cssi/SciSciGPT-SciSciNet huggingface dataset:
Interaction of Human Rights Law and Competition Law: The Right to Access to Medicines and Consumer Welfare in the Pharmaceutical Sector

Access to essential medicines as public goods arguably forms integral part of fundamental human rights. The current pharmaceutical industry faces serious challenges to access to medicines that result from anticompetitive business activities and structural shortcomings. Competition and human rights policies, though historically and theoretically following divergent paths, still have vigorously interacted with each other partly sharing policy goals one way or another. While such interaction occurs throughout a wide range of industries, those two policies commonly seek to safeguard and promote economic interests of consumers in the pharmaceutical industry. The right to access to medicines has a normative point of contact with consumer welfare in the competition context inasmuch as both right and welfare can receive sustainable protection particularly when the pharmaceutical industry effectively functions in a way to ensure the public equal and full access to lower–cost and higher–quality medicines.
Carbohydrate Characterization through Multidimensional NMR: An Undergraduate Organic Laboratory Experiment

Carbohydrates are an essential group of molecules to the organic chemistry classroom providing molecular relevance to a common ingredient in chemical biology. While the meticulous elucidation of the carbohydrate structures by Fischer and others is an engaging topic in the lecture, there are few laboratory experiments that can emulate carbohydrate complexity. Advanced and multidimensional NMR (2D NMR) techniques such as correlation spectroscopies (COrrelation SpectroscopY (COSY), 13C Distortionless Enhancement by Polarization Transfer (DEPT), and HETeronuclear CORrelation (HETCOR) or Heteronuclear Single Quantum Coherence (HSQC)) have become more routine as they require less time on today’s instruments and are taught more often in lecture. A laboratory experiment is described for second-year introductory undergraduate organic chemistry students that involves the transformation of nutraceutical N-acetyl-d-glucosamine to α-chloroglucosamine tetraacetate. After synthesis and simple workup, students collect four different NMR spectra from which they identify each 1H signal in the product. Students learn to identify each signal’s multiplicity and how multiple NMR experiments are used to characterize a product. Student confidence in NMR characterization was assessed on a small subset through postlab questions and pre- and postsurvey data.
Spin state evolution of asteroid (367943) Duende during its 2013 earth flyby

Abstract On February 15, 2013 asteroid (367943) Duende, provisionally named 2012 DA14, experienced an extremely close earth encounter, passing within 27,700 km altitude. An observation campaign was made possible by one year's notice of the flyby. This campaign, discussed in detail in the companion paper by Moskovitz et al. (2019), yielded visible-wavelength photometry before and after closest approach. Post-flyby Goldstone Doppler-delay radar data were also obtained. These data indicated a roughly 40 m × 20 m object in non-principal axis rotation. Leveraging light curve frequency analysis from the Moskovitz et al. companion paper, dynamical and inertia constraints from the rough radar-derived elongations, and simulated photometry, only two post-flyby states were deemed viable. These were a long axis mode (LAM) with long axis convention periods P ϕ ¯ = 6.36 h and Pψ = 8.73 h and a short axis mode (SAM) with P ϕ ¯ = 8.71 h and Pψ = 23.7 h (each with nominal long-intermediate and long-short ellipsoid axis ratios of 1.7:1 and 2.3:1 respectively). The SAM solution was more consistent with the post-flyby photometry and radar data. Nevertheless, there were differences between the amplitude and phase of the post-flyby and best-fit simulated SAM light curves at some epochs. These discrepancies may be due to a non-ellipsoidal shape, non-uniform albedo, and/or incorrect spin state solution (attitude, inertias, tumbling periods, or rotation mode). Analysis of the sparse pre-flyby photometry by Moskovitz et al. yielded poor Fourier series solutions for all principal axis states and different peaks in the pre and post-flyby WindowCLEAN power spectra. This suggests the asteroid was tumbling before the encounter and that its spin state changed. Propagating the best-fitting LAM and SAM solutions backwards through the flyby with terrestrial tidal torques resulted in significant dispersion of the rotation states. The pre-flyby SAM states coincided with the notable Moskovitz et al. Fourier solution P1 = 8.37 h and P2 = 24.2 h. Overall, we propose Duende was tumbling before the 2013 flyby and that its spin state may have changed during the flyby. Furthermore, our analysis suggests Duende is currently in SAM with P ϕ ¯ = 8 . 71 h and Pψ = 23.7 h with pole J2000 ecliptic longitude and obliquity of roughly 70° and 95° or 245° and 90° respectively. The spin state characterization approach outlined in this paper could be used for future analyses with inertia, dynamical, and observational constraints.
Scalebridge VR: Immersive Proportional Reasoning Game for Children with Brain-Computer Interface for Difficulty Scaling

We present the design and evaluation of Scalebridge VR, an immersive educational game that teaches children the mathematical skill of proportional reasoning. The game uses brain-computer-interface-based adaptive level difficulty to modulate difficulty of the game based on the player’s attention and meditation state. The game is an adaptation of previously introduced Scalebridge game that did not use virtual reality, but was shown to be an effective tool for learning proportional reasoning.
Chapter 28 – Succession Leadership

Part of the job of leadership includes preparing for the end of your tenure as a leader. This encompasses many tasks, but one of the most important is planning for your successor. For many leaders, this is like thinking about death. Most of us would rather live and work in the moment and not contemplate the end, let alone the person who will take our place. This chapter will provide you with advice about practical steps you can take to make this difficult process less painful.
Asymptomatic and presymptomatic transmission of SARS-CoV-2: A systematic review.

Background and Purpose Many of the statutes comprising the shelter-in-place and phased-reopening orders are centered around minimizing asymptomatic and presymptomatic transmission. Assumptions about the presence and relative importance of asymptomatic and presymptomatic transmission are based on case reports, the failing of quarantine measures aimed at sequestering ill patients, viral dynamic studies suggesting SARS-CoV-2 production peaks before symptoms appear, and modeling evidence that calculates serial interval between successive generations of infection. In aggregate, these data offer compelling evidence of asymptomatic and presymptomatic transmission, but individually these studies have notable shortcomings that undermine their conclusions. The purpose of this review is to discuss the literature of asymptomatic and presymptomatic transmission, highlight limitations of recent studies, and propose experiments that, if conducted, would provide a more definitive analysis of the relative role of asymptomatic and presymptomatic transmission in the ongoing SARS-CoV-2 pandemic. Methods We conducted a systematic review of literature on PubMed using search filters that relate to asymptomatic and presymptomatic transmission as well as serial interval and viral dynamics. We focused on studies that provided primary clinical data. Results 34 studies were eligible for inclusion in this systematic review: 11 case reports pertaining to asymptomatic transmission, 9 viral kinetic studies, 13 serial interval studies, and 1 study with viral kinetics and serial interval. Conclusion Different approaches to determining the presence and prevalence of asymptomatic and presymptomatic SARS-CoV-2 transmission have notable shortcomings, which were highlighted in this review and limit our ability to draw definitive conclusions. Conducting high quality studies with the aim of understanding the relative role of asymptomatic and presymptomatic transmission is instrumental to developing the most informed policies on reopening our cities, states, and countries.
Conditional formulation for the calibration of multi-level random fields with incomplete data

Abstract Random fields are widely used in the modeling of spatially varying quantities. As an extension, multi-level random fields capture not only the spatial variability, but also the relationship between inter-dependent quantities. To calibrate such a model, we need data of different variables measured at the same locations in each level. However, measurements of different quantities are usually made independently at inconsistent locations. Recent work addressed this issue by predicting the missing data first, and calibrating the model using the completed dataset. However, existing formulations cannot capture the spatial correlation and inter-level dependency. This paper proposes a conditional random field formulation that overcomes the limitations. Beginning from the lowest level, we calibrate the model using observed data and make predictions conditioned on the observations. The observed data and predictions are then used in the calibration and prediction of the higher levels. To propagate the uncertainties, we develop predictive distributions based on total probability rule for the predictions. We discuss how the formulation works for two missing data scenarios: 1) data partially missing, and 2) data completely missing at some levels. An example of the modeling of multi-level earthquake intensities is provided to illustrate how to implement the proposed formulation in practice.
Prevalence, control, and treatment of diabetes, hypertension, and high cholesterol in the Amish.

Background The burden of diabetes and cardiovascular risk is not uniform across the USA, with much of this disparity tracking differences in socioeconomic status, cultural practices and lifestyle. To further evaluate disparities in these disorders, we assessed the prevalence of diabetes, hypertension, and hypercholesterolemia in an Old Order Amish community that is characterized by distinctive sociocultural practices that include a very cohesive social structure and limited use of modern technologies and medications. We compared prevalence of these conditions with that of the overall US population. Method We performed a community-wide survey in 5377 Amish individuals aged 18 years and older from the Lancaster County, Pennsylvania, Amish settlement that included a basic physical examination and fasting blood draw during the period 2010–2018. We then compared the prevalence of diabetes, hypertension, and high cholesterol, defined using standard criteria, between the Amish and the European Caucasian subsample of the 2013–2014 US National Health and Nutrition Examination Survey (NHANES). Results Prevalence rates for diabetes, hypertension and hypercholesterolemia were 3.3%, 12.7%, and 26.2% in the Amish compared with 13.2%, 37.8% and 35.7% in NHANES (p Conclusion There is substantially lower prevalence of diabetes, hypertension and hypercholesterolemia in the Amish compared with non-Amish Caucasians in the USA. Possible factors contributing to this disparity include higher physical activity levels in the Amish or other protective sociocultural factors, a greater understanding of which could inform risk reduction interventions for these chronic diseases.
Studying Scale Dependency of Aerosol–Cloud Interactions Using Multiscale Cloud Formulations

The WRF-ACI model configuration is used to investigate the scale dependency of aerosol-cloud interactions (ACI) across the "grey zone" scales for grid and subgrid-scale clouds. The impacts of ACI on weather are examined across regions in the eastern and western U. S. at 36, 12, 4, and 1 km grid spacing for short-term periods during the summer of 2006. ACI impacts are determined by comparing simulations with current climatological aerosol levels to simulations with aerosol levels reduced by 90%. The aerosol-cloud lifetime effect is found to be the dominant process leading to suppressed precipitation in regions of the eastern U.S., while regions in the western U. S. experience offsetting impacts on precipitation from the cloud lifetime effect and other effects that enhance precipitation. Generally, the cloud lifetime effect weakens with decreasing grid spacing due to a decrease in relative importance of autoconversion compared to accretion. Subgrid-scale ACI are dominant at 36 km, while grid-scale ACI are dominant at 4 and 1 km. At 12 km grid spacing, grid-scale and subgrid-scale ACI processes are comparable in magnitude and spatial coverage, but random perturbations in grid-scale-ACI impacts make the overall grid-scale-ACI impact appear muted. This competing behavior of grid and subgrid-scale clouds complicate the understanding of ACI at 12 km within the current WRF modeling framework. The work implies including subgrid-scale-cloud microphysics and ice/mixed phase cloud ACI processes may be necessary in weather and climate models to study ACI effectively.
Charismatic Nonverbal Displays by Leaders Signal Receptivity and Formidability, and Tap Approach and Avoidance Motivational Systems.

Status cues and signals act as guidance systems by regulating social approach and avoidance. Applied to leadership, we hypothesized that nonverbal displays conveying the dual status messages of receptivity and formidability, and the approach/avoidance motives they activate, set conditions for charismatic, leader-follower relationships. We investigated perceptions of charisma, the nonverbal signals associated with them, the motives they energize, and the relationships they support across levels-of-analysis. At the social-perceptual level (Studies 1a-d), eligible voters rated political leaders’ traits after viewing silent, 30-second videos of speeches presented online. As predicted, perceptions of politicians’ receptivity (warmth and attractiveness) and formidability (competence and power) were independently associated with perceptions of their charisma; perceptions of trustworthiness and authenticity showed weak or negligible associations. Results were similar when the stimuli were female, Jamaican educational leaders. Leaders’ nonverbal behavior was linked to perceptions of their receptivity, formidability, and charisma in Study 2. At the brain-systems level, Studies 3a-b tested predictions that charismatic nonverbal performances stimulate equivalent degrees of approach and avoidance motivation in observers. Brain recordings via electroencephalography (EEG) were made while undergraduates viewed leaders rated high or low in charisma. Discrepancies in alpha activity in the left and right frontal hemispheres (associated with approach and avoidance, respectively) were relatively diminished when participants viewed highly charismatic political leaders, indicating that approach and avoidance motives are energized in response to charismatic performances. EEG patterns for Jamaican leaders were similar but not significant. At the group level-of-analysis, Study 4 sought evidence that charismatic leaders create uniquely influential relationships with followers. Video recordings of student leaders interacting with pairs of unfamiliar students during a group decision-making task were assessed for leader receptivity, formidability, and charisma by independent sets of undergraduate judges. Perceptions of student leaders’ receptivity and formidability predicted their charisma, and charismatic leaders were most effective in bringing followers to privately (but not publicly) accept a controversial group decision. Across studies, evidence generally supported hypotheses generated from status cues theory: charismatic leadership builds upon the nonverbal projection of dual status messages and the approach/avoidance motives they engender, setting conditions for a uniquely powerful brand of influence.
Evaluation for septic arthritis of the native adult knee is aided by multivariable assessment.

Abstract Introduction Evaluation of suspected septic arthritis of the native adult knee is a common diagnostic dilemma. Pre-aspirate criteria predictive of septic arthritis do not exist for the adult knee and investigations of aspiration results (cell count, differential, gram stain and crystal analysis) have been limited to univariate analyses. Given numerous clinical variables inform the risk of septic arthritis, multivariable analysis that incorporates all clinically available information is critical to allowing accurate decision-making. Methods We retrospectively identified 455 cases of potential septic arthritis of a native adult knee at a tertiary health system from 2012 to 2017, of which 281 underwent aspiration. We recorded demographics, comorbidities, history, exam, laboratory, and radiographic data. Among aspirated cases, we performed univariate analyses of all variables for association with septic arthritis followed by multivariable logistic regression analysis. Results Septic arthritis was confirmed in 61 of 281 patients who underwent aspiration. Independent associations of risk for septic arthritis included synovial fluid WBC ≥ 30,000 (Odds Ratio 90.8, 95% Confidence Interval 26.6–310.1, p 2 days (OR 6.9, 95% CI. 2.3–20.9, p Conclusion When evaluating for septic arthritis of a native adult knee, several independent associations were identified for variables related and unrelated to joint aspiration. The associated multivariable model discriminated very well between patients with and without septic arthritis, outperforming previous univariate assessments. A web-based tool was created that estimates the probability of septic arthritis based on this model. This may aid decision-making in complex clinical scenarios.
Towards a Sustainable Power Grid: Stochastic Hierarchical Planning for High Renewable Integration.

Driven by ambitious renewable portfolio standards, large-scale inclusion of variable energy resources (such as wind and solar) are expected to introduce unprecedented levels of uncertainty into power system operations. The current practice of operations planning with deterministic optimization models may be ill-suited for a future with abundant uncertainty. To overcome the potential reliability and economic challenges, we present a stochastic hierarchical planning (SHP) framework. This framework captures operations at day-ahead, short-term and hour-ahead timescales, along with the interactions between the stochastic processes and decisions. In contrast to earlier studies where stochastic optimization of individual problems (e.g., unit commitment, economic dispatch) have been studied, this paper studies an integrated framework of \emph{planning under uncertainty}, where stochastic optimization models are stitched together in a hierarchical setting which parallels the deterministic hierarchical planning approach that is widely adopted in the power industry. Our experiments, based on the NREL-118 dataset, reveal that under high renewable penetration, significant operational improvements can be expected by transitioning to the SHP paradigm. In particular, the computational results show that significant improvements can be achieved in several metrics, including system reliability, environmental sustainability, and system economics, solely by making a strategic choice to adopt the new SHP paradigm.
Shining a light on autophagy in neurodegenerative diseases.

Small-molecule modulators of autophagy have been widely investigated as potential therapies for neurodegenerative diseases. In a recent issue of JBC, Safren et al. described a novel assay that uses a photoconvertible fusion protein to identify compounds that alter autophagic flux. Autophagy inducers identified using this assay were found to either alleviate or exacerbate neurotoxicity in different cellular models of amyotrophic lateral sclerosis, challenging the notion that autophagy stimulation can be used as a one-size-fits-all therapy for neurodegenerative disease.
Stress as a medical and scientific idea and its implications.

Publisher Summary Stress is defined as a state of threatened homeostasis, which is re-established by a complex repertoire of physiological and behavioral adaptive responses of the organism. Hormones participate in a crucial fashion in the coordination of both basal and threatened homeostasis. The stress response is subserved by a complex system located in both the central nervous system (CNS) and the periphery. This system receives and integrates a large diversity of neurosensory (visual, auditory, somatosensory, nociceptive, visceral), blood-borne, and limbic-cortical signals, which arrive through distinct pathways. Activation of the stress system leads to behavioral and physical changes that are remarkably consistent in their qualitative presentation. These changes are normally adaptive and improve the chances of the individual for survival. There has been an exponential increase in knowledge regarding the interactions among the components of the stress system and between the stress system and other brain elements involved in the regulation of emotion, cognitive function, and behavior, as well as with the axes responsible for reproduction, growth, and immunity. This new knowledge has allowed association of stress system dysfunction characterized by sustained hyperactivity or hypoactivity to various pathophysiologic states that cut across the traditional boundaries of medical disciplines. These include a range of psychiatric, endocrine, and inflammatory disorders and/or susceptibility to such disorders. Of special interest is atypical-seasonal depression, which is associated with a hypofunctional stress system with weight gain in the dark winter months and/or autoimmune manifestations, and melancholic depression, which is associated with a hyperfunctional stress system and immunosuppression.
Thermally Induced Interdiffusion and Precipitation in a Ni/Ni3Al System

Ordered Ni3Al intermetallic precipitates constitute the main hardening sources of Ni-based superalloys. Here, we report the interdiffusion and precipitation behavior in a Ni/Ni3Al model system. The deposition of Ni3Al on a pure Ni layer at 500°C generated L12-structured γ′ (Ni3Al) precipitates, preferentially at the interface. After annealing at 800°C for 1 h, interdiffusion between Ni and Ni3Al layers occurred, and the γ′ precipitates that grew near the parent Ni/Ni3Al interface are ∼2.8 times larger in size than those formed in the matrix. Monte Carlo simulations indicate that vacancies preferentially diffuse along the Ni/Ni3Al interface, increasing the probability of precipitation.
Comparison of nonlinear coefficient of optical fibers at 1550 nm

Summary form only given. In this paper we report on measurements of the nonlinear coefficient (nonlinear refractive index/effective area) of different fibers of interest in transmission systems at 1550 nm: large-effective area fiber dispersion-shifted fiber (LEAF), dispersion-compensation fiber (DCF), and standard dispersion fibers.
A Review of: “The Goebbels Experiment, directed by Lutz Hochmeister and Michael Kloft”

The Goebbels Experiment views an era of German history through the eyes of its subject. Extensive quotations from the diaries of the Nazi minister of propaganda and public enlightenment are coupled...
The Masquerade, the Veil, and the Phallic Mask

I shall argue that the Islamic veil is a symptom of the question, “What is Woman?” As a symptom of male phallic castration, the veil works as “non-delivered meaning,” one definition Jacques-Alain Miller gives of the symptom. As a signifier of jouissance, the veil hides that which is impossible to say and leads to the object a, which refers to a jouissance beyond words, a jouissance whose first roots are in the attachment of an infant to the mother's body. The Father's Name signifier reappears in the veil as a third thing, a prohibition against a supposed Oneness between the infant and the mother. Thus, the veil proscribes the jouissance of woman, covering over her sexuality, her gaze, her lips, sometimes even her voice. Insofar as the veil is meant to calm the effects of the drives, it is a semblant, an emblem of the woman's being placed outside the symbolic, on the side of the real. What is woman's object, the veil asks, she herself being man's object? I would argue that the veil is the semblant that organizes the paternal metaphor (Oedipal structure) in Islamic culture around the Father's Name signifier while making the woman the coordinate of that signifier. Indeed, the veil is the semblant of the truth in jouissance and of the reality in the phallic function.
[The treatment of children with non-migrainous headaches]

Objetivo. Revisar las cefaleas no migranosas (CNM), los mecanismos del dolor y su tratamiento, con enfasis en la experiencia clinica del autor. Desarrollo. Las cefaleas son comunes en la practica diaria de la pediatria. Aproximadamente el 22% de los nuevos pacientes vistos en una consulta externa de neuropediatria presentan cefalea como motivo de consulta. Siempre que exista cefalea, debe estar involucrado algun mecanismo de dolor. Estos son: vasodilatacion, inflamacion, traccion y desplazamiento de estructuras intracraneales, tension muscular sostenida y mecanismo neurogenico. La evaluacion clinica nos permite diagnosticar el tipo de cefalea y realizar su tratamiento. Los examenes fisico y neurologico son normales en la mayoria de los ninos con cefalea. La clasificacion sindromica incluye: cefalea aguda generalizada, cefalea aguda localizada, cefalea aguda recurrente, cefalea cronica progresiva, cefalea cronica (recurrente) no progresiva. Las cefaleas recurrentes ocurren comunmente en ninos y se diagnostican mas bien sobre una base clinica que por examenes. El uso rutinario de cualquier estudio diagnostico no esta indica cuando la historia clinica no tiene factores de riesgo asociados y el examen del nino es normal. El tratamiento se basa en el tipo de cefalea existente. La mayoria de las cefaleas en los ninos tienen un mecanismo vascular. El autor se inclina por un tratamiento dietetico asociado con la ingesta diaria de una pequena dosis de cafeina BID. Conclusiones. El tratamiento de las CNM depende del tipo de sindrome existente, pero en su gran mayoria, es muy satisfactorio para los pacientes y sus padres.
On an Improvement over Rényi's Equivocation Bound

We consider the problem of estimating the probability of error in multi-hypothesis testing when MAP criterion is used. This probability, which is also known as the Bayes risk is an important measure in many communication and information theory problems. In general, the exact Bayes risk can be difficult to obtain. Many upper and lower bounds are known in literature. One such upper bound is the equivocation bound due to R\'enyi which is of great philosophical interest because it connects the Bayes risk to conditional entropy. Here we give a simple derivation for an improved equivocation bound. We then give some typical examples of problems where these bounds can be of use. We first consider a binary hypothesis testing problem for which the exact Bayes risk is difficult to derive. In such problems bounds are of interest. Furthermore using the bounds on Bayes risk derived in the paper and a random coding argument, we prove a lower bound on equivocation valid for most random codes over memoryless channels.
Abstract 303: Sexual Dimorphisms in Cardiomyocytes Exposed to a Pathological Stimulus

Background: Sex is an important modifier of the development of cardiovascular disease; women consistently display less hypertrophy, fewer changes in pathologic gene expression, and less cardiac dysfunction compared to men exposed to the same pathological stimuli. The signaling pathways responsible for these sexual dimorphisms, especially within the cardiomyocyte, are not well understood. Objective: To investigate sexual dimorphisms in activation of signaling pathways and expression of genes related to cardiomyocyte contractility in response to a pathological stimulus in isolated adult rat ventricular myocytes (ARVMs). Methods: ARVMs from both sexes were isolated using a Langendorff perfusion apparatus and treated with the β-adrenergic agonist isoproterenol (ISO) or vehicle (saline) for 24 hours. Activated signaling molecules were detected by performing a phospho-kinase antibody array (R&D Systems) in ARVMs isolated from two rats of each sex treated with ISO or vehicle. Total RNA was isolated from these cells, and real-time PCR was used to determine expression levels of calcium handling genes, including Cav1.2 and sodium calcium exchanger (NCX1). Results: A distinct profile of activated signaling molecules was observed between male and female ARVMs in response to ISO. Female ARVMs displayed activation of kinases such as Akt, ERK1/2, p38α, GSK3α/β and MSK1/2. Male ARVMs were characterized by an activation of signaling molecules such as PLCγ1, RSK1/2/3 and c-Jun. ARVMs of both sexes displayed activation of signaling molecules such as eNOS, STAT3 and mTOR. Because the activated signaling molecules identified with the array can modulate expression of calcium handling genes, expression of these genes was analyzed. In response to ISO treatment, female ARVMs displayed an increase in NCX1 expression normalized to vehicle (1.63 ± 0.079) as well as Cav1.2 expression (1.48 ± 0.072). However, these increases were not observed in male cells. Conclusions: Cardiomyocytes isolated from rats of different sexes display distinct responses to the pathological stimulus ISO. Understanding the mechanisms responsible for these sexual dimorphisms can lead to the development of more effective treatment options for both men and women with cardiovascular disease.
Entropic Formulation of Uncertainty for Quantum Measurements

A quantitative formulation of the uncertainty principle, based on Deutsch's idea of using entropy as a measure of uncertainty to remove the inadequacies of the standard treatment, is presented. This uncertainty in general involves the resolution of the measuring device.
The C-4 hydroxyl group of galactopyranosides is the major determinant for ligand recognition by the lactose permease of Escherichia coli.

Binding specificity in lactose permease toward galactopyranosides is governed by H-bonding interactions at C-2, C-3, C-4, and C-6 OH groups, while binding affinity can be increased dramatically by nonspecific hydrophobic interactions with the non-galactosyl moiety [Sahin-Toth, M., Akhoon, K. M., Runner, J., and Kaback, H. R. (2000) Biochemistry 39, 5097-5103]. To characterize the contribution of individual hydroxyls, binding of structural analogues of p-nitrophenyl alpha-D-galactopyranoside (NPG) was examined by site-directed N-[(14)C]ethylmaleimide (NEM) labeling of the substrate-protectable Cys148 in the binding site. NPG blocks NEM alkylation of Cys148 with an apparent affinity of approximately 14 microM. A deoxy derivative at position C-2 binds with 25-fold lower affinity (K(D) 0.35 mM), and the deoxy analogue at C-3 exhibits ca. 70-fold decreased binding (K(D) 1 mM), while binding of 6-deoxy-NPG is at least 130-fold diminished (K(D) 1.9 mM). Remarkably, the C-4 deoxy derivative of NPG binds with almost 1500-fold reduced affinity (K(D) approximately 20 mM). No significant substrate protection is afforded by NPG analogues with methoxy (CH(3)-O-) substitutions at positions C-3, C-4, and C-6. In contrast, the C-2 methoxy analogue binds almost normally (K(D) 26 microM). The results confirm and extend the observations that the C-2, C-3, C-4, and C-6 OH groups of galactopyranosides participate in important H-bonding interactions. Moreover, the C-4 hydroxyl is identified as the major determinant of ligand binding, suggesting that sugar recognition in lactose permease may have evolved to discriminate primarily between gluco- and galactopyranosides.
Conversational remembering: story recall with a peer versus for an experimenter

This research investigated the role social context plays in determining the content and organization of remembered information. As a manipulation of social context, subjects talked about a short story either with another subject (dyads) or for an experimenter (experimenter-tested). In addition, the instructions were manipulated: Subjects were asked about their memory of the story or their personal reactions to it. Regardless of instructions, the dyad subjects spoke more about their evaluations of the story, included more comments linking the story to a larger knowledge frame (metacomments), and more often used remembered details to support their positions. In contrast, the experimenter-tested subjects more often included story details and interpretations in narrative accounts of the story. The dyad subjects included in their recalls information that is part of story memory but seldom evidenced by single subjects remembering for an experiment. Thus conversational remembering often relies on a nonnarrative retrieval strategy. Regardless of social context, personal reaction instructions led to more meta-comments and evaluations, and less narrative than memory instructions. The organization and content of non-narrative conversational remembering may be explained by the dual demands of conforming to conversational rules and of establishing social bonds through self-revealing comments.
NIGMS Human/Rodent Somatic Cell Hybrid Mapping Panels 1 and 2

The NIGMS Human Genetic Mutant Cell Repository is currently distributing two well-characterized human/rodent somatic cell hybrid mapping panels. Mapping Panel 1 consists of DNA isolated from 18 hybrid cell cultures retaining from 1 to 19 human chromosomes. Mapping Panel 2 contains DNA from hybrids retaining 1 or 2 human chromosomes. All but 2 of the hybrids retain a single intact human chromosome. Mapping Panel 2 is also available as cell cultures. These resources should prove valuable to the Human Genome Project initiative. This article describes the sources of the hybrid cell cultures and the procedures utilized to prepare and characterize the panels.
TREATMENT OF LATE LYME BORRELIOSIS—RANDOMISED COMPARISON OF CEFTRIAXONE AND PENICILLIN

23 patients with clinically active late Lyme disease were randomly assigned to intravenous treatment with either penicillin or ceftriaxone. Of the 10 treated with penicillin, 5 were judged treatment failures; of the 13 who received ceftriaxone, only 1 did not respond. An additional 31 patients were subsequently treated with ceftriaxone 4 g/day (n = 17) or 2 g/day (n = 14); success rates in both groups were comparable to those in the cohort randomised to ceftriaxone. Patients unresponsive to ceftriaxone were more likely to have received corticosteroid treatment.
Establishment failure in biological invasions: a case history of Littorina littorea in California, USA.

Background: The early stages of biological invasions are rarely observed, but can provide significant insight into the invasion process as well as the influence vectors have on invasion success or failure. Methodology/Principal Findings: We characterized three newly discovered populations of an introduced gastropod, Littorina littorea (Linne´, 1758), in California, USA, comparing them to potential source populations in native Europe and the North American East Coast, where the snail is also introduced. Demographic surveys were used to assess spatial distribution and sizes of the snail in San Francisco and Anaheim Bays, California. Mitochondrial DNA was sequenced and compared among these nascent populations, and various populations from the North American East Coast and Europe, to characterize the California populations and ascertain their likely source. Demographic and genetic data were considered together to deduce likely vectors for the California populations. We found that the three large California L. littorea populations contained only adult snails and had unexpectedly high genetic diversity rather than showing an extreme bottleneck as typically expected in recent introductions. Haplotype diversity in Californian populations was significantly reduced compared to European populations, but not compared to East Coast populations. Genetic analyses clearly suggested the East Coast as the source region for the California introductions. Conclusions and Significance: The California L. littorea populations were at an early, non-established phase of invasion with no evidence of recruitment. The live seafood trade is the most likely invasion vector for these populations, as it preferentially transports large numbers of adult L. littorea, matching the demographic structure of the introduced California L. littorea populations. Our results highlight continued operation of live seafood trade vectors and the influence of vectors on the demographic and genetic structure of the resulting populations, especially early stages of the invasion process.
Ion sputter effects on HgTe, CdTe, and HgCdTe

Preferential ion sputtering of HgTe and HgCdTe is the dominant ion sputter effect observed in these material systems. There is little preferential sputtering of CdTe. The ion sputter behavior of HgCdTe can be predicted from the ion sputter behavior of HgTe and CdTe. The weakness of the Hg–Te bond compared to the Cd–Te bond accounts for the greater ion sputter rate of HgTe to CdTe and causes Hg to have a large relative ion sputter yield compared to the other elements and, most likely, plays a dominant role in the preferential sputtering of Te in HgCdTe. Preferential ion sputtering is dependent on the chemistry of Hg1−xCdxTe; elemental ion sputter yields depend on the amount of HgTe in the sample.
Addiction recovery for low-income pregnant and parenting women: A process of becoming

A naturalistic field study of low-income women ( N = 17) in an intensive outpatient addiction recovery program addressed the question: What is the nature of addiction recovery for pregnant and parenting-women in an addiction treatment program? Grounded theory methodology was used to determine the nature of the interpersonal and social processes that define addiction recovery for women in this study. Over 2 years, audiotaped semi-structured interviews, document reviews of medical records, treatment progress and group therapy notes, and participant observation notes were collected and analyzed. The constant comparison method of analysis involved an ongoing process of theoretical sampling, memoing, and open and then axial coding to identify, group, link, and reduce the categories produced. A developmental model of addiction recovery in pregnant and parenting women emerged that consisted of the dimensions of becoming drug and alcohol free, a partner in a relationship, a person, and a parent. These four dimensions parallel and transform each other, yielding different outcomes but similar patterns over time. This model of addiction recovery provides a beginning framework for understanding the transactional nature of addiction recovery for low-income women who are adapting to a drug and alcohol-free lifestyle and the task and role of parenting a newborn.
A spectral method for concordant polyhedral faces

Abstract For natural families of polytopes determined by substructures (e.g., tours or matchings) of a complete structure (e.g., undirected graph, directed graph, or uniform hypergraph), we show how D.G. Higman's theory of coherent configurations can be used to establish the spectra (and hence the dimension) of classes of faces induced by other substructures (e.g., cliques) of the structure. Furthermore, we show how the algebra can be used to derive a maximal irredundant set of equations satisfied by every point of such a face. We work out complete details of the proof machinery when the structure is the complete undirected graph and the faces are induced by cliques. As an example we consider the subtour elimination faces of the Hamiltonian tour polytope. Our approach extends the methodology introduced by J. Lee for determining the dimension of some combinatorially described polytopes.
Epidermal tumors of rainbow smelt with associated virus

Epithelial tumors of the skin occurred in landlocked populations of rainbow smelt (Osmerus mordax) in several lakes in New Hampshire (USA) during the spawning runs. Histologically, these were noninvasive epithelial cell lesions. Herpesvirus-like particles could be seen in the nucleus and cytoplasm. The lesions occurred in both males and females. Prevalence, which varied annually, was as high as 30%.
Development of a duplex real-time RT-qPCR assay to monitor genome replication, gene expression and gene insert stability during in vivo replication of a prototype live attenuated canine distemper virus vector encoding SIV gag

Advancement of new vaccines based on live viral vectors requires sensitive assays to analyze in vivo replication, gene expression and genetic stability. In this study, attenuated canine distemper virus (CDV) was used as a vaccine delivery vector and duplex 2-step quantitative real-time RT-PCR (RT-qPCR) assays specific for genomic RNA (gRNA) or mRNA have been developed that concurrently quantify coding sequences for the CDV nucleocapsid protein (N) and a foreign vaccine antigen (SIV Gag). These amplicons, which had detection limits of about 10 copies per PCR reaction, were used to show that abdominal cavity lymphoid tissues were a primary site of CDV vector replication in infected ferrets, and importantly, CDV gRNA or mRNA was undetectable in brain tissue. In addition, the gRNA duplex assay was adapted for monitoring foreign gene insert genetic stability during in vivo replication by analyzing the ratio of CDV N and SIV gag genomic RNA copies over the course of vector infection. This measurement was found to be a sensitive probe for assessing the in vivo genetic stability of the foreign gene insert.
Requirement for Caspase-2 in Stress-Induced Apoptosis Before Mitochondrial Permeabilization

A current view is that cytotoxic stress, such as DNA damage, induces apoptosis by regulating the permeability of mitochondria. Mitochondria sequester several proteins that, if released, kill by activating caspases, the proteases that disassemble the cell. Cytokines activate caspases in a different way, by assembling receptor complexes that activate caspases directly; in this case, the subsequent mitochondrial permeabilization accelerates cell disassembly by amplifying caspase activity. We found that cytotoxic stress causes activation of caspase-2, and that this caspase is required for the permeabilization of mitochondria. Therefore, we argue that cytokine-induced and stress-induced apoptosis act through conceptually similar pathways in which mitochondria are amplifiers of caspase activity rather than initiators of caspase activation.
Three-Dimensional Architecture of Inorganic Nanoarrays Electrodeposited through a Surface-Layer Protein Mask

Transmission electron microscopy was used to analyze the three-dimensional (3D) architecture of cuprous oxide electrochemically deposited through the pores of the hexagonally packed intermediate surface-layer protein from Deinococcus radiodurans SARK. Imaging at multiple tilt angles and averaging from five different samples allowed ∼3 nm computed 3D reconstructions of the inorganic deposit and protein template. We show that the electrodeposition process used here was able to fully access the pore structure that penetrates the protein layer, allowing the fabrication of a polycrystalline nanoarray with 18 nm periodicity and lateral interconnectivity among the pores with 3-fold symmetry. At the resolution of the reconstruction, the 6-fold symmetry pores also appear filled but are not connected laterally to the rest of the deposit. These results show that electrochemical deposition can produce interconnected 3D structures at dimensions an order of magnitude smaller than the most advanced integrated circuits (...
BEHAVIOR OF CERTAIN FUNGI INJECTED IN A MIXED SUSPENSION INTO MICE.

A total of 40 mice was injected with mixed suspensions ofC. albicans, C. neoformans, B. dermatitidis andH. capsulatum intraperitoneally, subcutaneously, intravenously and intracerebrally. Cultures from spleen, liver, kidney, lung and brain were made at intervals of 1, 4, 8, 15 and 30 days after inoculation. Results were recorded and compared with those obtained from a similar experiment where the organisms were injected separately.
A note on duality, Frobenius algebras and TQFTS

Topological quantum field theories (TQFTs) represent the structure present in cobordism categories. As an example, we review the correspondence between Frobenius algebras and (1+1)TQFTs. It is a corollary of the self-duality of the cobordism category, which is a rigid monoidal category generated by a Frobenius object (the circle). A self-dual definition of a Frobenius object without the use of a prefered dual is considered. The issue of duality as part of the definition of a TQFT is addressed. Note that duality is preserved by monoidal functors. Hermitian structures are modeled as a conjugation compatible with duality. It is the structure cobordism categories posses. A definition of generalized cobordism categories is proposed.
The riddle of MAP kinase signaling specificity

Cells encounter an enormous variety of signals in their environments and must respond to each stimulus appropriately with changes in their genetic programs. Many of these external signals are transduced by a highly conserved eukaryotic signaling mechanism, the mitogen-activated protein kinase (MAPK) cascade. How are the myriad of inputs transduced accurately so that each evokes a specific response? One mechanism would be to have a distinct MAPK cascade for each signal; however, the situation appears to be more complicated.
Effect of γ‐radiation on the dynamic mechanical properties of silicone rubbers

Dimethyl-, trifluoropropyl-, and high phenyl content polysiloxanes were irradiated in a 60Co source to doses of 100 Mrad. The hardness of the specimens increased with dose. Crosslink density changes did not directly reflect the hardness changes. The crosslink density of the dimethyl polymer increased significantly and that of the trifluoropropyl polymer increased only slightly. There was a slight decrease in the crosslink density of the aromatic material. The storage moduli reflected the changes in crosslink density. Loss moduli of the dimethyl- and trifluoropropylpolysiloxanes initially decreased and then increased on continuing irradiation. Dynamic moduli of the high aromatic content polymer were essentially unchanged by the radiation. All the dynamic data were correlated by the WLF time–temperature relationship.
Optimal control application for electrothermal multijet systems on synchronous earth spacecraft.

Multijet electrothermal systems for attitude control and stationkeeping of synchronous communications satellite
Inotropy, calcium, and heart failure: a personal perspective

The medical treatment of heart failure has improved significantly in the last decade, yet despite the reduction of morbidity and mortality, heart attacks and stroke cause 15 million deaths each year. Cardiovascular disease (CVD) constitutes 50% of all deaths worldwide. Indeed, heart disease represents a continuing global burden, despite all the advances. When considering the major objective of medical treatment of heart failure, the paradigm has shifted from increasing cardiac output of the failing heart by augmenting contractility to a decrease in afterload and inhibition of neurohumors affecting heart muscle. Nevertheless, a direct increase in contractility is still appropriate in some conditions of heart failure for a short-term beneficial effect. This article reviews certain aspects of cellular and molecular mechanisms to provide a framework for problem solving in this vital field.