mechanisms in the NTS on the ability of circulating arginine vasopressin (AVP) to modulate arterial baroreflex control of RSNA were evaluated. Electrical stimulation of the area postrema (15 microA, 0.3 ms, 5-80 Hz) produced progressive decreases in RSNA. Responses to area postrema activation were not altered by microinjection of the alpha 1-adrenergic antagonist, prazosin, or vehicle bilaterally into the NTS. Microinjection of the alpha 2-antagonist, yohimbine (4 injections of 20-40 nl, 1 ng/nl), unilaterally into the NTS significantly attenuated the RSNA response to area postrema stimulation. Bilateral injection of yohimbine into the NTS abolished the response to area postrema activation (P < 0.05). Baroreflex inhibition of RSNA was significantly greater during infusion of AVP than during infusion of phenylephrine (slopes = -5.18 +/- 0.39 and -2.64 +/- 0.27 for AVP and phenylephrine, respectively). Microinjection of yohimbine bilaterally into the NTS did not alter the slope of baroreflex control of RSNA for phenylephrine but normalized the slope for AVP (-2.85 +/- 0.54) to that of phenylephrine. Data are consistent with the hypothesis that AVP effects on baroreflex inhibition of RSNA and area postrema-mediated inhibition of RSNA require alpha 2-adrenergic signaling within the NTS.
The Effect of Transection of the Accessory Ligaments on Reproduction in the Rabbit

The mesotubarium superius (MTS) and uterovarian ligament (UOL) contain smooth muscle, are mechanically active, and have been implicated in ovum transport in a number of species. To assess the reproductive importance of these ligaments, they were unilaterally transected in 27 rabbits and the effects on reproduction determined. Reproductive function was characterized in terms of the numbers of corpora lutea, uterine implants, and normal conceptuses resulting from breeding with fertile bucks. Fertility was defined by the proportion of ovulating follicles resulting in implantation and normal conceptuses. Grouped and paired sample analyses of these data showed no differences between the experimental and control sides of the reproductive tracts of animals in which the UOL, MTS, or both were transected. The structural integrity of these ligaments is thus not necessary for normal conception and fertility in the rabbit.
Assessing drinking problems by history

Patients with alcohol problems can be categorized as either medical alcoholics or behavioral alcoholics. A detailed, accurate drinking history is required to diagnose behavioral alcoholism, because these patients have highly developed denial systems about their drinking problems.
Neuroendocrinology of aggression

Publisher Summary This chapter explains how aggression is a social interaction to determine the outcome of a conflict over resources. Aggressive behaviors take many forms, despite evidence that the regulatory factors and brain mechanisms are conserved across vertebrate species. Castrated animals are expected to show reduced aggression levels, whereas castrated animals with testosterone replaced via an implant are expected to display aggression levels similar to those of intact animals. Androgens such as testosterone can be converted to estrogens by the aromatase enzyme, and many brain regions known to regulate aggression express aromatase. Thus, in some cases, the effects of testosterone on aggression may actually be mediated by estrogenic metabolites. Dehydroepiandrosterone (DHEA) is an endogenous steroid that circulates at relatively high concentrations among humans. Similar to androgens, the relationship between glucocorticoids and aggressive behaviors is complex. The neuropeptides vasopressin and oxytocin have complex effects on aggressive behaviors. Vasopressin neurons in the bed nucleus of the stria terminalis (BNST) and medial amygdala send projections to the lateral septum.
Social Correlates of Suicide by Age

Sociological work on suicide has often neglected age-specific analysis. Although there has been a good deal of work on teenage suicide and some work on suicide among the elderly, people in midlife have been especially neglected (Stack, 1982, 1987b). The present study first discusses social correlates of suicide by broad age groups: young, middle-aged, and old. The shared-life circumstances of each group are used to predict age-group propensities to imitate suicide. A statistical model is then tested linking publicized suicide stories with age-specific suicide rates.
Fiducial-based registration with a touchable region model

Image-guided surgery requires registration between an image coordinate system and an intraoperative coordinate system that is typically referenced to a tracking device. In fiducial-based registration methods, this is achieved by localizing points (fiducials) in each coordinate system. Often, both localizations are performed manually, first by picking a fiducial point in the image and then by using a hand-held tracked pointer to physically touch the corresponding fiducial on the patient. These manual procedures introduce localization error that is user-dependent and can significantly decrease registration accuracy. Thus, there is a need for a registration method that is tolerant of imprecise fiducial localization in the preoperative and intraoperative phases. We propose the iterative closest touchable point (ICTP) registration framework, which uses model-based localization and a touchable region model. This method consists of three stages: (1) fiducial marker localization in image space, using a fiducial marker model, (2) initial registration with paired-point registration, and (3) fine registration based on the iterative closest point method. We perform phantom experiments with a fiducial marker design that is commonly used in neurosurgery. The results demonstrate that ICTP can provide accuracy improvements compared to the standard paired-point registration method that is widely used for surgical navigation and surgical robot systems, especially in cases where the surgeon introduces large localization errors. The results demonstrate that the proposed method can reduce the effect of the surgeon’s localization performance on the accuracy of registration, thereby producing more consistent and less user-dependent registration outcomes.
Marketing Processes and Consumer Need Fulfillment: Retrospective Views and Future Prospects

The connection between marketing processes and consumer need fulfillment is a critical issue for both scholars and practitioners. However, the strength of that relationship is somewhat in question....
Coeliac disease screening is suboptimal in a tertiary gastroenterology setting

Background and aims Coeliac disease (CD) is widely prevalent in North America, but case-finding techniques currently used may not be adequate for patient identification. We aimed to determine the adequacy of CD screening in an academic gastroenterology (GI) practice. Methods Consecutive initial visits to a tertiary academic GI practice were surveyed over a 3-month period as a fellow-initiated quality improvement project. All electronic records were reviewed to look for indications for CD screening according to published guidelines. The timing of screening was noted (before or after referral), as well as the screening method (serology or biopsy). Data were analysed to compare CD screening practices across subspecialty clinics. Results 616 consecutive patients (49±0.6 years, range 16–87 years, 58.5% females, 94% Caucasian) fulfilled inclusion criteria. CD testing was indicated in 336 (54.5%), but performed in only 145 (43.2%). The need for CD screening was highest in luminal GI and inflammatory bowel disease clinics, followed by biliary and hepatology clinics (p Conclusions More than 50% of patients in a tertiary GI clinic have indications for CD screening, but
CUDA M3: Designing Efficient CUDA Managed Memory-Aware MPI by Exploiting GDR and IPC

CUDA 6.0 introduced Managed Memory feature to boost the productivity on GPU systems. It removes the explicit memory management and data movement between the host and the accelerator burden from the programmer. However, these benefits restrict the pinning of the memory and hence limits its performance by depriving the usage of performance-centric features like CUDA-IPC and GPUDirect RDMA. On another hand, CUDA-Aware MPI runtimes, have been continuously improving the performance of data movement from/to native GPU memory allocations. In this paper, to maximize the productivity and performance potentials on GPU systems, we propose a novel CUDA M3 framework. We investigate and propose efficient designs to introduce Managed Memory Awareness to CUDA-Aware MPI. To do so, we analyze the behavior of managed memory and define a locality property. We propose novel schemes to optimize intra-node and inter-node communications using CUDA-IPC and GDR features. To the best of our knowledge, this is the first work to design Managed Memory-Aware data movement schemes that exploit CUDA-IPC and GDR features. The performance evaluation, with micro-benchmark, using a CS-Storm system, shows up to 32X improvement for intra-node configuration and up to 7X for inter-node configuration. Using a real world application, our designs show up to 1.92X improvement on 96 GPUs with GPULBM application.
Environmental Justice: A Deadly Symptom of Larger Problems a Response to the Plenary of Dr. Beverly Wright

Environmental justice describes the movement to challenge and avert the disproportionate burdening of pollution on people of color and poor and working class communities. Air pollution, water pollution, and waste disproportionately burden the most vulnerable and least protected communities of the nation. Race and class best predict where polluting facilities are located despite claims from business, government, political leaders that the race and class make up of communities does not affect environmental decision-making. Environmental justice concerns grow out of the longstanding fight for racial and economic justice in America. In light of the civil rights legislation and social welfare programs of the 1960s, contemporary America has little interest in claims of racial discrimination made by people of color or in the well being of the poor and needy. Although race and class identity continue to exert undue influence over everyday decision making throughout the society, most Americans are oblivious to the way race and class influence their thinking and practices. Viewing the world from an individualist perspective, America’s racial majority fails to recognize how their “racially neutral” policies and practices continue to perpetuate status quo racial advantages across a broad spectrum of social institutions. Likewise, the economic and social disadvantages facing poor and working class people are exacerbated and overlooked in order to increase and maintain the advantages of the wealthy and the upper middle classes.
Physics and Chance

I discuss the role of chance in the fundamental physical picture of the world, and in the connections between that fundamental picture and the various other pictures of the world that we have from the special sciences, and I make a few remarks about the sort of thing that chance would need to be in order to be able to play that role.
Physical therapy as non-pharmacological chronic pain management of adults living with HIV: self-reported pain scores and analgesic use.

Background HIV-related chronic pain has emerged as a major symptom burden among people living with HIV (PLHIV). Physical therapy (PT) has been shown to be effective as a non-pharmacological method of chronic pain management in the general population; however, there is a gap in research examining the role of PT for chronic pain among PLHIV. Materials and methods This study examined the effect of PT on self-reported pain scores and pain medication usage in PLHIV enrolled in a multidisciplinary HIV clinic. Data were collected via reviews of patient medical records within a certain timeframe. Data were gathered from patient charts for two points: initial PT encounter (Time 1) and PT discharge or visit ≤4 months after initial visit (Time 2). Results Subjects who received PT during this timeframe reported decreased pain (65.2%), elimination of pain (28.3%), no change in pain (15.2%), and increased pain (6.5%). Three-quarters of the subjects reported a minimal clinically important difference (MCID) in pain score, and more than half reported a decrease in pain score over the MCID. Subjects showed a trend of decreasing pain medication prescription and usage during the study period. Conclusion Results of the current study indicate that in this sample, PT intervention appears to be an effective, cost-effective, non-pharmacological method to decrease chronic pain in PLHIV.
AcuityView: An r package for portraying the effects of visual acuity on scenes observed by an animal

1.Visual acuity is one of three basic parameters that characterize a visual system. However, few comparative studies of signals, camouflage, and ecology in general have considered visual acuity. This is unfortunate, because humans have high acuity, and thus researchers may focus on visual details of animals and habitats that are not actually visible to the relevant species. 2.Here we present AcuityView, a package for use in the software R which uses Fourier methods, measures of a viewer's acuity, viewing distance, and the size of an image to modify images. 3.AcuityView renders an image in a way that preserves only the information that an animal with a given visual acuity can detect at a certain distance, thus displaying an image that shows only the visual information available to that viewer. 4Ultimately, this will allow for a more informed analysis of what aspects of an animal's visual world may be detectable, and thus relevant to their ecology. This article is protected by copyright. All rights reserved.
Additive manufacturing of compositionally gradient metal-ceramic structures: Stainless steel to vanadium carbide

Abstract Processing of hard, refractory ceramic coatings in a metal matrix is challenging due to various factors including delamination or cracking due to large material property differences at the interphase, and non-uniform distribution due to improper mixing. These issues can be reduced or even eliminated if the coating had a gradual change in material properties from the surface to the inside. Additive manufacturing is now being looked at to accomplish compositional control beyond the ability to produce net shape parts for repair as well as adding functionality. In this study, laser engineered net shaping (LENS™) was used to manufacture compositionally gradient structures of vanadium carbide (VC) and stainless steel 304 (SS304). Compositions ranging from 5 to 100 wt% of VC were mixed with SS304. The internal stress from the carbides significantly increased the hardness and wear resistance of the coatings. The 100%VC outer layer increased the hardness by 1450 HV and lowered the wear rate by 95% compared to SS304 substrate.
Five Alternative Myosin Converter Domains Influence Muscle Power, Stretch Activation, and Kinetics.

Muscles have evolved to power a wide variety of movements. A protein component critical to varying power generation is the myosin isoform present in the muscle. However, how functional variation in muscle arises from myosin structure is not well understood. We studied the influence of the converter, a myosin structural region at the junction of the lever arm and catalytic domain, using Drosophila because its single myosin heavy chain gene expresses five alternative converter versions (11a-e). We created five transgenic fly lines, each forced to express one of the converter versions in their indirect flight muscle (IFM) fibers. Electron microscopy showed that the converter exchanges did not alter muscle ultrastructure. The four lines expressing converter versions (11b-e) other than the native IFM 11a converter displayed decreased flight ability. IFM fibers expressing converters normally found in the adult stage muscles generated up to 2.8-fold more power and displayed up to 2.2-fold faster muscle kinetics than fibers with converters found in the embryonic and larval stage muscles. Small changes to stretch-activated force generation only played a minor role in altering power output of IFM. Muscle apparent rate constants, derived from sinusoidal analysis of the chimeric converter fibers, showed a strong positive correlation between optimal muscle oscillation frequency and myosin attachment kinetics to actin, and an inverse correlation with detachment related cross-bridge kinetics. This suggests the myosin converter alters at least two rate constants of the cross-bridge cycle with changes to attachment and power stroke related kinetics having the most influence on setting muscle oscillatory power kinetics.
Perfusion double-channel micropipette probes for oxygen flux mapping with single-cell resolution.

Measuring cellular respiration with single-cell spatial resolution is a significant challenge, even with modern tools and techniques. Here, a double-channel micropipette is proposed and investigated as a probe to achieve this goal by sampling fluid near the point of interest. A finite element model (FEM) of this perfusion probe is validated by comparing simulation results with experimental results of hydrodynamically confined fluorescent molecule diffusion. The FEM is then used to investigate the dependence of the oxygen concentration variation and the measurement signal on system parameters, including the pipette’s shape, perfusion velocity, position of the oxygen sensors within the pipette, and proximity of the pipette to the substrate. The work demonstrates that the use of perfusion double-barrel micropipette probes enables the detection of oxygen consumption signals with micrometer spatial resolution, while amplifying the signal, as compared to sensors without the perfusion system. In certain flow velocity ranges (depending on pipette geometry and configuration), the perfusion flow increases oxygen concentration gradients formed due to cellular oxygen consumption. An optimal perfusion velocity for respiratory measurements on single cells can be determined for different system parameters (e.g., proximity of the pipette to the substrate). The optimum perfusion velocities calculated in this paper range from 1.9 to 12.5 μm/s. Finally, the FEM model is used to show that the spatial resolution of the probe may be varied by adjusting the pipette tip diameter, which may allow oxygen consumption mapping of cells within tissue, as well as individual cells at subcellular resolution.
Impact Evaluations of EDUCO: A Critical Review

Despite the excitement around the Education with Community Participation (EDUCO) program during the early 1990s as it was being scaled up, the Ministry of Education and the representatives of the World Bank knew that they would need solid evidence which demonstrated that the program produced beneficial outcomes in order (a) to continue to promote the program as a central policy for education reform in El Salvador and (b) to be able to credibly promote the program internationally as a best practice. It was in this context of excitement and determination that the World Bank began to carry out evaluations of EDUCO. With this in mind, this chapter critically reviews six key studies that were carried out between 1994 and 2005 by the World Bank on the EDUCO program. These six studies are included here for critical review because they represent each of the studies that were produced as impact evaluations, all of which were generated by the World Bank. They represent the entire body of “legitimate” and “policy-relevant” knowledge that was created in order to evaluate whether the program worked by identifying the effects of the EDUCO intervention.
Noninvasive Detection of Mitochondrial Dysfunction in Ocular Hypertension and Primary Open-angle Glaucoma.

PURPOSE To assess mitochondrial dysfunction in vivo in ocular hypertension (OHT) and primary open-angle glaucoma (POAG) using retinal metabolic analysis. PATIENTS AND METHODS This was an observational, cross-sectional study performed from November 2015 to October 2016 at the New York Eye and Ear Infirmary of Mount Sinai. Thirty-eight eyes with varying stages of POAG, 16 eyes with OHT, and 32 control eyes were imaged on a custom fundus camera modified to measure full retinal thickness fluorescence at a wavelength optimized to detect flavoprotein fluorescence (FPF). Optical coherence tomography was used to measure the retinal ganglion cell-plus layer (RGC+) thickness. Macular FPF and the ratio of macular FPF to RGC+ thickness were the primary outcome variables and were compared among the three groups using an age-adjusted linear regression model. A mixed-effects model was used to assess correlations between FPF variables and clinical characteristics. RESULTS Both macular FPF and the macular FPF/RGC+ thickness ratio were significantly increased in OHT compared with control eyes (P<0.05 and <0.01, respectively). In POAG eyes, macular FPF was not significantly increased compared with controls (P=0.24). However, the macular FPF/RGC+ thickness ratio in POAG eyes was significantly increased compared with controls (P<0.001). FPF was significantly correlated to age in POAG eyes. CONCLUSIONS Despite lacking clinical evidence of glaucomatous deterioration, OHT eyes displayed significantly elevated macular FPF, suggesting that mitochondrial dysfunction may be detected before structural changes visible on current clinical imaging. Our preliminary results suggest that macular FPF analysis may prove to be a useful tool in assessing and evaluating OHT and POAG eyes.
Single-Molecule Imaging Reveals Conformational Manipulation of Holliday Junction DNA by the Junction Processing Protein RuvA

Interactions between DNA and motor proteins regulate nearly all biological functions of DNA such as gene expression, DNA replication and repair, and transcription. During the late stages of homologous recombination (HR), the Escherichia coli recombination machinery, RuvABC, resolves the four-way DNA motifs called Holliday junctions (HJs) that are formed during exchange of nucleotide sequences between two homologous duplex DNA. Although the formation of the RuvA–HJ complex is known to be the first critical step in the RuvABC pathway, the mechanism for the binding interaction between RuvA and HJ has remained elusive. Here, using single-molecule fluorescence resonance energy transfer (smFRET) and ensemble analyses, we show that RuvA stably binds to the HJ, halting its conformational dynamics. Our FRET experiments in different ionic environments created by Mg2+ and Na+ ions suggest that RuvA binds to the HJ via electrostatic interaction. Further, while recent studies have indicated that the HR process can be ...
Intramolecular Vibrational Redistribution on the Nanosecond Time Scale: v1and 2v1Spectra of Substituted Acetylene Compounds

Intramolecular vibrational energy redistribution (IVR) continues to be a subject of wide interest to chemical physics. Most previous work has found that NR is rapid (on the time scale of 10 psec or less) whenever the density of ro-vibrational states is on the order of 100 states per wavenumber or greater. We have been studying IVR in a series of substituted acetylene compounds using optothermal detection of the acetylenic C-H stretch or its first overtone absorption spectrum in a cold (few degrees K), collimated molecular beam. This gives a resolution of 10 MHz, which allows us to study IVR on times scales up to 30 nsec. Our results show that these molecules undergo statistical NR (energy spreads over all vibrational modes) but with lifetimes of 200 psec or greater. This is clearly long enough to allow bimolecular collisions before reactions, and thus possible mode specific chemistry even in the gas phase at modest pressure. Chemical modification is allowing us to make interesting correlations between structure and relaxation lifetime.
An Approach for Enhancing Inter-processor Data Locality on Chip Multiprocessors

The tighter integration on chip multiprocessors exerts a higher pressure on off-chip accesses to the memory system. This makes minimizing the number of off-chip accesses a critical optimization goal. This paper discusses a compiler-based solution to this problem for the embedded applications that perform stencil computations. An important characteristic of this solution is that it distinguishes between the intra-processor data reuse and inter-processor data reuse. The first of these captures the data reuse that occurs across loop iterations assigned to the same processor, whereas the second one represents the data reuse that takes place across the loop iterations assigned to different processors. The proposed approach then optimizes inter-processor reuse by re-organizing the loop iterations of each processor carefully, considering how data elements are shared across processors. The goal is to ensure that the different processors access the shared data within a short period of time, so that the data can be captured in the on-chip memory space at the time of the reuse. This paper also presents an evaluation of the proposed optimization and compares it to an alternate scheme that optimizes data locality for each processor in isolation. The results obtained by applying our implementation to eight loop-intensive benchmark codes from the embedded computing domain show that our approach improves over the mentioned alternate scheme by 15.6% on average.
The Doctrine of Analogous Sensory Attributes and Qualities

This chapter discusses the doctrine of analogous sensory attributes and qualities. The Doctrine of Correspondence among sensory attributes states that certain dimensions of sensory experience are similar or even identical in different modalities. Sensations of taste and smell are frequently confused, which may, in part, reflect the fact that they are frequently fused; it is a noteworthy characteristic of odors and tastes to merge into flavors whose olfactory and gustatory components may at times be difficult to distinguish. It is interesting to note that sensations produced by repetitive stimulation of the skin can also vary in phenomenal extent, and they do so in ways that are remarkably similar to sensations of sound. The present concern is not with the entire province of sound symbolism, but with a subset of the counties that it comprises, namely, with the ways that speech sounds can convey sensory meanings, whether visual, tactile, gustatory, or olfactory.
Molecular farming of industrial proteins from transgenic maize.

Recombinant egg white avidin and bacterial B-glucuronidase (GUS) from transgenic maize have been commercially produced. High levels of expression were obtained in seed by employing the ubiquitin promoter from maize. The recombinant proteins had activities that were indistinguishable from their native counterparts. We have illustrated that downstream activities in the production of these recombinant proteins, such as stabilizing the germplasm and processing for purification, were accomplished without any major obstacles. Avidin (A8706) and GUS (G2035) are currently marketed by Sigma Chemical Co.
TCT-46 Mitral Valve Gradient, Heart Failure Admissions and One Year Mortality Following MitraClip Repair in 5,378 Patients: Results from the ACC/STS TVT Registry

The MitraClip device reduces mitral regurgitation (MR) and improves outcomes. With leaflet repair, the diastolic orifice is reduced and increased mitral valve gradients (MVG) can develop. Whether residual MVG affects outcomes was explored. MitraClip cases from 11/3/13-6/30/16 from the TVT Registry
The Role of Astrocytes in Neurotransmitter Uptake and Brain Metabolism

Termination of synaptic transmission relies on neurotransmitter diffusion and removal from the extracellular space by specific molecules called transporters, abundantly expressed in astrocytes. Here we describe the biophysical mechanisms of neurotransmitter transport across the astrocyte membrane and the biochemical pathways that supply energy to these cells. These findings indicate that astrocytes are crucial regulators of brain activity, due to their ability to shape synaptic transmission and control the energy budget of the entire brain.
Epidural abscess resulting from traumatic esophageal rupture secondary to a flexion-extension injury

An epidural abscess developed several weeks after a traumatic esophageal rupture secondary to a reported flexion-extension injury in a restrained back seat passenger in a motor vehicle accident. Chest radiograph and an Indium study suggested the possibility of a posterior mediastinal abscess. Chest computed tomography (CT) also noted epidural abscess and osteomyelitis, which were confirmed by magnetic resonance imaging (MRI). Diagnosis was delayed significantly by underinterpretation of both chest and CT findings. Obvious positive findings (lower lobe infiltrate on chest radiograph and posterior mediastinal abscess on CT) were noted, but more subtle and very important findings of superior mediastinal widening and extra pulmonary gas bubbles on the chest radiograph and extradural disease displacing the spinal cord on CT were not described. We can find no previously reported case of esophageal rupture associated with flexion-extension injury of the neck. It is also extremely rare for esophageal rupture to remain asymptomatic for more than several hours.
Sombras da dúvida: a difícil incorporação da ciência de identificação na determinação legal da paternidade no Brasil

O surgimento dos testes de DNA para determinacao de paternidade, nos anos 1980, foi recebida com grande entusiasmo nos tribunais brasileiros. No entanto, ao longo das ultimas duas decadas, a doutrina juridica e a jurisprudencia brasileiras tem rejeitado cada vez mais a prova de DNA como condicao sine qua non para os casos de paternidade. Testes de paternidade de DNA geraram inumeros litigios que contestaram a prova biologica com o argumento de que a paternidade e principalmente “socioafetiva”. Os principais especialistas em direito de familia descrevem essa nova concepcao de paternidade como resultado das disposicoes “revolucionarias” da Constituicao Federal de 1988, que reconhece a “pluralidade” das formas familiares na sociedade moderna e garante direitos iguais para todas as criancas. Sem negar a importância de novos principios constitucionais, mostramos que os novos conceitos juridicos da paternidade representam menos uma mudanca de paradigma do que a continuacao de antigas tensoes historicas entre concepcoes biologicas e socioculturais da familia e da identidade. Neste artigo, exploramos o desenvolvimento da tipologia biologica e, posteriormente, genetica no Brasil, ambas ligadas aos campos da criminologia e da ciencia racial. Nossa analise sugere que as tecnicas de identificacao biologica, por mais sofisticadas ou precisas que fossem, eram meios ineficazes para estabelecer a identidade, seja da personalidade individual, como no caso da paternidade, ou da composicao nacional. Em vez disso, elas foram incorporadas como metodos suplementares para as decisoes legais, sociais e culturais complexas em torno das familias.
Phenolic Oxidation Using H2O2 via in Situ Generated para-Quinone Methides for the Preparation of para-Spiroepoxydienones

Phenols are attractive starting materials for the preparation of highly substituted cyclohexane rings via dearomative processes. Herein we report an efficient preparation of dearomatized 1-oxaspiro...
Efficacy of therapeutic plasma exchange in reducing the incidence of recurrent pancreatitis related to familial chylomicronemia

Background Familial chylomicronemia syndrome (FCS) is caused by a genetic defect in triglyceride (TG) metabolism that leads to severe hypertriglyceridemia, which in turn is associated with multiple morbidities and may cause severe pancreatitis that is both recurrent and progressive. Management of hypertriglyceridemia in FCS is challenging, as both dietary and medical interventions are often ineffective. Therapeutic plasma exchange (TPE) has been shown to rapidly decrease circulating levels of chylomicrons and TGs in patients presenting with acute hypertriglyceridemic-associated pancreatitis. Conversely, limited evidence exists to suggest that prophylactic use of TPE is effective at preventing recurrence of acute pancreatitis. Case report Herein, we report our experience with the use of chronic, prophylactic TPE to reduce the incidence of recurrent acute pancreatitis in a patient with FCS.