cssi/SciSciGPT-SciSciNet huggingface dataset:
Androgen receptor signaling induces prostate cancer cell proliferation through mTOR activation and post-transcriptional increases in cyclin D proteins

2925 Androgen receptor (AR) plays a central role in prostate cancer (PCa) growth, with most PCa being androgen dependent and responding to androgen deprivation therapies. Previous studies using PCa cell lines and xenografts have shown that androgens (testosterone or dihydrotestosterone, DHT) can stimulate cell cycle progression, and that androgen withdrawal results in a pRb dependent G0/G1dependent cell cycle arrest. However, the molecular targets of AR that mediate androgen stimulated proliferation have not been established. Using the LNCaP PCa cell line as a model, we initially confirmed in time course studies that increased phosphorylation of the pRb protein on a CDK4/cyclin D dependent site correlated with cell cycle progression after DHT stimulation. Significantly, there was no increase in cyclin D1 or D2 mRNA, and only a small increase in cyclin D3. Nonetheless, DHT stimulated a dramatic increase in cyclin D1, D2 and D3 proteins, indicating post-transcriptional regulation of D-type cyclin protein. This post-transcriptional mechanism was identified as mTOR activation, as demonstrated by increased phosphorylation of p70 S6 kinase 1 and ribosomal S6 protein in response to DHT. Importantly, this increase in mTOR activity was observed despite the high basal level in LNCaP cells due to PTEN loss and subsequent activation of the PI3 kinase/Akt pathway (which enhances mTOR activity through phosphorylation of tuberin). Activation of mTOR by amino acids supplementation similarly increased mTOR activity and cyclin D levels, while inhibition of mTOR by rapamycin decreased D-type cyclin protein levels in LNCaP cells and blocked the DHT stimulated D-type cyclin protein accumulation. Significantly, mTOR activation in response to DHT occurred after approximately 8 hours and did not reflect the previously described androgen stimulated rapid nontranscriptional activation of PI3 kinase and Akt. The DHT mediated mTOR activation was similarly independent of the Erk/Rsk and AMPK pathways, but was blocked by actinomycin D, indicating that it was dependent on new mRNA synthesis. Affymetrix oligonucleotide microarrays identified a series of genes that were rapidly induced by DHT, including amino acid transporters, which may contribute to mTOR activation. Finally, the basal level of mTOR activity was increased, and the DHT response was decreased, in an “androgen independent” subline of LNCaP cells (C4-2 cells). Taken together, these results indicate that the androgen liganded AR stimulates the expression of one or more proteins that activate mTOR downstream of Akt, potentially through increasing nutrient levels, and that increased expression of these proteins may be a mechanism for the progression to androgen independent PCa.
Integrating the Sustainable Development Goals into Teaching, Research, Operations, and Service: A Case Report of Yale University

Abstract Higher education institutions are important stakeholders in helping to advance the United Nations Sustainable Development Goals (SDGs). Recognizing this, in 2016 the Yale Office of Sustain...
Private Universities and NCAA D-III Athletics as a General Recruiting Tool

Most economic research on university athletics programs examines National Collegiate Athletic Association Division I universities with some consideration of universities in Division II. Division III universities are very different than Division I, consequently that which holds for athletics might be different. In this paper the relationship between athletics and the number of applications received per existing student is examined using a balanced panel of private Division-III universities from 2003 to 2014. Controlling for numerous common recruiting variables, the results indicate that a larger share of athletes on campus is positively associated with more applications per existing full time equivalent undergraduate students. The presence of football, a large, almost exclusively male set of athletes, is neutral in its relationship with total applications, though positive for male and negative for female applicants. Among Division-III universities with football programs, winning football programs have a neutral effecton applications.
Post Transplant Lymphoproliferative Disorders (PTLD) After Lung Transplantation: Comparison of Patients with Early Versus Late Disease.

Abstract Abstract 3947 Poster Board III-883 The incidence and natural history of post-transplant lymphoproliferative disorders (PTLD) vary considerably after different types of organ transplantation. Lung and heart-lung transplants pose a higher risk of PTLD than kidney, pancreas or liver transplantation, most likely due to higher intensity post transplant immunosuppression. While the number of lung transplants is growing, there are only a few studies that detail PTLD in this setting. We studied 33 PTLD patients identified among 639 lung transplant recipients (5.1%) seen at the University of Minnesota between January 1985 and December 2008. The median age at diagnosis was 52 years (20-67 years); 17 cases (51%) were male. The median interval from transplantation to PTLD was 95 months (3-242 months). The great majority (91%) presented with extranodal disease; bone marrow involvement was rare (6%). Eight patients (24%) developed PTLD within one year of transplantation (early group) and predominantly had PTLD involving the allograft or other intra-thoracic organs. These patients often presented with subacute respiratory symptoms and evidence of pulmonary infiltration, raising the question of infection or allograft rejection. Twenty five patients (76%) were diagnosed more than one year after transplantation (late group) with disease mainly affecting gastrointestinal organs. Their presentations predominantly included acute abdominal symptoms and GI bleeding. Patients in both the early and late groups had advanced stage disease and high International Prognostic Index scores at diagnosis. Thirteen percent of the early group and 44% of the late group had a poor performance status (PS > 2) (p=0.107). Median LDH was 1117 U/L in the early group and 1830 U/L in the late group (p=0.204). Monomorphic diffuse large B cell lymphoma was the most common pathological diagnosis (86%) in both early and late groups. Ebstein-Barr encoded RNA (EBER) stain was positive in 20 cases (61%) and was not different between the two groups (p=0.177). For management, 31 of the 33 patients (94%) had their immunosuppression reduced and 30 patients also underwent systemic treatment, including rituximab (31%), chemotherapy (36%) or both (33%). The 3 patients who did not receive systemic treatment had progressive disease and died. Eighty seven percent of the early group and 45% of the late group achieved remission. However, there was no statistical difference in treatment response in the two groups (p=0.137). A total of 25 patients (76%) died; median survival was 9 months (0-107 months). Again, there was no statistically significant difference in survival between early and late PTLD (p=0.230). Major causes of death were infection and PTLD. Univariate analysis using the Cox proportional hazards model revealed that treatment response (p Disclosures: No relevant conflicts of interest to declare.
Mice Engineered To Express a Form of Thrombin Favoring Protein C Are Resistant to S. aureus-Induced Sepsis.

Thrombin is central in thrombus formation as both a positive mediator of thrombus formation through the proteolytic activation of PARs, fibrinogen, fXI and other prothrombotic substrates, and a negative modulator of the coagulation cascade through the activation of protein C. Detailed structure-function studies have revealed that thrombin can be redesigned to favor either procoagulant or anticoagulant substrates. The introduction of W215A/E217A substitutions in the murine thrombin active site (fIIWE) results in a pronounced “specificity switch” that reduces catalytic efficiency with fibrinogen by at least 3-orders-magnitude while only modestly reducing activity for protein C activation. To evaluate the effects of fIIWE activity in vivo, we have used a gene-targeting strategy to generate mice carrying the W215A/E217A mutations in the endogenous murine prothrombin gene. The mutant allele was transmitted through the germline and was found to support the expression of normal levels of hepatic fII mRNA and plasma fII in both heterozygous and homozygous neonates. Unlike fII knockout mice, homozygous fIIWE mice were observed at term with the expected Mendelian frequency. Nevertheless, homozygous fIIWE offspring uniformly succumbed to spontaneous bleeding events within days of birth. Heterozygous fIIWE/WT animals generally survived to adulthood, were capable of carrying multiple liters to term, and unchallenged mice displayed a hematological profile similar to wildtype mice. However, consistent with a predicted anticoagulant phenotype, adult fIIWE/WT heterozygotes exhibited significantly delayed thrombus formation following ferric chloride injury of mesenteric arterioles and extended bleeding times following tail tip excision relative to control mice expressing wildtype fII. Given that activated protein C has been shown to be efficacious in the treatment of sepsis, we explored whether the shift in thrombin specificity in heterozygous fIIWE/WT mice would confer the benefit of rendering animals tolerant to acute septic challenges. Kaplan-Meier analyses following intravenous administration of S. aureus revealed that fIIWE/WT mice exhibited a significant survival advantage over littermate wildtype animals challenged in parallel and tracked over a 7-day observation period. Notably, extended thrombus formation and bleeding times as well as resistance to sepsis was not simply a function of half normal wildtype fII expression. When these analyses were performed in animals carrying one wildtype allele and one null mutation allele, results were similar to wiltype. These studies further underscore the interplay between the hemostatic and inflammatory systems in vivo and highlight the possible therapeutic utility of recombinant (pro)thrombin derivatives with selected alterations in substrate specificity.
Therapy at 30 days of life predicts lung function at 6 to 12 months in infants with congenital diaphragmatic hernia

Introduction Congenital diaphragmatic hernia (CDH) is associated with variable degrees of lung hypoplasia. Pulmonary support at 30 days postnatal age was found to be the strongest predictor of inpatient mortality and morbidity among CDH infants and was also associated with higher pulmonary morbidity at 1 and 5 years. It is not known, however, if there is a relationship between the need for medical therapy at 30 days of life and subsequent abnormalities in lung function as reflected in infant pulmonary function test (iPFT) measurements. Objective We hypothesized that CDH infants who require more intensive therapy at 30 days would have more abnormal iPFT values at the time of their first infant pulmonary function study, reflecting the more severe spectrum of lung hypoplasia. Methods A single-institution chart review of all CDH survivors who were enrolled in a Pulmonary Hypoplasia Program (PHP) through July 2019, and treated from 2002 to 2019 was performed. All infants were divided into groups based on their need for noninvasive (supplemental oxygen, high flow therapy, noninvasive mechanical ventilation) or invasive (mechanical ventilation, extracorporeal membrane oxygenation) respiratory assistance, bronchodilators, diuretic use, and pulmonary hypertension (PH) therapy (inhaled and/or systemic drugs) at 30 days. Descriptive and statistical analyses were performed between groups comparing subsequent lung function measurements. Results A total of 382 infants (median gestational age [GA] 38.4 [interquartile range (IQR) = 37.1-39] weeks, 41.8% female, 70.9% Caucasian) with CDH were enrolled in the PHP through July 2019, and 118 infants underwent iPFT. The median age of the first iPFT was 6.6 (IQR = 5.3-11.7) months. Those requiring any pulmonary support at 30 days had a higher functional residual capacity (FRC) (z) (P = .03), residual volume (RV) (z) (P = .008), ratio of RV to total lung capacity (RV/TLC) (z) (P = .0001), and ratio of FRC to TLC (FRC/TLC) (z) (P = .001); a lower forced expiratory volume at 0.5 seconds (FEV0.5) (z) (P = .03) and a lower respiratory system compliance (Crs) (P = .01) than those who did not require any support. Similarly, those requiring diuretics and/or PH therapy at 30 days had higher fractional lung volumes, lower forced expiratory flows and Crs than infants who did not require such support (P Conclusions Infants requiring any pulmonary support, diuretics and/or PH therapy at 30 postnatal days have lower forced expiratory flows and higher fractional lung volumes, suggesting a greater degree of lung hypoplasia. Our study suggests that the continued need for PH, diuretic or pulmonary support therapy at 30 days can be used as additional risk-stratification measurements for evaluation of infants with CDH.
Finite Impulse Response (FIR) Digital Filters

Digital filters are typically used to modify or alter the attributes of a signal in the time or frequency domain. The most common digital filter is the linear time-invariant (LTI) filter.
Building a successful Global Health curriculum: advice from a fellow trainee

Global health is an interprofessional collaboration to improve population health and individual clinical care worldwide. As interest in global health increases and educational programs respond to this growing interest, there is a need to re-evaluate the strength of rapidly growing global health training programs. As many other education systems move to competency-based training, so too should global health. Competency-based training focuses on the ability to perform a task, understand a concept or approach a problem with the appropriate attitude successfully.1–3 Much of the old model of global health education is content-based and emphasizes number of training hours completed. The Association of Schools and Programs of Public Health (ASPPH), the leaders of the competency-based educational effort, believes that global health education should be outcome-oriented.1 Outcome-based global health education will ensure that trainees are better equipped with the knowledge, skills and attitudes needed to enter the global health arena. Goals of global health programs should include competency-based curricula implementation and an emphasis on core competencies that span all disciplines related to global health. Developing these cross-disciplinary global health competencies has been an ongoing project of the Consortium of Universities for Global Health’s (CUGH) Global Health Competency Subcommittee for the past year. The Subcommittee members have collaborated and developed core competencies for two trainee levels of global health involvement. From this experience of competency development comes the inspiration for a trainee-led movement for the successful implementation of these competency sets. Trainee-driven global health curricula will encourage programs to shift their standards from hours invested to skills, knowledge and attitudes acquired. If done across all global health disciplines, this will ensure that all professions have the competencies needed to work together on achieving the collective goals of global health.
Quality Improvement of Primary Care Provider Communication on Hospital Discharge.

BACKGROUND AND OBJECTIVES Effective communication between inpatient and primary care providers (PCPs) is important for safe transition of care for hospitalized patients. In 2017, communication with PCPs was prioritized for the pediatric hospital medicine division. Our primary aim was to improve documented attempted communication with PCPs within 72 hours of discharge from 41% to at least 60% by January 1, 2018, and maintain this performance through 2019. METHODS This study included all inpatient encounters discharged by a pediatric hospital medicine provider from March 2017 to April 2020. An electronic health record phrase debuted March 2017. Successful documentation was defined as any attempt to contact the PCP, regardless of whether actual communication occurred. Group and individual audit and feedback occurred in July 2017 to April 2020. Provider communication was financially incentivized in July 2018 to June 2019. An annotated P-chart for the proportion of encounters with documented PCP communication occurring within 72 hours was established. Special-cause variation was determined by using Shewhart rules. RESULTS The mean proportion of encounters with documented PCP communication increased from 41% at baseline (March 2017 through July 2017) to 60% in August 2017 and 66% in December 2017. After the financial incentive was removed in July 2019, documentation decreased to 54%. Phone calls with clinic staff were the most common communication method (40% to 71%). Direct conversations with the PCP occurred rarely (0% to 3%). CONCLUSIONS Even when coupled with audit and feedback with EHR interventions, our work suggests that shifting to external financial motivation may hinder sustainability of behavior change to improve attempted documented PCP communication.
miR-17 acts as a tumor suppressor by negatively regulating the miR-17-92 cluster.

Anaplastic thyroid cancer (ATC) is an aggressive, highly metastatic cancer that expresses high levels of the microRNA (miR)-17-92 cluster. We employ an miR inhibitor system to study the function of the different miRs within the miR-17-92 cluster based on seed sequence homology in the ATC SW579 cell line. While three of the four miR-17-92 families were oncogenic, we uncovered a novel role for miR-17 as a tumor suppressor in vitro and in vivo. Surprisingly, miR-17 inhibition increased expression of the miR-17-92 cluster and significantly increased the levels of the miR-18a and miR-19a mature miRs. miR-17 inhibition increased expression of the cell cycle activator CCND2, associated with increased cell proliferation and tumor growth in transplanted SW579 cells in xenograft mice. miR-17 regulates MYCN and c-MYC expression in SW579 cells, and the inhibition of miR-17 increased MYCN and c-MYC expression, which increased pri-miR-17-92 transcripts. Thus, inhibition of miR-17 activated the expression of the oncogenic miRs, miR-18a and miR-19a. While many cancers express high levels of miR-17, linking it with tumorigenesis, we demonstrate that miR-17 inhibition does not inhibit thyroid tumor growth in SW579 and MDA-T32 ATC cells but increases expression of the other miR-17-92 family members and genes to induce cancer progression.
Stable and inheritable changes in genotype and phenotype of albino melanocytes induced by an RNA-DNA oligonucleotide

Experimental strategies have been developed to correct point mutations using chimeric oligonucleotides composed of RNA and DNA. We used these RNA-DNA oligonucleotides to correct a point mutation in mouse tyrosinase, a key enzyme for melanin synthesis and pigmentation. Melanocytes derived from albino mice contain a homozygous point mutation (TGT-->TCT) in the tyrosinase gene, resulting in an amino acid change from Cys-->Ser. Correction of this point mutation results in the restoration of tyrosinase activity and melanin synthesis, thus changing the pigmentation of the cells. Upon transfection of the RNA-DNA oligonucleotide to albino melanocytes, we detected black-pigmented cells and isolated multiple single clones. All black-pigmented clones exhibited a correction of the point mutation in a single allele of the tyrosinase gene. A full-length tyrosinase was detected by an antityrosinase antibody, and the enzymatic activity was restored in all converted black-pigmented clones. Only degraded fragments were detected in albino cells due to proteolytic cleavage of mutant tyrosinase. The phenotype and genotype of converted black-pigmented clones was stable. These results demonstrate a permanent and stable gene correction by the RNA-DNA oligonucleotide at the level of genomic sequence, protein, and phenotypic change by clonal analysis.
Dynamics of Cooper pair formation in Bi 2 Sr 2 Ca Cu 2 O 8+δ

We report ultrafast measurements of the transient terahertz conductivity in the high-${T}_{C}$ superconductor ${\mathrm{Bi}}_{2}{\mathrm{Sr}}_{2}\mathrm{Ca}{\mathrm{Cu}}_{2}{\mathrm{O}}_{8+\ensuremath{\delta}}$. After depletion of the superconducting condensate by optical excitation, the ensuing dynamics is tracked with high sensitivity at various excitation densities and temperatures. We measure low-energy spectra and shapes of decay that demonstrate a bimolecular kinetics of condensate formation on a picosecond time scale and yield a measure of quasiparticle interactions hidden in linear spectroscopy.
Deadly Censorship: Murder, Honor, and Freedom of the Press

There are books about infamous murder trials. There are books about crusading newspaper editors. And there are books about how notions of personal honor have guided behavior throughout American his...
The Nature of and X-Rays

IN a letter to NATURE of January 23 (p. 270) Prof. Bragg mentions the results of some experiments on rays from which he concludes that the ether pulse theory of rays is not tenable, but which support his theory that the rays consist of neutral pairs revolving in a plane containing their direction of translation. From the close resemblance of X-rays to rays he assumes that they also consist of neutral pairs. His reasoning seems to be that if the rays are ether pulses only, they should produce in any substance which they strike secondary kathode rays which come off equally in all directions, and if they do not the ether pulse theory cannot be correct.
A Multilateral Solution for the Income Tax Treatment of Interest Expenses

Recent developments - including greater taxpayer sophistication in structuring and locating international financing arrangements, increased government concerns with the role of debt in sophisticated tax avoidance techniques, and disruption by decisions of the European Court of Justice of member states' regimes limiting interest deductions - have stimulated new laws and policy controversies concerning the international tax treatment of interest expenses. National rules are in flux regarding the financing of both inbound and outbound transactions. Heretofore, the question of the proper treatment of interest expense has generally been looked at from the perspective of either inbound or outbound investment. As a result, the issues of residence countries' limitations on interest deductions on borrowing to finance low-taxed, exempt or deferred foreign source income, on the one hand, and of source countries' restrictions on interest deductions intended to limit companies' ability to strip income from a higher-tax to a lower-tax country, on the other, have generally been treated as separate issues. A fundamental contribution of this essay is to demonstrate their linkage and to call for a multilateral solution that would address both of these problems. The complexity, the incoherence, and the futility of countries acting independently to limit interest deductions are now clear. Worldwide allocation of interest expense by both source and resident countries would eliminate a host of problems now bedeviling nations throughout the world - problems that have produced varying, complex, and inconsistent responses among different countries, responses that frequently may result in zero or double taxation. Given the flexibility of multinational corporations to choose where to locate their borrowing and the difficulties nations have in maintaining their domestic income tax bases in the face of such flexibility, achieving a multilateral agreement for the treatment of interest expense based on a worldwide allocation should become a priority project for both source and residence countries.
The inverse problem for representation functions of additive bases

Let A be a set of integers. For every integer n, let r A,2 (n) denote the number of representations of n in the form n = a 1 + a 2, where a 1, a 2 ∈ A and a 1 ≤ a 2. The function r A,2 : Z → N 0 ∪ {∞} is the representation junction of order 2 for A. The set A is called an asymptotic basis of order 2 r A,2 −1 (0) is finite, that is, if every integer with at most a finite number of exceptions can be represented as the sum of two not necessarily distinct elements of A. It is proved that every function is a representation function, that is, if f : Z → N 0 ∪ {∞} is any function such that f −1(0) is finite, then there exists a set A of integers such that f(n) = r A,2(n) for all n ∈ Z. Moreover, the set A can be constructed so that card{a ∈ A : |a| ≤ x} ≫ x 1/3.
Monoamine Oxidase A Promoter Gene Associated With Problem Behavior in Adults With Intellectual/ Developmental Disabilities

A functional polymorphism in the promoter of the gene encoding monoamine oxidase A has been associated with problem behavior in various populations. We examined the association of MAOA alleles in adult males with intellectual/developmental disabilities with and without established histories of problem behavior. These data were compared with a gender, ethnicity, and age-matched contrast sample. About 43% (15/35) of adults with intellectual/developmental disabilities and problem behavior possessed the low-efficiency version of the MAOA gene. In comparison, 20% (7/35) of adults with intellectual/developmental disabilities and no problem behavior and 20% (7/35) of the contrast group had the short-allele MAOA polymorphism. Therefore, a common variant in the MAOA gene may be associated with problem behavior in adults with intellectual/developmental disabilities.
Do we really want the unification of psychology? A response to Krantz☆

David Krantz’ analysis of attempts to unify psychology is an appropriate blend of the objective and the personal. It ought to be a personal concern of anyone claiming membership in the discipline that what is called psychology is a mass of contradictions, and that too many of those contradictions approach the absurd in form and content. Myself, I have discontinued membership in APA; I remain a member of the Association for Behavior Analysis. But very recently, I have come to see an increasingly major part of psychology as an unaware branch of the entertainment industry. (I value professional entertainment as an exceptionally admirable, high-level class of human behavior.) One result of psychology’s failure to acknowledge its function as entertainment is bad management, compared with professional entertainment. That explains a lot about APA. Another result is that there is a minority of members who in fact want not to entertain but to know (scientists), or to help (practitioners), or to help better by knowing more, especially about helping (applied scientists); I suspect that these people eventually will see the unreality of their membership in the entertainment industry, and then will define themselves as something else (as some emerging cognitive scientists are doing, just as Krantz says, and as some behavior analysts have done, just as he said about 20 years ago.) That explains a lot about the proliferation of small alternative APAs. Interestingly, seeing much of psychology in the paradigm of professional entertainment dissolves correspondingly much of my former irritation with its disunity, its contradictions, and its too frequent embrace of the absurd: Self-contradictory forms of entertainment are natural and desirable. Personally, I value their existence mainly because I value pluralistic societies, which may be the only kind that will tolerate me: I am safer when different people can and are expected to buy radically different forms of anything, especially entertainment. A very large fraction of psychologists sell time regularly to people who use it to tell Their Story; that kind of psychologist is trained to evoke from them one of the more interesting of the possible variations of Their Story, and to be a very gratifying audience. One form of entertainment is to hire someone to entertain you; another is to hire someone to let you entertain them. (None of this denies that the process may also help the buyer.) A constant and probably expanding variety of paradigms of entertainment seems natural, too, not as a Kuhnian crisis needing resolution, but as a steady *Commentary on D. Krantz (1987) Psychology’s search for unity, Vol. 5, No. 3,
Large Population Multi-Center Study of Small Unruptured Intracranial Aneurysms in Prospective Cohorts: Initial Sac Morphology and Longitudinal Outcome

Most intracranial aneurysms (IA) that present unruptured at the clinic remain stable over time with no measurable change or symptoms, if left untreated. But a few do grow larger and occasionally rupture. The ability to preemptively identify aneurysms that will become unstable over time (i.e., those that will grow and/or rupture) can result in timely intervention for these few patients while avoiding unnecessary treatment for countless others [1]. Previous reports assessing potential factors including by our group [2–4] have been confined to comparing geometric and/or biomechanical indices of aneurysms between populations that presented with ruputred lesions from those that presented with unruptured lesions. But, such indices (that discriminate rupture ‘status’) need not necessarily distinguish unruptured aneurysms that fork toward growth and/or rupture over a period of time from those that remain stable over time. Further, the physician’s dilemma to treat or not to treat presents itself mostly only in small aneurysms (< 7mm).Copyright © 2012 by ASME
Inhibition of nuclear protein phosphatase activity in mouse hepatocytes by the cyanobacterial toxin microcystin-LR.

Microcystin-LR (MCLR) is a cyanobacterial hepatotoxin and protein phosphatase inhibitor that contaminates water reservoirs worldwide. MCLR localizes to the cytosol of hepatocytes, however, immunohistochemical studies indicate that it accumulates in the nucleus. MCLR toxicosis is associated with decreased hepatic protein phosphatase activity, but effects in nuclear protein phosphatase activity have not been investigated. Balb/c mice were given lethal (100 microg/kg) or sublethal (12, 23 and 45 microg/kg) i.p. doses of MCLR and hepatic nuclear extracts were analyzed for protein phosphatase 1 and 2A activity. There was profound inhibition of nuclear protein phosphatase activity within 50 min of lethal dosing, however an inhibition was not detected with sublethal doses. MCLR immunohistochemistry revealed widespread lobular staining in the lethal group and centrilobular staining in the sublethal groups. At the cellular level there was nuclear and cytoplasmic staining of equal intensity. As an indicator of nuclear protein phosphatase activity, the phosphorylation of p53, a nuclear phosphoprotein and known substrate for protein phosphatases 1 and 2A, was evaluated. Balb/c mice were treated with sublethal doses of MCLR or saline vehicle after induction of hepatic p53 by the DNA damaging agent diethylnitrosamine (DEN). P53 was immunoprecipitated and probed with phosphoserine specific antibodies by Western blotting. There was greater phosphoserine reactivity of p53 protein in animals treated with MCLR relative to saline treated controls, consistent with increased phosphorylation of serine sites. It is concluded that an interaction of this toxin with nuclear protein phosphatases occurs within 50 min of lethal dosing, which leads to a profound inhibition of enzymatic activity. Even sublethal doses of MCLR that do not result in significant inhibition of activity in bulk nuclei, result in detectable changes in phosphorylation of p53.
Management of Young Amsterdam- and Marker-Negative Patients with Colorectal Cancer

Colorectal cancer affects a significant number of patients younger than the age of 50, and the incidence may be increasing. Most of these cancers are caused by genetic mutations, some of which are well known, whereas others have yet to be identified. The mutations lead to an accelerated transformation from normal mucosa towards a cancer. Guidelines for the management of these marker-and/or family history positive patients are increasingly well defined. However, many young patients do not have a positive family history (Amsterdam negative), and/or they either had no genetic testing done or were found to be genetic marker-negative. There is no consensus in the literature about defining the best management for these patients. Approaches vary from a segmental resection to a (sub-) total colectomy with ileosigmoid or -rectal anastomosis or a proctocolectomy. The future risk of metachronous cancers after a limited resection and the role of a piece of mind need to be weighed against the potential negative impact on quality of life after more extensive resections. Although the literature is limited, we suggest that marker- and Amsterdam-negative young patients (
Design and development of a new endo biomedical surgical instrument

This paper describes the recent research and development of an endo surgical/biomedical instrument for minimally invasive therapy procedure. The new mechanism design aids in better ergonomic design, reliable functionality, and continuous cost reduction. 3-D modeling technique, functionality analysis, and computer aided solution have been applied to the instrument design and development The improved instrument can prevent patient's vessels and tissues from being damaging because the distal move of endoclips are well controlled without clip drop-off incident. Plus the operational force to form the clip is lower than regular surgical/biomedical instruments Also the manufacturing and product cost can be decreased because the dimensional tolerance of components can be loose due to this new instrument design. This new endo surgical/biomedical instrument design has been analyzed through computer aided modeling and simulation to prove its reliable performance and mechanical advantage. All these improved features have also been tested and verified through the prototypes.
Examining the Moderating Role of Family Cohesion on the Relationship Between Witnessed Community Violence and Delinquency in a National Sample of Adolescents

Witnessed community violence has been linked to a number of internalizing and externalizing problems in adolescents. Guided by Cicchetti and Lynch’s (1993) ecological-transactional model, this study aimed to examine the impact that family-level factors had on negative outcomes associated with witnessed community violence. Using a nationally representative sample, we explored the moderational role of family cohesion in the relationship between witnessing community violence and delinquent behavior while taking demographic variables into account. Results from the investigation suggested that low levels of family cohesion were predictive of delinquency after controlling for race, gender, past delinquency, and direct trauma. In addition, the findings suggested that family cohesion moderated the impact of witnessed community violence on future delinquent behavior. Future directions for research and implications for practice were also discussed.
Synthesis and Postpolymerization Functionalization of Poly(5-iodo-1,2,3-triazole)s

The step-growth, click polymerization of complementary azide and alkyne-containing monomers to produce polytriazoles (PTAs) has become a versatile and popular method of preparing structurally diverse high molecular weight polymers with a variety of useful functions. We describe here a new class of PTAs that contain 5-iodotriazole linkages prepared by the iodoalkyne version of the copper-catalyzed azide–alkyne cycloaddition (iCuAAC) of an α-azido-ω-iodoalkyne (A–B) monomer. We found this monomer to be highly reactive in the iCuAAC polymerization and show that the resulting poly(5-iodo-1,2,3-triazole) (iodo-PTA) can serve as a useful building block for further postpolymerization derivatization using palladium-catalyzed cross-couplings such as Suzuki and Heck reactions. The parent iodo-PTA and functionalized materials were successfully characterized by various spectroscopic techniques and shown to exhibit a wide range of chemical and thermal properties that are determined by the nature of functionalization a...
Academic application is not an oxymoron

Commentary on “A Performance-Based, Minimalist Human Resource Management Approach in Business Schools”
Masculinization of Female Crayfish, Procambarus Clarki (Girard)

Twenty-three immature female crayfish (Procambarus clarki (Girard); carapace length = 8.2–17.9 mm), implanted with androgenic gland implants obtained from P. clarki males, were observed for 326 day...
High energy diffusion equation for polar semiconductors

Abstract We present a novel method to explicity solve the Boltzman equation for highly energetic electrons interacting with polar optical phonons and scattering mainly in forward direction. Our approach reduces the collision integral of the Boltzmann equation into a differential operator which is much easier to manipulate than the integral form and does not require a relaxation time approximation. The spatial diffusion of highly energetic electrons is calculated and discussed in context with high speed velocity transients (“ballistic transport”). Explicit results compare favorably with sophisticated Monte Carlo simulations and are well suited to treat complex transport problems in submicron III–V devices. As an example we calculate the current voltage characteristic of a “camel-back diode”.
A re-assessment of factors associated with environmental concern and behavior using the 2010 General Social Survey

The associations between social and psychological influences and environmental attitudes, intentions and behavior have generated considerable interest, both in the fields of environmental behavior and of environmental education. We use the 2010 General Social Survey (GSS) to study these associations and expand the scope of earlier studies by including additional measures across social demographic, social psychological and behavioral blocks. The findings highlight the relationships between social psychological constructs and environmental concern and behavior, as well as the relationships between social demographic characteristics and environmental values and beliefs. The findings from this study will be useful to environmental educators and communicators interested in studying the social psychological and social demographic bases of environmental concern and behavior.
Tectonic Movement in the Chile Trench

An acoustic reflection profile across the Chile Trench off Valparaiso shows the trench floor to have a substantial sediment accumulation that is far from flat-lying. The morphology is transitional between the flat-lying sediment fill to the south (labeled a type I trench) and the bare V-notch character farther north (labeled type II). A sharp seaward slope break, downbowed reflectors, and a landward downthrown normal fault suggest that the oceanic lithosphere is failing in shear. This mode of failutre is more consistent with the observed features of trenches and Benioff zones than is the concept of bending and underthrusting.
Strain-Driven Mound Formation of Substrate under Epitaxial Nanoparticles

We observe the growth of crystalline SiC nanoparticles on Si(001) at 900 °C using in situ electron microscopy. Following nucleation and growth of the SiC, there is a massive migration of Si, forming a crystalline Si mound underneath each nanoparticle that lifts it 4–5 nm above the initial growth surface. The volume of the Si mounds is roughly five to seven times the volume of the SiC nanoparticles. We propose that relaxation of strain drives the mound formation. This new mechanism for relieving interfacial strain, which involves a dramatic restructuring of the substrate, is in striking contrast to the familiar scenario in which only the deposited material restructures to relieve strain.
Hypothalamic stimulation of prolactin release from the pituitary of turkey hens and poults.

The effects of hypothalamic extracts from turkey hens and poults were tested on homologous pituitary prolactin release in vitro. Neutralized acid hypothalamic extract was incorporated into medium containing pituitary tissue and incubated at 37°C for 1 or 2 hours. A two-fold increase in prolactin release into the medium was observed when the equivalent of .5 hypothalamus from turkey hens or poults per pituitary was incorporated into the medium. Greater increases in prolactin release were observed when 1 or 2 hypothalamic equivalents per pituitary were added to the medium. Hypothalamic extracts from the young turkeys appeared to contain as much prolactin releasing activity as in turkey hens, although pituitary prolactin content in the young turkeys was only about 14 of that in turkey hens. These results suggest the turkey hypothalamus contains a prolactin releasing factor similar to that reported in other avian species.
USING CONFIDENCE INTERVALS IN SUPPLY CHAIN AND OPERATIONS RESEARCH

Like research throughout the entire business discipline, supply chain management research has relied almost exclusively on hypothesis testing methods. This is unfortunate as hypothesis tests are routinely misinterpreted in scientific research. We explain the limitations of hypothesis testing and recommend the use of confidence intervals as the preferred inferential statistical method. In particular, the additional information provided by confidence interval methods is highlighted using several supply chain management examples. We conclude with a set of recommendations designed to enhance the quality of supply chain management research.
FAM83B mediates EGFR- and RAS-driven oncogenic transformation

Aberrant regulation of growth signaling is a hallmark of cancer development that often occurs through the constitutive activation of growth factor receptors or their downstream effectors. Using validation-based insertional mutagenesis (VBIM), we identified family with sequence similarity 83, member B (FAM83B), based on its ability to substitute for RAS in the transformation of immortalized human mammary epithelial cells (HMECs). We found that FAM83B coprecipitated with a downstream effector of RAS, CRAF. Binding of FAM83B with CRAF disrupted CRAF/14-3-3 interactions and increased CRAF membrane localization, resulting in elevated MAPK and mammalian target of rapamycin (mTOR) signaling. Ablation of FAM83B inhibited the proliferation and malignant phenotype of tumor-derived cells or RAS-transformed HMECs, implicating FAM83B as a key intermediary in EGFR/RAS/MAPK signaling. Analysis of human tumor specimens revealed that FAM83B expression was significantly elevated in cancer and was associated with specific cancer subtypes, increased tumor grade, and decreased overall survival. Cumulatively, these results suggest that FAM83B is an oncogene and potentially represents a new target for therapeutic intervention.
Cell–cell signaling during Dictyostelium development

Specific proteins and peptides, as well as cAMP, are used as intercellular signals in Dictyostelium. Our understanding of the signal transduction pathways activated by these signals has been expanded by inclusion of newly characterized proteins. cAMP-dependent protein kinase (PKA) and its associated phosphodiesterase, RegA, play multiple roles in these pathways.
Reassessing obsidian field relationships at Glass Buttes, Oregon

Abstract The Glass Buttes complex in the High Lava Plains of Oregon produced obsidians during a series of rhyolitic eruptions circa 5.8 to 6.5 Ma. These obsidians have been used to craft stone tools for millennia, from Clovis peoples to modern knappers, and have been recovered at sites throughout the Pacific Northwest. Glass Buttes is also the origin of much obsidian used for lithic replication experiments and to test new techniques for sourcing. Paradoxically, the spatial distributions of chemically distinct obsidians at this complex have received comparatively little attention. The only published study to connect obsidian compositional differences to the Glass Buttes landscape is Ambroz et al. (2001), who reported seven discrete, spatially constrained obsidian “chemical groups” based on clustered data in elemental scatterplots. Since its publication, their paper has been cited as an example of successful obsidian “subsource” characterization. During the course of a wider research program, we collected 337 specimens at Glass Buttes from loci originally sampled by Ambroz et al. (2001). While we could replicate the “chemical groups” observed by Ambroz et al. (2001), we were unable to reproduce the reported spatial distribution of sources across the landscape. Almost half of the resampled loci exhibited intermingled populations of chemical types due to their locations on alluvial–colluvial deposits. We also identified five additional obsidian chemical types at the complex; however, geochemically significant elements suggest that only a subset of these eleven types correspond to different flows and domes at Glass Buttes. A few appear to reflect chemical zoning within flows, whereas two other types may be exogenous, moved from nearby obsidian sources via secondary transport. Thus, we demonstrate here that the discrete subsource zones demarcated by Ambroz et al. (2001) do not reflect reality on the landscape. This, in turn, alters how artifact sourcing results are interpreted with respect to how mobile foraging groups interacted with the landscape and made choices regarding resource acquisition, toolstone provisioning, and land use.
Physical properties of isobutylene based block copolymers

Physical, mechanical and thermal properties of a new class of isobutylene based model block copolymers are studied and contrasted with those of traditional thermoplastic elastomers based on polydienes and saturated polydienes (polyolefins) such as Kraton (or Vector) and Kraton G block copolymers. Melt state rheological and dynamic mechanical measurements confirm that thermodynamic interactions between polystyrene (S) and polyisobutylene (iB) or poly-p-tert-butylstyrene (tbS) and iB are comparable to, if not larger than, those between S and polybutadiene (B) or S and ethylene/butene-1 copolymer (EB). Physical properties for the S-iB-S and tbS-iB-tbS block copolymers, particularly the injection-moldability and cut-growth characteristics, are found to be considerably different from those found for the S-B-S and S-EB-S systems. We attribute this behavior to the longer entanglement chain length of iB compared with those for B and EB.
Neutron-diffraction study of stripe order in La{sub 2}NiO{sub 4+{delta}} with {delta}= (2) /(15)

We report a detailed neutron-scattering study of the ordering of spins and holes in oxygen-doped La{sub 2}NiO{sub 4.133}. The single-crystal sample exhibits the same oxygen-interstitial order but better defined charge-stripe order than that studied previously in crystals with {delta}=0.125. In particular, charge order is observed up to a temperature at least twice that of the magnetic transition, T{sub m}=110.5 K. On cooling through T{sub m}, the wave vector {epsilon}, equal to half the charge-stripe density within an NiO{sub 2} layer, jumps discontinuously from (1) /(3) to 0.2944. It continues to decrease with further cooling, showing several lock-in transitions on the way down to low temperature. To explain the observed lock-ins, a model is proposed in which each charge stripe is centered on either a row of Ni or a row of O ions. The model is shown to be consistent with the l dependence of the magnetic peak intensities and with the relative intensities of the higher-order magnetic satellites. Analysis of the latter also provides evidence that the magnetic domain walls (charge stripes) are relatively narrow. In combination with a recent study of magnetic-field-induced effects, we find that the charge stripes are all O centered at T{gt}T{sub m}, with amore » shift towards Ni centering at T{lt}T{sub m}. Inferences concerning the competing interactions responsible for the temperature dependence of {epsilon} and the localization of charge within the stripes are discussed. {copyright} {ital 1998} {ital The American Physical Society}« less