cssi/SciSciGPT-SciSciNet huggingface dataset:
Protein structure evolution and the SCOP database.

Thestructureofaproteincanelucidateitsfunctionanditsevolutionaryhistory(seeChapters18, 21 and 23). Extracting this information requires knowledge of the structure and itsrelationshipswithotherproteins.Theseinturnrequireageneralknowledgeofthefoldsthatproteins adopt and detailed information about the structure of many proteins. Nearly allproteinshavestructuralsimilaritieswithotherproteins,andinmanycases,shareacommonevolutionaryorigin.Theknowledgeoftheserelationshipsmakesimportantcontributionstostructuralbioinformaticsandotherrelatedareasofscience.Further,theserelationshipswillplay an important role in the interpretation of sequences produced by genome projects. Tofacilitateunderstandingandaccesstotheinformationavailableforknownproteinstructures,Murzin,Brenner,Hubbard,andChothia(1995) haveconstructedastructuralclassiﬁcationofproteins(SCOP)database.TheSCOPdatabaseisbasedonevolutionaryrelationshipsandon the principles that govern their three-dimensional structure. It provides for each entrylinks to coordinates, images of the structure, interactive viewers, sequence data, andliterature references. The database is freely accessible on the World Wide Web (http://scop.mrc-lmb.cam.ac.uk/scop).Tounderstand the rationalebehindSCOP, webeginwith adiscussion of protein evolution from a sequence structure and functional perspective.
Mining genetic epidemiology data with Bayesian networks I: Bayesian networks and example application (plasma apoE levels)

Motivation: The wealth of single nucleotide polymorphism (SNP) data within candidate genes and anticipated across the genome poses enormous analytical problems for studies of genotype-to-phenotype relationships, and modern data mining methods may be particularly well suited to meet the swelling challenges. In this paper, we introduce the method of Belief (Bayesian) networks to the domain of genotype-to-phenotype analyses and provide an example application. Results: A Belief network is a graphical model of a probabilistic nature that represents a joint multivariate probability distribution and reflects conditional independences between variables. Given the data, optimal network topology can be estimated with the assistance of heuristic search algorithms and scoring criteria. Statistical significance of edge strengths can be evaluated using Bayesian methods and bootstrapping. As an example application, the method of Belief networks was applied to 20 SNPs in the apolipoprotein (apo) E gene and plasma apoE levels in a sample of 702 individuals from Jackson, MS. Plasma apoE level was the primary target variable. These analyses indicate that the edge between SNP 4075, coding for the well-known e2 allele, and plasma apoE level was strong. Belief networks can effectively describe complex uncertain processes and can both learn from data and incorporate prior knowledge. Availability: Various alternative and supplemental networks (not given in the text) as well as source code extensions, are available from the authors. Contact: arodin@uth.tmc.edu Supplementary information: http://bioinformatics.oxfordjournals.org
High-field transport of inversion-layer electrons and holes including velocity overshoot

In this paper, we experimentally address the effect of a wide range of parameters on the high-field transport of inversion-layer electrons and holes. The studied parameters include substrate doping level, surface micro-roughness, vertical field strength, nitridation of the gate oxide, and device channel length. We employ special test structures built on Silicon-On-Insulator (SOI) and bulk wafers to accurately measure the high-field drift velocity of inversion-layer carriers. Our findings point to electron velocity overshoot at room temperature, dependence of electron and hole saturation velocities on nitridation of the gate oxide, dependence of the high-field drift velocity on the effective vertical field, and relative insensitivity of electron and hole mobility and saturation velocity to moderate surface roughness.
Management Strategies After Cardiac Surgery in an Infant With Human Rhinovirus

This report presents management strategies after cardiopulmonary bypass surgery for an infant with community-acquired rhinovirus bronchiolitis. The case report emphasizes human rhinovirus as a lower respiratory pathogen, the difficulty treating the complications of human rhinovirus for an infant with cyanotic congenital heart disease after cardiac surgery, and the importance of preoperative evaluation for this respiratory infection in high-risk infants before cardiac surgery.
Open Reconstruction of Complex Proximal Metadiaphyseal Fragility Fractures of the Humerus

Purpose:A proactive surgical and rehabilitation protocol was implemented to manage humeral fractures involving both the proximal end and shaft in an older patient population. Primary treatment goal...
Influence of initial stresses on fracture of composite materials containing interacting cracks

Considered in this study are the axially-symmetric problems of fracture of composite materials with interacting cracks, which are subjected to initial (residual) stresses acting along the cracks planes. An analytical approach within the framework of three-dimensional linearized mechanics of solids is used. Two geometric schemes of cracks location are studied: a circular crack is located parallel to the surface of a semi-infinite composite with initial stresses, and two parallel co-axial penny-shaped cracks are contained in an infinite composite material with initial stresses. The cracks are assumed to be under a normal or a radial shear load. Analysis involves reducing the problems to systems of second-kind Fredholm integral equations, where the solutions are identified with harmonic potential functions. Representations of the stress intensity factors near the cracks edges are obtained. These stress intensity factors are influenced by the initial stresses. The presence of the free boundary and the interaction between cracks has a significant effect on the stress intensity factors as well. The parameters of fracture for two types of composites (a laminar composite made of aluminum/boron/silicate glass with epoxy-maleic resin and a carbon/plastic composite with stochastic reinforcement by short ellipsoidal carbon fibers) are analyzed numerically. The dependence of the stress intensity factors on the initial stresses, physical-mechanical parameters of the composites, and the geometric parameters of the problem are investigated.
Routing traffic in telephone networks

Telephone calls arriving at a switching center must be assigned to any one of the outgoing trunks which has idle links. With probability 1-?i the call may be lost due to congestion in subsequent trunks along the route, and with probability ?i the call is successful, and then the links along the route remain busy for an exponential holding time. If the ?i do not depend on the routing policy, then assigning the call to the trunk with largest such ?i minimizes the expected number of lost calls. When ?i does depend upon the policy, a suboptimal policy combining overflow and load sharing is proposed.
Analysis: Continuous glucose monitoring during intensive insulin therapy

Results of the Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial, intensive insulin therapy (IIT), and use of a continuous glucose sensor in intensive care units (ICU) were analyzed. The NICE-SUGAR trial was unable to determine if optimal intensive insulin therapy decreases mortality. Continuous glucose monitoring (CGM) technology has the potential to improve glycemic control with low glucose variability and low incidence of hypoglycemia. Interstitial fluid CGM may not be useful in perioperative and ICU settings. Studies evaluating the accuracy and reliability of CGM devices, based on a whole blood sample in perioperative and ICU settings, are needed. Once a reliable CGM sensor for ICU use is identified, a large, prospective, controlled, multicenter study could determine if optimal IIT with a low or zero incidence of hypoglycemic events improves mortality.
Perianal and genital basal cell carcinoma: A clinicopathologic review of 51 cases

Abstract Background: Basal cell carcinoma (BCC) occurring on non-sun-exposed sites, especially the perianal and genital regions, is very rare. Objective: We analyzed the incidence, clinical and pathologic features, and etiologic and prognostic factors of all non-nevoid perianal and genital BCCs diagnosed at our institution within a defined period (January 1985-September 1996). Methods: A retrospective review was performed with the use of patient clinical records and dermatopathologic slides. Cutaneous biopsy samples were tested for the presence of human papillomavirus (HPV) by in situ hybridization using biotinylated pan-HPV and serotype-specific (6, 11, 16, 18, 31, 33, 51) probes. Results: Of all non-nevoid BCC syndrome cases, 51 BCCs (0.27%) were located within the perianal and genital regions. The average age of the patients was 73 years. Nine perianal BCCs occurred in men, 6 in women. Ten BCCs occurred in the pubic area, 18 on the vulva, 6 on the scrotum, and 2 on the penis. Three patients had 2 tumor sites. The average size of BCC was 1.95 cm; 29.4% were ulcerated. Seventeen patients (36%) had a history of skin cancer on sun-exposed sites and 10 (21%) had a possibly relevant associated condition. HPV was not detected in the specimens tested. Treatments included wide excision (n = 32), electrodesiccation and curettage (n = 10), Mohs micrographic surgery (n = 8), and carbon dioxide laser (n = 1). Of 30 patients with 5 years' follow-up or longer, 1 recurrence was noted 7 years after wide excision. There were no metastases. Conclusion: BCC of the perianal and genital skin is rare and exhibits clinical and histologic heterogeneity. Advancing age and local trauma may contribute to the pathogenesis of BCC at these sites. (J Am Acad Dermatol 2001;45:68-71.)
High glycolytic flux improves pyruvate production by a metabolically engineered Escherichia coli strain.

We report pyruvate formation in Escherichia coli strain ALS929 containing mutations in the aceEF, pfl, poxB, pps, and ldhA genes which encode, respectively, the pyruvate dehydrogenase complex, pyruvate formate lyase, pyruvate oxidase, phosphoenolpyruvate synthase, and lactate dehydrogenase. The glycolytic rate and pyruvate productivity were compared using glucose-, acetate-, nitrogen-, or phosphorus-limited chemostats at a growth rate of 0.15 h−1. Of these four nutrient limitation conditions, growth under acetate limitation resulted in the highest glycolytic flux (1.60 g/g · h), pyruvate formation rate (1.11 g/g · h), and pyruvate yield (0.70 g/g). Additional mutations in atpFH and arcA (strain ALS1059) further elevated the steady-state glycolytic flux to 2.38 g/g · h in an acetate-limited chemostat, with heterologous NADH oxidase expression causing only modest additional improvement. A fed-batch process with strain ALS1059 using defined medium with 5 mM betaine as osmoprotectant and an exponential feeding rate of 0.15 h−1 achieved 90 g/liter pyruvate, with an overall productivity of 2.1 g/liter · h and yield of 0.68 g/g.
Detection in decentralized sensor networks

Advances in integrated technologies are making networks of many inexpensive deployable autonomous sensors a reality. Individually, each sensor may not accomplish much, but working cooperatively they have for example the potential to monitor large areas, detect the presence or absence of targets, or track moving objects. These sensors operate under constraints imposed by scarce power and other limited resources like bandwidth or computing capacity. The paper considers detection in such a distributed sensor environment. We investigate the impact on detection performance, as measured by the probability of error, of such parameters as number of sensors, number of quantization levels at each sensor, or signal to noise ratio, under a rate constraint on the common access communications channel. We optimize the local detectors when the number of sensors is large. We show that the performance loss due to quantization decays exponentially fast as the number of bits per sensor increases and that the choice between hard versus soft local detectors depends not only on the noise distribution and the quantization rate, but also on the SNR under which the sensors operate.
Divide and conquer martingales and the number of triangles in a random graph

The goal of this paper is to present a novel application of a recent and useful martingale inequality. As an illustration, we prove an essentially sharp bound for the probability that a random graph contains significantly more triangles than expected.
Set operations in object-based data models

The semantics of set operations are not adequate for the richer data models of object-based database systems that include object-oriented and semantic data modeling concepts. The reason is that precise semantics of set operations on complex objects require a clear distinction between the dual notions of a set and a type, both of which are present in the class construct found in object-based data models. This gap is filled here by a framework for executing set theoretic operations on the class construct. The proposed set operations, including set difference, union, intersection and symmetric difference, determine both the type description of the derived class as well as its set membership. For the former, inheritance rules are developed for property characteristics such as single-valued versus multivalued and required versus optional. For the latter, the object identity concept is developed if borrowed from data modeling research. The framework allows for property inheritance among classes that are not necessarily IS-A related. >
Does Sequential Innovation Decline in the Presence of Large Patent Portfolios? Examining Future Variety Creation in the U.S. Agricultural Biotechnology Industry

This paper examines the effect patent ownership has on firm variety creation in the U.S. agricultural biotechnology industry. Counts of new varieties include corn, soybean, or wheat varieties protected by either patents or plant variety protection certificates by firms in the years 1976-1999 and are modeled as a negative binomial variable. Although firms with larger patent portfolios create more varieties, firms do not experience scale economies in the production of new varieties through increased numbers of patents. Further, firms that have a greater diversity of technology in their portfolios create significantly more varieties. Meanwhile firms experience positive spillover effects from rival firms' patents, but these positive spillover effects lessen after 1990.
ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry

A coding variant in alcohol dehydrogenase 1B (ADH1B) (rs1229984) that leads to the replacement of Arg48 with His48 is common in Asian populations and reduces their risk for alcoholism, but because of very low allele frequencies the effects in European or African populations have been difficult to detect. We genotyped and analyzed this variant in three large European and African-American case-control studies in which alcohol dependence was defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and demonstrated a strong protective effect of the His48 variant (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.24, 0.48) on alcohol dependence, with genome-wide significance (6.6 × 10(-10)). The hypothesized mechanism of action involves an increased aversive reaction to alcohol; in keeping with this hypothesis, the same allele is strongly associated with a lower maximum number of drinks in a 24-hour period (lifetime), with P=3 × 10(-13). We also tested the effects of this allele on the development of alcoholism in adolescents and young adults, and demonstrated a significantly protective effect. This variant has the strongest effect on risk for alcohol dependence compared with any other tested variant in European populations.
Holographic Snapshots of Laser Wakefields

We report the first single-shot measurements of transverse and longitudinal structure of laser-generated wakefields. Real-time, non-averaged measurements of resonant wakes reveal detailed temporal and spatial features that depend on pulse energy and electron density.
Like a Veil: Cross-cultural Experiential Learning Online

There is extensive literature on the power of face-to-face cross-culturalexperience in developing the knowledge, skills, and dispositions of world-mindedness (Brislin, 1993; Brislin Y Germaine, 1998; Gochen-our, 1993; Gudykunst & Matsumoto,1996; Wilson, 1982, 1983, 1986; 1993a,1998). Multicultural and global educators agree that teachers need face-to-face experiential learning with people different from themselves if they are todevelop cross-cultural skills, knowledge, and competence (Chavez Chavez O Cushner & Brislin, 1996; Dasen, 1992; Deering & Stanutz,1995; Finney & Orr, 1995; Grant, 1992; Johnson & Johnson, 1992, Merryfield,2000b; Powell, Zehm, & Garcia, 1996). During the 1970s and 1980s manyuniversities and other organizations developed opportunities for studentsand teachers to study abroad or work in culturally diverse settings withAmerican minorities, immigrants, refugees, or international students. Andthen came the Internet, email, and the possibility for online interaction withpeople around the globe.Underwritten by numerous corporations and foundations, electronic cross-cultural projects have promised to increase cultural sensitivity and aware-ness as they develop the skills and experiences needed in a global society.Scholars have identified positive outcomes, such as perspective taking,critical thinking, increased task engagement, sensitivity to cultural diversity,and social cognition, in some of these projects (Bonk, Appelman & Hay,1996; Bonk & King, 1998; Daniels, Berglunc, & Petre, 1999; Kim & Bonk,2002, Sunal & Christensen, 2002). Others who have reviewed such projects
Système des coordonnées plates de la déformation verselle des singularités isolées simples d'hypersurface et zéros de l'intégrale d'Abel

Resume On etudie le systeme des equations differentielles satisfaites par l'integrale d'Abel associee au cycle γ s ⊂{(x,y)∈ R 2 : H(x,y ;s)=0} definie pour la deformation verselle d'une singularite isolee simple d'hypersurface. Comme application, on obtient une estimation de la multiplicite des zeros de l'integrale Iω(s)=∫γsω en fonction de poids quasihomogenes associes a H(x,y ;0) et de deg(ω).
TiF1-Gamma Plays an Essential Role in Murine Hematopoiesis and Regulates Transcriptional Elongation of Erythroid Genes

Transcriptional regulators play critical roles in the regulation of cell fate during hematopoiesis. Previous studies in zebrafish have identified an essential role for the transcriptional intermediary factor TIF1γ in erythropoiesis by regulating the transcription elongation of erythroid genes. To study if TIF1γ plays a similar role in murine erythropoiesis and to assess its function in other blood lineages, we generated mouse models with hematopoietic deletion of TIF1γ. Our results showed a block in erythroid maturation in the bone marrow following tif1γ deletion that was compensated with enhanced spleen erythropoiesis. Further analyses revealed a defect in transcription elongation of erythroid genes in the bone marrow. In addition, loss of TIF1γ resulted in defects in other blood compartments, including a profound loss of B cells, a dramatic expansion of granulocytes and decreased HSC function. TIF1γ exerts its functions in a cell-autonomous manner as revealed by competitive transplantation experiments. Our study therefore demonstrates that TIF1γ plays essential roles in multiple murine blood lineages and that its function in transcription elongation is evolutionally conserved.
Moving Beyond Deliberative Control of Impulses The Effect of Construal Levels on Evaluative Associations in Self-Control Conflicts

Many prominent models propose that self-control requires deliberative control of impulses. We propose that people's subjective mental construals of events can alter temptation impulses without requiring conscious deliberation. Research has indicated that high-level construals (subjective mental representations that capture the core, essential, and abstract features of events) lead to greater self-control than low-level construals (representations that capture secondary, incidental, and concrete features). We demonstrate that higher-level construals make it easier for people to associate temptations with negativity, as measured by the Implicit Association Test, and that, in turn, these construal-dependent changes in evaluative associations promote self-control. These findings indicate that subjective construals can influence self-control without conscious deliberation.
Endotoxin inhibits the reproductive neuroendocrine axis while stimulating adrenal steroids: a simultaneous view from hypophyseal portal and peripheral blood.

This study was designed to test the hypothesis that systemic immune challenge with endotoxin inhibits the reproductive axis centrally by suppressing GnRH pulsatile release into hypophyseal portal blood. Using alert, normally behaving, ovariectomized ewes, we sampled hypophyseal portal blood at 10-min intervals beginning 4 h before and continuing 10 h after endotoxin (400 ng/kg, iv bolus, n = 6) or saline (vehicle, iv, n = 6). Simultaneous jugular samples for measurement of LH, cortisol, and progesterone were taken, and core body temperature was monitored by telemetry. Saline had no effect on any of the parameters in control ewes. In contrast, endotoxin dramatically inhibited the reproductive neuroendocrine axis coincident with stimulating the adrenal steroids, cortisol and progesterone, and elevating body temperature. Mean GnRH collection rate and GnRH pulse amplitude were suppressed (pre- vs. 7 h postendotoxin: collection rate 0.93 ± 0.31 vs. 0.34 ± 0.13 pg/min; amplitude 4.13 ± 1.33 vs. 1.30 ± 0.41 pg/m...
The Biomechanics of Cycling with a Transtibial Amputation: Recommendations for Prosthetic Design and Direction for Future Research:

People with amputations may find cycling advantageous for exercise, transportation and rehabilitation. The reciprocal nature of stationary cycling also makes it a viable model for research in motor control because the body is supported by the saddle allowing the researcher to focus on the cyclic movement of the legs without the confounding variable of balance. The purpose of this article is to provide an overview of the cycling task in intact cyclists and relate this information to understanding the challenges faced by cyclists with transtibial amputations (CTA). Ongoing research into the biomechanics of CTAs will be summarized to expose the differences between intact and CTA cycling mechanics, asymmetries between limbs of CTAs as well as neuromuscular adaptation following amputation. The article will include recommendations for prosthetic design and modification of the bicycle to improve cycling performance for CTA at all experience levels.
Subthreshold Neutron-Induced Fission Cross Section of Am 241

The corona-type spark chamber has been adapted for detection of fission fragments and has been used as the detector for neutron-induced fission cross-section measurements of ${\mathrm{Am}}^{241}$. Measurements were made over the neutron energy range from 0.032 to 80 eV. The ratio of average fission width to spacing is in good agreement with that predicted from the shape of the fast-neutron fission threshold. The number of effective fission channels obtained from an analysis of the distribution of fission widths was found to be 2.9\ifmmode\pm\else\textpm\fi{}0.6 channels.
Effect of muscle opposition during rigor on development of broiler breast meat tenderness

Two experiments were conducted to determine the effect of mutual opposition of breast muscles during rigor development on ultimate tenderness of the cooked meat. In each experiment, 32 broilers were conventionally processed. Immediately after evisceration, the supracoracoideus tendon was cut at the humeral insertion on one wing (treatment) and the opposite wing was sham-operated with the tendon exposed but not cut (control). The tendon of insertion for the Pectoralis minor muscle was cut to prevent the opposition of breast muscles during rigor, while avoiding confounding effects caused by making cuts on the muscles, as would occur during typical deboning. Cutting the tendon significantly (P < 0.05) increased Warner-Bratzler shear values after cooking for both the Pectoralis major and P. minor. Deboning at 2 h post-mortem resulted in shear values for the P. major of 7.22 kg for controls and 9.08 kg for treated carcasses; P. minor shear values were 2.98 kg for controls and 4.04 kg for treated carcasses. Deboning at 24 h post-mortem produced P. major shear values of 4.68 kg for controls and 5.68 kg for treated carcasses. On whole carcasses, breast muscle opposition during rigor contributes to the tenderness of the cooked meat.
ROLLING OF HIGH PRECISION RAILS AND 3D FEMANALYSIS OF DEFORMATION BY ANSYS PROGRAM

In order to enhance size precision of rails, the rolling technology has been tested on 360 mm four high universe mill. The ANSYS program was applied to analyze 3dimensional displacement, stress and strain of the rail. It shows that the results estimated with ANSYS program correspond to those measured.
Dose Response Relations: The Effects of DNA Repair

Environmental agents that react with DNA, either directly or indirectly by conversion to reactive intermediates, are potentially harmful to people. The biological effects of concern are cell killing, mutation, and transformation. The magnitude of the potential danger to humans from changes in their DNA depends upon the types of changes made and their lifetimes relative to the times of important cellular processes, such as replication, transcription, and cell division. It should be obvious that we cannot wait for epidemiological data to assess the hazards or the safety of agents that affect DNA. If we did, the harm would have been done and perpetuated before any corrective action could be taken.
Fast, robust dynamic field-of-view adjustment for iterative reconstruction of dedicated breast CT

Dedicated breast CT (bCT) produces high-resolution cone-beam CT breast images at radiation doses comparable to that of a screen-film mammographic exam, potentially allowing for breast cancer screening with bCT. Early indicators for breast cancer include microcalcifications clusters (MC), which consist of groups of calcium specks ranging from 200µm to 500µm in size. Iterative image reconstruction (IIR) is well-suited for low-dose CT image reconstruction, as it can alleviate the impact of data noise on the reconstructed images, but IIR is computationally demanding. In addition, the need to visualize MC requires high resolution and consequently large array sizes. Adjusting the reconstructed image array to tightly fit the actual breast, rather than the scanner field-of-view (FOV), improves computational efficiency. Here, we describe an automated method for identifying the breast bounding-box based on the analysis of two projection views that are 90 degrees apart and aligned with the reconstructed image array. The method was shown to be robust for 15 patient cases. Depending on breast size, computation time was reduced by 30% to 40%, compared to the full FOV reconstruction.
Issues of Sexually Transmitted Infections and Violence Among Children in Prostitution in West Africa

By its pervasiveness throughout the world, child prostitution can be considered a public health problem. It poses serious health and safety risks for minors involved in this practice. Not only is child prostitution taboo in many communities in Sub-Saharan Africa, but its effects on minors in that region are also hardly explored. A descriptive cross-sectional research design, with a survey instrument consisting of 41 closed-ended questions, was used to conduct a study about the risks and effects of prostitution on the health and safety of prostituted children in three countries in the West African region. A convenience sample of 709 children in prostitution, including 696 girls and 13 boys, took part in the study. Issues explored include risks and consequences of child prostitution, prevalence of sexually transmitted infections and diseases (STIs/STDs) among the respondents, experiences of violence in prostitution, and strategies for prevention of STIs and violence. The findings show that the level of condom use among prostituted children was higher in major cities than in small ones. Less than 25% of the respondents contracted STIs/STDs; very few respondents among those who experienced such infections sought any medical care. Substantial proportions of respondents who experienced physical violence by clients, community members, and/or law enforcement, did not seek assistance from child protection services. Implications for practice, policy, and research are discussed.
Identification of mouse cochlear progenitors that develop hair and supporting cells in the organ of Corti

The adult mammalian cochlear sensory epithelium houses two major types of cells, mechanosensory hair cells and underlying supporting cells, and lacks regenerative capacity. Recent evidence indicates that a subset of supporting cells can spontaneously regenerate hair cells after ablation only within the first week postparturition. Here in vivo clonal analysis of mouse inner ear cells during development demonstrates clonal relationship between hair and supporting cells in sensory organs. We report the identification in mouse of a previously unknown population of multipotent stem/progenitor cells that are capable of not only contributing to the hair and supporting cells but also to other cell types, including glia, in cochlea undergoing development, maturation and repair in response to damage. These multipotent progenitors originate from Eya1-expressing otic progenitors. Our findings also provide evidence for detectable regenerative potential in the postnatal cochlea beyond 1 week of age.
0290 Investigating the reproducibility of metabolomics profiles of washington state metal workers

Manganese (Mn) is a known neurotoxicant, and given its health effects and ubiquitous nature in metal-working settings, identification of a valid and reproducible biomarker of exposure is of interest. Global metabolomics were previously utilised to determine metabolites that differ between occupational groups defined by Mn exposure status, in hopes of informing a biomarker of exposure. Nine metabolites were found to differ between exposure groups in urine samples collected October 2014. To test the reproducibility of these metabolites, these nine metabolites were investigated in a second set of urine samples collected January 2015 from the same workers. Levels of the nine metabolites found in October 2014 were compared to the January 2015 data using principal components analysis and descriptive measures. Also, an elastic net regression was fit using the nine metabolites from the October 2014 data; this model was tested in the January 2015 data. Four of the nine ions remained significantly different between exposed and unexposed workers in the January data, though levels of most ions also exhibited regression to the mean. The elastic net model was able to correctly classify exposure status in 66% of the January samples; slightly better than classification by chance alone. Metabolomics is a novel technique for exposure assessment, but few studies have looked at the reproducibility of metabolomics data by collecting repeat samples from the same workers. This analysis found several ions that do seem to remain stable over time, and identification of these ions should be pursued as potential biomarkers of Mn exposure.
Clustering-Based Anomaly Detection Approaches

This chapter explores anomaly detection approaches based on explicit identification of clusters in a data set. Points that are not within a cluster become candidates to be considered anomalies. Variations among algorithms result in evaluating the relative anomalousness of points that are near (but not inside) a cluster, and also the points at the periphery of a cluster.
Alternative NHEJ pathway proteins as components of MYCN oncogenic activity in human neural crest stem cell differentiation: implications for neuroblastoma initiation

Neuroblastoma is a cancer of neural crest stem cell (NCSC) lineage. Signaling pathways that regulate NCSC differentiation have been implicated in neuroblastoma tumorigenesis. This is exemplified by MYCN oncogene targets that balance proliferation, differentiation, and cell death similarly in normal NCSC and in high-risk neuroblastoma. Our previous work discovered a survival mechanism by which MYCN-amplified neuroblastoma circumvents cell death by upregulating components of the error-prone non-canonical alternative nonhomologous end-joining (alt-NHEJ) DNA repair pathway. Similar to proliferating stem cells, high-risk neuroblastoma cells have enhanced DNA repair capacity, overcoming DNA damage with higher repair efficiency than somatic cells. Adequate DNA maintenance is required for lineage protection as stem cells proliferate and during tumor progression to overcome oncogene-induced replication stress. On this basis, we hypothesized that alt-NHEJ overexpression in neuroblastoma is a cancer cell survival mechanism that originates from DNA repair systems of NCSC, the presumed progenitor cell of origin. A human NCSC model was generated in which inducible MYCN triggered an immortalized phenotype capable of forming metastatic neuroectodermal tumors in mice, resembling human neuroblastoma. Critical alt-NHEJ components (DNA Ligase III, DNA Ligase I, and Poly [ADP-ribose polymerase 1]) were highly expressed in normal early NCSC, and decreased as cells became terminally differentiated. Constitutive MYCN expression maintained high alt-NHEJ protein expression, preserving the expression pattern of the immature neural phenotype. siRNA knockdown of alt-NHEJ components reversed MYCN effects on NCSC proliferation, invasion, and migration. DNA Ligase III, Ligase I, and PARP1 silencing significantly decreased neuroblastoma markers expression (TH, Phox2b, and TRKB). These results utilized the first human NCSC model of neuroblastoma to uncover an important link between MYCN and alt-NHEJ expression in developmental tumor initiation, setting precedence to investigate alt-NHEJ repair mechanics in neuroblastoma DNA maintenance.
Collision induced unfolding detects subtle differences in intact antibody glycoforms and associated fragments

Abstract Glycosylation has a significant impact on the effector function, immunogenicity, plasmatic clearance, and resistance towards proteases for monoclonal antibodies. Antibody glycoforms directly result in a form of structural heterogeneity due to the variety of sugar moieties and the available range of assembly states for the sugar linkages involved. Thus, the rapid characterization of antibody glycosylation is a critical yet challenging objective in the development of antibody-based therapeutics. Recently, we introduced an ion mobility-mass spectrometry approach for intact antibody analysis, which involves the collision induced unfolding of intact antibody ions. In this report, we demonstrate the use of such gas-phase unfolding analyses to differentiate subtly-different glycoforms within both intact antibody monomers and antibody Fc fragments, using minimal sample preparation and purification. We find evidence for a strong correlation between the gas-phase stabilities of antibody ions and the number of sugars attached to their sequences. We conclude by projecting the utility of our gas-phase unfolding assay in the context of antibody characterization workflows aimed at differentiating antibody glycoforms that cannot be readily resolved by MS alone.
Surprising formation of quasi-stable Tc(VI) in high ionic strength alkaline media

Despite decades of research, the reduction behavior of pertechnetate, TcO4−, is not well understood and represents one of the largest knowledge gaps in the transition metal series. Conventional wisdom presumes the reduction of TcO4− in aqueous systems to predominantly follow either a rapid two electron, or three electron process to form either a TcV or TcIV species. This study for the first time demonstrates the importance of the TcVI species through systematic characterization by multiple spectroscopic techniques. The reduction of TcO4− was examined in a matrix of 5 M NaNO3 at 0–2 M NaOH. Results of the cyclic voltammetric evaluation of reduction to TcVI, Nernstian analysis of the visible spectroelectrochemical signal, and structural spectroscopic EPR and XPS analysis of the reduction product generated by bulk electrolysis consistently support an electron transfer stoichiometry corresponding to a 1e− reduction. This TcVI species is markedly more stable than had been previously considered, with decomposition kinetics that correspond to a half-life of 1.91 ± 0.07 days, fully 6 orders of magnitude longer than previously reported for an aqueous solution. These results reveal the importance of a TcVI intermediate species in high ionic strength alkaline solutions and significantly contribute to the understanding of the mechanism of TcO4− reduction and formation of low-valent Tc species.
An Interpersonal Skills Learning Taxonomy for Program Evaluation Instructors

Anyone who trains others in the practice of program evaluation should be aware of how necessary it is for the practitioner to maneuver the interpersonal dynamics within a program evaluation setting...
An IRAS-Based Search for New Dusty WCL Wolf-Rayet Stars

I have examined all InfraRed Astronomy Satellite (IRAS) data relevant to the 173 galactic Wolf-Rayet (WR) stars in an updated catalogue provided by van der Hucht (priv. comm.), including the 13 stars newly discovered by Shara et al. (1991). Using the exact coordinates given in these lists, I have examined the IRAS Point Source Catalog (PSC), the Faint Source Catalog, Faint Source Reject Catalog, and generated 1-dimensional spatial profiles (“ADDSCAN”s), and 2-dimensional full-resolution images (“FRESCO”s). The goal was to assemble the best set of observed IRAS colour indices for different WR types, in particular for known dusty WCL objects. These colour indices define zones in the IRAS colour-colour([12]–[25],[25]–[60]) plane. By searching the PSC for otherwise unassociated sources that satisfy these colours, I have identified potential new WR candidates, too faint to have been recognized in previous optical searches. I have extracted these candidates’ IRAS Low Resolution Spectrometer (LRS) data and compared the spectra with the highly characteristic LRS shape for known dusty WCL stars. Any surviving candidates must now be examined by optical spectroscopy. This work represents a much more rigorous and exhaustive version of the LRS study that identified IRAS 17380-3031 (WR98a) as the first new WR (WC9) star discovered by IRAS (Cohen et al. 1991).
On winking at the facts, and losing one's Hare: value pluralism and the harmful dysfunction analysis.

Disorder is partly a value concept; conditions that do not cause harm (e.g., benign angiomas, dyslexic dysfunction in a preliterate society where reading is neither taught nor valued) are not disorders. However, disorders are not merely disvalued conditions. Most negative conditions, from ignorance and lack of talent to shortness in an aspiring basketball player, are not disorders. Nor does need for treatment imply disorder, as in abortion and delinquency (1).
DD98: Der Profit der Anerkennung und mein Hass auf Hobby-Statistiker (September 2009)

Mitarbeiter klagen fast unisono uber mangelnde Anerkennung fur ihre Arbeit. Es gibt nur noch Geld, und das auch nur unwillig. Warum lobt uns keiner? Das wurde nichts kosten. Aber die Manager schweigen fast eisern. Der Management-Guru Reinhard Sprenger rief auf, Mitarbeiter fur Verdienste zu wurdigen, aber eine wissenschaftliche Studie widerspricht ihm diametral und „zeigt“, dass sich Anerkennung fur Unternehmen nicht auszahlt. Ich habe fast eine Stunde vor mich her geschimpft, nachdem ich das alles im Handelsblatt las.
Training Issues in Adolescent Health

Training of medical, educational, and mental health professionals working with adolescents is essential for the improvement of physical and psychological health outcomes. This chapter reviews the key issues inherent in training professions in the field of adolescent health. The chapter begins with a review of the unique features of adolescence. Training issues identified in the literature are then introduced including the limitations of training programs. A framework for adolescent health training is presented and best practices are reviewed within the context of that framework. This includes policy, training initiatives, and curricular development. Next, key curricular content areas and suggested topics for training are listed and explicated. Teaching methodologies are also examined. Finally, the chapter closes with a review of the challenges and barriers in teaching adolescent health. A list of resources is offered including journal articles and web resources.
Regularized reconstruction algorithms for dual-isotope myocardial perfusion SPECT (MPS) imaging using a cross-tracer edge-preserving prior

605 Objectives: In dual-isotope simultaneous acquisition (DISA) of myocardial perfusion SPECT (MPS) images, projection data represent the distributions of two radioisotopes. The goal of this work was to develop a cross-tracer edge-preserving prior and penalized maximum likelihood (PML) algorithms that reduces the noise in DISA images by exploiting the fact that the two images are perfectly registered in space, and thus share common organ boundaries. Methods: We implemented the one-step-late (OSL) PML algorithm and developed two convergent PML algorithms for the proposed prior. In particular, we formulated the DISA problem as a joint estimation problem using a convex prior that couples the pixel values both within and between the images of the two isotopes. We derived a separable surrogate function for the prior and a PML algorithm that converges to the MAP solution. A fast version of the convergent algorithm was then developed based on COSEM algorithm. To investigate effects of the cross-tracer prior, we performed a 3-class CHO study of images obtained using the OSL algorithm implementing the prior. We compared images reconstructed with and without the cross-tracer prior term using simulated DISA data that corresponded to 16 mCi of Tc-99m and 3 mCi Tl-201. We also investigated the convergence properties of the two convergent algorithms. Results: For the OSL algorithm, the volumes under 3-class ROC surfaces for unoptimized priors with and without the cross-tracer term were 0.79 and 0.76, respectively. For the convergent algorithms, we have shown convergence of the objective function. Conclusions: We have developed a novel prior and PML algorithms that exploit commonalities in DISA MPS images and improve the DISA MPS image quality. Research Support: NIH K99 EB007620-01, R01-EB000288
Autism spectrum disorders: Unbiased functional connectomics provide new insights into a multifaceted neurodevelopmental disorder

Abstract This chapter highlights the promise of functional connectomics in the study of autism spectrum disorders (ASD). Unlike task-based paradigms, functional connectomics allows us to quantify the synchrony between brain regions at both local and long-range scales. This flexibility offers a holistic perspective of ASD across multiple brain systems. Likewise, the absence of external stimuli allows us to focus on intrinsic or steady-state communication patterns. “ Functional Connectomics as a Window into ASD ” section of this chapter summarizes prior work in the field, from simple seed-based analyses to more complex network models. “ An Unbiased Bayesian Framework for Functional Connectomics ” section introduces our novel Bayesian framework to extract the altered subnetworks associated with ASD. In “ Multisite Network Analysis of Autism ” section, we evaluate this model on a multisite study of autism. Our results confirm theories of impaired sociocommunicative function and reduced intersystem connectivity in ASD. “ Toward Characterizing Patient Heterogeneity ” section presents a new extension of our framework that incorporates patient heterogeneity. This additional flexibility allows us to pinpoint more subtle effects than conventional analysis. Finally, we conclude with general recommendations for future work in the field.
Technology Positioning for mm Wave Applications: 130/90nm SiGe BiCMOS vs. 28nm RFCMOS

Over the last few decades, SiGe BiCMOS has survived the continued onslaught of RF-CMOS technologies. SiGe HBT invented in late 1980's and later introduced as a BiCMOS technology served as a sweet spot in the emerging RF market, thanks to the SiGe HBT's higher power and better noise characteristics. It did not take very long for RFCMOS scaling roadmap to catch up to SiGe HBT performance levels and displace it from high-volume market segment like RF cellular transceivers. Now with the advent of 5G millimeter-wave (mmWave) applications demanding higher power and lower noise for the front-end, will SiGe BiCMOS once again come back to the forefront to address this market? In this paper we will take a closer look at some of the key aspects of a 130 / 90nm SiGe BiCMOS relative to a 28nm bulk RFCMOS technology for addressing mmWave front-end as well as potential opportunities that lie ahead with scaling.
A phase 1 trial of Vorinostat in combination with concurrent chemoradiation therapy in the treatment of advanced staged head and neck squamous cell carcinoma

Purpose Vorinostat is a potent HDAC inhibitor that sensitizes head and neck squamous cell carcinoma (HNSCC) to cytotoxic therapy while sparing normal epithelium. The primary objective of this Phase I study was to determine the maximally tolerated dose (MTD) and safety of Vorinostat in combination with standard chemoradiation therapy treatment in HNSCC. Patients and Methods Eligible patients had pathologically confirmed Stage III, IVa, IVb HNSCC, that was unresectable or borderline resectable involving the larynx, hypopharynx, nasopharynx, and oropharynx. Vorinostat was administered at the assigned dosage level (100-400 mg, three times weekly) in a standard 3 + 3 dose escalation design. Vorinostat therapy began 1 week prior to initiation of standard, concurrent chemoradiation therapy and continued during the entire course of therapy. Results Twenty six patients met eligibility criteria and completed the entire protocol. The primary tumor sites included tonsil (12), base of tongue (9), posterior pharyngeal wall (1), larynx (4) and hypopharynx (3). Of the 26 patients, 17 were HPV-positive and 9 were HPV-negative. The MTD of Vorinostat was 300 mg administered every other day. Anemia (n = 23/26) and leukopenia (n = 20/26) were the most commonly identified toxicities. The most common Grade3/4 events included leukopenia (n = 11) and lymphopenia (n = 17). No patient had Grade IV mucositis, dermatitis or xerostomia. The median follow time was 33.8 months (range 1.6–82.9 months). Twenty four of 26 (96.2%) patients had a complete response to therapy. Conclusion Vorinostat in combination with concurrent chemoradiation therapy is a safe and highly effective treatment regimen in HNSCC. There was a high rate of complete response to therapy with toxicity rates comparable, if not favorable to existing therapies. Further investigation in Phase II and III trials is strongly recommended.