cssi/SciSciGPT-SciSciNet huggingface dataset:
A pilot study on the evaluation of eye, head, and trunk coordination in subjects with chronic whiplash during a target-tracking task - A driving context approach.

Abstract Background Motor vehicle accidents (MVA) are the most common causes of whiplash injuries. Difficulties with driving and changes in driving behavior are reported by subjects with chronic whiplash associated disorders (WAD). Proper eye and head coordination is required for driving tasks. Disturbances of eye and head coordination were found in these subjects with chronic WAD. Objectives The objective of this pilot study is to evaluate eye, head and trunk coordination in subjects with chronic WAD due to MVA and healthy controls during a target-tracking task using a functionally oriented approach in the context of driving. Design Cross-sectional. Method The subjects performed target tracking tasks that reproduced eye and head movements required while driving. Head and trunk motion was captured using a motion capture system and eye movement was captured with an eye-tracker. Response time, time to target, and eye, head, and trunk contribution of movement were measured. Results/findings Subjects with chronic WAD presented delayed response time and time to reach the targets with both eyes and head compared to the control group, and tended to compensate the lack of neck motion with increased eye motion. Conclusions This study shows indications of impairments of eye and head coordination in chronic WAD due to MVA when compared to healthy subjects. These alterations may have implications for driving safety.
Glucagon-Like Peptide-1: Actions and Influence on Pancreatic Hormone Function

GLP-1 was described as an incretin over 30 years ago. GLP-1 is encoded by the preproglucagon gene (Gcg), which is expressed in the intestine, the pancreas, and the central nervous system. GLP-1 activates GLP-1 receptors (GLP-1r) on the β-cell to induce insulin secretion in a glucose-dependent manner. GLP-1 also inhibits α-cell secretion of glucagon. As few, if any, GLP-1r are expressed on α-cells, indirect regulation, via β- or δ-cell products has been thought to be the primary mechanism by which GLP-1 inhibits glucagon secretion. However, recent work suggests that there is sufficient expression of GLP-1r on α-cells for direct regulation as well. Although the predominant source of circulating GLP-1 is the intestine, the α-cell becomes a source of GLP-1 when the islet is metabolically stressed. Recent work suggests the possibility that this source of GLP-1 is also be important in regulating nutrient-induced insulin secretion in a paracrine fashion. More work is also accumulating regarding the role of glucagon, another Gcg-derived protein produced by the α-cell, in stimulating insulin secretion by acting on GLP-1r. Altogether, these data clearly demonstrate the important role of Gcg-derived peptides in regulating insulin secretion. Because of GLP-1's important role in glucose homeostasis, it has been implicated in the success of bariatric surgery and has been successfully targeted for the treatment of type 2 diabetes mellitus. © 2020 American Physiological Society. Compr Physiol 10:577-595, 2020.
JUSTICIA AMBIENTAL Y LA GESTIÓN DE LOS BIENES COMUNES

Worldwide concerns about the impacts of climate change and in line with the international agreements reached in Rio to Paris, a new generation of experts, scientists and citizens have begun to look for rational solutions that can be implemented by local and national governments and international institutions. We are facing an abundance of possible solutions, both technological and scientific. The problem is that, in implementing the new actions, they encourage the most powerful minorities in the world, which have created the problems under the model of consumer and wild capitalism, while those with the least resources are still the victims, suffering the consequences of climate change. This situation has been called an issue of environmental justice.
A multiparametric CAR T cell potency assay that employs real-time cellular impedance and live cell imaging

Background & Aim Chimeric antigen receptors (CARs) are engineered proteins that consist of an extracellular antigen binding domain that is linked, via a hinge region and transmembrane domain, to intracellular activation domains that drive T cell activation, proliferation, and target cell killing. A few decades of CAR engineering efforts have made it clear that merely linking these protein domains together is insufficient for generating an effective CAR; subtle differences in how the domains are linked to each other can greatly impact functionality. During CAR optimization biochemical assays can be used to assess critical quality attributes such as potency. Although these reductionistic approaches are useful, their results don't necessarily correlate with cancer killing efficacy within a more physiologically relevant context. To rigorously compare different CAR constructs and identify unwanted behavior such as tonic signaling, it is widely acknowledged that CAR function should be evaluated within the complex milieu of the immune synapse, using bona fide cancer cell killing as the readout. For this purpose, release assays (51Cr, LDH) have historically been the gold standard, but suffer from the fact that they require significant “hands on” time and only provide end point data. Requiring just target cancer cell seeding and a subsequent CAR T cell addition step, herein we use the Agilent xCELLigence RTCA eSight to quantitatively evaluate CAR T cell-mediated killing of cancer cells in real-time over multiple days and at physiologically relevant low E:T ratios. Methods, Results & Conclusion Providing a direct and objective assessment of target cancer cell number, cell size, and cell-substrate attachment strength, impedance biosensors embedded within the base of eSight microplates are shown to quantitatively track the continuum of target cell killing, spanning from early (reduced cell-substrate adhesion strength) to late (lysis) events. Concurrently, eSight is shown to capture live cell images in brightfield and three fluorescence channels, providing an orthogonal readout of the killing process – including real-time assessment of T cell activation and exhaustion markers such as CD69, CD107a, CTLA4, and LAG-3. By combining the strengths of real-time impedance monitoring (simplicity, analytical sensitivity, and objectivity) with that of live cell imaging (specificity of the readout), eSight is shown to increase the information richness of the CAR T cell killing assay without increasing the workload.
Sexual Desire and Subjective Distress among Pornography Consumers.

Clients are increasingly seeking professional help related to pornography viewing in the digital age. Given distress is a key reason clients seek help, the purpose of this study was to identify var...
A 9.7-nTᵣₘₛ, 704-ms Magnetic Biosensor Front-End for Detecting Magneto-Relaxation

This article reports a low-noise magnetic sensor front-end with an 18-bit Zoom ADC for detecting temporal magnetic nanoparticle (MNP) relaxation. Techniques such as dynamic element matching (DEM) and magnetoresistive correlated double sampling (MRCDS) are proposed to remove the sensor and analog front-end (AFE) 1/ ${f}$ noise while a fast-settling Miller compensation (FSMC) technique is proposed to reduce the amplifier power. Collectively, these result in state-of-the-art input-referred noise performance (9.7 nTrms) and a figure-of-merit (FoM) that is 6.6 $\times $ and 210 $\times $ better than previously reported magnetic sensor and relaxation-based AFEs, respectively. A relaxation-based magnetic immunoassay (MIA) was performed to demonstrate the concept. This design is implemented in a 0.18- $\mu \text{m}$ CMOS process and consumes 4.32 mW from a 1.8-V supply.
Hard Evidence and Mechanism Design

This paper addresses how hard evidence can be incorporated into mechanismdesign analysis. Two classes of models are compared: (a) ones in which evidentiary decisions are accounted for explicitly, and (b) ones in which the players make abstract declarations of their types. Conditions are provided under which versions of these models are equivalent. The paper also addresses whether dynamic mechanisms are required for Nash implementation in settings with hard evidence. The paper shows that static mechanisms suffice in the setting of “evidentiary normality” and that, in a more general environment, one can restrict attention to a class of three-stage dynamic mechanisms. JEL Classification: C70, D74, K10.
Selective aortic arch perfusion versus open cardiac massage in exsanguination cardiac arrest: A comparison of coronary pressure dynamics in swine.

Abstract Aim To evaluate the mean aortic-right atrial pressure (AoP-RAP) gradients and mean coronary perfusion pressures (CPPs) observed during open cardiac massage (OCM) versus those obtained with selective aortic arch perfusion (SAAP) in post-mortem hypovolemic swine. Methods Post-mortum, male swine, utilized in prior studies of hemorrhage, were included in the study. Animals were bled ∼25–50% of circulating volume prior to death. Animals either underwent clamshell thoracotomy and OCM immediately after death was confirmed (n = 6) or underwent SAAP within 5−15 min of death (n = 6). Aortic root and right atrial pressures were recorded continuously during each method of resuscitation using solid state blood pressure catheters. Representative five beat samples were extracted; short, similarly timed segments of SAAP were also extracted. Mean AoP-RAP gradient and CPPs were calculated and compared. Results Mean AoP-RAP gradient and CPP were significantly higher in SAAP animals compared to OCM animals (mean ± SD; 29.1 ± 8.4 vs. 24.5 ± 5.0, p 15 mmHg, only 17% of OCM segments had a CPP > 15 mmHg (p Conclusion SAAP appears to create a more favorable and efficient hemodynamic profile for obtaining ROSC when compared to OCM in this preclinical porcine study.
Risk of SARS-CoV-2 reinfection in a university student population.

We assess protection from previous SARS-CoV-2 infection in a population of 16,101 university students (2,021 with and 14,080 without previous infection). The risk of re-infection during the Spring 2021 semester was 2.2% among previously infected students; estimated protection from previous SARS-CoV-2 infection was 84% (95% CI: 78%-88%).
Log-concave polynomials in theory and applications (tutorial)

Log-concave polynomials give rise to discrete probability distributions with several nice properties. In particular, log-concavity of the generating polynomial guarantees the existence of efficient algorithms for approximately sampling from a distribution and finding the size of its support. This class of distributions contains several important examples, including uniform measures over bases or independent sets of matroids, determinantal point processes and strongly Rayleigh measures, measures defined by mixed volumes in Mikowski sums, the random cluster model in certain regimes, and more. In this tutorial, we will introduce the theory and applications of log-concave polynomials and survey some of the recent developments in this area.
Masses Involving the Heart and Vasculature

Nearly 17 million people in the U.S. are living with cancer [1]—survivorship has markedly improved in the past decades, highlighting the importance of effective strategies to surveil cancer complications in this population.
My Fair Lady? Inferring Organizational Trust From the Mere Presence of Women in Leadership Roles:

The history of male dominance in organizational hierarchy can leave a residue of mistrust in which women in particular do not expect fair treatment. The mere presence of a female leader relative to...
Digital Storytelling as Pedagogy in Linguistic Anthropology

This article explores teaching linguistic anthropology through digital storytelling as a pedagogical foundation. In a course titled Language, Power, and Social Identity offered remotely in the fall of 2020 at Kenyon College in Ohio, storytelling practices provided a way to explore connections between language and identities among a diverse group of twelve students. Using storytelling throughout the semester in multiple ways, activities and assignments culminated in a final class project of a digital storytelling video. Integrating digital storytelling as pedagogy suggests there is potential to generate greater understanding of experiences of identity formation through creative and inclusive learning practices.
Vitamin D and uterine leiomyoma among a sample of US women: Findings from NHANES, 2001-2006.

Abstract Scientific understanding of the etiology of uterine leiomyomata (UL) remains incomplete, but recent investigations have suggested an association between low Vitamin D and UL risk. In this study, we conducted a cross-sectional analysis of Vitamin D exposure, measured using serum levels of 25(OH)D (a Vitamin D metabolite), and self-reported UL diagnosis among 3590 women aged 20–54 in the National Health and Nutrition Examination Survey (NHANES 2001–2006). Multivariate logistic regression models comparing each quartile of 25(OH)D to the lowest quartile indicated no relationship between 25(OH)D and odds of UL in the whole population ( P trend = 0.37), or in sensitivity analyses. However, a probabilistic analysis correcting outcome misclassification indicated that insufficient 25(OH)D was associated with UL in white (Odds ratio (OR) median estimate: 2.17; 2.5, 97.5 percentiles: (1.26, 23.47)), but not black women (OR median estimate: 1.70; 2.5, 97.5 percentiles: (0.89, 3.51)), suggesting misclassification may have driven some of the null findings.
Chemotherapy of chlamydial infections.

Publisher Summary Chlamydiae are obligate intracellular parasites, related to Gram-negative bacteria but quite distinct from viruses. They produce a variety of human and animal infections that are characterized by strong chronicity and latency. Chlamydiae are susceptible to a variety of antibacterial drugs in laboratory models. This chapter discusses the efficacy of drugs that are acceptable for general use. While acute infections in animals or man can sometimes be cured by the administration of certain drugs, treatment of chronic infection is difficult. Usually drug administration results in the suppression of signs and symptoms of disease, but fails to eradicate the infectious agent. Prolonged administration of relative large doses of drugs is advisable in treating chronic chlamydial infections. However, more commonly, the administration of antimicrobial drugs suppresses active replication of chlamydiae, and thereby aids in clinical recovery, but fails to eliminate the infectious agent. Ultimately, the eradication of infection is a function of host responses. It is in this general framework that chemotherapy of chlamydial infections must be considered. Many different experimental infections have been employed in attempts to quantify and compare the activity of antimicrobial drugs on chlamydiae. The infected mouse, embryonated egg, and cell culture have been used most widely. Each of the models has its own peculiarities and no model entirely mirrors the treatment of infection in the natural host. The greatest weight must, therefore, be given to controlled therapeutic studies in natural hosts. Regrettably, only few adequately controlled treatment trials are available and most clinical reports rely on the anecdotal method. The greatest hazard in attributing therapeutic significance to a drug is the failure to acknowledge that spontaneous, sometimes dramatic, recovery is a part of the natural history of infectious diseases. This is a particular problem in chlamydial infections, because they exhibit a very wide spectrum of clinical severity.
The Spiral Array: An Algorithm for Determining Key Boundaries

Computer models for determining key boundaries are important tools for computer analysis of music, computational modeling of music cognition, content-based categorization and retrieval of music information and automatic generating of expressive performance. This paper proposes a Boundary Search Algorithm (BSA) for determining points of modulation in a piece of music using a geometric model for tonality called the Spiral Array. For a given number of key changes, the computational complexity of the algorithm is polynomial in the number of pitch events. We present and discuss computational results for two selections from J.S. Bach's "A Little Notebook for Anna Magdalena". Comparisons between the choices of an expert listener and the algorithm indicates that in human cognition, a dynamic interplay exists between memory and present knowledge, thus maximizing the opportunity for the information to coalesce into meaningful patterns.
The Tasks of Philosophy: The ends of life, the ends of philosophical writing

We are sitting with friends at a diner or standing in line to buy tickets for a movie, chatting idly, when suddenly one of us, unable to contain himself in the face of our trivialities, bursts out with some existential question which we might later on paraphrase in polite terms as “What is it to live a human life well or badly?” or one which we might paraphrase as “What law, if any, has authority over us?” or one which we might paraphrase as “What is the significance of death in our lives?” The questions that actually burst out on such occasions will be expressed in cruder and rawer terms, as much a scream as an utterance, whose obscenities can be heard as expressions of anger and pain. And the response by those who hear both the questions and the emotions expressed through them is likely to be deep embarrassment, a strong wish to change the subject, a will to behave as if the questions had not been asked. We think: what can have got into him to talk like that ? Is he perhaps having a break-down? Yet provide these very same questions with a different context, that, say, of a graduate seminar in philosophy, utter them in a quiet academic tone of voice and in a suitably purged vocabulary, and they no longer sound naive, they no longer evoke embarrassment.
Insider Trading: An Overview

Insider trading is one of the most controversial aspects of securities regulation, even among the law and economics community. One set of scholars favors deregulation of insider trading, allowing corporations to set their own insider trading policies by contract. Another set of law and economics scholars, in contrast, contends that the property right to inside information should be assigned to the corporation and not subject to contractual reassignment. Deregulatory arguments are typically premised on the claims that insider trading promotes market efficiency or that assigning the property right to inside information to managers is an efficient compensation scheme. Public choice analysis is also a staple of the deregulatory literature, arguing that the insider trading prohibition benefits market professionals and managers rather than investors. The argument in favor of regulating insider trading traditionally was based on fairness issues, which predictably have had little traction in the law and economics community. Instead, the economic argument in favor of mandatory insider trading prohibitions has typically rested on some variant of the economics of property rights in information. A comprehensive bibliography is included.
Specialty level II fieldwork in low vision rehabilitation.

OBJECTIVE: Low vision rehabilitation is an emerging practice area for the field of occupational therapy. As a result there is a need to develop tools and training for fieldwork educators in this practice area. PARTICIPANTS: Occupational therapists with no experience in low vision rehabilitation participated in the pilot of the tools and training developed. METHOD: A literature review was completed in the areas of low vision rehabilitation and fieldwork education. Additional evidence was gathered for relevant training modules, methods, and organizational training and development tools. A best-practice model for specialty Level II fieldwork in low vision rehabilitation was then developed for a partnering site. Best-practice was defined as the triangulation of the research evidence, consensus from a panel of occupational therapists with specialty certification in low vision (SCLV) and academic fieldwork coordinators, and feedback from the partnering site. RESULTS: After three training sessions, the occupational therapists were able to achieve entry-level practice using the model developed. CONCLUSION: While the model was not intended for training therapists it proved successful with the occupational therapists trained with it. Therefore, it is expected that an occupational therapy student, completing a third specialty placement in low vision rehabilitation, would achieve this status during the twelve-week fieldwork placement.
An experimental comparison of continuous motion and step-and-shoot modes in digital breast tomosynthesis

There are two basic tomosynthesis data acquisition modes: step-and-shoot. Most experimental research on tomosynthesis has been done using commercial breast tomosynthesis systems, which can operate in only a single mode, either step-and-shoot or continuous motion. Thus the only studies that have been done to compare these two imaging modes for otherwise identical systems have been simulation studies. In this paper we describe a versatile, bench-top 3D breast imaging system that can acquire tomosynthesis data using either mode. Preliminary experimental studies of in-plane blur and artifact propagation using different acquisition protocols are discussed. Our initial results indicate that, noticeable difference was observed in system MTF from projection views between step-and-shoot mode and continuous motion mode while there was little difference in other measures from reconstruction slices. This system provides great flexibility for studying breast imaging and image quality under different acquisition protocols.
Exploiting Modern Computing Architectures for Efficient Large-Scale Nonlinear Programming

Abstract While large-scale nonlinear programming (NLP) has seen widespread use within the process industries, the desire to solve larger and more complex problems drives continued improvements in NLP solvers. Because of physical hardware limitations, manufacturers have shifted their focus towards multi-core and other modern parallel computing architectures, and we must focus efforts on the development of parallel computing solutions for large-scale nonlinear programming. In this paper we briefly describe some existing and emerging architectures for parallel computing and demonstrate the potential of some of these architectures for parallel solution of nonlinear programming problems. In particular, we show the scalability of an integrated design and control problem using two techniques within a multi-core architecture.
'Teaching Must Be Our Demonstration!': Activism in the Prince Edward County Free School Association, 1963-1964

Article for LiCS special issue The New Activism: Composition, Literacy Studies, and Politics.
A type 1 phosphoprotein phosphatase active with phosphorylated Mr = 68,000 initiation factor 2 kinase

A type 1 protein phosphatase from reticulocytes is shown to efficiently dephosphorylate the Mr = 68,000 phosphopeptide of the double-stranded RNA-dependent kinase that phosphorylates the α subunit of eukaryotic peptide initiation factor 2, eIF-2. The kinase, activated in the presence of double-stranded RNA with concomitant phosphorylation of the Mr = 68,000 peptide, causes inhibition of peptide initiation and thereby effects translational control of protein synthesis. The Mn2+-dependent phosphatase is classified as a type 1 enzyme in that it is inhibited by inhibitor 2 in nanomolar concentrations and appears to have a Mr = 35,000 catalytic subunit. Dephosphorylation of the Mr = 68,000 peptide by the phosphatase is directly associated with a loss in kinase activity which can be restored by incubation with double-stranded RNA in the presence of ATP. The results demonstrate that the eIF-2α kinase can undergo cyclic activation-inactivation that appears to be directly related to the phosphorylation state of the Mr = 68,000 peptide. They strongly support the previous conclusion that double-stranded RNA is required only for activation of the kinase and phosphorylation of the Mr = 68,000 peptide.
An integrated top-down and bottom-up strategy for characterization of protein isoforms and modifications.

Bottom-up and top-down strategies are two commonly used methods for mass spectrometry (MS) based protein identification; each method has its own advantages and disadvantages. In this chapter, we describe an integrated top-down and bottom-up approach facilitated by concurrent liquid chromatography-mass spectrometry (LC-MS) analysis and fraction collection for comprehensive high-throughput intact protein profiling. The approach employs a high resolution reversed phase (RP) LC separation coupled with LC eluent fraction collection and concurrent on-line MS with a high field (12 Tesla) Fourier-transform ion cyclotron resonance (FTICR) mass spectrometer. Protein elusion profiles and tentative modified protein identification are made using detected intact protein mass in conjunction with bottom-up protein identifications from the enzymatic digestion and analysis of corresponding LC fractions. Specific proteins of biological interest are incorporated into a target ion list for subsequent off-line gas-phase fragmentation that uses an aliquot of the original collected LC fraction, an aliquot of which was also used for bottom-up analysis.
Excess pore pressures within subducting sediments: Does the proportion of accreted versus subducted sediments matter?

[1] Although previous numerical modeling studies have examined pore pressures in both accretionary and non-accretionary subduction zones, they have not addressed the question of whether the proportion of accreted versus subducted sediments significantly affects pore pressures. This modeling study used consistent parameters to compare excess pore pressures directly below the decollement for varying proportions of accreted sediment. Within the initial 5 to 12 kilometers arcward of the deformation front, subduction zones with lesser accretion thickness show lower simulated excess pore pressures than those with greater accretion thickness due to the ease of fluid escape when overlying wedge sediments are thin. However, at greater distances arcward of the deformation front, the magnitude of excess pore pressures significantly increases and the excess pore pressures peak further arcward as the proportion of underthrust sediments increases. This difference suggests that the proportion of accreted versus subducted sediment could potentially affect seismogenesis.
Composite co-activator ARC mediates chromatin-directed transcriptional activation

Gene activation in eukaryotes is regulated by complex mechanisms in which the recruitment and assembly of the transcriptional machinery is directed by gene- and cell-type-specific DNA-binding proteins. When DNA is packaged into chromatin, the regulation of gene activation requires new classes of chromatin-targeting activity. In humans, a multisubunit cofactor functions in a chromatin-selective manner to potentiate synergistic gene activation by the transcriptional activators SREBP-1a and Sp1. Here we show that this activator-recruited cofactor (ARC) interacts directly with several different activators, including SREBP-1a, VP16 and the p65 subunit of NF-kappaB, and strongly enhances transcription directed by these activators in vitro with chromatin-assembled DNA templates. The ARC complex consists of 16 or more subunits; some of these are novel gene products, whereas others are present in other multisubunit cofactors, such as CRSP, NAT and mammalian Mediator. Detailed analysis indicates that the ARC complex is probably identical to the nuclear hormone-receptor cofactor DRIP. Thus, ARC/DRIP is a large composite co-activator that belongs to a family of related cofactors and is targeted by different classes of activator to mediate transcriptional stimulation.
An efficient and simple method for the conversion of 15-HPETE to 14,15-EPETE (lipotriene A) and 5-HPETE to leukotriene a as the methyl esters

Abstract Simple new methodology is described for the synthesis from arachidonic acid of the important eicosanoids lipotriene A methyl ester (5) and leukotriene A methyl ester (10), a key feature being the use of a novel chemical method for effecting the allylic hydroperoxide → oxiranyl carbinol rearrangement.
An introduction to the application of interpretive structural modeling

Interpretive structural modeling is an emerging methodology which appears to be very useful as an aid to individuals and small groups in developing an understanding of complex situations. This paper presents an introduction to the fundamental concepts and operations of the methodology and reports on the results of two exercises conducted with a group of graduate students who had minimal mathematical training. The first exercise involved the structuring of personal values and was intended to acquaint the individuals with the methodology. The second was a group exercise focusing on barriers to investment in the central city, a subject of substantive interest to the participants. The results of the exercises demonstrate the utility of the methodology for capturing and communicating individual and group perceptions regarding complex issues.
Computed tomography in the evaluation of Dirofilaria immitis granuloma of the lung

Abstract Dirofilariasis is an infestation found primarily among canine species in the United States. Humans are imperfect hosts, and in them the worm dies, is embolized to the pulmonary vasculature, and presents as a solitary lung nodule. With routine radiographic techniques, this lesion cannot be differentiated from any other lung nodule or coin lesion. However, computerized tomography (CT) demonstrates its subpleural location, presence or absence of calcification, and further narrows the differential diagnosis, among which one should consider circumscribed pleural mesothelioma, loculated pleural effusion, pleural metastasis, and tumors of bone and soft tissue of the chest wall. This is the first report of CT evaluation of Dirofilaria immitis granuloma of the lung.
"Adaptive" behavior of ligand-gated ion channels: constraints by thermodynamics

The calcium-induced calcium release channel of the cardiac sarcoplasmic reticulum has been reported to inactivate in a novel manner (termed "adaptation"), which permits reactivation by exposure to successively higher concentrations of calcium. I examined the limitations placed by thermodynamics on the possible kinetic mechanisms for such behavior. The mechanism suggested by Gyorke and Fill, in which the affinity of a calcium-binding site decreases during adaptation, is not thermodynamically feasible for a passive system, but requires an external input of free energy. Possible sources of such energy are 1) metabolic energy, which is excluded by the fact that adaptation was observed in isolated channels in the absence of ATP, or 2) coupling of ion permeation to gating, for which there is currently no evidence. I derived a general limit on the thermodynamic feasibility of a sequence of channel activations and adaptations, irrespective of channel kinetics, from the requirement that the free energy must decrease during the spontaneous evolution of the system from the state existing immediately after a step increase in [Ca2+] to the state of maximum open probability that follows. The opening of the channel must involve an increase in free energy, which must be compensated by the free energy released by the incremental binding of calcium. This requirement leads to a complicated system of inequalities, which was simplified and manipulated algebraically into the form of a linear programming problem. Numerical solution of this problem showed that the sequence of adaptations of the SR channel observed by Gyorke and Fill requires the presence of at least 10 calcium-binding sites on the channel if it is to occur in the absence of exogenous sources of free energy. This indicates either that a large number of calcium-binding sites participate in the regulation of the SR calcium release channel, or that the existing data are significantly flawed with respect to the low open probability in the resting state, the importance of "calcium spike" artifacts from flash photolysis, or both.
Targeting the JMJD2 Histone Demethylases to Epigenetically Control Herpesvirus Infection and Reactivation from Latency

Chromatin and the chromatin modulation machinery not only provide a regulatory matrix for enabling cellular functions such as DNA replication and transcription but also regulate the infectious cycles of many DNA viruses. Elucidation of the components and mechanisms involved in this regulation is providing targets for the development of new antiviral therapies. Initiation of infection by herpes simplex virus (HSV) requires the activity of several cellular chromatin modification enzymes including the histone demethylases LSD1 and the family of JMJD2 proteins that promote transcriptional activation of the initial set of viral genes. Depletion of the JMJD2 members or inhibition of their activity with a new drug results in repression of expression of viral immediate early genes and abrogation of infection. This inhibitor also represses the reactivation of HSV from the latent state in sensory neurons. Like HSV, the β-herpesvirus human cytomegalovirus also requires the activity of LSD1 and the JMJD2s to initiate infection, thus demonstrating the potential of this chromatin-based inhibitor to be useful against a variety of different viruses.
Applying translucid contracts for modular reasoning about aspect and object oriented events

The Implicit Invocation (II) architectural style improves modularity and is promoted by aspect-oriented (AO) languages and design patterns like Observer. However, it makes modular reasoning difficult, especially when reasoning about control effects of the advised code (subject). Our language Ptolemy, which was inspired by II languages, uses translucid contracts for modular reasoning about the control effects; however, this reasoning relies on Ptolemy's event model, which has explicit event announcement and declared event types. In this paper we investigate how to apply translucid contracts to reasoning about events in other AO languages and even non-AO languages like C#
On the means of bio-production: Bioinformatics and how to make knowledge in a high-throughput genomics laboratory

Accounts of ‘biocapital’ abound in studies of the contemporary biosciences. However, these have tended to pay attention to the use and consumption of biological knowledge rather than the means and conditions of the production of data. This article draws on an ethnographic account of a high-throughput genomics laboratory (the Eli and Edythe L. Broad Institute, Cambridge, MA) to show how the means through which biological data is produced exerts a determinative effect on the kind of knowledge that is generated by the laboratory. High-speed, high-volume, high-efficiency production of data requires the high-throughput consumption of data by statistical and computational techniques. These techniques, in turn, generate general, broad-scale accounts of biological systems, rather than particular knowledge about individual genes or biological components. This cycle of production and consumption is described as ‘bioinformatics’ in order to indicate the centrality of computers and computing to the knowledge production process in contemporary biology.
The mitochondrial pyruvate dehydrogenase complex: nucleotide and deduced amino-acid sequences of a cDNA encoding the Arabidopsis thaliana E1 alpha-subunit

A cDNA encoding the E1 alpha subunit of the Arabidopsis thaliana (At) mitochondrial (mt) pyruvate dehydrogenase complex (PDC) was sequenced. The 1435-bp cDNA consists of a 1167-bp open reading frame encoding a 43.0-kDa polypeptide of 389 amino acids (aa) (pI 7.1). The plant E1 alpha subunit has 47-51% aa sequence identity with other eukaryotic sequences. Among the regions that are highly conserved are the aa surrounding phosphorylation sites 1 and 2 of the mammalian sequence, including the conserved Ser292 residue of At at site 1. An essential active site residue, Cys62 of the bovine subunit, is also conserved. A 32-aa presumptive mt targeting sequence is present at the N terminus.
The effects of uncertainty about age at transition on bias in the Mayfield family of estimators

Recent theoretical advances in nest survival estimation have demonstrated the importance of knowledge of nest age in improving nest survival estimates. However, data on the age of nests may be difficult to collect because nests may vary in developmental rate, handling eggs or nestlings may be too intrusive, or candling eggs and measuring nestlings may be infeasible due to nest location. We use a Mayfield Markov chain formulation to explore how bias in nest survival estimates arising from age-specific heterogeneity in transition probabilities can be managed through careful timing of nest visits. In general, the magnitude of bias is minimized when the dates of transitional events (hatching and fledging) are known exactly through daily monitoring. However, researchers can maintain similarly low levels of bias by concentrating nest visits around anticipated hatching and fledging dates, and allowing longer intervals between visits when no transition is imminent. This can reduce the number of required nest visits by about one third, depending on sample size. Accurate characterizations of the joint probability distributions of hatching and nest age, and fledging and nest age, can also reduce bias in daily survival estimates and are particularly important for overall success estimates.
Systems analysis of human brain gene expression: mechanisms for HIV-associated neurocognitive impairment and common pathways with Alzheimer’s disease

Human Immunodeficiency Virus-1 (HIV) infection frequently results in neurocognitive impairment. While the cause remains unclear, recent gene expression studies have identified genes whose transcription is dysregulated in individuals with HIV-association neurocognitive disorder (HAND). However, the methods for interpretation of such data have lagged behind the technical advances allowing the decoding genetic material. Here, we employ systems biology methods novel to the field of NeuroAIDS to further interrogate extant transcriptome data derived from brains of HIV + patients in order to further elucidate the neuropathogenesis of HAND. Additionally, we compare these data to those derived from brains of individuals with Alzheimer’s disease (AD) in order to identify common pathways of neuropathogenesis. In Study 1, using data from three brain regions in 6 HIV-seronegative and 15 HIV + cases, we first employed weighted gene co-expression network analysis (WGCNA) to further explore transcriptome networks specific to HAND with HIV-encephalitis (HIVE) and HAND without HIVE. We then used a symptomatic approach, employing standard expression analysis and WGCNA to identify networks associated with neurocognitive impairment (NCI), regardless of HIVE or HAND diagnosis. Finally, we examined the association between the CNS penetration effectiveness (CPE) of antiretroviral regimens and brain transcriptome. In Study 2, we identified common gene networks associated with NCI in both HIV and AD by correlating gene expression with pre-mortem neurocognitive functioning. Study 1: WGCNA largely corroborated findings from standard differential gene expression analyses, but also identified possible meta-networks composed of multiple gene ontology categories and oligodendrocyte dysfunction. Differential expression analysis identified hub genes highly correlated with NCI, including genes implicated in gliosis, inflammation, and dopaminergic tone. Enrichment analysis identified gene ontology categories that varied across the three brain regions, the most notable being downregulation of genes involved in mitochondrial functioning. Finally, WGCNA identified dysregulated networks associated with NCI, including oligodendrocyte and mitochondrial functioning. Study 2: Common gene networks dysregulated in relation to NCI in AD and HIV included mitochondrial genes, whereas upregulation of various cancer-related genes was found. While under-powered, this study identified possible biologically-relevant networks correlated with NCI in HIV, and common networks shared with AD, opening new avenues for inquiry in the investigation of HAND neuropathogenesis. These results suggest that further interrogation of existing transcriptome data using systems biology methods can yield important information.
On a singular feature of critical G/M/1 queues

Abstract In this paper, we consider a critically loaded G/M/1 queue and contrast its transient behaviour with the transient behaviour of stable (or unstable) G/M/1 queues. We show that the departure process from a critical G/M/1 queue converges weakly to a Poisson process. However, as opposed to the stable (or unstable) case, we show that the departure process of a critical GI/M/1 queue does not couple in finite time with a Poisson process (even though it converges weakly to one). Thus, as the traffic intensity (ratio of arrival to service rates), ϱ, ranges over (0, ∞), the point ϱ = 1 represents a singularity with regard to the convergence mode of the departure process.
A Graph−Theoretical View of Chemical Transport and Reaction on Networks

Certain new results are presented for the matrix representation of graphs, as it pertains to the graph-theoretical treatment of physicochemical transport networks. With the incidence matrix of graph theory identified as a derivative on a digraph, it is shown that the stoichiometric matrix plays a similar role on the digraph of chemical-reaction networks. These ideas are then applied to obtain the graph-theoretic representation of facilitated transport, one of several fields to which Professor John Quinn has made significant contributions (AIChE J. 1979, 25, 197−200).
The “Bail-Out” Technique: The Use of Segmental Mega-Prosthetic Reconstructions for Bony Nonunions

At best, failure to achieve bony union is an unusual occurrence with modern fracture care. The overwhelming majority of fractures unite uneventfully, and there are many techniques available to the surgeon to deal with difficult osteosynthesis. In certain situations, however, achieving union may prove impossible or may require more time than the patient has available. Mega-prosthetic reconstruction can provide a salvage or “bail-out” procedure for these difficult cases.
An integrated fast Fourier transform-based phase-field and crystal plasticity approach to model recrystallization of three dimensional polycrystals

A fast Fourier transform (FFT) based computational approach integrating phase-field method (PFM) and crystal plasticity (CP) is proposed to model recrystallization of plastically deformed polycrystals in three dimensions (3-D). CP at the grain level is employed as the constitutive description to predict the inhomogeneous distribution of strain and stress fields after plastic deformation of a polycrystalline aggregate while the kinetics of recrystallization is obtained employing a PFM in the plastically deformed grain structure. The elasto-viscoplastic equilibrium is guaranteed during each step of temporal phase-field evolution. Static recrystallization involving plasticity during grain growth is employed as an example to demonstrate the proposed computational framework. The simulated recrystallization kinetics is compared using the classical Johnson-Mehl-Avrami-Kolmogorov (JMAK) theory. This study also gives us a new computational pathway to explore the plasticity-driven evolution of 3D microstructures.
Cultured carrot cell mutants: 5-methyltryptophan-resistance trait carried from cell to plant and back

Abstract A mutant Daucus carota (carrot) cell line resistant to growth inhibition by 5-methyltryptophan was selected from normal cells by growth in the presence of this analog. Plants were regenerated from both normal and resistant cell cultures. Cell cultures were reinitiated from petioles of 32 plants which had originated from the resistant cell line and 4 from the normal line. All but one of these cultures derived from the resistant mutant, and none of those cultures derived from the normal plants, were resistant to growth inhibition by 5-methyltryptophan. The resistance to growth inhibition was apparently due to decreased uptake of the tryptophan analog and not due to altered feedback control of anthranilate synthetase as reported for other 5-methyltryptophan-resistant mutants described previously.
Indirect ego‐strengthening in treating PTSD in immigrants from Central America

As a result of civil war in El Salvador and Guatemala, hundreds of thousands of refugees fled to the USA during the 1980s. Many of these refugees experienced torture and other abuse, and current adaptation is complicated by post-traumatic stress disorder (PTSD). The scope of the problem is examined along with cultural factors in mental health treatment and the limitations of conventional exposure therapy. The authors describe two indirect, hypnotic ego-strengthening techniques that are useful in treating PTSD in this refugee population. Copyright © 2001 British Society of Experimental and Clinical Hypnosis
Proteomic Analysis of Vascular Endothelial Cells in Response to Laminar Shear Stress

Isotope-coded affinity tags (cICAT) coupled with mass spectrometric analysis is one of the leading technologies for quantitative proteomic profiling and protein quantification. We performed proteomic analysis of bovine aortic endothelial cells (BAEC) in response to laminar shear stress using cICAT labeling coupled with LC-MS/MS. Protein expressions in BAEC under 15 dynes/cm2 of shear stress for 10 min, 3 h, and 6 h were compared with matched stationary controls. Analysis of each sample produced 1800-2400 proteins at >or=75% confidence level. We found 142, 213, and 186 candidate proteins that were up- or down-regulated by at least two-fold after 10 min, 3 h, and 6 h of shear stress, respectively. Some of these proteins have known cellular functions and they encompass many signaling pathways. The signaling pathways that respond to shear stress include those of integrins, G-protein-coupled receptors, glutamate receptors, PI3K/AKT, apoptosis, Notch and cAMP-mediated signaling pathways. The validity of the mass spectrometric analysis was also confirmed by Western blot and confocal immunofluorescence microscopy. The present quantitative proteomic analysis suggests novel potential regulatory mechanisms in vascular endothelial cells in response to shear stress. These results provide preliminary footprints for further studies on the signaling mechanisms induced by shear stress.
Generalized gradient approximations for exchange and correlation : a look backward and forward

Abstract Ground-state properties of many-electron systems are calculable from the exchange-correlation energy as a functional of the electron spin densities n↑ (r), n↓ (r). After a review of the local spin density (LSD) approximation, the second-order density-gradient expansion (GEA), and the generalized gradient approximation (GGA) for exchange, prospects are discussed for a simple, first-principles GGA for correlation. The new GGA for correlation, like that for exchange, is based upon a real-space cut-off of the spurious long-range part of the gradient expansion for the fluctuation hole around an electron. Scaling relations, which lead to simple functionals, are stressed.