cssi/SciSciGPT-SciSciNet huggingface dataset:
The neurogenetics of lissencephaly.

A comprehensive approach to diagnosis of patients with lissencephaly will allow a specific diagnosis to be made in a majority of patients. The most common diagnoses in order of decreasing frequency are Walker-Warburg syndrome, Miller-Dieker syndrome, and isolated lissencephaly sequence. Clinical diagnosis, counseling, and prenatal diagnosis have been improved by recent advances.
Is Leadership in Creativity and Innovative Technology the Cure for Quality Affordable Healthcare

Disruptive innovation is necessary in healthcare if we are to solve America's healthcare crisis. Patients need access to high quality, convenient, cost-effective healthcare. Industry leadership and the government together need to facilitate the transformation of the healthcare industry through innovative multidisciplinary models that will improve health outcomes, decrease costs, and improve access to care. Such a transformation can be realized by embracing the concept of precision medicine, where outcomes are managed and government facilities advancements through effective regulation.
Multi-threshold dual-spacer dual-rail delay-insensitive logic: An improved IC design methodology for side channel attack mitigation

As more sensitive data are shared, transmitted, and stored on electronic devices, data security has become an important concern. Encryption algorithms that are safe against software-based attacks still face security threats from side channel attacks. For example, an encryption device's power consumption or operational timing can be correlated to the data being processed by the device, which can give away the device's secret key. Dual-spacer Dual-rail Delay-insensitive Logic (D3L) is an IC design methodology that has been proved effective in mitigating power and timing attacks; however, large energy and area overheads of D3L circuits have hindered their applicability. In this paper an IC design methodology named Multi-Threshold D3L (MTD3L) is presented that achieves all D3L security advantages with considerably reduced overhead.
Outcomes for olfactory neuroblastoma treated with induction chemotherapy

Background Oncologic outcomes for induction chemotherapy and its role in patients with advanced olfactory neuroblastoma (ONB) remain unclear. Methods A retrospective review of 15 consecutive patients with extensive local invasion and/or nodal disease treated with induction chemotherapy with curative intent followed by definitive local therapy. Results The majority of patients were treated with cisplatin and etoposide. The response to chemotherapy was 68% (10/15). Response was 78% (7/9) in the high Hyams high-grade group and 50% (3/6) in the Hyams low-grade group. Seven patients had complete response (CR) and 3 patients were able to avoid orbital exenteration. The 5-year disease-free survival (DFS) and overall survival (OS) were 71% and 78%, respectively, with a trend toward improved survival in patients with CR. Conclusion ONB is a chemosensitive tumor and induction chemotherapy is an acceptable strategy for aggressive and locoregional advanced disease. Hyams grade may predict chemosensitivity and CR may be associated with improved survival.
Rate of weight loss of small round timber.

In certain markets for small round wood, purchase by weight is preferred to purchase by solid or stacked volume. Where produce is sold by weight it is desirable to know the relative green weights of different species and also how weight, for a given volume oftimber, changes with time as this can influence prices. Among the relatively limited information on this subject for Northern Irish conditions, Jack (1966), working with Sitka spruce, showed that the rate of weight loss over a 20 week period was linear and was likely to remain so up to the time 'the material reached a density of about 550kg/m3 • He found large variations in the rate of loss according to the time the material was felled, ranging from 2.7kg/m3 per day for material felled in April to 0.99kg/m3 per day for material felled in November. Small sized material lost weight about 50 per cent faster than larger sizes. There were small differences in the rate of weight loss of produce from different forests and of different yield classes.
Treatment Modalities for Fibroids, Indications, Risks, and Benefits

Uterine fibroids are the most common benign neoplasm of the uterus in women of reproductive age. Although they are often asymptomatic, uterine fibroids may present abnormal uterine bleeding, pressure symptoms such as urinary frequency and constipation, abdominal pain or increasing abdominal girth, dyspareunia, and infertility. Various management options are available for the treatment of fibroids, which include medical management, such as hormonal therapies, and the use of gonadotropin-releasing hormone agonists. Surgical management includes uterine-sparing interventions, minimally invasive surgery, interventional radiological approaches, myomectomy, and hysterectomy. The choice of management approach for fibroids is dictated by size, number, location, nature of clinical manifestations, and future desire for fertility. No routine single management strategy is optimal because of the variable location and size of fibroids. Treatment should be tailored to the patient’s symptoms, disease location, and disease severity. With recent advancements in the minimally invasive surgeries and interventional radiological procedures, new treatment options for fibroid management have been proven successful and demonstrated efficacy and safety, along with reduced long-term reoccurrence. The purpose of this chapter is to summarize the various treatment modalities and available evidence for the management of fibroids with the focus on procedural indications, risk, and benefits.
Glass particle resuspension from a contaminated (dirty) glass surface

Abstract A wealth of adhesion force measurements between a variety of particle/surface pairs have been gathered via Atomic Force Microscopy (AFM) in the past years. However, these measurements deal mostly with clean surfaces and particles for reproducibility. It is therefore up for debate whether particle resuspension could be calculated using these measurements as surrogates for real outdoor particles and surfaces, which often carry both organic and inorganic contaminants (“urban grime”). Two components are necessary to investigate this question: (1) adhesion force measurements on both clean and contaminated surfaces and (2) estimation of particle resuspension from both surface types. In this work, AFM was used to measure the distribution of the adhesion force between a 5-µm clean glass particle and two glass surfaces: the first cleaned according to conventional laboratory standards and a second one left outdoors for six weeks in Albuquerque (New Mexico). The Rock ‘n′ Roll model was modified to use experimental adhesion force distributions of arbitrary shape and number of modes instead of a lognormal distribution, as in the original work Reeks & Hall (2001). The results of this analysis showed that the differences in the fraction of particles resuspended were small for a friction velocity of 0.5 m/s but increased for 1 and 2 m/s. For instance, for a friction velocity of 3 m/s, 71% of the original deposit was still on the surface after a day for the clean glass, while only 33% remained on the contaminated glass.
EXTENDING CONTENT-BASED RECOMMENDATION: THE CASE OF INDIAN CLASSICAL MUSIC

We describe a series of experiments that attempt to create a content-based similarity model suitable for making recommendations about North Indian classical music (NICM). We introduce a dataset (nicm2008) consisting of 897 tracks of NICM along with substantial ground-truth annotations, including artist, predominant instrument, tonic pitch, raag, and parent scale (thaat). Using a timbre-based similarity model derived from short-time MFCCs we find that artist R-precision is 32.69% and that the predominant instrument is correctly classified 90.30% of the time. Consistent with previous work, we find that certain tracks (“hubs”) appear falsely similar to many other tracks. We find that this problem can be attenuated by model homogenization. We also introduce the use of pitch-class distribution (PCD) features to measure melodic similarity. Its effectiveness is evaluated by raag R-precision (16.97%), thaat classification accuracy (75.83%), and comparison to reference similarity metrics. We propose that a hybrid timbral-melodic similarity model may be effective for Indian classical music recommendation. Further, this work suggests that “hubs” are a general features of such similarity modeling that may be partially alleviated by model homogenization
Mechanism of non-enzymic transamination reaction between histidine and α-oxoglutaric acid

Non-enzymic transamination reactions at 85° between various amino acids and α-oxoglutaric acid are catalysed by metal ions, e.g. Al3+, Fe2+, Cu2+ and Fe3+. The reaction is optimum at pH4·0. Of the 14 amino acids studied histidine is the most active. In the presence of Al3+ histidine transaminates with α-oxoglutaric acid, forming glutamic acid and Al3+–imidazolylpyruvic acid complex as the end products. However, in the presence of Fe2+ or Cu2+ the products are glutamic acid and a 1:2 metal ion–imidazolylpyruvic acid chelate. The greater effectiveness of histidine in these reactions is attributed to the presence of the tertiary imidazole nitrogen atom, which is involved in the formation of stable sparingly soluble metal ion–imidazolylpyruvic acid complexes or chelates as end products of these reactions. Of the metal ions studied only Al3+, Fe2+, Fe3+ and Cu2+ are effective catalysts for the transamination reactions, and EDTA addition completely inhibits the catalytic effect of the Al3+. Spectrophotometric evidence is presented to demonstrate the presence of metal ion complexes of Schiff bases of histidine as intermediates in the transamination reactions. These results may contribute to understanding the role of histidine in enzyme catalysis.
On a Theorem of Camps and Dicks

We provide a short, intuitive proof of a theorem of Camps and Dicks [1]. Mathematics Subject Classification (2000). Primary 16P20, Secondary 16D60.
The Anatomy of Hypocretin Neurons

Much has been accomplished regarding the neuronal interaction between the hypocretin network and other circuits, but eve more lies ahead to be unveiled. The hypocretin circuitry has emerged as a key player in the regulation of arousal and associated autonomic, endocrine and metabolic regulation. Its unique afferent and efferent connectivity predicts that this system will further emerge as critical component of a broadening array of brain functions most of which provide necessary support for higher brain functions.
Low-cost, bio-based composite materials for housing applications

Publisher Summary This chapter provides an overview of natural fiber reinforced polyester composites highlighting the future aspects of such bio-based composite materials in building applications. The polyester resins, because of their versatility and low cost, are widely used in polymer composites. Natural fiber (NF) unsaturated polyester (UP) composites show lower density, equal flexural modulus, and comparable flexural strength but relatively poor impact strength as compared to a glass fiber (GF) composites. Engineered bio-fibers are defined as a blend of surface treated bast and a leaf fiber. Selection of blends of biofibers is also based on the fact that the correct blend achieves an optimum balance in mechanical properties. The Kenaf and/or Hemp based composites exhibit excellent tensile and flexural properties, while leaf fiber composites give the best impact properties of the composites. A blended composition of two bast and one leaf fiber is selected to achieve a balance of flexural and impact properties of the targeted bio-composites. Biocomposites can now compete with glass-polyester composites both on a cost and performance basis. Most of the existing results on biocomposites are based on hand-lay-up labscale fabrication techniques.
CHAPTER 105 – Serine/Threonine Phosphatase Inhibitor Proteins

Emerging evidence suggests that mammalian cells express a multitude of serine/threonine phosphatase inhibitors, many of which are not fully analyzed. Comparison of known serine/ threonine phosphatase inhibitor proteins suggests that they utilize many different mechanisms to inhibit phosphatases. Moreover, the phosphatase inhibitors may be regulated by hormone-induced changes in expression, alternate splicing, or reversible phosphorylation. Finally, inhibitor proteins most likely collaborate with other phosphatase regulators to control unique phosphatase populations and integrate multiple physiological signals that regulate protein phosphorylation. A number of protein kinases respond to changes in intracellular second messengers but only one serine/threonine phosphatase, calcineurin (or PP2B), is activated by the second messenger calcium. This observation fostered the opinion that most phosphatases are unregulated, and it was suggested that hormone-induced increases in protein kinase activity must be sufficiently high as to overcome the opposing actions of phosphatases. It also meant that hormone signals are severely dampened and/or slowed by the constitutive activity of phosphatases. However, it was found that phosphatase inhibitors allow cells to lower this barrier and accelerate or even amplify the kinase signals. The inherent appeal of this mechanism prompted an active search for hormone-regulated phosphatase inhibitors. Work over the last two decades has identified numerous gene products that regulate protein serine/threonine phosphatases, firmly dismissing the idea of unregulated serine/threonine phosphatases.
Contesting Slavery in the Global Market: John Brown’s Slave Life in Georgia

John Brown, author of Slave Life in Georgia, published in London in 1854, proffered a radical approach to ending slavery in the USA in step with Marxian economics. In this paper, we will explain ho...
Building a game-enhanced formative assessment to gather evidence about middle school students’ argumentation skills

In this paper, we describe an effort to develop and evaluate an innovative formative assessment to gather evidence about middle school students’ argumentation skills. Specifically, this game-enhanced scenario-based assessment (Seaball—Semester at Sea) includes a series of argumentative reasoning activities in the context of an extended scenario wherein students debate the issue of whether junk food should be sold to students. These activities were designed around argumentation learning progressions (i.e., hypotheses about the qualitative shifts that occur as students achieve higher levels of sophistication in argumentation) which serve as a framework to determine the targeted skills, levels and activity sequences. Performance feedback is also provided in the assessment. We conducted a pilot study, aimed at examining student performance and the validity of the tasks as a measure of argumentation skills. More than 100 middle school students completed this assessment and additional external measures of argumentation in a pre/post design. Descriptive statistics of student performance in the activities, analyses of item difficulty, and correlations are reported. Results indicated that students’ total scores were significantly correlated with external measures of argumentation skills, and with students’ state reading and writing test scores. In addition, students achieved higher average scores in a post-test of argumentation skills after having completed the Seaball activities. Finally, explanatory feedback about students’ task performance was found to be beneficial to those who were “Below” or “Approaching” proficient on the state reading and writing test. We conclude with implications for assessment design and instruction in argumentation.
Patterns and predictors of fatigue following living donor nephrectomy: Findings from the KDOC Study.

This study sought to identify the prevalence, pattern, and predictors of clinical fatigue in 193 living kidney donors (LKDs) and 20 healthy controls (HCs) assessed at predonation and 1, 6, 12, and 24 months postdonation. Relative to HCs, LKDs had significantly higher fatigue severity (P = .01), interference (P = .03), frequency (P = .002), and intensity (P = .01), and lower vitality (P < .001), at 1-month postdonation. Using published criteria, significantly more LKDs experienced clinical fatigue at 1 month postdonation, compared to HCs, on both the Fatigue Symptom Inventory (60% vs. 37%, P < .001) and SF-36 Vitality scale (67% vs. 16%, P < .001). No differences in fatigue scores or clinical prevalence were observed at other time points. Nearly half (47%) reported persistent clinical fatigue from 1 to 6 months postdonation. Multivariable analyses demonstrated that LKDs presenting for evaluation with a history of affective disorder and low vitality, those with clinical mood disturbance and anxiety about future kidney failure after donation, and those with less physical activity engagement were at highest risk for persistent clinical fatigue 6 months postdonation. Findings confirm inclusion of fatigue risk in existing OPTN informed consent requirements, have important clinical implications in the care of LKDs, and underscore the need for further scientific examination in this population.
User-centered development of a digital exposure treatment for youth with chronic pain

Chronic pain affects the lives of over a quarter of youth, with societal costs exceeding $19.5 billion dollars in the U.S. each year. Many barriers limit access to available efficacious behavioral interventions, highlighting the critical need to develop digitally delivered versions to increase reach. Graded exposure treatment targets pain-related impairment by exposing patients to previously feared and avoided activities. Our group is developing a digital prototype of an interdisciplinary outpatient graded exposure intervention (iGET Living). The purpose of this study is to present acceptability data from user-centered focus groups. Utilizing an iterative, user-experience design, we will collect acceptability data on treatment content and structure via qualitative interviews with adolescents. Data collection will proceed in iterations of n = 5-7 until the goal is met. Data included in the present study are from the first round of qualitative interviews (n = 6). Participants ranged in age from 10-15 years (50% female). Participants rated treatment content for clarity and satisfaction on a 0 (not clear/satisfied) to 4 (very clear/satisfied) scale after each module (10 modules in total). Open-ended questions assessing acceptability, ease of use, comprehensibility, and suggestions for improvement were collected. All treatment modules received a 3 or 4 out of 4 for clarity and satisfaction. Average satisfaction rating of the overall intervention was 7 out of 10 (10 = very satisfied) and 83% of participants said it would be feasible to complete on a daily basis. Common qualitative themes included: tailoring content to age groups, desire for engaging and interactive visuals, and inclusion of patient testimonials. Acceptability data is critical to refining the digital solution. The iterative development of key recommended features such as patient testimonials will ultimately lead to feasibility and preliminary effectiveness assessment of iGET Living for youth with chronic pain. Drotar-Crawford Postdoctoral Fellowship Research Grant in Pediatric Psychology.
The genetics of cardiac amyloidosis

Heritable cardiac amyloidosis (CA) is an underrecognized cause of morbidity and mortality in the USA. It results from the accumulation of the misfolded protein transthyretin within the myocardium, resulting in amyloid transthyretin-associated cardiomyopathy (ATTR-CM). Over 150 different pathologic point mutations within the transthyretin gene have been identified, each carrying variable clinical phenotypes and penetrance. In the USA, the most common cause of hereditary ATTR is the Val122Ile point mutation, with a prevalence of 3.4-4.0% in North Americans of African and Caribbean descent. Among Caucasians with hereditary ATTR-CM, the V30M mutation is the most commonly identified variant. Overall, the incidence of ATTR disease in the USA has been increasing, likely due to an increase in practitioner awareness, utilization of new non-invasive imaging technologies for ATTR diagnosis, and the growth of multidisciplinary amyloid programs across the country. Yet significant numbers of patients with evidence of left ventricular thickening on cardiac imaging, senile aortic stenosis, and/or symptoms of heart failure with preserved ejection fraction likely have undiagnosed CA, especially within the African American population. With the emergence of new disease-modifying therapies for ATTR, recognition and the prompt diagnosis of CA is important for patients and their potentially affected progeny. Herein, we review the genetics of heritable CA as well as the importance of genetic counseling and testing for patients and their families.
Multi-Disciplinary Analysis and Optimization Frameworks

Since July 2008, the Multidisciplinary Analysis & Optimization Working Group (MDAO WG) of the Systems Analysis Design & Optimization (SAD&O) discipline in the Fundamental Aeronautics Program s Subsonic Fixed Wing (SFW) project completed one major milestone, Define Architecture & Interfaces for Next Generation Open Source MDAO Framework Milestone (9/30/08), and is completing the Generation 1 Framework validation milestone, which is due December 2008. Included in the presentation are: details of progress on developing the Open MDAO framework, modeling and testing the Generation 1 Framework, progress toward establishing partnerships with external parties, and discussion of additional potential collaborations
Multiplex real‐time PCR (TaqMan) assay for the simultaneous detection and discrimination of potato powdery and common scab diseases and pathogens

Aims: To develop a multiplex real-time PCR assay using TaqMan probes for the simultaneous detection and discrimination of potato powdery scab and common scab, two potato tuber diseases with similar symptoms, and the causal pathogens Spongospora subterranea and plant pathogenic Streptomyces spp. Methods and Results: Real-time PCR primers and a probe for S. subterranea were designed based on the DNA sequence of the ribosomal RNA ITS2 region. Primers and a probe for pathogenic Streptomyces were designed based on the DNA sequence of the txtAB genes. The two sets of primer pairs and probes were used in a single real-time PCR assay. The multiplex real-time PCR assay was confirmed to be specific for S. subterranea and pathogenic Streptomyces. The assay detected DNA quantities of 100 fg for each of the two pathogens and linear responses and high correlation coefficients between the amount of DNA and Ct values for each pathogen were achieved. The presence of two sets of primer pairs and probes and of plant extracts did not alter the sensitivity and efficiency of multiplex PCR amplification. Using the PCR assay, we could discriminate between powdery scab and common scab tubers with similar symptoms. Common scab and powdery scab were detected in some tubers with no visible symptoms. Mixed infections of common scab and powdery scab on single tubers were also revealed. Conclusions: This multiplex real-time PCR assay is a rapid, cost efficient, specific and sensitive tool for the simultaneous detection and discrimination of the two pathogens on infected potato tubers when visual symptoms are inconclusive or not present. Significance and Impact of the Study: Accurate and quick identification and discrimination of the cause of scab diseases on potatoes will provide critical information to potato growers and researchers for disease management. This is important because management strategies for common and powdery scab diseases are very different.
Application of the J-integral to mixed mode fracture analysis of orthotropic composites

Abstract The J- integral is derived for mode I and mode II cracks in orthotropic composite materials and it is shown to be independent of the integral path around the crack tip. The J- integral is then extended and applied to a newly developed energy based fracture criterion for orthotropic composite materials and then applied to the mixed mode fracture analysis of composites.
Self-Creation or Choosing the Self: A Critique of Richard Rorty's Idea of Democratic Education

In his book Contingency, Irony, Solidarity, Richard Rorty presents a democratic pragmatism centered on the individual’s pursuit of happiness, a project he understands to encompass far more than the pursuit of material well being. Central to Rorty’s account is the figure he calls the “liberal ironist,” liberal in the desire not to be cruel, ironic to the extent of knowing her most central beliefs are contingent. Despite her rejection of foundational truths, the liberal ironist is passionately engaged in making sense of her life, which she does by means of what Rorty calls “self creation.” Rorty argues that the survival of contemporary democracies depends on such committed yet undogmatic citizens. His project suggests to me that the individual pursuit of meaning should not be left out of public education.
Traumatic Victimization in the Lives of Lesbian and Bisexual Women

SUMMARY This paper takes a contextual approach to understanding traumatic victimization experiences of lesbian and bisexual women over the life span. Expanding on feminist perspectives on violence against women, the concept of "cultural victimization" is used to explore the role of societal homophobia in shaping the experience of victimization for lesbian and bisexual women. An overview of the existing literature on the prevalence and impact of childhood abuse, domestic violence, sexual assault, and hate crimes among this population is provided. The relationship between sexual identity development and trauma is discussed. This article provides a framework for understanding lesbian and bisexual women's victimization, lends insight to clinicians working with lesbian/bisexual survivors, and provides direction for future research.
Anaerobic capacity as a function of somatotype and participation in varsity athletics.

Abstract Anaerobic capacity and somatotype were evaluated on 51 varsity college athletes. Anaerobic capacity was evaluated through blood lactate determinations and administration of the Margaria-Kalamen Test of Anaerobic Power (3). Morphological conformations were determined for each subject by utilizing the Heath-Carter Anthropometric Rating Method (1). Results indicate that participants in each of the athletic specialties investigated—football, basketball, soccer, gymnastics, wrestling, and cross country running possess a relatively homogeneous somatotype particular to their sport. Anaerobic capacity was enhanced as a result of 8 weeks of conditioning. Those sports which constitute work periods of high intensity but short duration made the most significant increases in both the lactacid and alactacid components of anaerobic capacity.
Habermas, Foucault and Nietzsche: A Double Misunderstanding

The article analyses Habermas' interpretation of Foucault in the Philosophical Discourse of Modernity and argues that the former misunderstands the Foucaultian project of genealogy fundamentally. While Habermas assumes that Foucault aims at a strictly scientific approach to the writing of history it can be shown that Foucaultian genealogy is strongly characterised by rhetorical aspects, creating a hybrid model of critique that stands in between science and literature. The essay goes on arguing that this misreading can be explained with reference to Habermas' reconstruction of Nietzsche's philosophy in the Philosophical Discourse. On the basis of this clarification the article analyses what a Habermasian position vis-a-vis genealogy including the rhetorical element would look like. Making use of Habermas' remarks on Derrida in the Philosophical Discourse the essay concludes that, counter-intuitively, a rhetorically understood genealogy has to be considered a valid philosophical approach even on Habermas' own terms.
Mass Hierarchy and Flat Directions in String Models

Idiscuss a method for generating an effective μ parameter and quasi-realistic generational mass hierarchy based on intermediate scales between M Z and M string. Application to string models is briefly discussed. Additionally, a method based on the singular value decomposition (SVD) of a matrix is presented for determining, en masse, a complete basis of D-flat directions in supersymmetric models.
The Dissemination of Antibiotic Resistance by Bacterial Conjugation

In areas where trachoma is highly endemic, that is, where about 70% of the population is infected, many individuals typically carry Streptococcus pneumoniae. Of these, 2% were originally macrolide resistant. After 2 weeks of trachoma treatment, the carrier rate for macrolide-resistant pneumococci rose to 50%, with an increase in the carrier rate of the more highly resistant strains. This study dramatically illustrates the potential for rapid in vivo selection of resistance. In this study it was also found that one chronically ill child was carrying a strain with very high level resistance. This chapter defines gene dissemination mechanisms and shows how and why conjugative mechanisms are the most proficient in multiple drug resistance (MDR) transfer. The plasmid is an interesting variation on the theme of MDR dissemination. The chapter reviews aspects of bacterial conjugation in terms of basic science and clinical relevance. A unifying model can be developed because the general mechanism for classical bacterial conjugation appears to be conserved in conjugative transposons. It is reasonable to suggest that bacterial conjugation is the greatest mover of genes in the microbial world and, in the clinical world, that these genes are often antibiotic resistance genes. The cycle of antibiotic resistance and pathogen genome sequencing are showcasing the prominent role of bacterial conjugation in gene dissemination.
VEGFA, FLT1, KDR and colorectal cancer: Assessment of disease risk, tumor molecular phenotype, and survival

Angiogenesis is essential for tumor progression. Vascular endothelial growth factor (VEGFA) and its receptors 1 (FLT1) and 2 (KDR), have been identified as major mediators of this process. We hypothesized that genetic variation in FLT1 (38 SNPs), KDR (22 SNPS), and VEGFA (11 SNPs) would be associated with colon and rectal cancer development and survival. Data from a case–control study of 1555 colon cancer cases and 1956 controls and 754 rectal cancer cases and 959 controls were used. An adaptive rank truncation product (ARTP), based on 10 000 permutations, was used to determine the statistical significance of the candidate genes and angiogenesis pathway. Based on ARTP results, FLT1 was significantly associated with risk of colon cancer (PARTP = 0.045) and VEGFA was significantly associated with rectal cancer (PARTP = 0.036). After stratifying by tumor molecular subtype, SNP associations observed for colon cancer were: VEGFA rs2010963 with CIMP+ colon tumors; FLT1 rs4771249 and rs7987649 with TP53; FLT1 rs3751397, rs7337610, rs7987649, and rs9513008 and KDR rs10020464, rs11941492, and rs12498529 with MSI+ and CIMP+/KRAS2-mutated tumors. FLT1 rs2296189 and rs600640 were associated with CIMP+ rectal tumors and FLT1 rs7983774 was associated with TP53-mutated rectal tumors. Four SNPs in FLT1 were associated with colon cancer survival while three SNPs in KDR were associated with survival after diagnosis with rectal cancer. Aspirin/NSAID use, smoking cigarettes, and BMI modified the associations. These findings suggest the importance of inflammation and angiogenesis in the etiology of colorectal cancer and that genetic and lifestyle factors may be targets for modulating disease risk. © 2013 Wiley Periodicals, Inc.
The domestication of legal argumentation: A case study of the formalism of the legal realists

This essay explores the discourse of the legal realists. The pragmatists and the legal realists of the late nineteenth and early twentieth centuries have become an important part of Anglo‐American jurisprudence. These jurists, lawyers, and legal theorists are considered to be influential legal scholars because of their critiques of transcendental, certain, and deductive proofs in legal argumentation. The essay argues that while the legal realists added to our understanding of informal logic and legal pragmatism, they nevertheless domesticated their arguments by replacing deductive formalisms with inductive formalisms.
Determinants of normal coronary artery dimensions in humans.

BACKGROUNDStudies of normal human coronary dimensions have been performed primarily in postmortem hearts. We evaluated the influence of age, body habitus, and regional myocardial mass on coronary dimensions in living patients with normal coronary vessels.METHODS AND RESULTSArteriographically normal coronary angiograms were analyzed from the following groups of subjects: group 1 (age, 15-34 years) consisted of 30 post-cardiac transplant patients with donor hearts from male subjects aged 15-34 years, group 2 (age, 35-54 years) consisted of 12 post-cardiac transplant patients with donor hearts from male subjects aged 35-54 years and 26 male subjects investigated for atypical chest pain, and group 3 (age, 55-74 years) consisted of 26 male subjects investigated for atypical chest pain. All angiograms were performed after sublingual nitroglycerin. Measurements of the dimensions of the left main, proximal left anterior descending, proximal left circumflex, and proximal right coronary arteries were made using a c...
γ-Aminobutyric acid inhibits the potassium-stimulated release of somatostatin from rat spinal cord slices

Abstract Evidence supports the idea that somatostatin (SO) is a neurotransmitter or neuromodulator of primary afferent neurons involved in nociception. Since γ-aminobutyric acid (GABA), norepinephrine, and morphine alter nociception at the level of the spinal cord, we examined whether these agents could alter the potassium-stimulated release of somatostatin from rat spinal cord slices. Male Sprague-Dawley rats were decaptitated and a 2 cm segment of the lumbar spinal cord removed and chopped into0.5 × 0.5mm pieces and perfused at 37 °C in individual perfusion chambers with a modified Krebs-bicarbonate buffer at a flow rate of 0.5 ml/min. Perfusates were collected at 2 min intervals and assayed for SO using radioimmunoassay. Exposure of spinal cord tissue to 50 mM KCl resulted in a 3-fold increase in release of SO from a basal level of approximately 0.2 to 0.6 pg/mg tissue/min. This evoked release was calcium dependent. Pre-exposure of tissue to GABA at 10−4 and 10−5 M significantly inhibited the potassium-stimulated release of SO, but did not alter basal release. The GABA receptor antagonist, bicuculline methiodide, at 10−5 but not 10−6 M attenuated the GABA-induced inhibition of somatostatin release. Bicuculline methiodide alone did not significantly alter either basal or stimulated release. Neither baclofen (10−5M, 5 × 10−5M), norepinephrine (10−5 M), nor morphine (10−5 M) had any significant effect on basal or stimulated release of SO from spinal cord tissue. These results demonstrate a differential regulation of SO release from spinal cord tissue, but do not support the hypothesis that inhibition of SO release in the spinal cord is a mechanism to explain antinociception produced by GABA agonists, norepinephrine or morphine at the level of the spinal cord.
Reproductive choices among HIV-positive women

The objective of this study was to describe the characteristics of HIV-positive women who become pregnant, who choose to get sterilized, and who have an elective abortion after an HIV diagnosis. All HIV-infected women between the ages of 14 and 35 years (N = 403) who were enrolled in the HIV Outpatient Program in New Orleans, U.S.A., between 1987 and 1995 were included in the study. Medical records were abstracted for reproductive outcomes and demographic and medical characteristics. The mean age of the participants was 25.8 years, 83% were African American, 71% were single, 20% had a history of IV drug use, and 35% had a history of non-IV drug use at entry. Mean followup time was 2.9 years. The overall incidence of pregnancy subsequent to HIV diagnosis was 6.3% per person-year of observation. Twenty-four percent of the population underwent a sterilization procedure subsequent to HIV diagnosis, and 25% of the women who became pregnant subsequent to diagnosis had an induced abortion. Factors associated with subsequent pregnancy in multivariate analysis included young age and a history of sexual assault. Factors associated with subsequent sterilization in multivariate analysis were CD4 count over 200, having one or more living children, and not living with a family member. Factors associated with subsequent abortion included being White and non-single. Sexual assault history and living with a sex partner were associated with abortion at the p < 0.1 level. The study concludes that HIV-infected women tend to have lower rates of pregnancy and higher rates of sterilization and abortion than their uninfected counterparts. Counseling messages that are culturally sensitive, non-coercive, and that take into consideration the complexities of the decision-making process should be standardized for all HIV-infected women so that they can make informed decisions.
Energy Deposition in SN2 Reaction Products and Kinetic Energy Effects on Reactivity

Translational energy dependence of reaction kinetics and internal energy depositions in reaction products were examined for gas-phase SN2 reactions of Cl- and F- with NCCO2CH3 and CF3CO2CH3 in a Fourier transform ion cyclotron resonance mass spectrometer (FTICR). The energy dependence of the kinetics was examined by measuring the SN2 rate constants as a function of reactant ion translational energies and by comparing the experimental results with those calculated using RRKM theory. Negative kinetic energy dependence was observed, and the changes of rate constants agree with RRKM theory predictions. The internal energy deposition in the SN2 products was examined by measuring the fraction of secondary fragments resulting from dissociation of the ionic SN2 product. A statistical model was used to calculate the statistical fraction of internally excited SN2 product ion under thermal conditions. For the least exothermic reaction (<20 kcal/mol), the measured fraction of secondary ion is comparable to the statis...
How to keep the practice of librarianship relevant in the age of the Internet

This article considers what contribution traditional library practices — identification, selection, organisation and retrieval — can make to managing networked information, and how those practices need to be updated to take account of the special difficulties of the Internet. The answer is found in cooperation. Cooperation between librarians and authors in the creation of metadata. International cooperation between librarians to select resources. The article defines a workflow for cooperation in both fields, and proposes a library search engine to hold jointly created records and a catalogue of Websites online to support selection.
ORLaND - Oak Ridge Laboratory for Neutrino Detectors

The proposed Oak Ridge Laboratory for Neutrino Detectors (ORLaND), to be located adjacent to the Spallation Neutron Source (SNS), is described. ORLaND will take advantage of the fact that the SNS will be the world's best intermediate-energy pulsed neutrino source in the world. A broad range of neutrino measurements is contemplated by means of a number of detectors, including the large CoNDOR detector. Specifics of neutrino oscillation investigations, and of the possible impact of certain neutrino measurements on our understanding of supernova explosions, are discussed.
Decaspec: a fiber optics adapter for multiobject spectroscopy

An automated fiber optics manipulator that allows the acquisition of up to 10 spectra simultaneously with an existing long slit spectrograph has been placed in operation at the Michigan-Dartmouth-MIT Observatory. Pickoff optics that view mirrors at the fiber probe tips allow visual alignment of the probes on the target objects. This feature eliminates the requirement for subarcsecond astrometry, careful focal plane calibration and highly precise actuator motion.
Membrane-associated protein synthesis in Streptococcus faecalis

Abstract 1. Cell-free extracts of Streptococcus faecalis were separated centrifugally into a ribosomal, a washed membrane, and several intermediate fractions. All fractions incorporate labeled amino acids into hot trichloroacetic acid-insoluble material. The requirements for amino acid incorporation are similar for all fractions, and electro-phoresis of the reaction products gives identical polypeptide peaks. 2. All particulate fractions contain phospholipid, and the level of amino acid incorporation is proportional to phospholipid content. No qualitative differences are found in the phospholipid composition of the various fractions. 3. Incorporation by cell fractions is also proportional to RNA content, except for the ribosomal fraction and a first membrane washing, where “excess” RNA appears to be present. On sucrose density gradients of ribosomal fractions the bulk of the “excess” RNA is isolated as a broad peak with a sedimentation coefficient of 80–150 S. On mild ribonuclease (EC 2.7.7.16) treatment this peak dissociates into 30-20 S ribosomal subunits. 4. In addition to large 30-20 S ribosomal aggregates, crude extracts of S. faecalis contain large polyribosomal aggregates. The polyribosomes, consisting of 30-S and 50-S subunits are released from membranes on exposure to deoxycholate. The ribosomes appear to be bound to membranes through the 50-S subunit. These membrane-bound polyribosomes are ribonuclease-sensitive, but are not degraded on incubation with a soluble fraction of S. faecalis . 5. It is concluded that in S. faecalis the bulk of the ribosomes are in a high state of aggregation. In fractionated extracts, protein synthesis is a function of the concentration of membrane-associated polyribosomes. Possible implications of this finding on mechanisms of protein synthesis are discussed.
Mutations in the GTP-binding and synergy loop domains of Mycobacterium tuberculosis ftsZ compromise its function in vitro and in vivo.

Abstract The Mycobacterium tuberculosis FtsZ (FtsZTB), unlike other eubacterial FtsZ proteins, shows slow GTP-dependent polymerization and weak GTP hydrolysis activities [E.L. White, L.J. Ross, R.C. Reynolds, L.E. Seitz, G.D. Moore, D.W. Borhani, Slow polymerization of Mycobacterium tuberculosis FtsZ, J. Bacteriol. 182 (2000) 4028–4034]. In an attempt to understand the biological significance of these findings, we created mutations in the GTP-binding (FtsZG103S) and GTP hydrolysis (FtsZD210G) domains of FtsZ and characterized the activities of the mutant proteins in vitro and in vivo. We show that FtsZG103S is defective for binding to GTP and polymerization activities, and exhibited reduced GTPase activity whereas FtsZD210G protein is proficient in binding to GTP, showing reduced polymerization activity but did not show any measurable GTPase activity. Visualization of FtsZ-GFP structures in ftsZ merodiploid strains by fluorescent microscopy revealed that FtsZD210G is proficient in associating with Z-ring structures whereas FtsZG103S is not. Finally, we show that Mycobacterium smegmatis ftsZ mutant strains producing corresponding mutant FtsZ proteins are non-viable indicating that mutant FtsZ proteins cannot function as the sole source for FtsZ, a result distinctly different from that reported for Escherichia coli. Together, our results indicate that optimal GTPase and polymerization activities of FtsZ are required to sustain cell division in mycobacteria and that the same conserved mutations in different bacterial species have distinct phenotypes.
INDUCED PROTECTION OF ADRENAL CORTEX AGAINST 7,12-DIMETHYLBENZ[a]ANTHRACENE : INFLUENCE OF ETHIONINE. INDUCTION OF MENADIONE REDUCTASE. INCORPORATION OF THYMIDINE-H3

7,12-Dimethylbenz[a]anthracene (7,12-DMBA) exerts adrenocorticolytic effects which set it apart from all other polynuclear aromatic hydrocarbons and aromatic amines which have been investigated. Adrenal damage by this compound appears to be due to its steric and electronic properties together with its unusually high solubility in lipides. Many compounds given prior to 7,12-DMBA induced protection of adrenal. The most efficient inducers of protection are flat condensed aromatics possessing 4 or 5 rings; very small doses of these compounds were required to induce protection. Other compounds devoid of these properties induced protection but large or repeated doses were necessary. All inducers of protection had to be given prior to 7,12-DMBA to prevent adrenal necrosis; when given simultaneously with, or later than, this compound adrenal apoplexy resulted. Protective aromatics and 7,12-DMBA as well induced synthesis of menadione reductase in liver. 3-Methylcholanthrene (3-MC) induced this enzyme in many normal organs including liver, lung, adrenal, and in mammary cancer as well. dl-Ethionine under appropriate conditions of time and dosage eliminated the adrenal protection induced by aromatics and also delayed the induction of menadione reductase while depressing the amount of this enzyme which was synthesized. 7,12-DMBA caused a greatly reduced incorporation of tritium from thymidine-H(3) into washed acid-insoluble residue of adrenal. 3-MC given in advance mitigated the drastic effect of 7,12-DMBA on DNA synthesis and increased considerably the amount of tritium which was incorporated. The specific damage to adrenal by 7,12-DMBA is a direct effect on cells. Protection of adrenal is a secondary effect which requires induction of protein synthesis and it results in improvement in synthesis of DNA.
Hypothesis: the peroxydicarbonic acid cycle in photosynthetic oxygen evolution

Peroxydicarbonic acid (Podca), a proposed intermediate in photosynthetic oxygen evolution, was synthesized electrochemically. Consistent with literature descriptions of this compound, it was shown to be a highly reactive molecule, spontaneously hydrolyzed to H2O2, as well as susceptible to oxidative and reductive decomposition. In the presence of Mn2+ or Co2+, Podca was quickly broken down with release of O2. The liberation of O2, however, was partially suppressed at high O2 concentrations. In the presence of Ca-washed photosystem II-enriched membranes lacking extrinsic proteins, Podca was decomposed with the release of O2, but only under conditions favoring photosynthetic electron flow (light plus a Hill oxidant). A model is proposed that details how peroxydicarbonic acid could act as an oxygen-evolving intermediate. The hypothesis is consistent with the well-established Kok model and with recent findings related to the chemistry of oxygen evolution.
NAD hydrolysis: Chemical and enzymatic mechanisms

The pyridine nucleotides have important non-redox activities as cellular effectors and metabolic regulators [1–3]. The enzyme-catalyzed cleavage of the nicotinamide-ribosyl bond of NAD+ and the attendant delivery of the ADPRibosyl moiety to acceptors is central to these many diverse biological activities. Included are the medically important NAD-dependent toxins associated with cholera, diphtheria, pertussis, and related diseases [4]; the reversible ADPRibosylation-mediated biological regulatory systems [5,6]; the synthesis of poly(ADPRibose) in response to DNA damage or cellular division [7]; and the synthesis of cyclic ADPRibose as part of an independent, calcium-mediated regulatory system[8]. As will be presented in this chapter, all evidence points to both the chemical and enzyme-catalyzed cleavage of the nicotinamide-ribosyl bond being dissociative in character via an oxocarbenium intermediate. (Mol Cell Biochem 138: 245–252, 1994)