cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 1562: Drug repurposing for hepatocellular carcinoma enabled via transcriptomics data from experimental models of sorafenib resistance

Hepatocellular carcinoma (HCC) is often diagnosed in patients with advanced disease who are ineligible for curative surgical therapies. Sorafenib is the only approved drug for treating late stage HCC patients. However, patients rapidly become unresponsive due to inherent and acquired drug resistance. The promise of drug repurposing is that identifying new uses for existing drugs may reduce the high costs and time required for drug discovery. This is the first study employing connectivity mapping, a transcriptomics-based drug repurposing method, to identify drugs for use against sorafenib resistant (SR)-HCC via reversal of gene expression patterns. As a first step, we characterized gene expression signatures of different models of sorafenib resistance. We obtained gene expression signatures from an in vitro and an in vivo model of (SR)-HCC (publicly available microarray data) as well as from sorafenib-resistant (pool and clone) Huh7 cells generated in our lab. We determined the presence of the SR-HCC gene signatures across six patient-derived HCC gene expression datasets from the Gene Expression Omnibus (GEO) database using the nearest template method (FDR Citation Format: Kelly Regan, Ryan Reyes, Samson Jacob, Philip Payne, Tasneem Motiwala. Drug repurposing for hepatocellular carcinoma enabled via transcriptomics data from experimental models of sorafenib resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1562. doi:10.1158/1538-7445.AM2017-1562
Triple synchronous primary lung cancer: a case report and review of the literature.

Multiple primary lung cancer may present in synchronous or metachronous form. Synchronous multiple primary lung cancer is defined as multiple lung lesions that develop at the same time, whereas metachronous multiple primary lung cancer describes multiple lung lesions that develop at different times, typically following treatment of the primary lung cancer. Patients with previously treated lung cancer are at risk for developing metachronous lung cancer, but with the success of computed tomography and positron emission tomography, the ability to detect both synchronous and metachronous lung cancer has increased. We present a case of a 63-year-old Hispanic man who came to our hospital for evaluation of chest pain, dry cough, and weight loss. He had recently been diagnosed with adenocarcinoma in the right upper lobe, with a poorly differentiated carcinoma favoring squamous cell cancer based on bronchoalveolar lavage of the right lower lobe for which treatment was started. Later, bronchoscopy incidentally revealed the patient to have an endobronchial lesion that turned out to be mixed small and large cell neuroendocrine lung cancer. Our patient had triple synchronous primary lung cancers that histologically were variant primary cancers. Triple synchronous primary lung cancer management continues to be a challenge. Our patient’s case suggests that multiple primary lung cancers may still occur at a greater rate than can be detected by high-resolution computed tomography.
"I Didn't Do That!" Event Valence and Child Age Influence Adults' Discernment of Preschoolers' True and False Statements.

Justice can hinge on adults’ abilities to distinguish accurate from inaccurate child testimony. Yet relatively little is known about factors that affect adults’ abilities to determine the accuracy of children’s eyewitness reports. In this study, adults (N = 108) viewed videoclips of 3- and 5-year-olds answering open-ended and leading questions about positive and negative actually experienced (“true”) events or never experienced (“false”) events that the children either affirmed or denied. Analyses revealed that adults were more accurate at determining the veracity of negative compared with positive incidents, particularly when children said that they had experienced the event. Moreover, adults’ accuracy was at chance for older children’s false denials. Psycholegal implications are discussed.
Environmental taxation and the double dividend hypothesis in CGE modelling literature: A critical review

Abstract Computable general equilibrium (CGE) modelling is a flexible and open way to model the economic systems that allow practitioners to assess the impacts of different policies or external shocks over an economic system. There is some empirical literature dedicated to test the double dividend hypothesis of an environmental tax reform using CGE models. This hypothesis claims that is possible to obtain an improvement of both environmental and economic conditions by imposing an environmental tax and recycling revenues obtained to reduce other pre-existing taxes. This research provides a comprehensive review of this literature including a statistical and a meta-regression analysis. 69 different simulations from 40 studies have been analyzed. 55% of simulations have achieved a double dividend, concluding that although the environmental dividend is almost always achieved, the economic dividend still remains an ambiguous question that needs further research.
Inverse transformation: unleashing spatially heterogeneous dynamics with an alternative approach to XPCS data analysis

X-ray photon correlation spectroscopy (XPCS), an extension of dynamic light scattering (DLS) in the X-ray regime, detects temporal intensity fluctuations of coherent speckles and provides scattering-vector-dependent sample dynamics at length scales smaller than DLS. The penetrating power of X-rays enables XPCS to probe the dynamics in a broad array of materials, including polymers, glasses and metal alloys, where attempts to describe the dynamics with a simple exponential fit usually fail. In these cases, the prevailing XPCS data analysis approach employs stretched or compressed exponential decay functions (Kohlrausch functions), which implicitly assume homogeneous dynamics. This paper proposes an alternative analysis scheme based upon inverse Laplace or Gaussian transformation for elucidating heterogeneous distributions of dynamic time scales in XPCS, an approach analogous to the CONTIN algorithm widely accepted in the analysis of DLS from polydisperse and multimodal systems. Using XPCS data measured from colloidal gels, it is demonstrated that the inverse transform approach reveals hidden multimodal dynamics in materials, unleashing the full potential of XPCS.
CSRO-Based Reconfigurable True Random Number Generator Using RRAM

In this paper, we propose a high-speed (kilohertz–megahertz), reconfigurable current starved ring oscillator (CSRO)-based true random number generator (TRNG) design. The proposed TRNG exploits the intradevice stochastic variations in resistive RAM switching parameters and random telegraph noise (RTN). We demonstrate the effect of RTN on the jitter of CSRO oscillations. We also propose a methodology to reconfigure the TRNG to generate new random numbers. The proposed 10-bit TRNG is validated by NIST test suite for randomness in the data stream. Energy/bit is 22.8 fJ for generation, and the speed of random data generation is 6 MHz. Security vulnerabilities and countermeasures of the proposed TRNG are also investigated.
Effective altruism and collective obligations

Effective altruism (EA) is a movement devoted to the idea of doing good in the most effective way possible. EA has been the target of a number of critiques. In this article, I focus on one prominent critique: that EA fails to acknowledge the importance of institutional change. One version of this critique claims that EA relies on an overly individualistic approach to ethics. Defenders of EA have objected that this charge either fails to identify a problem with EA's core idea that each of us should do the most good we can, or makes unreasonable claims about what we should do. However, I argue that we can understand the critique in a way that is well motivated, and that can avoid these objections.
A Balanced Approach to Research in Supply Chain Management

When choosing a research strategy, there are tradeoffs in control, realism and generalizability. Quantitative research methods optimize control and generalizability (external validity), while qualitative research maximizes realism (internal validity). Logistics scholars agree that logistics and supply chain management are steeped in the positivist paradigm and that past research is primarily normative and quantitative. An imbalance exists in the conduct and publishing of rigorous qualitative research studies such as grounded theory, ethnography, phenomenology, semiotics, and historical analysis. At the same time, the business environment in which logistics and supply chain phenomena are located is becoming increasingly complex and less amenable to using just a quantitative approach. In order to accurately describe, truly understand and begin to explain these complex phenomena, research streams should include more studies using qualitative methods. Researchers who exclusively choose one approach or the other seriously delimit the scope of their inquiry and, thereby, their ability to contribute to the body of knowledge.
The limitations of on-site inspection

For the first time since the Treaty of Versailles, highly intrusive inspection rights are being incorporated into a treaty. But the risks of some forms of inspection may exceed their benefits.
Braille Reading: Factors Affecting Achievement of Dutch Elementary School Children.

This study compares reading skills of visually impaired children with those of sighted children. It also investigates the relationships between reading achievement and residual vision, hand movemen...
Anorexia nervosa: psychological considerations for nutrition counseling.

Abstract This article presents the underlying psychological beliefs and self-perceptions held by individuals with anorexia nervosa. The intent of this article is to help dietitians and other nutrition counselors become more aware of the psychological characteristics of individuals with anorexia nervosa and become familiar with various counseling skills that can assist counselors when they are working toward reaching the goal of re-establishing normal eating patterns and attitudes about food. Counseling approaches that may be used by the nutrition counselor in an effort to deal effectively with the various psychological characteristics displayed by anorexics are provided. Nutrition counselors must be well informed of the psychodynamic aspects that prevail in the disorder, such as low self-esteem, frustration over gaining weight, and a distorted body image. In addition, nutrition counselors must be aware of the particular communication skills (e.g., attentive listening, empathic responses, and verbal encouragement) and basic therapeutic methods (e.g., encouraging self decision making and providing support and acceptance of thoughts, feelings, and actions) that can be used for effecting positive growth and changes in dietary behavior of individuals with anorexia. J Am Diet Assoc 88:49, 1988.
Leveraging Elsevier’s Creative Commons License Requirement to Undermine Embargo

This article builds upon a poster previously presented at the 2017 Kraemer Copyright Conference. The poster is included here as a supplementary file.
Autonomous Heat Leakage Detection from Unmanned Aerial Vehicle-Mounted Thermal Cameras

The efficiency of thermal insulation of buildings has direct impact on power consumption for heating and ventilation. Thermal leaks are critical defects on building insulation. Infrared sensitive handheld thermal cameras are commonly used to perform manual inspection of buildings to detect thermal leaks by human experts. In this paper, we propose an algorithm that autonomously detects heat leakages from thermal images of building structures. The target platform for the proposed algorithm is an unmanned aerial vehicle (UAV) that collects thermal images of buildings, and detects heat leakages autonomously. Using UAVs, as opposed to the current practice of doing manual inspection, not only speeds up the process, but also provides the capability of capturing data from hard to reach places, such as roofs, in a more convenient and safe manner. For evaluation, thermal images have been captured both from inside, by a handheld camera, and outside. The outside thermal images have been captured by either a handheld camera or an IR camera installed on a UAV. Experimental results show that the proposed approach is very promising with overall precision and recall rates of 91% and 89%, respectively on handheld dataset, and 34% and 77%, respectively on the UAV dataset.
Syntheses and Biological Evaluation of Ring‐C Modified Colchicine Analogues.

Diels—Alder reactions of colchicine (I) with iminonitroso agents (II) afford the ring-C modified alkaloids (III) and (IV) as regioisomeric adducts.
Hospitalization Rates in Older Adults With Albuminuria: The Cardiovascular Health Study

Background Albuminuria is highly prevalent among older adults, especially those with diabetes. It is associated with several chronic diseases, but its overall impact on the health of older adults, as measured by hospitalization, has not been quantified. Method We followed up 3,110 adults, mean age 78 years, for a median 9.75 years, of whom 654 (21%) had albuminuria (≥30 mg albumin/gram creatinine) at baseline. Poisson regression models, adjusted for cardiovascular, renal, and demographic factors, were used to evaluate the association of albuminuria with all-cause and cause-specific hospitalizations, as defined by ICD, version 9, categories. Results The rates of hospitalization per 100 patient-years were 65.85 for participants with albuminuria and 37.55 for participants without albuminuria. After adjustment for covariates, participants with albuminuria were more likely to be hospitalized for any cause than participants without albuminuria (incident rate ratio, 1.39 [95% confidence intervals, 1.27. 1.53]) and to experience more days in hospital (incident rate ratio 1.56 [1.37, 1.76]). The association of albuminuria with hospitalization was similar among participants with and without diabetes (adjusted incident rate ratio for albuminuria versus no albuminuria: diabetes 1.37 [1.11, 1.70], no diabetes 1.40 [1.26, 1.55]; p interaction nonsignificant). Albuminuria was significantly associated with hospitalization for circulatory, endocrine, genitourinary, respiratory, and injury categories. Conclusions Albuminuria in older adults is associated with an increased risk of hospitalization for a broad range of illnesses. Albuminuria in the presence or absence of diabetes appears to mark a generalized vulnerability to diseases of aging among older adults.
The Effects of Obesity on Outcome in Preclinical Animal Models of Infection and Sepsis: A Systematic Review and Meta-Analysis.

Background Clinical studies suggest obesity paradoxically increases survival during bacterial infection and sepsis but decreases it with influenza, but these studies are observational. By contrast, animal studies of obesity in infection can prospectively compare obese versus nonobese controls. We performed a systematic review and meta-analysis of animal investigations to further examine obesity's survival effect in infection and sepsis. Methods Databases were searched for studies comparing survival in obese versus nonobese controls. We performed a systematic review and meta-analysis of animal investigations to further examine obesity's survival effect in infection and sepsis. Methods. Databases were searched for studies comparing survival in obese versus nonobese animals following bacteria, lipopolysaccharide, or influenza virus challenges. Results Twenty-one studies (761 obese and 603 control animals) met the inclusion criteria. Obesity reduced survival in 19 studies (11 significantly) and the odds ratio (95% CI) of survival (0.21(0.13, 0.35); I2 = 64%, p < 0.01p < 0.01p < 0.01) but with high heterogeneity. Obesity reduced survival (1) consistently in both single-strain bacteria- and lipopolysaccharide-challenged studies (n = 6 studies, 0.21(0.13, 0.34); I2 = 64%, p < 0.01p < 0.01) but with high heterogeneity. Obesity reduced survival (1) consistently in both single-strain bacteria- and lipopolysaccharide-challenged studies (n = 6 studies, 0.21(0.13, 0.34); I2 = 64%, p < 0.01p < 0.01) but with high heterogeneity. Obesity reduced survival (1) consistently in both single-strain bacteria- and lipopolysaccharide-challenged studies (n = 6 studies, 0.21(0.13, 0.34); I2 = 64%, p < 0.01p < 0.01) but with high heterogeneity. Obesity reduced survival (1) consistently in both single-strain bacteria- and lipopolysaccharide-challenged studies (n = 6 studies, 0.21(0.13, 0.34); I2 = 64%, p < 0.01p < 0.01p < 0.01) but with high heterogeneity. Obesity reduced survival (1) consistently in both single-strain bacteria- and lipopolysaccharide-challenged studies (n = 6 studies, 0.21(0.13, 0.34); I2 = 31%, p=0.20 and n = 5, 0.22(0.13, 0.36); I2 = 0%, p=0.59, respectively), (2) not significantly with cecal ligation and puncture (n = 4, 0.72(0.08, 6.23); I2 = 75%, p < 0.01), and (3) significantly with influenza but with high heterogeneity (n = 6, 0.12(0.04, 0.34); I2 = 73%, p < 0.01). Obesity's survival effects did not differ significantly comparing the four challenge types (p=0.49). Animal models did not include antimicrobials or glycemic control and study quality was low. Conclusions Preclinical and clinical studies together emphasize the need for prospective studies in patients accurately assessing obesity's impact on survival during severe infection.
A sort of friend: narratives from young people and parents about collaboration with a mental health outreach team

Mental health issues among young people have received increasing attention in Norway as more are diagnosed with and report mental health problems. In this study, we focus on the personal and social...
Publishing trends in the field of urgent care medicine from 2000 to 2020: A bibliometric analysis.

Abstract Background With a steady rise in the number of urgent care centers in the United States and the establishment of urgent care medicine as a specialty, research in the field is likely to emerge. Objectives To perform a bibliometric analysis of published studies in the field of urgent care medicine over the past two decades. Methods A comprehensive literature review was conducted, including original and review articles pertaining to urgent care medicine published 2000–2020. Data abstracted from each article included publication year, journal, research study design, study population, clinical relevance (clinical or non-clinical), and study topics. Results A total of 144 publications from 94 peer-reviewed journals were analyzed. There has been a steady increase in the annual number of publications from 2010 to 2019. The most common study designs were retrospective (55.5%), study specific (24.3%), prospective (15.3%), and quality improvement (4.9%). Adults were the most frequently identified study population (33.3%), followed by pediatrics (18%), and both adults and pediatrics (16.7%). Publications were categorized as clinical (48.6%) and non-clinical (51.4%). The most common research topics were urgent care utilization [n = 34, 23.6%; especially effectiveness (n = 9) and disease based (n = 7)], diagnostic testing [(n = 20, 13.9%; especially HIV (n = 7) and sexually transmitted infections (n = 6)], and antibiotic stewardship (n = 17, 11.8%). Conclusion Based on our sample, published research in the field of urgent care medicine has evolved. By describing current trends, we hope that clinicians and researchers continue to advance the field by developing high quality research, including prospective, multi-institutional/center studies involving both clinical and non-clinical topics.
“The Only Thing That’s Real Is Me”: CM Punk and the Rhetorical Framework of the American Dream

Although the world of professional wrestling is characterized as larger than life, a speech by World Wrestling Entertainment (WWE) wrestler Phillip Brooks appeared to cross the line between fantasy...
Alarming Eosinophilia From Dobutamine Infusion

A 49-year-old male with a history of nonischemic heart failure with reduced ejection fraction, hypertension, diabetes was admitted for cardiogenic shock. Treatment started with a high dose of dobutamine infusion. While the patient's volume status improved, his clinical status declined as he became febrile and hypotensive. He was found to have severe dobutamine-induced eosinophilia, corrected only upon dobutamine cessation and steroid administration. A comprehensive investigation ruled out other potential etiologies. Peripheral eosinophilia is a rare adverse effect associated with dobutamine, leading to a significant deterioration in already decompensated patients.
Flea beetles of the West Indies: new combinations and new species (Coleoptera: Chrysomelidae: Galerucinae: Alticini)

As a result of changes in the flea beetle classification in the last 20 years, the following new combinations are proposed for West Indian flea beetles: Acallepitrix nigrita (Jacoby 1897) comb. nov., Centralaphthona crucifera (Blake 1964) comb. nov., Centralaphthona grenadensis (Jacoby 1897) comb. nov., Centralaphthona inornata (Blake 1949) comb. nov., Centralaphthona insularis (Blake 1964) comb. nov., Centralaphthona lepta (Blake 1964) comb. nov., Centralaphthona nana (Blake 1949) comb. nov., Centralaphthona ruficollis (Blake 1970) comb. nov., Centralaphthona salaisa (Bechyne 1956) comb. nov., Centralaphthona schwarzi (Blake 1949) comb. nov., Dibolia dissita (Blake 1931) comb. nov., Erinaceialtica antennata (Medvedev 2004) comb. nov., Gioia crassicornis (Baly 1877) comb. nov., Homoschema auripennis (Suffrian 1868) comb. nov., Homoschema compressa (Suffrian 1868) comb. nov., Hypolampsis ferruginea (Suffrian 1868) comb. nov., Monomacra pallens (Fabricius 1792) comb. nov., Parchicola androsensis (Blake 1946) comb. nov., Parchicola religata (Jacquelin du Val 1857) comb. nov., Syphrea pauxilla (Suffrian 1868) comb. nov. Lectotypes are designated for the following species: Cyrsylus volkameriae (Fabricius 1792), Gioia crassicornis (Baly 1877), Homoschema auripennis (Suffrian 1868), Homoschema compressa (Suffrian 1868), Hypolampsis ferruginea (Suffrian 1868), Monomacra pallens (Fabricius 1792), Syphrea pauxilla (Suffrian 1868). The following new species are described from the Dominican Republic: Cyrsylus lasabejas sp. nov. (Sierra de Baoruco, Las Abejas); Dibolia sierradebaoruco sp. nov. (Sierra de Baoruco, Casete 1); Gioia elcachote sp. nov. (Barahona Province, El Cachote); Syphrea baoruco sp. nov. (Sierra de Baoruco, Las Abejas). New species and representatives of the genera – recipients of new combinations are illustrated. Key words: Dominican Republic, habitat, host plant, leaf beetles, Neotropical Region, new taxa
Reduced Systemic Corticosteroid Use among Pediatric Patients With Inflammatory Bowel Disease in a Large Learning Health System.

OBJECTIVES Corticosteroids have long been used to treat inflammatory bowel disease. However, cumulative corticosteroid exposure is associated with adverse effects, particularly in growing children. Professional guidelines recommend steroid-sparing strategies. It remains unknown whether corticosteroid use has decreased in children with inflammatory bowel disease. METHODS We performed retrospective cohort study using data from 2007 to 2018 from the international multi-center ImproveCareNow Network, a pediatric inflammatory bowel disease quality improvement collaborative. Pediatric patients diagnosed with inflammatory bowel disease were included. Patients with missing diagnosis or corticosteroid use data were excluded. We performed serial cross-sectional analyses of period prevalence and used multivariate regression models. RESULTS 27,321 patients were included (65% Crohn disease, 28% ulcerative colitis, 7% indeterminate colitis). Corticosteroids were used in 10,206 (37%). Corticosteroid use decreased from 28% (2007) to 12% (2018). Black patients received corticosteroids more commonly than white patients. This disparity improved as corticosteroid use decreased in both groups. Most corticosteroid use occurred <120 days after diagnosis. Corticosteroid or 5-aminosalicylate use <120 days after diagnosis predicted later corticosteroid use. Anti-tumor necrosis factor-alpha medication use <120 days after diagnosis was associated with a reduction in corticosteroid use. As corticosteroid use decreased, steroid-sparing therapy use increased and height and weight z scores improved, particularly among children with Crohn disease. Despite improvement across the network, variation in corticosteroid usage remains. CONCLUSIONS Corticosteroid use among pediatric patients with inflammatory bowel disease in the ImproveCareNow Network has decreased over time. Racial disparities in corticosteroid use were found, but gradually improved.
Comparison of injuries between US Army paratroopers and their non-paratrooper soldier counterparts

Introduction Military studies have investigated acute injuries associated with parachute jumps, but the literature does not address paratroopers’ cumulative microtraumatic (CMT) injury risk, nor does it compare injury risks between paratroopers and the rest of the military population. This study determined whether US active duty Army paratroopers experienced greater injury risks than their non-paratrooper soldier counterparts and whether their injuries cost more to treat suggesting greater injury severity. Methods This retrospective study evaluated electronic medical records (2016–2018) for 31 621 paratroopers and a randomly selected comparison group of 170 715 non-paratrooper soldiers. Analyses included univariate and multivariate regression to quantify odds of injuries associated with risk variables and additional descriptive statistics. Results Paratroopers had a 57% increase in the odds of experiencing one or more injuries (OR=1.57, 95% CI: 1.52 to 1.62) after controlling for sex, race and age, with a greater proportion of acute injuries (OR=1.38, 95% CI: 1.34 to 1.42), relative to comparison group soldiers. Injury types proportionally higher among paratroopers included head trauma and shoulder injuries. Average injury cost among paratroopers was 13% lower than for non-paratroopers ($2470 vs $2830 per injury). Among both populations, acute injury costs were notably higher than for CMT injuries (paratroopers, $1710/$630; non-paratroopers, $1860/$880 per injury). Conclusions Paratroopers were more likely to incur injury, especially an acute injury, than non-paratroopers. However, paratroopers’ average injury costs were less. This may be due to higher return-to-duty motivations, fitness levels, and/or facility-specific cost of care. Future studies should investigate causes of injuries found to be proportionally higher among paratroopers.
A yeast DNA J protein required for uncoating of clathrin-coated vesicles in vivo

Clathrin-coated vesicles mediate diverse processes such as nutrient uptake, downregulation of hormone receptors, formation of synaptic vesicles, virus entry, and transport of biosynthetic proteins to lysosomes. Cycles of coat assembly and disassembly are integral features of clathrin-mediated vesicular transport (Fig. 1a). Coat assembly involves recruitment of clathrin triskelia, adaptor complexes and other factors that influence coat assembly, cargo sequestration, membrane invagination and scission1,2,3 (Fig. 1a). Coat disassembly is thought to be essential for fusion of vesicles with target membranes and for recycling components of clathrin coats to the cytoplasm for further rounds of vesicle formation. In vitro, cytosolic heat-shock protein 70 (Hsp70) and the J-domain co-chaperone auxilin catalyse coat disassembly4. However, a specific function of these factors in uncoating in vivo has not been demonstrated, leaving the physiological mechanism and significance of uncoating unclear. Here we report the identification and characterization of a Saccharomyces cerevisiae J-domain protein, Aux1. Inactivation of Aux1 results in accumulation of clathrin-coated vesicles, impaired cargo delivery, and an increased ratio of vesicle-associated to cytoplasmic clathrin. Our results demonstrate an in vivo uncoating function of a J domain co-chaperone and establish the physiological significance of uncoating in transport mediated by clathrin-coated vesicles.
A uniqueness theorem with moving targets without counting multiplicity

In this paper, we prove a uniqueness theorem for holomorphic curves with moving targets without counting multiplicity.
Can spermatogenesis be maintained quantitatively in intact adult rats with exogenously administered dihydrotestosterone

: It is well established that testosterone (T) is required to maintain spermatogenesis in the mammalian testis, presumably acting through a receptor mechanism, as elsewhere. It is puzzling, however, that the T concentration that is required to maintain spermatogenesis quantitatively in intact adult rats (15–20 ng/ml) is well in excess of the concentration required to saturate testicular androgen receptors. If, indeed, T regulation of spermatogenesis is mediated through the androgen receptor, 5α-dihydrotestosterone (DHT) would be expected to more effectively maintain spermatogenesis than T because of its greater affinity for, and slower rate of dissociation from, the androgen receptor. To test this hypothesis experimentally, the quantitative relationship between the intratesticular concentration of exogenously administered DHT and the maintenance of germ cell production was examined in intact rats in which endogenous T production was suppressed. To this end, rats received increasing doses of DHT via polydimethylsiloxane implants of 6–36 cm in length for 8 weeks. In each DHT-treated rat, serum luteinizing hormone (LH) concentration was reduced to below the limit of detectability by radioimmunoassay (RIA), and intratesticular T concentration was reduced by >90%. Serum and intratesticular DHT concentrations increased with increasing implant size. The serum and intratesticular concentrations of 5α-androstane-3α, 17β-diol (3α-Diol) were consistently higher than DHT concentrations because of conversion of DHT to 3α-Diol. Spermatogenesis was maintained qualitatively in some rats that received implants of 6 cm, in most rats that received implants of 12 cm, and in all rats that received implants of 18 cm. Spermatogenesis was maintained quantitatively in most rats that received implants of 24 cm and 36 cm. The minimal average intratesticular concentration of DHT associated with the quantitative maintenance of spermatogenesis was approximately 50% of the T concentration shown previously to be minimally required. These results indicate that DHT, with its greater affinity for, and slower rate of dissociation from, the androgen receptor, more effectively maintains spermatogenesis than T at comparable intratesticular concentrations.
Vitamin A and feeding statuses modulate the insulin-regulated Pck1 and Srebp-1c expression in primary hepatocytes from lean and obese rats (645.1)

The hepatic insulin resistance occurs with profound changes of the expression of genes for glucose and lipid metabolism. Previously, we compared insulin-regulated gene expression in hepatocytes of Zucker lean (ZL) and fatty (ZF) rats. We found that insulin-regulated Srebp-1c and Pck1 expressions are impaired in hepatocytes of ZF, but not ZL, rats fed ad libitum, which can be corrected by fasting. As vitamin A (VA) deficiency causes reduction of body mass and food intake in rats, we set up a pair-feeding experiment to study the effects of energy intake and VA status on the insulin-regulated gene expression. Rats were fed a VA deficient (VAD) diet ad libitum (VAD-AD) for 8 weeks. An isocaloric VA sufficient (VAS) diet equal to the amount of the VAD diet taken by the VAD-AD rat in 24-hour was given to the pair-fed rats in two ways. On the last day, VAS-PF-AD rat was allowed to ingest the VAS diet ad libitum to avoid the fasting state. VAS-PF-4M rat was given one fourth of the daily ration every 6 hours. Here...
Nonlinear δ Scuti models: The main sequence catastrophe?

For nonlinear models of 0.4 M⊙ and 2.0 M⊙ δ Scuti stars, pulsation amplitudes obtained in this region depend critically upon artificial viscosity parameters. Models with limited viscosity attain huge amplitudes. Furthermore, it is found that nonlinear stability properties depend primarily upon the amplitude. Determination of the actual dissipation mechanism is thus crucial to our understanding of these objects, and probably other main sequence pulsators as well. At present the most likely mechanisms appear to be 1) dissipation in the atmosphere, corona and wind; 2) turbulent dissipation in the convective zones; 3) magnetic fields.
Myocardial Protection during Bypass Surgery

Precise coronary artery bypass grafting requires a bloodless, motionless operative field, and various techniques of cardioplegia are used to obtain these operative conditions while systemic blood flow is provided by a heart-lung machine. The technique of ischemic arrest provides the most optimal operating conditions for construction of distal bypass graft anastomoses. Placement of a clamp across the ascending aorta interrupts coronary flow and produces ischemic cardiac arrest, permitting precise execution of distal coronary artery anastomoses under optimal conditions. Although the best interests of the patient are served when bypass grafts are sutured precisely into well-exposed, immobile and bloodless coronary arteries, the surgeon must not irreversibly damage the myocardium while attempting to revascularize it. Most surgeons have found that only ischemic (anoxic) cardiac arrest provides the operating conditions necessary for precise distal bypass graft anastomoses (Table 22),1 and have therefore striven to develop techniques which can best protect the myocardium during the ischemic interval.2
Dimerization Domain of Retinal Membrane Guanylyl Cyclase 1 (RetGC1) Is an Essential Part of Guanylyl Cyclase-activating Protein (GCAP) Binding Interface *

The photoreceptor-specific proteins guanylyl cyclase-activating proteins (GCAPs) bind and regulate retinal membrane guanylyl cyclase 1 (RetGC1) but not natriuretic peptide receptor A (NPRA). Study of RetGC1 regulation in vitro and its association with fluorescently tagged GCAP in transfected cells showed that R822P substitution in the cyclase dimerization domain causing congenital early onset blindness disrupted RetGC1 ability to bind GCAP but did not eliminate its affinity for another photoreceptor-specific protein, retinal degeneration 3 (RD3). Likewise, the presence of the NPRA dimerization domain in RetGC1/NPRA chimera specifically disabled binding of GCAPs but not of RD3. In subsequent mapping using hybrid dimerization domains in RetGC1/NPRA chimera, multiple RetGC1-specific residues contributed to GCAP binding by the cyclase, but the region around Met823 was the most crucial. Either positively or negatively charged residues in that position completely blocked GCAP1 and GCAP2 but not RD3 binding similarly to the disease-causing mutation in the neighboring Arg822. The specificity of GCAP binding imparted by RetGC1 dimerization domain was not directly related to promoting dimerization of the cyclase. The probability of coiled coil dimer formation computed for RetGC1/NPRA chimeras, even those incapable of binding GCAP, remained high, and functional complementation tests showed that the RetGC1 active site, which requires dimerization of the cyclase, was formed even when Met823 or Arg822 was mutated. These results directly demonstrate that the interface for GCAP binding on RetGC1 requires not only the kinase homology region but also directly involves the dimerization domain and especially its portion containing Arg822 and Met823.
Oxidation states of239,240Pu in global fallout

Oxidized Pu species [Pu(V+VI)] have been found in surface waters and rainfall both from atmospheric and surface nuclear test debris. This paper presents experimental data which suggests that this oxidized Pu may be a “memory” of the oxidation state of239,240U formed during thermonuclear explosions, and which β-decayed to239,240Pu through239,240Np following condensation on atmospheric particles.
The Risk of Dying from Lung Cancer by Race: A Prospective Cohort Study in a Biracial Cohort in Charleston, South Carolina

Purpose Compared to European Americans (EAs), African Americans (AAs) suffer a disproportionate share of the lung cancer mortality burden. To investigate whether this disparity in lung cancer mortality is due to differential racial risks related to socioeconomic status (education, occupation), body mass index (BMI), hypertension, or cigarette smoking, we compared associations between these factors and lung cancer mortality by race in a biracial prospective cohort study. Methods The Charleston (South Carolina) Heart Study ( N = 2,054) was established in 1960; 40% of the study participants are AAs. The participants have been followed up for mortality for 40 years. Using Cox proportional hazards models, we investigated whether there were racial differences in the associations between the study factors and lung cancer mortality. Results Cigarette smoking was the strongest lung cancer risk factor in both races. The association between cigarette smoking and lung cancer mortality was stronger in EAs than AAs (hazards ratio [HR] 26.1 vs. 7.6). In both races, men were at significantly greater risk than women and BMI was significantly inversely associated with lung cancer mortality. Conclusions The evidence from the present study does not yield strong clues for the excess lung cancer mortality in AAs. Our results do not support the hypothesis that differential susceptibility to cigarette smoking is a major contributor to the racial disparity in lung cancer. This suggests we must expand our scope of inquiry beyond the factors included in the present study to fully understand why lung cancer mortality rates are greater in AAs than EAs.
Different effects of genistein on molecular markers related to apoptosis in two phenotypically dissimilar breast cancer cell lines

The association between consumption of genistein-containing soybean products and lower risk of breast cancer suggests a cancer chemopreventive role for genistein. Consistent with this suggestion, exposing cultured human breast cancer cells to genistein inhibits cell proliferation, although this is not completely understood. To better understand how genistein works, the ability of genistein to induce apoptosis was compared in phenotypically dissimilar MCF-7 and MDA-MB-231 human breast cancer cells that express the wild-type and mutant p53 gene, respectively. After 6 days of incubation with 50 microM genistein, MCF-7 but not MDA-MB-231 cells, showed morphological signs of apoptosis. Marginal proteolytic cleavage of poly-(ADP-ribose)-polymerase and significant DNA fragmentation were also detected in MCF-7 cells. In elucidating these findings, it was determined that after 2 days of incubation with genistein, MCF-7 but not MDA-MB-231 cells, had significantly higher levels of p53. Accordingly, the expression of certain proteins modulated by p53 was studied next. Levels of p21 increased in both of the genistein-treated cell lines, suggesting that p21 gene expression was activated but in a p53-independent manner, whereas no significant changes in levels of the pro-apoptotic protein, Bax, were found. In MCF-7 cells, levels of the anti-apoptotic protein, Bcl-2, decreased slightly at 18-24 h but then increased considerably after 48 h. Hence, the Bax:Bcl-2 ratio initially increased but later decreased. These data suggest that at the genistein concentration tested, MCF-7 cells in contrast to MDA-MB-231 cells were sensitive to the induction of apoptosis by genistein, but Bax and Bcl-2 did not play clear roles.
Solution 13C NMR spectroscopy of polyamide homopolymers (nylons 6, 11, 12, 66, 69, 610 and 612) and several commercial copolymers

Abstract Well-resolved 13C NMR spectra of nylons 6, 11, 12, 66, 69, 610, and 612 dissolved in 4:1 TFE/CDCl3 allowed complete assignment of all major backbone peaks. In addition, several low intensity peaks were identified representing cis amide groups, acid end-groups and amine end-groups. Several peaks associated with the trans amide units in the spectra of each polyamide homopolymer were identified as uniquely characteristic of that polymer. Using these unique peaks, all the polyamides studied could be distinguished from each other as homopolymers and as repeat units in copolymers. For example, three unknown polyamides (supplied by a colleague) were identified as nylon 6, nylon 66 and nylon 610 using only solution 13C NMR spectroscopy. Based on these results, several commercial polymers were examined. Using solution 13C NMR spectroscopy, the copolymer compositions, molecular weights, end-group and cis amide contents, plus the amount of residual e-caprolactam were all determined. For example, Spiderwire Super Mono® fishing line was found to have a number average molecular weight of 25,333 g/mol and to contain 82 mol% nylon 6 repeat units and 18 mol% nylon 66 repeat units. The residual e-caprolactam, acid end-group and amine end-group contents were calculated as 1.25, 0.61 and 0.0 mol%, respectively. The cis amide contents were calculated to be 1.2 mol% for nylon 6 units and 0.61 mol% for nylon 66 segments.
Enantiomerically pure zirconium and hafnium complexes containing a chiral cyclopentadiene derivative prepared from (−)-β-pinene

Abstract Chirally homogeneous (1 S ,8 R )-3,5,9,9-tetramethyltricyclo[6.1.1.0 2,6 ]deca-2,5-diene 1 has been prepared in five steps and 42% overall yield from (−)-β-pinene; its successive treatment first with n -BuLi and then with ZrCl 4 or HfCl 4 provides, in high yields with high π-facial selectivity, the corresponding dichlorobis { η 5 -(1 S ,8 R )-3,5,9,9-tetramethyltricyclo[6.1.1.0 2,6 ]deca-3,5-dien-2-yl}zirconium or hafnium, respectively.
Statistics of correlation functions from molecular dynamics.

The statistical uncertainty in the calculation of velocity autocorrelation functions and self-diffusion coefficients from molecular dynamics is empirically determined from the spread of the molecular-dynamics results for an ensemble of macroscopically identical systems. The ``experimental'' uncertainties of the velocity-autocorrelation-function values at equilibrium and in the presence of flow agree well with theoretical predictions. The uncertainty of the self-diffusion coefficient is found to decrease as the inverse square root of the averaging time.
Efficient Estimation of Protein Binding Constants

Assays of cyclic AMP typically employ a Scatchard-like data analysis to estimate the total binding protein RT and the dissociation constant Kd. The linear regression procedure employed is statistically ad hoc because the response variable (bound counts) occurs on both sides of the Scatchard equation. The alternative analysis presented here is derived from the cyclic AMP binding reaction. The resulting data analysis, employing non-linear least squares, results in estimators that on the basis of Monte Carlo studies have less bias and greater precision than the Scatchard method.
Reinforced variability enhances object exploration in shy and bold rats

In an open-field test, the Long-Evans (LE) strain of rats was identified as "bold" and the PVG strain as "shy." Some members of each strain then experienced 14 sessions of a common enrichment procedure, namely exposure to a series of novel objects (Exposed). Others in each strain were explicitly reinforced with food pellets for variable interactions with the same objects (Reinforced). Both experience and strain influenced object interactions. In particular, Reinforced rats interacted more variably with the objects - contacting, probing, pushing and so forth - than did the Exposed; and LEs interacted more variably than PVGs. Foraging proficiency in the same rats was then studied in a transfer-of-training test. Food pellets were hidden among never-before experienced objects and the rats were permitted to explore freely. Reinforced rats discovered and consumed more pellets than Exposed; and LEs discovered and consumed more than PVGs. Thus a bold genetic strain and reinforcement of variability independently contributed to successful foraging behavior.
Parasites of the Nantucket Pine Tip Moth in Virginia with Notes on Ecological Relationships

In large plantations of loblolly and shortleaf pine ( Pinus taeda L. and P. echinata Miller), shoots infested With Rhyacinia frustrana (Comstock) were collected at 3 levels in trees at 3 dates to determine variations in parasite abundance. Of the 22 species of parasites, 4 were not previously reported from this species of Rhyacionia and 6 species were new to the parasite complex of the tip moth in Virginia. Twenty-one species were reared from tip moth-infested shoots on loblolly pine and 16 from shortleaf pine. Atrometus clavipes (Davis) and Campoplex frustranae Cushman were most abundant in the tops of trees, and Haltichella rhyacioniae Gahan, Bracon mellitor Say, and Habrocytus thyridopterigis Howard were most abundant at the bottom of trees. A. clavipes, H. rhyacioniae , and Eurytoma pini . Bugbee were more abundant on shortleaf pine, and C. frustranae and B. mellitor were more abundant on loblolly pine. B. mellitor was the only common parasite conspicuously more abundant in the first tip moth generation than in the second.
Antigen presentation to specific T cells by la molecules selectively altered by site-directed mutagenesis

A functional analysis of mutant class II molecules was conducted to identify regions important for antigen-specific T cell activation. Site-directed mutagenesis was used to construct a panel of mutant A beta k genes containing either single or multiple d allele substitutions in the beta 1 domain. The product of each of these genes was expressed with either the A alpha d or A alpha k polypeptide in the Ia-negative B cell lymphoma M12.C3. These mutant class II molecule-bearing cells were tested for their ability to present antigen to a panel of Ak-restricted T cell clones specific for various epitopes of myoglobin. Results from this analysis demonstrate that T helper clones recognized complex determinants interacting with multiple residues on the beta 1 domain and also requiring the haplotype-matched alpha 1 domain. This is in contrast to monoclonal antibodies that recognize a domain-specific, immunodominant region involving residues 40, 63, and 65-67. Every T helper clone was found to interact with a distinct pattern of residues, even among clones recognizing the same combination of peptide and major histocompatibility complex (MHC) molecule. The 3 for 1 residue substitution between k and d alleles at residues 65-67 was one of the most important, because it resulted in loss of ability to present antigen to 7 of 7 I-Ak-restricted T cell clones. These residues have been shown previously to comprise the immunodominant allo-specific serological determinants and to stimulate some alloreactive T cell clones. Substitution at residues 12 and 13 also abrogated antigen presentation to all the T cell clones, but this may be a consequence of a conformational change due to altered alpha beta chain pairing. Substitution at position 9, which is predicted to be located in the floor of the peptide-binding groove where it should not interact directly with the T cell receptor, enhanced presentation of the antigenic site 102-118 to some T cells and diminished it to others. This finding suggests a most interesting conclusion that the same antigenic site may bind in different conformations or orientations to the same MHC molecule, although an indirect effect on the conformation of the MHC molecule itself cannot be excluded. Substitutions at residues 85, 86 and 88 also abrogated the response of one T cell clone but not others specific for the same peptide with the same Ia molecule.(ABSTRACT TRUNCATED AT 400 WORDS)