cssi/SciSciGPT-SciSciNet huggingface dataset:
Fingolimod: A Novel Immunosuppressant for Multiple Sclerosis

Objective:To review the pharmacology, pharmacokinetics, efficacy, and safety of fingolimod, a novel immune modulator.Data Sources:Information was obtained through a MEDLINE search (1966–February 2007) and from published abstracts. Search terms included fingolimod, FTY720, FTY-720, and sphlngosine-1-phosphate receptor agonist.Study Selection and Data Extraction:All English-language studies and abstracts pertaining to fingolimod were considered for inclusion. Preference was given to human data.Data Synthesis:Fingolimod Is the first in a new class of immune modulators known as the sphingosine-1-phosphate receptor agonists. It is administered orally once dairy and causes a dose-related reduction in the number ot circulating lymphocytes by preventing their egress from secondary lymph organs, but it does not alter T-cell activation or proliferation. Bradycardia and lymphopenia are the most common adverse effects. Clinical trials have evaluated the efficacy of fingolimod in renal transplantation and multiple scl...
Nest Guarding in Chesapeake Bay Bald Eagles

Abstract As Bald Eagle (Haliaeetus leucocephalus) populations approach carrying capacity in the Chesapeake Bay, competition for breeding territories appears to be intensifying. Frequent territorial interactions may force breeders to adjust nest-guarding behavior. We examined nest-guarding behaviors at active Bald Eagle nests in the lower Chesapeake Bay during the nesting season (2012 and 2013). Guarding coverage was 13.7 ± 4.2% of total observation time during the pre-laying period, 6.8 ± 2.2% of observation time in the incubation period, and 26.3 ± 3.2% of observation time in the nestling period. Females were present in the nest area for 80.0 ± 2.7% of the nestling period. Although males were present only 51.2 ± 2.8% of the nestling period, male breeders guarded nests twice as often as females. Adults guarded most often from perches in adjacent trees and within 25 m of the nest. If increasing rates of conspecific interactions force males to allocate more time to nest guarding, a tradeoff may occur, with ...
Integrated Inertial Navigation System/Global Positioning System (INS/GPS) for automatic space return vehicle

A digital GN&C system that automatically returns a space vehicle from orbit to a precision touchdown/landing is described. It is demonstrated that a capsule or lifting body manned return vehicle (MRV) with integrated INS/GPS (inertial navigation system/global positioning system) provides a highly autonomous and automatic deorbit, entry, and precision landing capability. Simulation results are used to demonstrate automatic MRV landing feasibility using absolute GPS for a vertically landing capsule vehicle and the feasibility of using integrated differential GPS/INS to provide the accuracy for a lifting body to perform a safe runway landing without needing TACAN (tactical air navigation) or microwave landing system (MLS) navigational aids. Testing of an advanced system using differential GPS/INS is expected to provide an extensive database on GPS/INS system accuracies and to demonstrate a lower cost alternative to TACAN, DME (distance measuring equipment), and MLS navigation aids. >
Cape Verdean identity in a land of Black and White

Cape Verde is an island group off the African coast with a history of slavery. Its residents having both European and African ancestors, they consider themselves a mixed-race people. Residents of t...
Using Ultrasound to Identify the Central Venous Catheter Tip in the Superior Vena Cava

In this case series of 5 patients, ultrasound was used to verify the position of the central venous catheter in the superior vena cava using the supraclavicular approach. In all patients, the position of the catheter in the superior vena cava could be verified and the results compared with a postprocedure chest X ray.
Bovine herpesvirus 4 BORFE2 protein inhibits Fas- and tumor necrosis factor receptor 1-induced apoptosis and contains death effector domains shared with other gamma-2 herpesviruses.

Fas- and tumor necrosis factor receptor 1 (TNFR1)-induced apoptosis is mediated by the interaction of FADD with caspase-8. Here, we report that the bovine herpesvirus 4 (BHV4) BORFE2 gene encodes a protein that inhibits Fas- and TNFR1-induced apoptosis and contains death effector domains (DEDs). Using the yeast two-hybrid system, we found that the BORFE2 protein interacts with the prodomain of caspase-8. Furthermore, we show that BHV4 BORFE2 is a member of a family of DED-containing proteins that includes other gamma-2 herpesviruses, such as Kaposi9s sarcoma-associated herpesvirus and herpesvirus saimiri.
Progression of Coronary Artery Calcification in Patients Taking Alendronate for Osteoporosis

Abstract Rationale and Objectives As with their actions on bone, bisphosphonates may play a role in coronary artery calcification (CAC) by inhibiting calcium resorption from plaque. The objective of this study was to determine whether the osteoporosis treatment agent alendronate accelerates the rate of CAC. Materials and Methods The study was a pilot comparative analysis of 56 alendronate-treated patients with osteoporosis compared with 56 control subjects matched for age, sex, risk factors, and CAC scores and with a reference cohort that included 213 control subjects. Patients received alendronate sodium (10 mg daily) for a mean of 24 months and underwent annual assessment of CAC with electron-beam computed tomography and bone mineral density with dual x-ray absorptiometry. The principal outcome measure was the rate of change in CAC score in patients and control populations. Results There was significant progression of CAC in both alendronate-treated and matched-control groups (paired t test, P = .004 and .006, respectively) but no difference in the rates of CAC progression between the alendronate-treated patients and either the matched or reference control cohort. Conclusions This small pilot study indicates that oral alendronate administration does not accelerate the rate of CAC, but a larger cohort should be studied to confirm these findings.
Compressed sensing in photoacoustic tomography in vivo

The data acquisition speed in photoacoustic computed tomography (PACT) is limited by the laser repetition rate and the number of parallel ultrasound detecting channels. Reconstructing an image with fewer measurements can effectively accelerate the data acquisition and reduce the system cost. We adapt compressed sensing (CS) for the reconstruction in PACT. CS-based PACT is implemented as a nonlinear conjugate gradient descent algorithm and tested with both phantom and in vivo experiments.
Some observations on the relative dehydration rates of negative stains and biological objects.

SUMMARY In an attempt to explain the possible mechanism of negative staining a series of experiments are described in which the relative drying rates of two commonly used negative stains and two biological specimens were measured. Turnip yellow mosaic virus and phosphatidyl-L-serine were used to represent biological specimens and their dehydration rates were measured against potassium phosphotungstate or ammonium molybdate after tritiated water had been added to the solutions containing protein, lipid, negative stains or mixtures of both. From these experiments it was possible to demonstrate that the protein or lipid retains water for longer periods than the negative-staining material. The results are in agreement with an earlier proposal that some negative stains set in a rigid ‘glass’ and thus preserve the biological structures before the latter are completely dehydrated either in air on the supporting films, or when finally dried in the vacuum of the electron microscope.
Construction of Salmonella strains with both antigen O4 (of group B) and antigen O9 (of group D).

A Salmonella live vaccine causing both O4- and O9-specific immune responses would be of use, but no reported Salmonella serotype has both of these O antigens. Constructed Salmonella typhimurium strains with an rfb (O-antigen-specifying) gene cluster of type D in the chromosome and one of type B in an F'-rfb+ factor, and those with the reverse combination reacted strongly with both anti-O4 (and anti-O5) and anti-O9 sera and, if they carried recA, could be maintained in this state by growth conditions selective for retention of the F' factor. One of the two B.rfb+ gene clusters of a (P22-lysogenic) S. typhimurium strain with a tandem duplication of a chromosomal segment including hisD and B.rfb+ was replaced (by transduction) by a D.rfb+ gene cluster; the resulting strain was O1+ O4+ O5+ O9+ and stable as such after being made recA. A stable O4+ O9+ derivative of a virulent S. enteritidis (O-group D) strain was made by transducing into it first the join point of an appropriate tandem duplication strain, together with the adjacent B.rfb+ gene cluster, and then srl::Tn10 recA.
Aerosol–cloud drop concentration closure in warm cumulus

Our understanding of the activation of aerosol particles into cloud drops during the formation of warm cumulus clouds presently has a limited observational foundation. Detailed observations of aerosol size and composition, cloud microphysics and dynamics, and atmospheric thermodynamic state were collected in a systematic study of 21 cumulus clouds by the Center for Interdisciplinary Remotely-Piloted Aircraft Studies (CIRPAS) Twin Otter aircraft during NASA's Cirrus Regional Study of Tropical Anvils and Cirrus Layers–Florida Area Cirrus Experiment (CRYSTAL-FACE). An “aerosol-cloud” closure study was carried out in which a detailed cloud activation parcel model, which predicts cloud drop concentration using observed aerosol concentration, size distribution, cloud updraft velocity, and thermodynamic state, is evaluated against observations. On average, measured droplet concentration in adiabatic cloud regions is within 15% of the predictions. This agreement is corroborated by independent measurements of aerosol activation carried out by two cloud condensation nucleus (CCN) counters on the aircraft. Variations in aerosol concentration, which ranged from 300 to 3300 cm^(−3), drives large microphysical differences (250–2300 cm^(−3)) observed among continental and maritime clouds in the South Florida region. This is the first known study in which a cloud parcel model is evaluated in a closure study using a constraining set of data collected from a single platform. Likewise, this is the first known study in which relationships among aerosol size distribution, CCN spectrum, and cloud droplet concentration are all found to be consistent with theory within experimental uncertainties much less than 50%. Vertical profiles of cloud microphysical properties (effective radius, droplet concentration, dispersion) clearly demonstrate the boundary layer aerosol's effect on cloud microphysics throughout the lowest 1 km of cloud depth. Onboard measurements of aerosol hygroscopic growth and the organic to sulfate mass ratio are related to CCN properties. These chemical data are used to quantify the range of uncertainty associated with the simplified treatment of aerosol composition assumed in the closure study.
Experiments with fast Fourier transform, linear predictive and cepstral coefficients in dysarthric speech recognition algorithms using hidden Markov model

In this study, a hidden Markov Model was constructed and conditions were investigated that would provide improved performance for a dysarthric speech (isolated word) recognition system. The speaker dependant system was intended to act as an assistive/control tool. A small size vocabulary spoken by three cerebral palsy subjects was chosen. Fast Fourier transform, linear predictive, and Mel frequency cepstral coefficients extracted from data provided training input to several whole-word hidden Markov model configurations. The effect of model structure, number of states, and frame rates were also investigated. It was noted that a 10-state ergodic model using 15 msec frames was better than other configurations. Furthermore, it was found that a Mel cepstrum based model outperformed a fast Fourier transform and linear prediction based model. The system offers effective and robust application as a rehabilitation and/or control tool to assist dysarthric motor impaired individuals.
Site-specific modification of Shigella flexneri virF mRNA by tRNA-guanine transglycosylase in vitro

Shigella flexneri is an enteropathogen responsible for severe dysentery in humans. VirF is a key transcriptional regulator that activates the expression of the downstream virulence factors required for cellular invasion and cell-to-cell spread of this pathogen. There are several environmental factors that induce the translation of VirF including temperature, pH, osmolarity and post-transcriptional RNA modification. Durand and colleagues (vacC, a virulence-associated chromosomal locus of Shigella flexneri, is homologous to tgt, a gene encoding tRNA-guanine transglycosylase of Escherichia coli K-12. J. Bacteriol., 176, 4627–4634) have demonstrated a correlation between VirF and tRNA-guanine transglycosylase (TGT), which catalyzes the exchange of the hypermodified base queuine for the guanine in the wobble position of certain tRNAs. They characterized tgt- mutant S. flexneri strains in which the translation of VirF is markedly reduced and the bacteria are unable to invade host cells. Although the function of TGT is to modify tRNA, we report that the virF mRNA is recognized by the Escherichia coli TGT (99% identity to the S. flexneri TGT) in vitro. Further, we show that this recognition results in the site-specific modification of a single base in the virF mRNA. In the context of previous reports that small molecule binding motifs (‘riboswitches’) in mRNAs modulate mRNA conformation and translation, our observations suggest that TGT may modulate the translation of VirF by base modification of the VirF encoding mRNA.
Behavioral effects on rats of high strength magnetic fields generated by a resistive electromagnet

Abstract It has been reported previously that exposure to static high magnetic fields of 7 T or above in superconducting magnets has behavioral effects on rats. In particular, magnetic field exposure acutely but transiently suppressed rearing and induced walking in tight circles; the direction of circular locomotion was dependent on the rats' orientation within the magnet. Furthermore, when magnet exposure was paired with consumption of a palatable, novel solution, rats acquired a persistent taste aversion. In order to confirm these results under more controlled conditions, we exposed rats to static magnetic fields of 4 to 19.4 T in a 189 mm bore, 20 T resistive magnet. By using a resistive magnet, field strengths could be arbitrary varied from − 19.4 to 19.4 T within the same bore. Rearing was suppressed after exposure to 4 T and above; circling was observed after 7 T and above. Conditioned taste aversion was acquired after 14 T and above. The effects of the magnetic fields were dependent on orientation. Exposure to + 14 T induced counter-clockwise circling, while exposure to − 14 T induced clockwise circling. Exposure with the rostral–caudal axis of the rat perpendicular to the magnetic field produced an attenuated behavioral response compared to exposure with the rostral–caudal axis parallel to the field. These results in a single resistive magnet confirm and extend our earlier findings using multiple superconducting magnets. They demonstrate that the behavioral effects of exposure within large magnets are dependent on the magnetic field, and not on non-magnetic properties of the machinery. Finally, the effects of exposure to 4 T are clinically relevant, as 4 T magnetic fields are commonly used in functional MRI assays.
Theory of Planned Behavior and Multivitamin Supplement Use in Caucasian College Females

The objective of this study was to identify predictors of the use of multivitamin supplements (MVS) among Caucasian college females utilizing the Theory of Planned Behavior (TPB). Variables of the TPB and the self-reported use of multivitamin supplements were measured by two separate surveys within 1 week with a convenience sample of 96 Caucasian college student females. Two attitudinal beliefs and one control belief significantly predicted behavioral intention to use multivitamin. A belief that taking multivitamin supplements helps to feel and look good was the most important predictor of the use of multivitamin supplements. Editors’ Strategic Implications: Findings from this study, although in need of replication, suggest that prevention campaigns would be more successful if messages used to reach these females were consistent with perceived beliefs regarding benefits of using MVS. More broadly, TPB appears to offer a useful framework for understanding or predicting behavior based on psychological constructs theorized to influence behavior.
The Rb7 Matrix Attachment Region Increases the Likelihood and Magnitude of Transgene Expression in Tobacco Cells: A Flow Cytometric Study

Many studies in both plant and animal systems have shown that matrix attachment regions (MARs) can increase expression of transgenes in whole organisms or cells in culture. Because histochemical assays often indicate variegated transgene expression, a question arises: Do MARs increase transgene expression by increasing the percentage of cells expressing the transgene (likelihood), by increasing the level of expression in expressing cells (magnitude), or both? To address this question, we used flow cytometry to measure green fluorescent protein (GFP) expression in individual tobacco (Nicotiana tabacum) cells from lines transformed by Agrobacterium tumefaciens. We conclude that MAR-mediated overall increases in transgene expression involve both likelihood and magnitude. On average, cell lines transformed with the Rb7 MARcontaining vector expressed GFP at levels 2.0- to 3.7-fold higher than controls. MAR lines had fewer nonexpressing cells than control lines (10% versus 45%), and the magnitude of GFP expression in expressing cells was greater in MAR lines by 1.9- to 2.9-fold. We also show that flow cytometry measurements on cells from isogenic lines are consistent with those from populations of independently transformed cell lines. By obviating the need to establish isogenic lines, this use of flow cytometry could greatly simplify the evaluation of MARs or other sequence elements that affect transgene expression.
Performativitat i aporia derridianes en la creació del món segons Hasday Cresques

L’objectiu d’aquest article es fer llum a la complexa i ambigua explicacio sobre la creacio del mon que proposa Hasday Cresques —un rabi, metge i filosof jueu nascut a Barcelona al segle xiv— a Or Adonay (La llum del Senyor). Harry A. Wolfson (1953) analitza com Cresques intenta conciliar la doctrina de l’emanacio, d’arrel plotiniana, amb la de la creacio del no-res, d’origen biblic. Es a dir, les dues explicacions, d’entrada excloents, que filosofs i teolegs jueus, musulmans i cristians empraven per explicar l’origen del mon. Al nostre entendre, Cresques i, en menys mesura, Wolfson sembla que passen per alt que l’esmentada conciliacio nomes es pot dur a terme a costa de desembocar en una serie de contradiccions logiques vinculades a la voluntat divina i a la temporalitat. En aquest article, les assenyalem. Tambe hi mostrem com l’aporia en la qual desemboca l’argumentacio de Cresques no es fruit de la seva manca de destresa logica, sino del fet que esta intuint, sense encara disposar de les eines conceptuals per enfrontar-s’hi, que el concepte de creacio del mon es aporetic perque produeix les seves propies condicions de possibilitat. Explorem aquesta idea amb l’ajut de les reflexions que Jacques Derrida fa d’altres fenomens performatius aporetics.
Detector design and complexity analysis for cooperative communications in intersymbol interference fading channels

The area of cooperative communications has recently attracted lots of research interest because of the potential benefit of increased spatial diversity. In this paper, we study the detector design for cooperative communications in intersymbol interference (ISI) channels. A novel system framework employing nonorthogonal amplify-and-forward half-duplex relays through ISI channels is introduced.We focus on detector design and first consider an optimal detector that consists of a whitening filter and a maximum-likelihood sequence estimator (MLSE). However, such an optimal detector embedded with Viterbi algorithm has practical issues of high complexity if the relay period is long. Consequently, we adopt a multitrellis Viterbi algorithm (MVA) that reduces the complexity significantly but still achieves near-optimal performance. Simulation results demonstrate the performance of both the optimal and near-optimal detector designs.
Perceived Stigma, Social Support, and Depression

This short-term longitudinal study examined the effect of perceived stigma on perceived support availability, negative interactions, and depression. Two interviews were conducted over a 4-month period with 109 parents of special needs children. Cross-sectional analyses revealed that perceived stigma was consistently related to less perceived support availability from respondents’ parents (i.e., the child’s grandparents), more negative interactions with spouse and grandparents, and increased depressive symptomatology. Longitudinal analyses indicated that perceived stigma increased negative interactions with grandparents as well as the respondent’s depression over time. Structural equation modeling also suggested that perceived support availability of grandparents partially mediated the longitudinal relation between perceived stigma and depression. Findings highlight the need for future studies to examine the complex relation between stressor dimensions, social support processes, and mental health.
Argonaute2 Is Essential for Mammalian Gastrulation and Proper Mesoderm Formation

Mammalian Argonaute proteins (EIF2C1−4) play an essential role in RNA-induced silencing. Here, we show that the loss of eIF2C2 (Argonaute2 or Ago2) results in gastrulation arrest, ectopic expression of Brachyury (T), and mesoderm expansion. We identify a genetic interaction between Ago2 and T, as Ago2 haploinsufficiency partially rescues the classic T/+ short-tail phenotype. Finally, we demonstrate that the ectopic T expression and concomitant mesoderm expansion result from disrupted fibroblast growth factor signaling, likely due to aberrant expression of Eomesodermin. Together, these data indicate that a factor best known as a key component of the RNA-induced silencing complex is required for proper fibroblast growth factor signaling during gastrulation, suggesting a possible micro-RNA function in the formation of a mammalian germ layer.
An empirical evaluation of a testing and debugging methodology for Excel

Spreadsheets are one of the most commonly used types of programs in the world, and it is important that they be sufficiently dependable. To help end users who create spreadsheets do so more reliably, we have created a testing and debugging methodology and environment for use in spreadsheets, known as the WYSIWYT methodology. Our prior experiments with WYSIWYT show that users can utilize it to ensure that their spreadsheets are more dependable, but these experiments to date have considered only an unfamiliar prototype spreadsheet environment, and have not involved spreadsheet creation tasks. In this work we conducted a controlled experiment that addresses these limitations. The results of this study indicate that the use of WYSIWYT did not affect the correctness of spreadsheets created by users, but it did significantly reduce the amount of effort required to create them. Further, the subjects' evaluation of the help provided by WYSIWYT was very positive. Our results provide several insights into the use of the WYSIWYT methodology by end users.
Optimal Thresholds in Accounting Recognition Standards

This paper investigates the design of recognition thresholds in accounting standards. In statistics, a threshold classi.es evidence to balance two types of recognition errors weighted by their respective costs to a decision maker. In accounting recognition standards, a threshold induces firms to respond strategically and thus affects the very distribution of evidence the threshold classi.es. With this strategic effect, the optimal recognition threshold is determined by not only the decision maker’s loss function but also the transaction’s features. We compare the optimal threshold’s properties under the statistical and strategic approaches, provide their respective empirical predictions, and discuss the limitations of using a statistical approach to guide accounting standard setting.
Reproductive Factors and Risk of Intermediate- or High-Grade B-Cell Non-Hodgkin’s Lymphoma in Women

PURPOSE: The incidence rates of non-Hodgkin’s lymphoma (NHL) unrelated to human immunodeficiency virus infection are lower for women than for men; yet, few factors have been identified that may account for this difference in risk. NHL is difficult to study epidemiologically because this disorder represents a group of malignancies that differ in terms of morphologic presentation, immunologic features, genetic characteristics, prognosis, and etiology. PATIENTS AND METHODS: We conducted a population-based case-control study in women to determine whether reproductive factors or hormonal exposures might be related to the risk of high- or intermediate-grade B-cell NHL. We interviewed 177 female residents of Los Angeles County who were diagnosed with high- or intermediate-grade B-cell NHL between 1989 and 1992; each case patient was individually matched on age and race to a control subject who lived in her neighborhood. RESULTS: Women who had used oral contraceptives had significantly lower risk of intermediate-...
Exploring Family Group Counseling

Interest in family group counseling by social workers has been accelerating rapidly. In the last few years, many articles and books have been written on the subject. Even a cursory review of these publications quickly reveals semantic confusions and methodological confoundations. Many so cial workers have accepted, seemingly with out question, methods that are alien to their own professional frame of reference and have incorporated them into their practice. The purpose of this article is to review the current thinking in family group counsel ing, to compare methods, and to state a social work frame of reference.
Thermal trauma: therapeutic achievements and investigative horizons.

It is important to recognize that 80 per cent of burn injuries are preventable accidents. In no other area of illness or injury is education of the general public so severely lacking. Without relaxing efforts toward improving burn care, it is essential that prevention be given still greater emphasis.
Germination of Spores of Glomus Macrocarpus (Endogonaceae) After Passage Through a Rodent Digestive Tract

(1976). Germination of Spores of Glomus Macrocarpus (Endogonaceae) After Passage Through a Rodent Digestive Tract. Mycologia: Vol. 68, No. 2, pp. 433-436.
Preoperative psychosocial predictors of hospital length of stay after heart transplantation.

The effect of psychosocial factors on hospital length of stay (LOS) after heart transplantation has not been reported. This study examines relationships between preoperative psychosocial variables and LOS and identifies preoperative psychosocial predictors of LOS after transplant. A nonrandom sample
Whole-Genome Sequencing (WGS) and the Changing Landscape of Bacterial Genetics

Shotgun sequencing of Haemophilus influenzae in 1995 is traditionally considered to be the dawn of the modern era of whole genome sequencing (WGS). In 2004, the introduction of pyrosequencing based (454/Roche) massively parallel sequencing (MPS) brought about the second wave of advances in WGS. The advent of NextGen sequencing technologies is making great impacts in many areas of research and is already changing the landscape of bacterial genetics as well. Genetic mapping of mutations in bacteria is an arduous process taking anywhere from months to years. Because of the availability of rapid and low-cost WGS technologies, mapping mutations directly without resorting to traditional genetic approaches is now feasible even in bacteria for which genetic mapping systems are not available.
The Effects of Naltrexone on Neural Responses to Methamphetamine Cues

Background: No medications are approved by the FDA for the treatment of methamphetamine use disorders; yet, preclinical and clinical evidence advances naltrexone as a promising candidate. This dissertation investigated the effects of naltrexone on functional magnetic resonance imaging (fMRI) measures of functional connectivity during methamphetamine cue processing and subjective craving for methamphetamine.Methods: A final sample of 23 non-treatment seeking individuals with methamphetamine use disorders (74% male, mean age=34.70 [SD=8.95]) were enrolled within a randomized, placebo controlled, within-subject design and underwent two blood-oxygen-level dependent (BOLD) methamphetamine cue-reactivity paradigms following three days of naltrexone treatment (50mg) and matched time for placebo. fMRI analyses tested naltrexone-induced differences in BOLD activation associated with methamphetamine and control cues, resting-state cerebral blood flow (CBF), and functional connectivity (using psychophysiological interaction analysis) during methamphetamine cue processing. Results: Analyses revealed that (1) the novel methamphetamine cues task employed was successful in eliciting cue-induced craving and relevant regional activation, (2) greater subjective methamphetamine craving is related to enhanced recruitment of prefrontal regions, (3) naltrexone moderates methamphetamine cue-reactivity in sensorimotor regions, (4) the BOLD results are not a reflection of CBF changes induced by naltrexone, (5) reduced activation of sensorimotor regions during methamphetamine cue processing by naltrexone is related to functional connectivity of dorsal striatum, ventral tegmental area (VTA), periaqueductal gray, and precuneus with visual, sensory, and motor-related regions, (6) naltrexone enhances dorsal striatum, VTA, and sensorimotor region functional connectivity with the frontal cortex during methamphetamine cues processing , and (7) naltrexone weakens the associations between subjective craving and precuneus functional connectivity with sensorimotor regions and strengthens the associations between subjective craving and dorsal striatum and precuneus connectivity with frontal regions during methamphetamine cue processing, as compared to placebo. Conclusions: The results of this study provide the first evidence of naltrexone-induced changes in BOLD measures of methamphetamine cue-induced craving. The results suggest that naltrexone may be functioning to reduce the salience of the methamphetamine cues by reducing sensorimotor processing and integration, and by engaging greater frontal regulation of salience attribution via pathways linking the dorsal striatum, midbrain, and precuneus to frontal, dorsal striatal, and sensorimotor regions during cue processing.
Rennes and Rehabilitation (1899–1906)

The cruiser Sfax arrived off the coast of France on 30 June 1899 bearing the most famous prisoner the world had known since Napoleon’s exile on Saint Helena. The case of the bordereau had become an Affair followed by millions from Moscow to Melbourne, from high aristocrats to poor peasants, yet the prisoner himself knew almost nothing about it. ‘I remained in 1894, with the bordereau the only document in the dossier’, Dreyfus later wrote, ‘I believed in the good faith of General Boisdeffre, I believed in a head of state, Felix Faure, who was wholly concerned with justice and truth.’ Boisdeffre had resigned in the aftermath of Henry’s suicide nearly a year before, while Faure had been dead four months. ‘I believed that people had recognized their error, I was expecting to find my family, and beyond them my comrades who would be awaiting me with open arms, with tears in their eyes.’
Changes in sarcomere lengths of the human vastus lateralis muscle with knee flexion measured using in vivo microendoscopy

Abstract Sarcomeres are the basic contractile units of muscle, and their lengths influence muscle force-generating capacity. Despite their importance, in vivo sarcomere lengths remain unknown for many human muscles. Second harmonic generation (SHG) microendoscopy is a minimally invasive technique for imaging sarcomeres in vivo and measuring their lengths. In this study, we used SHG microendoscopy to visualize sarcomeres of the human vastus lateralis, a large knee extensor muscle important for mobility, to examine how sarcomere lengths change with knee flexion and thus affect the muscle׳s force-generating capacity. We acquired in vivo sarcomere images of several muscle fibers of the resting vastus lateralis in six healthy individuals. Mean sarcomere lengths increased (p=0.031) from 2.84±0.16 μm at 50° of knee flexion to 3.17±0.13 μm at 110° of knee flexion. The standard deviation of sarcomere lengths among different fibers within a muscle was 0.21±0.09 μm. Our results suggest that the sarcomeres of the resting vastus lateralis at 50° of knee flexion are near optimal length. At a knee flexion angle of 110° the resting sarcomeres of vastus lateralis are longer than optimal length. These results show a smaller sarcomere length change and greater conservation of force-generating capacity with knee flexion than estimated in previous studies.
Unlocking the Neurogenic Potential of Mammalian Müller Glia.

Muller glia (MG) are the primary support cells in the vertebrate retina, regulating homeostasis in one of the most metabolically active tissues. In lower vertebrates such as fish, they respond to injury by proliferating and reprogramming to regenerate retinal neurons. In mammals, MG may also react to injury by proliferating, but they fail to initiate regeneration. The barriers to regeneration could be intrinsic to mammalian MG or the function of the niche that cannot support the MG reprogramming required for lineage conversion or both. Understanding these mechanisms in light of those being discovered in fish may lead to the formulation of strategies to unlock the neurogenic potential of MG and restore regeneration in the mammalian retina.
A Study of the Growth Patterns of Breast Carcinoma Using 3D Reconstruction: A Pilot Study

Lumpectomy with microscopically clear margins is a safe and effective approach for surgical management of breast carcinoma. Margins are positive for tumor in 18–50% of lumpectomies, as it is not possible to accurately determine the shape or microscopic borders of a tumor preoperatively or intraoperatively. We examined the 3D microanatomy and growth patterns of common breast carcinoma subtypes to provide guidance for lumpectomy surgery. Prospective consent was obtained for the use of excess tissue from patients undergoing lumpectomy or mastectomy for breast carcinoma. Tissue blocks from nine breast carcinomas were serially sectioned. Hematoxylin and eosin-stained slides at 100 μm intervals were scanned using a Nanozoomer (Hamamatsu, Japan) microscopic-resolution scanner. Three-dimensional reconstructions of tumors were created from scanned images using Reconstruct, open-access software. Breast carcinoma subtypes demonstrated characteristic growth patterns within breast tissue, which may have implications for lumpectomy surgery. Invasive ductal carcinomas showed a spherical shape, with a spiculated surface representing tumor cells infiltrating into surrounding parenchyma. Ductal carcinoma in situ appeared to spread along the duct system, creating dilated, tortuous, tumor-filled ducts. The invasive lobular carcinomas examined had a haphazard, linear, infiltrative growth pattern, different from the shape seen in ductal carcinomas. Our preliminary work suggests that invasive ductal and invasive lobular carcinomas appear to have distinct growth patterns in three dimensions and ductal carcinoma in situ appears to grow in a linear fashion along the duct network. The microanatomy studies described have the potential to guide refinements in breast lumpectomy technique.
Valveless pumping mechanics of the embryonic heart during cardiac looping: Pressure and flow through micro-PIV

Abstract Cardiovascular development is influenced by the flow-induced stress environment originating from cardiac biomechanics. To characterize the stress environment, it is necessary to quantify flow and pressure. Here, we quantify the flow field in a developing zebrafish heart during the looping stage through micro-particle imaging velocimetry and by analyzing spatiotemporal plots. We further build upon previous methods to noninvasively quantify the pressure field at a low Reynolds number using flow field data for the first time, while also comparing the impact of viscosity models. Through this method, we show that the atrium builds up pressure to ~0.25 mmHg relative to the ventricle during atrial systole and that atrial expansion creates a pressure difference of ~0.15 mmHg across the atrium, resulting in efficient cardiac pumping. With these techniques, it is possible to noninvasively fully characterize hemodynamics during heart development.
Bayesian Markov games with explicit finite-level types

In impromptu or ad hoc settings, participating players are precluded from precoordination. Subsequently, each player's own model is private and includes some uncertainty about the others' types or behaviors. Harsanyi's formulation of a Bayesian game lays emphasis on this uncertainty while the players each play exactly one turn. We propose a new game-theoretic framework where Bayesian players engage in a Markov game and each has private but imperfect information regarding other players' types. Consequently, we construct player types whose structure is explicit and includes a finite level belief hierarchy instead of utilizing Harsanyi's abstract types and a common prior distribution. We formalize this new framework and demonstrate its effectiveness on two standard ad hoc teamwork domains involving two or more ad hoc players.
P238 Working memory enhancement in young and older adults using rTMS

Question A great deal of the cognitive decline due to aging can be explained by decline in working memory (WM). Our previous work has demonstrated a TMS paradigm which has enhanced WM performance in young adults and has remediated WM deficits in the context of sleep deprivation. Methods Here, following an initial fMRI session to obtain individual cortical targets, two groups, older adults ( N = 17) and younger adults ( N = 17), performed a delayed-match-to-sample WM task while 5 Hz rTMS was applied during the 7 s delay period in the task. As part of a repeated measures design, across four TMS sessions each subject received active or sham rTMS, targeted to either left lateral occipital complex (LOC) or left premotor cortex (PMC) using individualized fMRI targeting. Results There were Site × TMS interactions for both %Correct and reaction time (RT) ( p p p Conclusions The opposing results of PMC stimulation prior to task onset or during the delay period demonstrate the sensitivity of task phase as to when to apply TMS to produce cognitive enhancement. Our interpretation of the results is that TMS to PMC during the delay period most likely disrupted ongoing verbal rehearsal, a phonological loop process known to rely on this region, while stimulation prior to such processing augmented that processing in young adults. For LOC, TMS during the delay period likely enhanced processing occurring during the test phase of the WM task in both age groups. Processing in the LOC may act as part of the visuo-spatial scratchpad, which, along with the phonological loop, are two components of WM suggested by Baddeley in his model of WM. These results encourage our continuing work to use TMS to remediate WM deficits found with aging.
Mechanism of Human Apohemoglobin Unfolding.

Removal of heme from human hemoglobin (Hb) results in formation of an apoglobin heterodimer. Titration of this apodimer with guanidine hydrochloride (GdnHCl) leads to biphasic unfolding curves indicating two distinct steps. Initially, the heme pocket unfolds and generates a dimeric intermediate in which ∼50% of the original helicity is lost, but the α1β1 interface is still intact. At higher GdnHCl concentrations, this intermediate dissociates into unfolded monomers. This structural interpretation was verified by comparing GdnHCl titrations for adult human hemoglobin A (HbA), recombinant fetal human hemoglobin (HbF), recombinant Hb cross-linked with a single glycine linker between the α chains, and recombinant Hbs with apolar heme pocket mutations that markedly stabilize native conformations in both subunits. The first phase of apoHb unfolding is independent of protein concentration, little affected by genetic cross-linking, but significantly shifted toward higher GdnHCl concentrations by the stabilizing d...
Operative Versus Nonoperative Management of Civilian Gunshot Wounds to the Spinal Cord: Novel Use of the Functional Independence Measure for Validated Outcomes.

Background Surgery for patients with gunshot wound spinal cord injury (GSCI) remains controversial. Few recent studies provide standardized follow-up and detailed functional outcomes. To our knowledge, the research we present in this study is unique in that we are the first to incorporate Functional Independence Measure (FIM) scores as an outcomes measure for neurologic recovery in patients with GSCI. Methods Patients with GSCI were divided into surgical and nonsurgical groups. Neurologic function was measured according to the American Spinal Injury Association impairment scale and defined as either complete or incomplete injury. Outcomes were then analyzed separately for complete and incomplete GSCI groups during hospitalization and rehabilitation. Results Baseline admissions characteristics were similar between surgical and nonsurgical groups except for a greater median injury severity score in the nonsurgical group (34 vs. 27; P = 0.02). For complete GSCI, total length of stay (LOS) was significantly longer in the surgical group (52 vs. 42 days; P = 0.04), and no difference was observed in overall FIM scores (58 vs. 54; P = 0.7). For incomplete GSCI, rehabilitation LOS was longer (35 vs. 21; P = 0.02) and a trend towards longer total LOS was observed in the surgical group (40 vs. 32; P = 0.07). No difference was observed in overall FIM scores (61 vs. 62; P = 0.9). Conclusions Surgery for patients with GSCI is associated with increased LOS and is not associated with improved FIM scores for patients with either complete or incomplete spinal cord injuries.
Chapter 11 Synapse Formation in Retina I s Influenced by Molecules That Identify Cell Position

Publisher Summary Molecules that identify cell type and position in the nervous system are detected by monoclonal antibodies. One molecule, toponymic (TOP), is distributed in a 35-fold topographic gradient from the dorsoposterior margin to the ventroanterior margin of avian retina. The gradient is present in young embryos, increases with retinal growth, and persists in the adult. TOP molecules are present in most or all cells of retina. The number of TOP molecules detected per cell varies continuously along the axis of the antigen gradient. Thus, TOP can be used to identify position in the plane of retina along that axis. Other antigens that identify cell type and position across the thickness of retina have also been detected. Molecules that mark such cellular organization may represent a neuronal recognition system. Antibodies to these molecules are used to examine the role of such molecules in the development of the nervous system. Antibodies provide a means of blocking molecular function, and antibodies to neuronal surface molecules have been used to disturb growth cone behavior and disrupt neurite outgrowth.
DyPO: Dynamic Pareto-Optimal Configuration Selection for Heterogeneous MpSoCs

Modern multiprocessor systems-on-chip (MpSoCs) offer tremendous power and performance optimization opportunities by tuning thousands of potential voltage, frequency and core configurations. As the workload phases change at runtime, different configurations may become optimal with respect to power, performance or other metrics. Identifying the optimal configuration at runtime is infeasible due to the large number of workloads and configurations. This paper proposes a novel methodology that can find the Pareto-optimal configurations at runtime as a function of the workload. To achieve this, we perform an extensive offline characterization to find classifiers that map performance counters to optimal configurations. Then, we use these classifiers and performance counters at runtime to choose Pareto-optimal configurations. We evaluate the proposed methodology by maximizing the performance per watt for 18 single- and multi-threaded applications. Our experiments demonstrate an average increase of 93%, 81% and 6% in performance per watt compared to the interactive, ondemand and powersave governors, respectively.
Sparse quadratic classification rules via linear dimension reduction.

Abstract We consider the problem of high-dimensional classification between two groups with unequal covariance matrices. Rather than estimating the full quadratic discriminant rule, we propose to perform simultaneous variable selection and linear dimension reduction on the original data, with the subsequent application of quadratic discriminant analysis on the reduced space. In contrast to quadratic discriminant analysis, the proposed framework does not require the estimation of precision matrices; it scales linearly with the number of measurements, making it especially attractive for the use on high-dimensional datasets. We support the methodology with theoretical guarantees on variable selection consistency, and empirical comparisons with competing approaches. We apply the method to gene expression data of breast cancer patients, and confirm the crucial importance of the ESR1 gene in differentiating estrogen receptor status.
Investigations Concerning the Structure of Complete Sets

This chapter will discuss developments bearing on three related research directions where Somenath Biswas has made pioneering contributions: Isomorphism of Complete Sets Creative Sets Universal Relations Some open questions in each of these directions will be highlighted.
Case Study: ISCRM — A Study of the Business Benefits Achieved through Integrated Supply and Customer Relationship Management

Over the past several years, numerous companies have reported reductions in cost and increases in revenue through improvements in the management of both their supply chain and their customer relationships. However, rarely have companies integrated these business processes to achieve significant increases in value to their respective businesses. This case study describes the business benefits achieved by a US specialty magazine retailer and its suppliers through the integration of Customer Relationship Management (CRM) and Supply Chain Management (SCM). By integrating these business processes, both the retailer and the suppliers were able to achieve a number of improvements in their financial and performance metrics that would have been unachievable using only stand alone CRM and SCM techniques. The increases in value achieved by the retailer include: Price benefits provided by the supplier in return for the shared information Reduced inventory carrying costs Increased revenue due to reduced out of stock positions