cssi/SciSciGPT-SciSciNet huggingface dataset:
A Change Management Case Study for Safe Opioid Prescribing and Opioid Use Disorder Treatment.

Background: Given that prescribing practices have contributed to the current opioid epidemic and that primary care clinicians are the largest prescribers of opioids, family physicians must consider the twin goals of safely prescribing opioids for patients with chronic pain while effectively identifying and treating those who have developed opioid use disorder (OUD). However, family physicians may feel constrained by a culture and systems in their offices that do not support achieving these twin goals. Methods: In a family medicine clinic within a larger academic institution that cares for an underserved, multicultural patient population in the greater Boston area, we provide a case study that illustrates the twin goals of safe opioid prescribing and treating OUD. We used 2 models of change management—Lewin9s Three-Step Change Theory and the McKinsey 7S Model of Change—as a framework to describe our 5-year process of using cultural and structural elements to support these efforts. Results: Deliberate use of change management theory to support both safe opioid prescribing and treating patients with OUD over the past 5 years resulted in changes to the practices, people, skills, and infrastructure within our clinic. These changes have demonstrated a sense of stability and sustainability and hence now represent our clinic9s current culture. Conclusion: The Lewin and 7S models of change can be helpful guides to creating and maintaining a foundation of office-wide culture and structural support to meet the twin goals of safe opioid prescribing and treating patients with OUD.
Intraspecific competition reduces plant size and quality and damage severity increases defense responses in the herbaceous perennial, Asclepias syriaca

Competition among plants within populations affects plant size, nutrient status and allocation to defenses. Herbivory places additional stress on plant allocation of resources. When resources are limited due to intraspecific competition, induced defenses may reduce costs of defense responses and trade-offs between allocation to growth or defense. We hypothesized that increased intraspecific competition would result in a decrease in plant size and leaf tissue nutrient quality, and that both intraspecific competition and leaf damage severity would affect inducibility of leaf defensive traits. We tested these hypotheses in common milkweed (Asclepias syriaca) using greenhouse experiments that manipulated plant density and damage severity treatments. We measured a suite of leaf traits generally related with herbivore performance, including size; nitrogen, carbon, lignin, and fiber concentrations; and latex production. Increased density decreased plant size and leaf nutrient quality, but increased lignin levels. Damage severity increased leaf lignin levels and latex production. There were no density–damage severity interactions. We additionally addressed the question of whether plants respond differently to simulated or natural herbivory and hypothesized that insect herbivores and mechanical plant tissue removal would similarly affect induced defensive responses. Leaf fiber and lignin increased in response to damage, but the response was greater on plants subjected to simulated, compared with caterpillar herbivory. Other plant traits responded similarly to either damage type. Our findings suggest that intraspecific competition has the potential to generate feedbacks among plants and herbivores as plants respond to herbivory.
3D-printed microfluidic device with in-line amperometric detection that also enables multi-modal detection

Microfluidic amperometric detectors often include a reservoir to house auxiliary and reference electrodes, making subsequent detection downstream challenging. Here, we present an in-line microfluidic device with amperometric detection that incorporates a three-electrode set-up, made possible by threading electrodes into a 3D-printed flow cell. The electrodes consist of a commercially available threaded reference electrode and electrodes fabricated in commercially available fittings. This approach centers the working electrode in the fluidic channel enabling the use of a pillar working electrode that is shown to increase sensitivity, as compared to a traditional thin-layer electrode. In addition, the working and auxiliary electrodes can be directly opposed, with this configuration leading to a more uniform potential being applied to the working electrode as well as fewer issues with any iR drop. To demonstrate the ability to incorporate a separate mode of detection downstream from the electrochemical flow cell, the device is modified to include a mixing T for introduction of reagents for chemiluminescent detection of ATP (via the luciferin–luciferase reaction), leading to a single 3D-printed device that can be used to detect norepinephrine and ATP, nearly simultaneously, by amperometry and chemiluminescence, respectively. This approach opens numerous possibilities, where microfluidics with in-line amperometry can be used in continuous circulation studies or in conjunction with other downstream detection events to study complex systems.
Entrepreneurship, Coping, and Eudaimonic Well-Being

Using data from wave 2 and 3 of the National Study of Midlife in Development in the United States (N=3669), the present study investigates the link between entrepreneurship and eudaimonic well- bei...
Effects of Intensive Systolic Blood Pressure Control on All-Cause Hospitalizations.

Intensive blood pressure control decreases the rate of cardiovascular events by >25% compared with standard blood pressure control. We sought to determine whether the decrease in cardiovascular events seen with intensive blood pressure control is associated with an increased rate of other causes of hospitalization. This is a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial) in 9361 adult participants with hypertension and elevated cardiovascular risk. Participants were randomly assigned to an intensive or standard systolic blood pressure goal ( 1 hospitalization was seen in 38.8% of intensive arm participants and 41.9% of standard arm participants (P=0.08). The mean cumulative count of nonprimary event hospitalizations was comparable between the two arms. The most common causes of hospitalization were cardiovascular (23.6%) followed by injuries, including bone and joint therapeutic procedures (15.7%), infections (12.0%), and nervous systems disorders (10.7%). No categories of hospitalization were statistically more common in the intensive arm compared with the standard arm. Thus, the decrease in cardiovascular events seen with intensive blood pressure control is not associated with an increased rate of other causes of hospitalization. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.
Clinical effects associated with five-year retinal nerve fiber layer thinning in multiple sclerosis.

BACKGROUND Neurodegenerative changes in multiple sclerosis (MS) are associated with long-term disability progression (DP). Optical coherence tomography (OCT) measures may be used to monitor DP. OBJECTIVE To determine significant effects driving the changes in OCT-based peripapillary retinal nerve fiber layer (pRNFL) in heterogeneous group of MS patients. METHODS Total of 144 MS patients (109 relapsing-remitting MS and 35 progressive MS (PMS) with mean age at baseline of 47.6 and 56.5 years old, respectively) underwent clinical and OCT examination over 5-year follow-up. All OCT exams were reviewed using the OSCAR-IB criteria. The 5-year DP was determined based on Expanded Disability Status Scale (EDSS) changes and MS clinical trial criteria. Data regarding previous history of MS optic neuritis (MSON) and use of disease modifying treatment (DMT) was derived by in-person interview and review of electronic medical records. Mixed model-type of repeated measure analysis determined effects driving pRNFL change for analysis which utilized all eyes separately. RESULTS Over an average of 5.3-years follow-up, the MS population demonstrated significant pRNFL thinning (F = 16.108, p < 0.001). The pRNFL thinning was greater due to progressive MS subtype (F = 5.102, p = 0.025), greater age at baseline (F = 4.554, p = 0.034), occurrence of DP (F = 6.583, p = 0.011), and previous history of MSON (F = 7.053, p = 0.008). Use of any or highly potent DMT (natalizumab versus first-line injectable treatments versus no DMT) significantly reduced the pRNFL thinning (F = 8.367, p = 0.004) over the follow-up. Lastly, occurrence of DP in PMS patients older than 50 years old was associated with greater pRNFL thinning (F = 6.667, p = 0.013). CONCLUSION Longitudinal pRNFL changes are modified by age, disease subtype, disabiltiy progression, history of MSON, DMT use and their interactions.
Evaluation of Seizure Risk in Infants After Cardiopulmonary Bypass in the Absence of Deep Hypothermic Cardiac Arrest.

Guidelines recommend evaluation for electrographic seizures in neonates and children at risk, including after cardiopulmonary bypass (CPB). Although initial research using screening electroencephalograms (EEGs) in infants after CPB found a 21% seizure incidence, more recent work reports seizure incidences ranging 3–12%. Deep hypothermic cardiac arrest was associated with increased seizure risk in prior reports but is uncommon at our institution and less widely used in contemporary practice. This study seeks to establish the incidence of seizures among infants following CPB in the absence of deep hypothermic cardiac arrest and to identify additional risk factors for seizures via a prediction model. A retrospective chart review was completed of all consecutive infants ≤ 3 months who received screening EEG following CPB at a single center within a 2-year period during 2017–2019. Clinical and laboratory data were collected from the perioperative period. A prediction model for seizure risk was fit using a random forest algorithm, and receiver operator characteristics were assessed to classify predictions. Fisher’s exact test and the logrank test were used to evaluate associations between clinical outcomes and EEG seizures. A total of 112 infants were included. Seizure incidence was 10.7%. Median time to first seizure was 28.1 h (interquartile range 18.9–32.2 h). The most important factors in predicting seizure risk from the random forest analysis included postoperative neuromuscular blockade, prematurity, delayed sternal closure, bypass time, and critical illness preoperatively. When variables captured during the EEG recording were included, abnormal postoperative neuroimaging and peak lactate were also highly predictive. Overall model accuracy was 90.2%; accounting for class imbalance, the model had excellent sensitivity and specificity (1.00 and 0.89, respectively). Seizure incidence was similar to recent estimates even in the absence of deep hypothermic cardiac arrest. By employing random forest analysis, we were able to identify novel risk factors for postoperative seizure in this population and generate a robust model of seizure risk. Further work to validate our model in an external population is needed.
Redistributing the world's wealth: Cancun ‘summit’ discord

Abstract The aim of the North-South ‘summit’ conference in 1981 was to bridge the wealth gap between the few industrial nations and the hundred-odd poor countries. Unfortunately no firm proposals materialized. The rich nations refused to increase their aid transfers to the developing countries or to correct the growing inequalities in world trade. The multiplication of wealth is the basic concern of the North in an era of recession and unemployment. The division of wealth is an urgent necessity for the South, but their demands for a global reallocation of resources remained unmet. The gap is likely to widen considerably in future.
Sialic acid contents of sindbis virus from vertebrate and mosquito cells. Equivalence of biological and immunological viral properties.

Abstract Sindbis virus grown in Aedes albopictus cells, in contrast to virus grown in vertebrate cells, lacks sialic acid. The presence or absence of sialic acid has no effect on the antigenic properties of these viruses as tested by complement fixation, hemagglutination inhibition, neutralization, and immune virolysis. The particle/hemagglutination unit and particle/plaque-forming unit ratios are not significantly different for virus grown in CEF (chick embryo fibroblast), BHK, or A. albopictus cells.
Regulation of glutamine synthetase in cultured Chinese hamster cells. Induction and repression by glutamine.

Abstract Glutamine synthetase activity in Chinese hamster cells in tissue culture possesses properties identical with purified liver glutamine synthetase. The cellular level of enzyme is regulated by the concentration of glutamine in the growth media. Induction by removal of glutamine leads to an 8- to 10-fold increase in enzyme activity within 48 hours. Repression is a much more rapid process. Half of the activity is lost within 12 min after adding 1 mm glutamine to the media, and full repression occurs in 8 hours. The decrease in enzyme activity is directly proportional to glutamine for concentrations less than 0.3 mm. Actinomycin D has little effect on induction or repression, indicating that regulation does not occur at the level of messenger RNA synthesis. Cycloheximide blocks induction, indicating that protein synthesis (perhaps of new enzyme) is required for increased enzyme levels. Protein synthesis is not required for repression. We propose that a glutamine-mediated modification of glutamine synthetase is responsible for repression of enzyme activity.
Individuality and Variation of Personal Regulomes in Primary Human T Cells

Here we survey variation and dynamics of active regulatory elements genome-wide using longitudinal samples from human individuals. We applied Assay of Transposase Accessible Chromatin with sequencing (ATAC-seq) to map chromatin accessibility in primary CD4+ T cells isolated from standard blood draws of 12 healthy volunteers over time, from cancer patients, and during T cell activation. Over 4,000 predicted regulatory elements (7.2%) showed reproducible variation in accessibility between individuals. Gender was the most significant attributable source of variation. ATAC-seq revealed previously undescribed elements that escape X chromosome inactivation and predicted gender-specific gene regulatory networks across autosomes, which coordinately affect genes with immune function. Noisy regulatory elements with personal variation in accessibility are significantly enriched for autoimmune disease loci. Over one third of regulome variation lacked genetic variation in cis, suggesting contributions from environmental or epigenetic factors. These results refine concepts of human individuality and provide a foundational reference for comparing disease-associated regulomes.
Intracellular compartmentalization and degradation of free polymannose oligosaccharides released during glycoprotein biosynthesis

Abstract The intracellular site for the degradation of free polymannose oligosaccharides released during glycoprotein biosynthesis has been studied by permeabilizing the plasma membrane of metabolically radiolabeled HepG2 cells with streptolysin O. This pore-forming agent permitted us to examine the breakdown in both the cytosolic and vesicular compartments of the previously recognized (Anumula, K. R., and Spiro, R. G. (1983) J. Biol. Chem. 258, 15274-15282) polymannose components terminating in a di-N-acetylchitobiose sequence (OS-Glc-NAc2) or a single N-acetylglucosamine residue (OS-Glc-NAc1) residue. Pulse-chase studies indicated that although the OS-GlcNAc2 saccharides were about equally distributed between vesicles and cytosol and rapidly disappeared after reaching the Man8 stage, the OS-GlcNAc1 species were found predominantly in the extravesicular compartment and there underwent a distinctive demannosylation sequence resulting in the formation of a Man5GlcNAc isomer (Man alpha 1-->2Man alpha 1-->2Man alpha 1-->3(Man alpha 1-->6)Man beta 1-->4GlcNAc) which was different from the product of Golgi processing enzymes. Further trimming of this cytosolic limit product required its translocation into a vesicular compartment, believed to be lysosomes, in which Man2-4GlcNAc components appeared as the metabolic chase progressed. The accumulation of Glc1Man5GlcNAc in the cytosol during the chase suggested that glucose interferes with the cytosolic-vesicular transfer and this became even more evident by the pronounced pile-up of extravesicular Glc3Man5GlcNAc when the cells were incubated in the presence of castanospermine. Although the biological significance and mechanism of free polymannose oligosaccharide entry into the cytosol is not yet known, the possibility that it may reflect an endoplasmic reticulum-situated degradative process of glycoproteins merits consideration.
Marker Grids for Observing Motion in MRI

The sections in this article are 1 Introduction 2 Tag Production 3 Tagged Image Analysis 4 Applications 5 Biographical Sketch Related Articles
The Duty to Creditors Reconsidered - Filling a Much Needed Gap in Corporation Law

The most fundamental question of corporation law is to whom does the board of directors of a corporation owe its fiduciary duty. Recently, the question has tended to be whether and under what circumstances the board of directors has the duty to maximize stockholder wealth. But if a corporation is insolvent (or close to it), business decisions designed to maximize stockholder wealth may result in a reduction of creditor wealth. Although the conventional wisdom is that creditors must protect themselves by contractual means, there is a substantial body of case law that says that creditors can assert claims sounding in fiduciary duty. Until recently, most such decisions have come from the bankruptcy courts. The state courts, who have primary jurisdiction with regard to the interpretation of corporation law, have had few opportunities to say otherwise. But in Credit Lyonnais Bank Nederland v. Pathe Communications (1991) and Production Resources Group v. NCT Corporation (2004), the Delaware Court of Chancery confirmed that the protections of fiduciary duty extend to creditors (in addition to stockholders) - at least when a corporation is in fact insolvent and possibly when it may be rendered so by the business decision in question - on the theory that the board of directors ultimately has the duty to maximize the value of the firm as a whole. These unfortunate decisions have led creditors and commentators to argue for a wholly new body of creditor rights and have encouraged further loose talk from the bankruptcy courts who must apply state law in this difficult setting. The fallacy inherent in extending the protections of fiduciary duty to creditors is that stockholders themselves enjoy no remedy except in situations in which the corporation is for sale - a situation in which there is little danger of harm to creditors. The board of directors is otherwise under no enforceable duty to maximize stockholder wealth. And the CEO typically has a strong incentive to ensure the survival of the firm. In situations in which the board of directors has failed to maximize stockholder wealth, the stockholders are protected by the market for corporate control rather than a legal remedy. Under the business judgment rule, the stockholders cannot challenge such decisions in court. Neither should the creditors be able to do so. Thus, even though creditors might favor a rule that favors them when the board of directors is tempted to bet the farm on a risky business strategy, they have no need for a remedy. Fortunately, the cases in which creditors have prevailed up to now are cases in which they should have prevailed anyway under fraudulent transfer law. But the law would be better served if the courts made it clear once and for all that fiduciary duty is about the stockholders and no one else.
Hot and Bothered: Women, Medicine, and Menopause in Modern America

Introduction 1. "Hold Oneself Well in Hand": Medicine, Menopause, and the New Woman 2. "Endocrine Perverts" and "Derailed Menopausics": Gender Transgressions and Mental Disorders, 1897-1937 3. "Consider the Patent as a Woman and Not a Groups of Gland": Women, Menopause, and the Medical Encounter, 1938-1962 4. Domesticity and Liberation: Menopause in the Popular Literature, 1938-1962 5. "Casting an Evil Spell over Her Once Happy Home": Menopause as a Family Disease, 1938-1962 6. "Why All the Fuss?" Middle-Class Women and the Denial of the Menopausal Body, 1938-1962 7. Feminine Forever: Robert A. Wilson and the Hormonal Revolution, 1963-1980 8. "At the Will and Whim of My Hormones": Women, Menopause, and the Hormonal Imperative 9. "What Do These Women Want?" Feminist Responses to Feminine Forever Epilogue. Aging Supermodels and Inner Crones: Menopause at the Turn of the Twenty-First Century Notes Index
Multiculturalism in medical decisionmaking: the notion of informed waiver.

Beginning with the proposition that the western medical tradition of emphasizing patient autonomy undermines a patient’s ability to limit his or her role in medical decision-making, the author of this student note proposes a model of informed waiver to counterbalance the perceived legal bias towards informed consent. Part I explains the western notion of patient autonomy in two distinct ways: first, autonomy is rooted in western ideals of self-governance and political freedom; second, the article discusses how this idea has been developed in American courts. In Part II, the author draws on anecdotal and empirical evidence to demonstrate that autonomy is not an appropriate standard for the experience of all patients. Finally, the article concludes by proposing a framework whereby culture might be incorporated into a definition of autonomy in legal and medical practice. In particular, the author offers a notion of informed waiver as a compromise for patients who choose to forego the western-defined approach to decision-making. MULTICULTURALISM IN MEDICAL DECISIONMAKING: THE NOTION OF
Necessary and sufficient factors in classical conditioning.

The issue of necessary and sufficient factors (pairing-contiguity vs. contingency-correlation) in classical (Pavlovian) excitatory conditioning is examined: first, in terms of definitional (logical) and manipulational requirements of "necessary" and "sufficient"; second, in terms of Boolean logic test models indicating experimental and control manipulations in tests of pairing and contingency as necessary and sufficient factors; and, third, by a selective review of reference experiments showing appropriate experimental and control manipulations of pairing and contingency indicated in the Boolean logic test models. Results of examination show pairing-contiguity as the sole necessary and sufficient factor for excitatory conditioning, while contingency-correlation is conceptualized as a modulating factor controlling minimal-maximal effects of pairing-contiguity. Reservations and diagnostic experiments are indicated to assess effects of uncontrolled conditioned stimulus--unconditioned stimulus (--CS--US) probability characteristics (e.g., p (CS--US)/p (--CS--US) in truly random (TR) schedule manipulations). Similar analysis of conditioned inhibition reveals insufficient evidence to support a choice among current alternatives.
General Formulation of an HCDA Bubble Rising in a Sodium Pool and the Effect of Nonequilibrium on Fuel Transport

Consideration is given to a fuel-dominated bubble, which is assumed to have just penetrated into the sodium pool in a spherical form subsequent to a hypothetical core disruptive accident. The two-p...
Far Ultraviolet Spectroscopic Explorer Observations of CO and H2 Emission in Comet C/2001 A2 (LINEAR)

Observations of comet C/2001 A2 (LINEAR) were made with the Far Ultraviolet Spectroscopic Explorer beginning 2001 July 12.58 and coinciding with a photometric increase of ~1.5 mag. Spectra were obtained in the 905-1180 A range at 0.25 A spectral resolution using the 30'' × 30'' aperture. Several new cometary emissions were identified, particularly the (0, 0) bands of the CO Hopfield-Birge systems C-X and B-X at 1088 and 1151 A, respectively, O I (1D-1D) at 1152 A, and three lines of the H2 Lyman system at 1071.6, 1118.6, and 1166.8 A, pumped by solar Lyβ fluorescence. Also detected were O I multiplets at 989, 1027, and 1040 A and several lines of the H I Lyman series. The rotational envelopes of the CO bands are resolved and appear to consist of both "cold" and "hot" components, the cold component accounting for 70% of the flux and with a rotational temperature of 55 ± 5 K. The hot component may be indicative of a CO2 source. The CO bands, H2 lines, and O I λ1152 all decreased by a factor of 2 over the 7.5 hr observation. The derived time-averaged production rates are Q(CO) = 1.3 × 1027 molecules s-1 and Q(H2O) = 2.1 × 1029 molecules s-1. These values may be uncertain by as much as a factor of 2 because of uncertainties in the solar flux and the electron impact contribution to the excitation.
The GLAST Guest Investigator Program

We provide an overview of the GLAST Guest Investigator (GI) program, which will support basic research relevant to the GLAST mission in yearly cycles beginning approximately two months after launch. Current details about the GLAST GI program will always be posted on the GLAST Science Support Center (GSSC) website: http://glast.gsfc.nasa.gov/ssc/.
A C-terminal skeletal muscle sodium channel mutation associated with myotonia disrupts fast inactivation.

Missense mutations in the skeletal muscle sodium channel α-subunit gene (SCN4A) are associated with a group of clinically overlapping diseases caused by alterations in the excitability of the sarcolemma. Sodium channel defects may increase excitability and cause myotonic stiffness or may render fibres transiently inexcitable to produce periodic paralysis. A patient with cold-aggravated myotonia did not harbour any of the common SCN4A mutations. We therefore screened all 24 exons by denaturing high-performance liquid chromatography, followed by direct sequencing. Two novel missense changes were found with predicted amino acid substitutions: T323M in the DIS5-S6 loop and F1705I in the intracellular C-terminus. The functional impact of these substitutions was assessed by recording whole-cell Na+ currents from transiently transfected HEK293 cells. T323M currents were indistinguishable from wild-type (WT). Fast inactivation was impaired for F1705I channels, as demonstrated by an 8.6-mV rightwards shift in voltage dependence and a two-fold slowing in the rate of inactivation. Recovery from fast inactivation was not altered, nor was there an increase in the persistent current after a 50- ms depolarization. Activation and slow inactivation were not appreciably affected. These data suggest that T323M is a benign polymorphism, whereas F1705I results in fast inactivation defects, which are often observed for myotonia. This is the first example of a C-terminal mutation in SCN4A associated with human disease. Like the cardiac disorders (long QT syndrome type 3 or Brugada syndrome) and generalized epilepsy with febrile seizures plus (GEFS+) associated with C-terminal mutations in other NaV channels, the primary effect of F1705I was a partial disruption of fast inactivation.
Uncertainty reasoning for the world wide web: report on the URW3-XG incubator group

The Uncertainty Reasoning for the World Wide Web Incubator Group (URW3-XG) was chartered as a means to explore and better define the challenges of reasoning with and representing uncertain information in the context of the World Wide Web. The objectives of the URW3-XG were: (1) To identify and describe situations on the scale of the World Wide Web for which uncertainty reasoning would significantly increase the potential for extracting useful information; and (2) To identify methodologies that can be applied to these situations and the fundamentals of a standardized representation that could serve as the basis for information exchange necessary for these methodologies to be effectively used. This paper describes the activities undertaken by the URW3-XG, the recommendations produced by the group, and next steps required to carry forward the work begun by the group.
Arbitragem Como Mecanismo de Solução de Controvérsias Envolvendo Relações Jurídicas de Caráter Patrimonial

A arbitragem comercial tem-se consolidado como um dos metodos preferenciais para a resolucao de litigios, especialmente, no caso dos contratos. Litigios sobre contratos internacionais ja sao tradicionalmente resolvidos por meio de arbitragem, pois os particulares preferem uma instância que atue de forma rapida, de modo sigiloso e, em regra, realizada por instituicoes tambem privadas que se dedicam a materia. Os arbitros sao escolhidos pelas partes e, em geral, tem notavel experiencia nas questoes submetidas a seu julgamento. A sentenca arbitral tem forca obrigatoria, podendo ser executada nos mesmos moldes da sentenca judicial. Tendo o Brasil finalmente promulgado a Convencao de Nova York de 1958 sobre o Reconhecimento e a Execucao de Laudos Arbitrais Estrangeiros, insere-se o Pais, de forma cada vez mais solida, na vasta corrente do comercio internacional.
Elevated Expression of Hepatoma Up‐Regulated Protein Inhibits γ‐Irradiation‐Induced Apoptosis of Prostate Cancer Cells

Despite progression in diagnosis and treatment, prostate cancer (PCa) still represents the main cause of cancer-related mortality and morbidity in men. Although radiation therapy offers clinical benefit over other therapeutic modalities, the success of this therapeutic modality is commonly hampered by the resistance of advanced tumors. So far, the mechanisms governing tumor resistance to radiotherapy are not discussed in detail. Here, we demonstrate for the first time that the resistance of PCa to radiation therapy is attributed to elevated expression of Hepatoma Up-Regulated Protein (HURP). In PCa cells, the induction of HURP expression suppresses γ-irradiation-induced apoptosis. γ-irradiation-induced apoptosis of PCa cells is associated with expression of E2F1, p53, p21 proteins together with the phosphorylation of apoptosis signal-regulating kinase1 (ASK1), c-jun-N-terminal kinase (JNK) and Ataxia-telangiectasia mutated (ATM) and histone family member X (H2AX). Whereas, the induction of HURP expression is able to suppress γ-irradiation-induced effects on E2F1, p53, p21, ATM, ASK1, JNK and ATM, and H2AX. Also, inhibition of γ-irradiation-induced- cytochrome c release, cleavage of caspase-9, caspase-3, PARP, and reactive oxygen species (ROS) were noted in PCa cells induced for HURP expression. The observed radio-resistance of PCa is thought to be the consequence of HURP-mediated destabilization of p53 and ATM proteins that are essential for the modulation of γ-irradiation-induced apoptosis. Thus, based on our findings, PCa resistance to radiation therapy results from the deregulation of ASK1/ JNK; ATM/ H2AX; ATM/p53 and checkpoint kinase 2 (Chk2)/ E2F-1 in response to the elevated expression of HURP.
Optimizing the pattern of essential amino acids as the sole source of dietary nitrogen supports near-maximal growth in kittens

Most experiments conducted to determine the optimal essential amino acid (EAA) nitrogen to total nitrogen (E:T) ratio in rats, chicks and other species have shown that weight gain and nitrogen retention are optimal when the ratio is between 0.5 and 0.65. Two experiments were conducted to determine if weight gains of kittens fed EAA as a sole source of dietary nitrogen were equivalent to those of kittens fed a control diet that contained equal amounts of EAA and dispensable amino acids (DAA). In the first experiment, kittens fed diets that contained only EAA lost weight. Amino acid analysis of plasma showed that the concentration of methionine was 9.1 times that of controls, supporting the premise that the weight loss that occurred was the result of an adverse effect of excess methionine. Also, plasma threonine and arginine were elevated whereas proline and asparagine were very low. In the second experiment, feeding lower concentrations of methionine and arginine in a diet containing only EAA resulted in weight gains and nitrogen retention that were not significantly different from results for kittens fed the control diet (E:T ratio = 0.5). The addition of proline and asparagine to this EAA diet or their removal from the control diet did not improve or reduce weight gain or nitrogen retention. It is concluded that the decreased weight gain found in kittens (and probably other species) fed only EAA is the result of an adverse effect of excesses of methionine and possibly other EAA, and not the inability to synthesize DAA. If excesses of certain EAA are avoided, near-maximal weight gain can be achieved without any DAA in the diet.
Development of a high-pressure hydrogen injection for SI engine and results of engine behavior

Abstract A high-pressure hydrogen injector was designed and developed in the laboratory. The injector was hydraulically operated by a separate pump. Measurement of injection characteristics on a bench stand showed very repetitive performance of the injector. The injection system was used to supply hydrogen fuel to a single-cylinder spark ignition engine. Results of the tests showed that the engine performance was superior to that achieved with carbureted gasoline fuel.
Quality Improvement Strategies to Enhance Physical Activity

Physical activity is beneficial for both primary and secondary prevention of most chronic diseases. This is particularly true with relation to cardiovascular disease. Initiation and maintenance of regular physical activity has been demonstrated to positively impact the control of blood pressure, lipids, blood sugars, weight gain, and overall cardiovascular risk. The challenge lies in finding effective methods to promote physical activity with patients as well as in helping them to sustain such behaviors across the lifespan. Numerous barriers exist that inhibit physicians and the healthcare system from participating in prescribing physical activity for their patients despite the known benefits. This article examines strategies to assist patients in improving levels of physical activity and discusses the barriers to implementation.
How to calibrate edge sensors on segmented mirror telescopes

The next generation of large ground based telescopes use segmented mirrors. Sensors mounted on the edge of the segments measure the relative heights of the segments. The segments are actively controlled in height by three actuators per segment, but lateral motion is only passively constrained. Thus there will be some small change in the gap and shear between segments as changing telescope orientation and temperature make small distortions in the telescope structure. These "in-plane" motions place an additional performance burden on the edge sensors, and on the precision with which they must be mounted relative to the optical surface. In addition, both the scaling and offset of sensor edge height readings also vary with changes in gap.
Challenges and Limitations of Subtractive Processing in PWB and Substrate Fabrication

This paper examines the limitations of subtractive processes. Conventional process sequences such as pint & etch, pattern plating, panel plate/tent & etch, and semi-additive processing (SAP) are briefly reviewed to emphasize the commonality of resolution limitation due to lateral etching. While semi-additive processing is still the technology of choice for fine line substrates, it too may find its limit in the inherent limitations of isotropic etching. Process improvements are reviewed which address etching problems. Several damascene-like processes are reviewed that show promise to provide finer lines and spaces than the semi-additive process can achieve.
A solvable conjugacy problem for finitely presented C (3) semigroups

In his thesis, Remmers (Thesis, Univ. of Mich., 1971), introduced semigroup derivation diagrams and used them to prove that the word problem for finitely presented C(3) semigroups was solvable. In this article we introduce the annular analog of semigroup derivation diagrams and use them to demonstrate the solution to a conjugacy problem for finitely presented C(3) semigroups.
Alternative approaches for Phase I studies of anticancer drugs: a role for therapeutic drug monitoring.

The traditional approach to conducting Phase I studies of anticancer drugs is to select a starting dosage for humans based on preclinical data, then empirically escalate dosages in cohorts of patients until the maximum tolerated dosage (MTD) is established. Although this empirical study design has worked reasonably well and continues to be in widespread use, its statistical shortcomings and clinical inefficiencies have been recognized. An alternative strategy involves the use of pharmacokinetic principles to systematically escalate systemic exposur-area under the plasma concentration-time-curve (AUC)-instead of dosage of Phase I trials
Beyond Density: An Inquiry-Based Activity Involving Students Searching for Relationships

This paper describes an inquiry-based laboratory activity for introductory chemistry students that goes beyond the traditional "displacement of water" density experiments found in the literature and commercial laboratory manuals. The activity shows how teachers can allow their students to design their own experiments in order to determine the relationships between an object's properties and the volume of water that object displaces. Through an analysis of their data, students construct for themselves three important physical relationships: (i) increasing an object's area doesn't affect the volume of water displaced by the object (composition and mass constant), (ii) the volume of an object equals the volume of water displaced by the object, and (iii) different substances have different volumes when mass is constant. As students perform this activity they act like scientists: they design their own experiments, control variables, take measurements, represent their results in tables and graphs, and make claims based on an analysis of their results.
Left ventricular dysfunction and duration of mechanical ventilatory support in the chronically critically ill: a survival analysis.

Abstract Objective The purpose of this study was to determine whether there was a greater risk for prolonged duration of mechanical ventilatory support (MVS) for those who demonstrated left ventricular dysfunction (LVD) compared to those without evidence of LVD when controlling for nutritional and general health status and spontaneous breathing pattern. Design A secondary analysis was used on data obtained in a retrospective survey of patient records. Setting Five adult critical care units at an academic medical center in the Midwest. Subjects Twenty-seven chronically critically ill adults requiring MVS who later successfully weaned from MVS. Outcome Measure Duration of MVS. Instrumentation LVD was determined with use of a criterion-based checklist. Serum albumin level as determined by the hospital's clinical laboratory served as the indicator of nutritional and general health status. The rapid shallow breathing index was used to describe the spontaneous breathing pattern. Results Adjusted survival function estimates were obtained on fitting a Cox proportional hazards model. When adjusting for the known covariates, serum albumin level and rapid shallow breathing index, the duration of MVS was significantly longer for those who demonstrated LVD when compared to those without evidence of LVD [ X 2 Wald (1)=4.72, p Conclusions The findings of this secondary analysis lend support to the fact that when controlling for serum albumin level and rapid shallow breathing index, LVD is related to the duration of MVS in patients who successfully wean.
Screw Dislocations in MBE GaN Layers Grown on Top of HVPE Layers: Are They Different?

Transmission Electron Microscopy was applied to study HVPE template and MBE over-layers in plan-view and cross-section. It was observed that screw dislocations in the HVPE layers are decorated by small voids arranged along the screw axis. However, no voids were observed along screw dislocations in MBE overlayers grown with excess Ga, despite the fact that Ga droplets were observed on the layer surface as well as imbedded in the layer. By applying a direct reconstruction of the phase and amplitude of the scattered electron wave from a focal series of high-resolution images, the core structures of screw dislocations in both materials have been studied and show that all screw dislocations have filled cores. Dislocation cores in MBE samples grown Ga-rich and N-rich show no substantial differences and no stoichiometric change compared to the matrix. However, in HVPE materials, single atomic columns show substantial differences in intensities and indicate the possibility of Ga presence. These Ga-rich cores might be responsible for the attraction impurities forming voids in their close vicinity.
Organizational Factors and Instructional Decision-Making: A Cognitive Perspective

Given the limited adoption of research-based teaching methods at the postsecondary level, research is necessary that examines why faculty choose to teach the way they do. In this article, I draw on insights from research on teacher cognition and naturalistic decision-making research to identify how perceptions of organizational factors influence instructional decision-making. Results indicate that respondents perceive structural and socio-cultural factors as constraining and affording practice by exerting normative pressures on teaching decisions, imposing logistical constraints, and encouraging autonomy. The relationship between these factors and teaching practice was moderated by factors such as status and other individual characteristics.
Studies on the transition from quasi-static to impact electron contributions of linear stark broadening☆

The ratio of halfwidth to critical value for the transition between quasi-static and impact domain of electron contributions to linear Stark broadening (according to Unsold) is expected to vary approximately with n4, where n is the upper principal quantum number of the line considered. Low-density plasmas generated by a radio frequency arrangement permit the observation of many non-overlapping Balmer lines and thus a drastic variation of the ratio; for identical plasma parameters, access deep into the quasi-static as well as the impact regime of electron broadening is realized to a degree not achieved previously. As recently suggested, the observed broadening can be approximated in terms of an effective quasi-static perturber density, which is a universal function of the displacement from the line center expressed in units of the above mentioned critical transition value. Normalization of the resultant profiles is maintained. Doppler and apparatus broadening contributions are quantitatively taken into account in the analysis of the observations. The limitations of the approach are discussed. The greatly simplified description of the complex broadening phenomena summarizes all low-density observations, in good approximation, and agrees in its essential qualitative features with the generalized impact theory as recently corrected by Griem for the asymptotic regime, although these recent calculations favor stronger electron impact contributions.
Effect of Calcium and Other Ions on Vasopressin Release from Rat Neurohypophyses stimulated electrically in vitro

THE rat posterior pituitary in vitro secretes vasopressin in response to a rise in extracellular potassium concentration. This effect of excess potassium is inhibited by magnesium and sodium ions and is strongly dependent on calcium. Secretion is abolished by omitting calcium from the incubation medium; it increases with increasing calcium concentration over a wide range, and is accompanied by uptake of calcium-45. From such evidence it has been concluded that calcium entry into the neurosecretory terminals on their depolarization by action potentials is the normal physiological event initiating secretion1–3. This concept is supported by the demonstration of vasopressin release from rat3,4 and guinea-pig5 neurohypophyses in vitro in response to electrical stimuli and of action potentials recorded from the supra-opticohypophyseal tract6. It would clearly strengthen the hypothesis if it were shown that the effects of calcium and other ions on vasopressin release, elicited by electrical stimulation, were similar to their effects on secretion elicited by excess potassium. This communication presents evidence that this is so.
Dynamic Motion of Helix A in the Amino-terminal Domain of Calmodulin is Stabilized Upon Calcium Activation

Calcium-dependent changes in the internal dynamics and average structures of the opposing globular domains of calmodulin (CaM), as well as their relative spatial arrangement, contribute to the productive association between CaM and a range of different target proteins to affect their functional activation. To identify dynamic structural changes involving individual ?-helical elements and their modulation by calcium activation, we have used site-directed mutagenesis to engineer a tetracysteine binding motif within helix A near the amino-terminus of calmodulin (CaM), permitting the selective and rigid attachment of the fluorescent probe 4?,5?-bis(1,3,2-dithioarsolan-2-yl) fluorescein (FlAsH) with full retention of function. The rigid tetracoordinate linkage of FlAsH to CaM, in conjunction with frequency-domain fluorescence anisotropy measurements, allows assessment of dynamic changes associated with calcium activation without interference from independent probe motion. Taking advantage of the large fluorescent enhancement associated with FlAsH binding to CaM, rates of FlAsH binding to apo- and calcium-activated CaM were 2500 ? 10 M-1 sec-1 and 187 ? 2 M-1 sec-1, respectively. There is no difference in the solvent accessibility of the bound FlAsH irrespective of calcium binding to CaM. Thus, given that FlAsH selectively labels disordered structures, the large difference in rates of FlAsH binding indicates that calcium binding stabilizesmore » helix A. Frequency-domain anisotropy measurements of bound FlAsH indicate that prior to calcium activation, helix A undergoes large amplitude nanosecond motions. Following calcium activation, helix A becomes immobile, and structurally coupled to the overall rotation of CaM. We discuss these results in the context of a model that suggests stabilization of helix A relative to other domain elements in the CaM structure is critical to defining high-affinity binding clefts, and in promoting specific and ordered biding of the opposing lobes of CaM to target proteins.« less
The ground state far infrared spectrum of NH3

The NH3 far infrared spectrum is particularly useful for the study of planetary composition and atmospheric dynamics. Studies of this spectrum were conducted by Dowling (1969), Helminger et al. (1971), and Urban et al. (1981). Sattler et al. (1981) have reported measurements of a few nu2 lines with tunable diode lasers. By using simple sum rules, these lines and accurate ground state inversion lines considered by Poynter and Kakar (1975) have been employed in the present investigation to deduce a few of the far infrared ground state transitions. An extensive set of high signal/noise, high resolution (0.0048 per cm) scans of the nu2 bands of NH3 from about 600 per cm through about 1300 per cm ait a series of low pressures have been made in order to accurately determine both the line positions and strengths. The obtained data provide line positions with an absolute accuracy of about 0.0001 per cm in the more favorable cases.