cssi/SciSciGPT-SciSciNet huggingface dataset:
Expression of p16INK 4a is a biomarker of chondrocyte aging but does not cause osteoarthritis.

Cellular senescence drives a functional decline of numerous tissues with aging by limiting regenerative proliferation and/or by producing pro‐inflammatory molecules known as the senescence‐associated secretory phenotype (SASP). The senescence biomarker p16 INK 4a is a potent inhibitor of the cell cycle but is not essential for SASP production. Thus, it is unclear whether p16 INK 4a identifies senescence in hyporeplicative cells such as articular chondrocytes and whether p16 INK 4a contributes to pathologic characteristics of cartilage aging. To address these questions, we examined the role of p16 INK 4a in murine and human models of chondrocyte aging. We observed that p16 INK 4a mRNA expression was significantly upregulated with chronological aging in murine cartilage (~50‐fold from 4 to 18 months of age) and in primary human chondrocytes from 57 cadaveric donors (r 2 = .27, p < .0001). Human chondrocytes exhibited substantial replicative potential in vitro that depended on the activity of cyclin‐dependent kinases 4 or 6 (CDK4/6), and proliferation was reduced in cells from older donors with increased p16 INK 4a expression. Moreover, increased chondrocyte p16 INK 4a expression correlated with several SASP transcripts. Despite the relationship between p16 INK 4a expression and these features of senescence, somatic inactivation of p16 INK 4a in chondrocytes of adult mice did not mitigate SASP expression and did not alter the rate of osteoarthritis (OA) with physiological aging or after destabilization of the medial meniscus. These results establish that p16 INK 4a expression is a biomarker of dysfunctional chondrocytes, but that the effects of chondrocyte senescence on OA are more likely driven by production of SASP molecules than by loss of chondrocyte replicative function.
Indications for Investigation of the Urinary Tract in the Newborn

The urinary tract in the newborn may require investigation for a number of reasons. The urinary tract is the commonest system in which abnormalities are detected during antenatal ultrasonography (USS). The majority will have isolated hydronephrosis, with mild dilatation detected in as many as 1:100 pregnancies. Others will have more significant urological abnormalities thus investigation of the urinary tract is indicated to interpret the antenatal USS findings. Investigation is also indicated for those neonates presenting with urinary tract related symptoms. Equally, in neonates presenting with non-specific symptoms such as failure to thrive, poor feeding or prolonged jaundice, urinary tract pathology should be considered. Finally, there are neonates with congenital anomalies or syndromes with known associated uropathies who require further investigation. The range of such conditions or syndromes in which the urinary tract may be involved is extensive.
Statistical Theory of Coulomb Blockade and Resonant Tunneling Oscillations in Quantum Dots

We develop a statistical theory of the amplitude of Coulomb blockade and resonant tunneling oscillations in semiconductor quantum dots based on the hypothesis that chaotic dynamics in the dot potential leads to behavior described by random matrix theory. We obtain a universal one-parameter distribution describing the fluctuations of the resonance amplitudes in the regime where a single thermally-broadened level dominates. As with other mesoscopic fluctuation phenomena, changing the fundamental symmetries of the dot hamiltonian(e.g. breaking time-reversal symmetry with a weak magnetic field) leads to changes in this distribution which should have experimentally-observable effects. The theory is tested numerically by calculating the resonance-width distribution of a very weakly disordered ensemble of dots and good agreement is found.
From CO2 to cell: energetic expense of creating biomass using the Calvin-Benson-Bassham and reductive citric acid cycles based on genome data.

The factors driving the dominance of the Calvin-Benson-Bassham cycle (CBB) or reductive citric acid cycle (rCAC) in autotrophic microorganisms in different habitats are debated. Based on costs for synthesizing a few metabolic intermediates, it has been suggested that the CBB poses a disadvantage due to higher metabolic cost. The purpose of this study was to extend this estimate of cost from metabolite synthesis to biomass synthesis. For 12 gammaproteobacteria (CBB) and 5 epsilonproteobacteria (rCAC), the amount of ATP to synthesize a gram of biomass from CO2 was calculated from genome sequences via metabolic maps. The eleven central carbon metabolites needed to synthesize biomass were all less expensive to synthesize via the rCAC (66–89% of the ATP needed to synthesize them via CBB). Differences in cell compositions did result in differing demands for metabolites among the organisms, but the differences in cost to synthesize biomass were small among organisms that used a particular pathway (e.g., rCAC), compared to the difference between pathways (rCAC vs CBB). The rCAC autotrophs averaged 0.195 moles ATP per g biomass, while their CBB counterparts averaged 0.238. This is the first in silico estimate of the relative expense of both pathways to generate biomass.
OPTIMAL ADVANCED TREATMENT AND PHOSPHOROUS REMOVAL BY DEEP BED FILTRATION

ABSTRACT Flocculation-filtration applied for advanced wastewater treatment and phosphorus elimination is discussed on the basis of practical experience gathered with the aid of a medium-sized pilot plant. It is shown that filtration allows very low residual phosphorus concentrations to be attained and that filtration as the second stage of phosphorus elimination results in substantial coagulant savings. Data from four computercontrolled parallel filters and long-term filtration tests (including backwashing) show the influence of the main parameters, e.g. addition of coagulant and flocculant aids, height and granulometry of filter layers, filtration, etc. It is thus possible to determine the filter characteristics and its operating conditions for optimal operation is a given case.
Jet cleansing: Separating data from secondary collision induced radiation at high luminosity

One of the greatest impediments to extracting useful information from high luminosity hadron-collider data is radiation from secondary collisions (i.e. pileup) which can overlap with that of the primary interaction. In this paper we introduce a simple jet-substructure technique termed cleansing which can consistently correct for large amounts of pileup in an observable independent way. Cleansing works at the subjet level, combining tracker and calorimeter-based data to reconstruct the pileup-free primary interaction. The technique can be used on its own, with various degrees of sophistication, or in concert with jet grooming. We apply cleansing to both kinematic and jet shape reconstruction, finding in all cases a marked improvement over previous methods both in the correlation of the cleansed data with uncontaminated results and in measures like $S/\sqrt{B}$. Cleansing should improve the sensitivity of new-physics searches at high luminosity and could also aid in the comparison of precision QCD calculations to collider data.
Thermosensitive, fast gelling, photoluminescent, highly flexible, and degradable hydrogels for stem cell delivery.

Abstract Stem cell therapy is a promising approach to regenerate ischemic cardiovascular tissues yet experiences low efficacy. One of the major causes is inferior cell retention in tissues. Injectable cell carriers that can quickly solidify upon injection into tissues so as to immediately increase viscosity have potential to largely improve cell retention. A family of injectable, fast gelling, and thermosensitive hydrogels were developed for delivering stem cells into heart and skeletal muscle tissues. The hydrogels were also photoluminescent with low photobleaching, allowing for non-invasively tracking hydrogel biodistribution and retention by fluorescent imaging. The hydrogels were polymerized by N-isopropylacrylamide (NIPAAm), 2-hydroxyethyl methacrylate (HEMA), 1-vinyl-2-pyrrolidinone (VP), and acrylate-oligolactide (AOLA), followed by conjugation with hypericin (HYP). The hydrogel solutions had thermal transition temperatures around room temperature, and were readily injectable at 4 °C. The solutions were able to quickly solidify within 7 s at 37 °C. The formed gels were highly flexible possessing similar moduli as the heart and skeletal muscle tissues. In vitro, hydrogel fluorescence intensity decreased proportionally to weight loss. After being injected into thigh muscles, the hydrogel can be detected by an in vivo imaging system for 4 weeks. The hydrogels showed excellent biocompatibility in vitro and in vivo, and can stimulate mesenchymal stem cell (MSC) proliferation and paracrine effects. The fast gelling hydrogel remarkably increased MSC retention in thigh muscles compared to slow gelling collagen, and non-gelling PBS. These hydrogels have potential to efficiently deliver stem cells into tissues. Hydrogel degradation can be non-invasively and real-time tracked. Statement of Significance Low cell retention in tissues represents one of the major causes for limited therapeutic efficacy in stem cell therapy. A family of injectable, fast gelling, and thermosensitive hydrogels that can quickly solidify upon injection into tissues were developed to improve cell retention. The hydrogels were also photoluminescent, allowing for non-invasively and real-time tracking hydrogel biodistribution and retention by fluorescent imaging.
Tuberous Sclerosis Complex

Tuberous sclerosis complex is a genetic neurocutaneous syndrome affecting 1/6000 live births. Neurobiologically, the manifestations have been linked to excessive activity of the protein kinase mammalian target of rapamycin, and treatments to target this aberration are clinically available. Sleep in TSC is a comorbidity that is not often studied; however, review of the literature reveals cases that warrant consideration when treating these patients. Increasing knowledge and study of sleep in TSC is a worthy pursuit as the targeted therapies currently available for tumors in this population may also have utility for sleep disturbances.
Sequencing Cell-Free DNA in the Maternal Circulation to Screen for Down Syndrome, Other Common Trisomies, and Selected Genetic Disorders

Up to three-quarters of pregnant women in the USA receive prenatal screening for Down syndrome (DS) and other fetal disorders. Historically, such testing has been based on combinations of maternal age, biochemical markers, and ultrasound findings with maximal detection rate for Down syndrome of 90% (sensitivity) at a false-positive rate of 2% (1-specificity) in a general pregnancy population. In 1997, a group from Hong Kong identified “fetal” cell-free (cf)DNA in maternal circulation. Unlike serum screening, cfDNA screening for Down syndrome is based directly on detection of extra chromosome 21 material from the fetal/placental unit. Following the 2011 publication of a prospective clinical trial of cfDNA, the first commercial prenatal screening test for Down syndrome based on circulating cfDNA was introduced into clinical practice. Among over 2000 DS and 200,000 euploid samples successfully tested, the detection rate for Down syndrome by a variety of cfDNA methods is presently over 99%, with a false-positive rate of about 0.2%. Multiple methodologies introduced by different laboratories have also shown detection rates at or above 95% for both trisomy 18 and trisomy 13. Occasionally (<1% to 5%), cfDNA testing fails to provide a usable results. Many of the commercial cfDNA tests also can identify the fetal sex as well as the common sex chromosome aneuploidies. This chapter discusses the use of cfDNA for the common autosomal trisomies, sex chromosome aneuploidies, microdeletions, nonviable chromosome disorders, emerging applications, technical limitations, emerging social and ethical issues, and areas for future study.
Sedentary lifestyle associated with mortality in rural patients with heart failure.

Background:The incidence of mortality five years after the onset of symptomatic heart failure is about 50%. Lifestyle behaviors differ substantially and likely lead to prognostic differences.Aims:W...
The Mechanism of Binding of Metabolites Derived from Polynuclear Hydrocarbons to Key Cellular Sites

This chapter presents studies on the mechanism of binding of metabolites derived from polynuclear hydrocarbons to key cellular sites. Much of the biological interest in diol epoxides was stimulated by the key observation by Borgen's group who discovered that binding of the trans -7, 8- dihydrodiol of benzo[a]pyrene to DNA is greatly enhanced in the presence of an active hepatic microsomal preparation. Subsequently, Sims and coworkers provided evidence that 7,8-diol-9,10-oxide ultimately accounts for such covalent binding of the ubiquitous polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP), to DNA of hamster embryo cells grown in the presence of this carcinogen. Further studies in this area by Sims and his group established that the fluorescence spectrum of DNA adducts isolated from mouse skin following treatment with BaP was similar to that obtained from salmon sperm DNA treated with BaP-7,8-diol-9,10-oxide. Even human bronchial explants have been utilized with success in these BaP diol epoxide binding studies. Thus, the evidence accumulated to date is consonant with the theory that the diol epoxide(s) is the primary reactive intermediate responsible for covalent binding of BaP to DNA that occurs in vivo .
Physical properties of RBi2 (R = La, Ce) under pressure

We present a study of electrical transport properties of $R{\mathrm{Bi}}_{2}$ $(R=\mathrm{La},\mathrm{Ce})$ under hydrostatic pressure up to $\ensuremath{\sim}2.5$ GPa. These measurements are complemented by thermodynamic measurements of the specific heat on ${\mathrm{CeBi}}_{2}$ at different pressures up to 2.55 GPa. For ${\mathrm{CeBi}}_{2}$, we find a moderate increase of the antiferromagnetic transition, ${T}_{\text{N}}$, from 3.3 K to 4.4 K by pressures up to 2.55 GPa. Notably, resistance measurements for both ${\mathrm{CeBi}}_{2}$ and ${\mathrm{LaBi}}_{2}$ show signatures of superconductivity for pressures above $\ensuremath{\sim}1.7$ GPa. However, the absence of superconducting features in specific-heat measurements for ${\mathrm{CeBi}}_{2}$ indicates that superconductivity in ${\mathrm{CeBi}}_{2}$ (and most likely ${\mathrm{LaBi}}_{2}$ as well) is not bulk and likely originates from traces of Bi flux, either on the surface of the platelike samples, or trapped inside the sample as laminar inclusions. Finally, we point out that extra caution should be exercised when claiming superconductivity based just on transport measurements, especially for Bi-containing compounds.
Agreement of claims-based methods for identifying sepsis with clinical criteria in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort

Claims-based algorithms are commonly used to identify sepsis in health services research because the laboratory features required to define clinical criteria may not be available in administrative data. We evaluated claims-based sepsis algorithms among adults in the US aged ≥65 years with Medicare health insurance enrolled in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Suspected infections from baseline (2003–2007) through December 31, 2012 were analyzed. Two claims-based algorithms were evaluated: (1) infection plus organ dysfunction diagnoses or sepsis diagnoses (Medicare-Implicit/Explicit) and (2) Centers for Medicare and Medicaid Services Severe Sepsis/Septic Shock Measure diagnoses (Medicare-CMS). Three classifications based on clinical criteria were used as standards for comparison: (1) the sepsis-related organ failure assessment (SOFA) score (REGARDS-SOFA), (2) “quick” SOFA (REGARDS-qSOFA), and (3) Centers for Disease Control and Prevention electronic health record criteria (REGARDS-EHR). There were 2217 suspected infections among 9522 participants included in the current study. The total number of suspected infections classified as sepsis was 468 for Medicare-Implicit/Explicit, 249 for Medicare-CMS, 541 for REGARDS-SOFA, 185 for REGARDS-qSOFA, and 331 for REGARDS-EHR. The overall agreement between Medicare-Implicit/Explicit and REGARDS-SOFA, REGARDS-qSOFA, and REGARDS-EHR was 77, 79, and 81%, respectively, sensitivity was 46, 53, and 57%, and specificity was 87, 82, and 85%. Comparing Medicare-CMS and REGARDS-SOFA, REGARDS-qSOFA, and REGARDS-EHR, agreement was 77, 87, and 85%, respectively, sensitivity was 27, 41, and 36%, and specificity was 94, 92, and 93%. Events meeting the REGARDS-SOFA classification had a lower 90-day mortality rate (140.7 per 100 person-years) compared with the Medicare-CMS (296.1 per 100 person-years), REGARDS-qSOFA (238.6 per 100 person-years), Medicare-Implicit/Explicit (219.4 per 100 person-years), and REGARDS-EHR classifications (201.8 per 100 person-years). Claims-based sepsis algorithms have high agreement and specificity but low sensitivity when compared with clinical criteria. Both claims-based algorithms identified a patient population with similar 90-day mortality rates as compared with classifications based on qSOFA and EHR criteria but higher mortality relative to SOFA criteria.
Distributed Estimation of an Uncertain Environment using Belief Consensus and Measurement Sharing

Recent advances in technology have increased the capability of mobile platforms while decreasing the cost. It has become more feasible to deploy a team of agents to cooperatively accomplish an objective. While multi-agent systems provide advantages, including lower cost and robustness to failure, there is a need for additional study of principles for the design and test of these decentralized systems. The main contribution of this paper is a novel estimation and path planning algorithm that can be used for improved estimation of uncertain environments. The estimation algorithm utilizes Bayesian fusion, measurement sharing on a graph, and belief consensus. One new component of this approach is the reward-based path planning algorithm that incentivizes agents to collect the best local information as well as improve coverage of the environment. When agents plan paths to collect more valuable information, the estimation error is reduced. This approach is studied for the application of estimating the state of a forest fire but can be applied in many domains. Simulations were performed to demonstrate the effectiveness of the algorithm compared to other approaches.
Investigating the relationship between working time characteristics on musculoskeletal symptoms: a cross sectional study.

How working hours are organized can have a substantial effect on workers' health. Using a questionnaire and cross-sectional study design, we evaluated the relationship between working time characteristics, job demands, and health behaviors on musculoskeletal symptoms among 316 Department of Transportation (N = 174) and Department of Corrections (N = 142) workers. Low schedule control was associated with neck/shoulder musculoskeletal symptoms (prevalence ratio: 1.20, 95% confidence interval: 1.06-1.34, p 48 hours per week) hours more frequently was associated with leg/foot musculoskeletal symptoms (prevalence ratio: 1.26 95% confidence interval: 1.06-1.50, p = 0.02). Some working time characteristics were associated with musculoskeletal symptoms, and should be taken into consideration as part of interventions to prevent musculoskeletal disorders and promote health of workers.
Effect of maternal overnutrition on predisposition to insulin resistance in the foal: Maternal parameters and foal pancreas histoarchitecture.

Results from previous studies indicate that maternal overnutrition during late gestation predisposes foals to metabolic disease, however, specific mechanisms resulting in disease remain unknown. Quarter Horse mares (n = 16), were randomly assigned to dietary treatments, beginning on gestational day 235, and consisted of a control group (CON- diet meeting nutrient requirement; n = 8) or an overfed diet (HIGH; n = 8) where mares received an additional 40 % above CON. On gestational days 285 and 315, an intravenous glucose tolerance test (FSIGTT) was conducted. Following parturition, foals were separated from the mare, prohibited from nursing, and an FSIGTT was conducted at 2 h postpartum. Foals were immediately euthanized and tissues preserved for analyses. There was no effect of treatment on foal BW (P = 0.50), pancreas weight (P = 0.60), or FSIGTT area under the curve for glucose (P = 0.80) and insulin (P = 0.70). Colocalization of α-amylase to isolate pancreatic islets of Langerhans indicated increased islet number and size in foals from HIGH mares (P 0.10). Foals exposed to overnutrition during peak fetal growth had altered pancreatic islet development that may lead to adult-onset metabolic disease.
The Edge-Distinguishing Chromatic Number of Petal Graphs, Chorded Cycles, and Spider Graphs

The edge-distinguishing chromatic number (EDCN) of a graph $G$ is the minimum positive integer $k$ such that there exists a vertex coloring $c:V(G)\to\{1,2,\dotsc,k\}$ whose induced edge labels $\{c(u),c(v)\}$ are distinct for all edges $uv$. Previous work has determined the EDCN of paths, cycles, and spider graphs with three legs. In this paper, we determine the EDCN of petal graphs with two petals and a loop, cycles with one chord, and spider graphs with four legs. These are achieved by graph embedding into looped complete graphs.
An insulator that regulates chromatin extrusion and class switch recombination.

In PNAS, Zhang et al. (1) report the discovery of the insulator function of a cluster of CTCF-binding elements (CBEs) that defines the 3′-boundary of the immunoglobulin (Ig) heavy (H) chain locus and regulates IgH class switch recombination (CSR) (Fig. 1). This study not only resolves uncertainties surrounding the functional relevance of these CBEs in CSR (2, 3) but further strengthens a “cohesion-mediated chromatin loop extrusion” model put forth in paradigm-shifting studies from the same investigators (4⇓–6). The CSR loop extrusion model postulates a “recombination center” composed minimally of Sµ, the synapsed donor switch (S) region, and a group of enhancers located at the 3′ end of the IgH locus. Cohesion-mediated chromatin extrusion within this ∼200-kb loop is responsible for recruiting a transcription-activated acceptor switch region into the recombination center to participate in CSR (5). This model has broadly applicable implications—beyond the realm of antigen receptor gene rearrangements (both V(D)J recombination and CSR)—as it is likely applicable to many biological processes that involve long-range chromatin dynamics. Fig. 1. A cluster of CBEs at the 3′ boundary of IgH locus regulate cohesion-mediated chromatin loop extrusion and CSR. In wild-type (WT) cells, the 3′IgH CBEs function as an insulator to restrict transcription activation by the 3′IgHRR and cohesion-mediated chromatin extrusion. In 3′IgH CBEs-deleted (∆) cells, 3′IgHRR spreads transcription activation in downstream regions, resulting in cohesion loading, chromatin extrusion, and generation of an eS region to participate in aberrant recombination. CSR is initiated by the B cell-specific enzyme activation-induced cytidine deaminase (AID), and … [↵][1]1Email: yuke{at}msu.edu. [1]: #xref-corresp-1-1
Understanding CBO's Medicare for All Cost Estimates

In December 2020, the Congressional Budget Office (CBO) released a comprehensive report analyzing the costs of a single-payer healthcare system of the kind usually referred to as “Medicare for All” (M4A). The report has not yet received as much public attention as it deserves, most likely because of ongoing controversies in the aftermath of November’s presidential election. CBO’s M4A federal cost estimates are significantly lower than those produced in other studies (including my own). The CBO report also provides much information about M4A not readily found elsewhere. In particular, the report illuminates the extent to which M4A would increase congestion in the US healthcare system and would likely lead to more denials of sought-after care. The purpose of this policy brief is to highlight the most significant information and findings in the CBO report and to explain how CBO’s estimates diverge from mine and those in other studies.
Quality of Life Evaluation in Chronic Illness Across Cultures

Quality of life (QOL) evaluation in chronic illness is a challenge even in one culture. Expanding that effort from our North American experience into Japanese language and culture has been an exciting and interesting challenge. Rigorous translation methods, followed by evaluation of measurement bias, will allow us to compare QOL in patients suffering from the same chronic diseases, who live in different cultures.
Influence of residual gravity on crystal growth processes

The effects of steady and time-dependent residual accelerations on representative melt and solution crystal growth systems have been investigated using numerical models. For the melt growth system, it was found that the lateral nonuniformity in crystal composition, depending on the particular operating conditions, can be very sensitive to the orientation of the steady component of the residual gravity vector down to 10 to the -6th g. Oscillatory residual accelerations (g-jitter) were found to lead to transients in the dopant distribution. For the solution growth, longtime simulations showed that at 10 to the -5th g, and the cooling rates used in Spacelab 3 experiments, diffusive transport dominates only in the beginning. Convective transport becomes increasingly significant after 3 to 5 hours, depending on the orientation of the crystal in the residual gravity field.
Sarbanes-Oxley: Legislating in Haste, Repenting in Leisure

This essay was prepared for presentation as a lecture to the Hoover Institution. In it, I focus on three areas in which the Public Company Accounting Reform and Investor Protection Act, popularly known as the Sarbanes-Oxley Act (SOX), has proven especially problematic. First, the legal ethics rules added to the Act at the last minute have proven incapable of dealing with the incentives that condition lawyers to turn a blind eye to client misconduct. Second, the structure Congress chose for the Public Company Accounting Oversight Board (PCAOB), the accounting oversight board created by SOX, turns out to have serious constitutional defects. Finally, and most importantly, corporate compliance costs have gone up far more than anyone anticipated and are staying up far longer than even Cassandra might have predicted. Worse yet, these costs disproportionately impact smaller public corporations, which are an important engine of economic growth. Taken together, these three areas of concern highlight why Congress should think twice before trying instant legislation in the future.
Non-Equilibrium Resonant Tunneling in Semiconductor Nanostructures

Resonant tunneling through quantum dots is reviewed. The spectrum corresponds to resonant tunneling from laterally-confined emitter contact subbands through the discrete 3-dimensionally confined quantum dot states. Momentum non-conservation is observed in these structures. We also present results on “molecule” structures (two dots connected by a tunnel barrier), and show that different mechanisms are required to explain the spectrums of the dot and molecule.
Towards formal verification of analog designs

We show how model checking methods developed for hybrid dynamic systems may be usefully applied for analog circuit verification. Finite-state abstractions of the continuous analog behavior are automatically constructed using polyhedral outer approximations to the flows of the underlying continuous differential and difference equations. In contrast to previous approaches, we do not discretize the entire continuous state space, and our abstraction captures the relevant behaviors for verification in terms of the transitions between "states" (regions of the continuous state space) as a finite state machine in the hybrid system model. The approach is illustrated for two circuits, a standard oscillator benchmark, and a much larger and more realistic delta-sigma (AI) modulator.
Mutations of Voltage‐gated Sodium Channels in Movement Disorders and Epilepsy

Spontaneous and induced mutations of neuronal Na+ channels in human patients and mutant mice result in a broad range of neurological-disease. Epilepsy, a disorder of neuronal hyperexcitability, has been associated with delayed inactivation of SCN2A in mice, and with altered kinetics of SCN1A in human patients. Movement disorders including tremor, ataxia, dystonia and paralysis have been observed in mice with mutations of SCN8A. Electrophysiological recordings from neurons isolated from mice with mutations in individual channels reveal the contributions of each channel to in vivo firing patterns. In addition to monogenic disease, Na+ channel mutations are likely to contribute to polygenic disease susceptibility and to normal variation in neuronal function. Advances in molecular methods coupled with genomic sequences from the Human Genome Project will permit identification of many new patient mutations and generation of animal models to dissect their physiological and cellular consequences.
Inside Mesons: Coupling Constants and Form Factors

We illustrate the progress of covariant QCD phenomenology for the description of meson coupling constants and form factors. As examples, we discuss the $\rho\pi\pi$ and $\gamma \pi\rho$ interactions, the $\rho$ contribution to the pion charge radius, and the $\rho NN$ and $\omega NN$ vector and tensor coupling constants and form factors.
Implementing intra-organizational learning:: A phased-model approach supported by intranet technology

Abstract The learning organization has been heralded as a proactive structure to address the amount and rate of change facing businesses today. A learning culture provides managers with the information and analyses necessary to modify their organizations to satisfy both internal and external stakeholders. Information technology has been identified as an enabler of organizational learning, yet it is insufficient in and of itself. Furthermore, the specific mechanisms to bring about learning in an organizational context have not yet been well articulated. This paper explores a phased-model implementation of learning in an organization and an intranet as the supporting information technology infrastructure that is most effective in creating and maintaining such a learning environment.
Soil organic carbon and nutrient status in old-growth montane coniferous forest watersheds, Isla Chiloé, Chile

Montane temperate forests of the Cordillera de Piuchue Ecosystem Study, Isla Chiloe, Chile, are unaffected by air pollution, timber exploitation and agricultural clearing, and the current floristic assemblage has been relatively stable for the past 7500 years. The apparent absence of major perturbation at this location makes it an appropriate baseline site for ecosystem analysis. We measured soil bulk density, pH, soil organic C (SOC), total N, and NH4Cl–exchangeable cations (Ca+2, Mg+2, K+, Na+, Al+3) in 0–10 and 10–40 cm depth samples from 72 soil profiles representing three vegetation zones: Fitzroya cupressoides Forest, Pilgerodendron uvifera–Tepualia stipularis Forest, and Magellanic Moorland. Fitzroya and Pilgerodendron–Tepualia Forests were indistinguishable for all measured soil characteristics (P > 0.05, Dunn's multiple comparison test on ranked data); these included very high median SOC concentrations (0–10 cm = 49.6%) and correspondingly low bulk density values (0–10 cm = 0.07). Moorland soil median values (0-10 cm) were significantly higher for bulk density (0.12) and lower for SOC (28.5%), but not for total N (Forests = 0.99%, Moorland = 0.95%), resulting in lower median C:N ratios for the moorland (Forests = 44.7; Moorland = 30.3). Across both depths and all three vegetation zones regression analysis indicated that SOC was an excellent predictor (R2; = 0.93, P < 0.001) of Σ (exchangeable Ca+2 + Mg+2 + K+ + Na+). Comparison with other old growth montane environments indicates that the Fitzroya and Pilgerodendron–Tepualia soil profiles are characterized by C:N ratios typical of other relatively unpolluted conifer forest soils (33.0–49.3). Soil profiles of representative polluted montane conifer forests have lower C:N ratios (16.2–23.5). Organic horizons from representative polluted montane conifer forests also retain fewer exchangeable base cations per unit SOC than are retained by organic horizons from the Cordillera de Piuchue forests.
Allowable imprecision for laboratory tests based on clinical and analytical test outcome criteria

The allowable imprecision for laboratory tests has been estimated from criteria based on clinical and analytical test outcome. The analytical outcome criteria studied are the Clinical Laboratory Improvement Amendments (CLIA) criteria for proficiency testing. The clinical outcome criteria are estimates of medically significant changes in test results taken from a study in the literature. The estimates of allowable imprecision were obtained from quality-planning models that relate test outcome criteria to the allowable amount of imprecision and inaccuracy and to the quality control that is necessary to assure achievement of the desired outcome criteria in routine operation. These operating specifications for imprecision are consistently more demanding (require lower CVs) than the medically useful CVs originally recommended in the literature because the latter do not properly consider within-subject biological variation. In comparing estimates of allowable imprecision, the CLIA outcome criteria are more demanding than the clinical outcome criteria for aspartate aminotransferase (asymptomatic patients), cholesterol, creatinine (asymptomatic patients), glucose, thyroxine, total protein, urea nitrogen, hematocrit, and prothrombin time. The clinical outcome criteria are more demanding for bilirubin (acute illness), iron, potassium, urea nitrogen (acute illness), and leukocyte count. The estimates of allowable imprecision from analytical and clinical outcome criteria overlap for aspartate aminotransferase (acute illness), bilirubin (asymptomatic patients), calcium, creatinine (acute illness), sodium, triglyceride, and hemoglobin.
Resonant tunneling in tunneling hot-electron transfer amplifier (THETA) structures

We have investigated a series of Tunneling Hot-Electron Transfer Amplifiers (THETAs) fabricated from the InGaAlAs system with abrupt collector-base isolation barriers. The turn-on characteristics of these structures can be modified by resonant tunneling, via a confined state in the base, occurring just before the expected ballistic turn-on.
Power, politics and MIS implementation

Theories of resistance to management information systems (MIS) are important because they guide the implementation strategies and tactics chosen by implementors. Three basic theories of the causes of resistance underlie many prescriptions and rules for MIS implementation. Simply stated, people resist MIS because of their own internal factors, because of poor system design, and because of the interaction of specific system design features with aspects of the organizational context of system use. These theories differ in their basic assumptions about systems, organizations, and resistance; they also differ in predictions that can be derived from them and in their implications for the implementation process. These differences are described and the task of evaluating the theories on the bases of the differences is begun. Data from a case study are used to illustrate the theories and to demonstrate the superiority, for implementors, of the interaction theory.
Analysis of the effects of fixture clamping sequence on part location errors

Abstract Several fixture-related error sources are known to contribute to part location error, which can lead to poor part quality. In addition to typical error sources, such as fixture geometric error and elastic deformation of the fixture and part due to clamping forces, the clamping sequence used can also influence part position and orientation. In this paper, the effect of clamping sequence on workpiece location error is modeled analytically for a fixture–workpiece system where all major compliance sources and fixture geometric error are considered. Part location error is quantified by the displacement of a response point on the part surface. An algorithmic procedure designed to understand how forces and deformations change as clamps are applied sequentially is presented. The effect of clamping sequence on part location error and locator reaction force is examined through model simulations and experiments via an example involving a 3-2-1 machining fixture.
TRAGEDY OF THE COMMONS AMONG ANTIBIOTIC RESISTANCE PLASMIDS

As social interactions are increasingly recognized as important determinants of microbial fitness, sociobiology is being enlisted to better understand the evolution of clinically relevant microbes and, potentially, to influence their evolution to aid human health. Of special interest are situations in which there exists a "tragedy of the commons," where natural selection leads to a net reduction in fitness for all members of a population. Here, I demonstrate the existence of a tragedy of the commons among antibiotic resistance plasmids of bacteria. In serial transfer culture, plasmids evolved a greater ability to superinfect already-infected bacteria, increasing plasmid fitness when evolved genotypes were rare. Evolved plasmids, however, fell victim to their own success, reducing the density of their bacterial hosts when they became common and suffering reduced fitness through vertical transmission. Social interactions can thus be an important determinant of evolution for the molecular endosymbionts of bacteria. These results also identify an avenue of evolution that reduces proliferation of both antibiotic resistance genes and their bacterial hosts.
Subclassifying Atypia in Urine Cytology: Is it Reproducible?

Results: The study group consisted of 8 male and 6 female patients; aged 49-83 years (mean: 71 years). 13/14 casees were diagnosed as positive; a single lymphoma case was orinaly classified as "negative", the overall accuracy of cytologic diagnoses was 93%. Of the ten cytomorphologic/ background features that were recorded; small clustering, nuclear molding, inconspicuous nucleoli characterized small cell carcinoma. Prominent nucleoli and inflamed background/diathesis were prevalent in lymphoma and melanoma cases. Intracellular pigment and multi-nucleation were recorded only in melanoma cases. Hyperchromasia was prominent feature in small cell carcinoma and melanoma cases. Conclusion: 1. The presence of small atypical cells in urine cytology should raise the possibility of underlying malignancy in urinary tract, even if the cystoscopic or other imaging findings are normal. 2. Small cell carcinoma can be accurately diagnosed in urine ThinPrep cytology by detecting cell clustering, nuclear molding, and hyperchromasia without prominent nucleoli. 3. The presence of small atypical cells with prominent nucleoli raise the suspicion for lymphoma or melanoma, while the accompaniment of tingible body macrophages may suggest follicular cystitis.
Bayesian Analysis Made Simple: An Excel GUI for WinBUGS

Brief Introduction to Statistics, Bayesian Methods, and WinBUGS Bayesian Paradigm WinBUGS Why Bother Using Bayesian Methods? BugsXLA Overview and Reference Manual Downloading and Installing BugsXLA BugsXLA Toolbar Bayesian Model Specification Set Variable Types MCMC & Output Options Predictions and Contrasts Prior Distributions Graphical Feedback Interface Model Checks Import Results Posterior Plots BugsXLA Options WinBUGS Utilities Normal Linear Models Generalized Linear Models Binomial Data Poisson Data Survival or Reliability Data Multivariate Categorical Data Normal Linear Mixed Models Generalized Linear Mixed Models Emax or Four-Parameter Logistic Non-Linear Models Bayesian Variable Selection Longitudinal and Repeated Measures Models Robust Models Beyond BugsXLA: Extending the WinBUGS Code Using BugsXLA's WinBUGS Utilities Editing the Initial MCMC Values Estimating Additional Quantities of Interest Appendix A: Distributions Referenced in BugsXLA Appendix B: BugsXLA's Automatically Generated Initial Values Appendix C: Explanation of WinBUGS Code Created by BugsXLA Appendix D: Explanation of R Scripts Created by BugsXLA Appendix E: Troubleshooting References Index
Scaling Laws of Bulk Plasma Parameters for a 1-D Flow through a Capillary with Extended Converging–Diverging Nozzle for Simulated Expansion into Fusion Reactor Chamber

A capillary-extended converging–diverging transition region was previously proposed to allow for the flow and expansion of plasma into a large volume simulating aerosol expansion and particle transport in the active volume of a fusion reactor. It has been shown that the pulsed electrothermal plasma source was adequate for the simulation, and the expansion into the chamber is at steady conditions for the main plasma parameters indicating a uniform expansion of the aerosol following a disruption event. These parameters are the bulk temperature, density, pressure, plasma bulk velocity and Mach number for the same system geometrical configuration. Scaling laws in 1-D for bulk plasma parameters have been developed for ranges of axial length traversed by the flow to predict these parameters along the axis of the expansion chamber.
Pet Loss and Mental Health

AbstractThe purpose of this article is to present results from a pilot study designed to assess the feasibility of conducting research among bereaved pet owners and to present a preliminary description comparing bereaved pet owners who received counseling to bereaved pet owners who did not. The overall response rate, calculated as all who returned a consent form divided by all who were mailed a consent form, was 45.1%, indicating a need to modify the contact procedure for future studies. Depressive symptoms were used as the outcome measure to assess differences between the bereaved owners who received counseling and those who did not. Controlling for the influences of age, gender, self-reported health, negative life changes, and type of pet, there were significant differences in depressive symptoms comparing those who received counseling and those who received no counseling. Individuals who received counseling were significantly more likely to have high depressive symptoms compared with those who received...
Radiological evaluation of bone status in the jaw and in the vertebral column in a group of women

Vertebral bone mineral content was determined in a group of 56 women, ages 30-62. These measurements were compared with the status of supporting bone in the jaws (alveolar, molar and bicuspid) and with gingival health. There was a significant decline in vertebral bone mineral content from the pre- to post-menopausal group. Molar and bicuspid measurements were highly correlated. There was some association between lumbar bone mineral content and molar bone status for postmenopausal women. For postmenopausal women, the cases of greatest percent bone loss in alveolar crest were associated with lower lumbar bone mineral content. Gingival health did not confound the bone status measurements. The 56 subjects did not exhibit the degree of reduction in bone density that is observed in the general population. Further investigation using these radiographic techniques may reveal a link between substantial bone loss in the jaw and moderate to severe bone loss in the lumbar vertebrae.
Synthesis of bicyclo[5.3.0]azulene derivatives

Azulene has been recognized for its application in medicinal therapy against inflammation. Recently, azulene analogs have been used in optical technology. Nevertheless, synthesis of this family of compounds is always associated with multiple challenges. In this protocol, we describe a time-efficient and cost-effective procedure for the preparation of azulene derivatives from 2-hydroxycyclohepta-2,4,6-trienone (tropolone), a readily available starting material. The technique illustrated here involves a cycloaddition reaction of a lactone with the in situ-generated vinyl ether from 2,2-dimethoxypropane during the thermolysis reaction. The three-step synthesis should take <4 d, resulting in an overall yield of 74% with a final step yield of 91%.
Blocking HIV-1 gp120 at the Phe43 Cavity: If the Extension Fits…

The Phe43 cavity is a mysterious feature in crystallographic structures of HIV-1 gp120-CD4 complexes. In this issue of Structure, Acharya and colleagues provide structural explanations for the potent neutralization by CD4 mimetic miniproteins with chemical extensions that fit into this cavity.
A quality control framework for bus schedule reliability

Abstract This paper develops and demonstrates a quality control framework for bus schedule reliability. Automatic vehicle location (AVL) devices provide necessary data; data envelopment analysis (DEA) yields a valid summary measure from partial reliability indicators; and panel data analysis provides statistical confidence boundaries for each route-direction’s DEA scores. If a route-direction’s most recent DEA score is below its lower boundary, it is identified as in need of immediate attention. The framework is applied to 29 weeks of AVL data from 24 Chicago Transit Authority bus routes (and therefore 48 route-directions), thereby demonstrating that it can provide quick and accurate quality control.
Research note on evaluation of the plastic deformation of beams under transverse impact

Abstract The permanent deformation of a rigid perfectly plastic beam subjected to a time-dependent line load is calculated. The beam has finite length, and the load is applied transversely in the middle of the span. At the initial time, the load is zero. Thereafter, the load has a triangular time dependence. For sufficiently large values of the peak load, static and moving plastic hinges appear, and the beam is subjected to plastic bending. Previous studies of this problem have provided a numerical solution of a system of approximate equations. In this article, a numerical solution of the system of exact equations is provided. The numerical results represent a significant improvement over those that were previously available.
Cognitive style and adult learning principles

(1992). Cognitive style and adult learning principles. International Journal of Lifelong Education: Vol. 11, No. 1, pp. 3-14.
"Muy poco se sabe de los resultados": Francis E. Bond's expedition to the Paria Peninsula and delta of the Orinoco, Venezuela (1911).

The natural history expedition of the American banker and stock broker Francis E. Bond and companions to the Paria Peninsula and delta of the Orinoco, Venezuela, in early 1911 is described. Biographical details are provided for the three principals; Francis E. Bond, Stewardson Brown and Thomas S. Gillin. The itinerary of their three and a half month expedition is elaborated, and notes are provided on the collections of plants, animals, and artefacts that they gathered in South America and deposited in the Academy of Natural Sciences of Philadelphia on their return.
Borrow or Buy? Cost-Effective Delivery of Monographs

ABSTRACT In an effort to reduce Interlibrary borrowing activity, while enhancing the Library collection, the Bertrand Library has initiated a program to purchase current monographs requested through ILL by Bucknell University students and faculty. The results have been a successful reduction in ILL workload, and a cost-effective means of document delivery as measured by average delivery time, cost-per-title, processing costs, and circulation statistics. This procedure reflects an overall change in our philosophy concerning document access and delivery, which led to the reorganization of ILL services and staff in the Bertrand Library.