cssi/SciSciGPT-SciSciNet huggingface dataset:
Next-generation genotyping of hypervariable loci in many individuals of a non-model species: technical and theoretical implications

Across species, diversity at the Major Histocompatibility Complex (MHC) is critical to disease resistance and population health; however, use of MHC diversity to quantify the genetic health of populations has been hampered by the extreme variation found in MHC genes. Next generation sequencing (NGS) technology generates sufficient data to genotype even the most diverse species, but workflows for distinguishing artifacts from alleles are still under development. We used NGS to evaluate the MHC diversity of over 300 captive and wild ring-tailed lemurs (Lemur catta: Primates: Mammalia). We modified a published workflow to address errors that arise from deep sequencing individuals and tested for evidence of selection at the most diverse MHC genes. In addition to evaluating the accuracy of 454 Titanium and Ion Torrent PGM for genotyping large populations at hypervariable genes, we suggested modifications to improve current methods of allele calling. Using these modifications, we genotyped 302 out of 319 individuals, obtaining an average sequencing depth of over 1000 reads per amplicon. We identified 55 MHC-DRB alleles, 51 of which were previously undescribed, and provide the first sequences of five additional MHC genes: DOA, DOB, DPA, DQA, and DRA. The additional five MHC genes had one or two alleles each with little sequence variation; however, the 55 MHC-DRB alleles showed a high dN/dS ratio and trans-species polymorphism, indicating a history of positive selection. Because each individual possessed 1–7 MHC-DRB alleles, we suggest that ring-tailed lemurs have four, putatively functional, MHC-DRB copies. In the future, accurate genotyping methods for NGS data will be critical to assessing genetic variation in non-model species. We recommend that future NGS studies increase the proportion of replicated samples, both within and across platforms, particularly for hypervariable genes like the MHC. Quantifying MHC diversity within non-model species is the first step to assessing the relationship of genetic diversity at functional loci to individual fitness and population viability. Owing to MHC-DRB diversity and copy number, ring-tailed lemurs may serve as an ideal model for estimating the interaction between genetic diversity, fitness, and environment, especially regarding endangered species.
4-1BB agonism: adding the accelerator to cancer immunotherapy.

The success of checkpoint inhibitors has validated immunomodulatory agents as a valuable class of anticancer therapeutics. A promising co-stimulatory immunologic target is 4-1BB, or CD137, a member of the tumor necrosis factor receptor superfamily. Ligation of 4-1BB induces an activating signal in CD8+ T cells and natural killer cells, resulting in increased pro-inflammatory cytokine secretion, cytolytic function, and antibody-dependent cell-mediated cytotoxicity. Targeting 4-1BB with agonistic monoclonal antibody (mAb) therapy demonstrated potent antitumor effects in murine tumor models. While anti-4-1BB mAbs have entered clinical trials, optimal efficacy of 4-1BB-targeted agents will inevitably come from combination therapeutic strategies. Checkpoint blockade is a compelling combination partner for 4-1BB agonism. This novel immunotherapeutic approach has the potential to active antitumor immune effectors by a complementary mechanism: simultaneously “removing the brakes” via blocking inhibitory signaling and “stepping on the accelerator” via co-stimulation. While important considerations should be given to 4-1BB-mediated toxicities, the current understanding of 4-1BB biology suggests it may play a key role in advancing the capabilities of cancer combination therapy.
Closing the Gaps and Filling the STEM Pipeline: A Multidisciplinary Approach

There is a growing demand for degreed science, technology, engineering and mathematics (STEM) professionals, but the production of degreed STEM students is not keeping pace. Problems exist at every juncture along the pipeline. Too few students choose to major in STEM disciplines. Many of those who do major in STEM drop out or change majors. Females and minorities remain underrepresented in STEM. The success rate of college students who are from low-income background or first-generation students is much lower than that of students who do not face such challenges. Some of those who successfully complete their degree need help in making the transition to the workforce after graduation. A program at Lamar University takes a multidisciplinary approach to addressing these problems. It is designed to recruit, retain and transition undergraduates to careers in STEM, focusing its efforts on five science disciplines and on these “at-risk” students. The program was supported by a 5-year grant from the National Science Foundation and is supported through August 31, 2016 by Lamar University and a grant from ExxonMobil. A formal assessment plan documents the program’s success. The program received an award from the Texas Higher Education Board for its contributions towards Closing the Gaps in Higher Education in Texas. This paper describes the program’s theoretical framework, research questions, methods, evaluation plan, and instruments. It presents an analysis of the results achieved using these methods and implications for improvements to the program resulting from lessons learned.
Metallurgical results on control devices of fluid flow in tundish

Fluid flow behavior in tundish during continous casting has important influence on the ability to remove non-metallic inclusions from liquid metal to slag phase.The effect by using control flow devices with weirs and dams in the tundish are presented.The most significant effect of control flow devices is that the contents of total oxygen,micro-inclusions and macro-inclusions are remarkably decreased and the molten steel cleanliness from tundish to mold are improved.
A smoking cessation program plus inhaled ipratropium improved survival in smokers with asymptomatic airway obstruction.

Source Citation Anthonisen NR, Skeans MA, Wise RA, et al. The effects of a smoking cessation intervention on 14.5-year mortality: a randomized clinical trial. Ann Intern Med. 2005;142:233-9. 15710956
Teachers as Learners: A Review of Teachers as Learners, by Sharon Feiman-Nemser

Teachers as Learners is a collection of essays based on the vast experiences and research of the author, Sharon Feiman-Nemser. A noted scholar in the field of teacher education, she has served in m...
Cost, time and technical performance risk mitigation in large, complex and innovative aeronautics development projects

Abstract: Large, complex, innovative development projects, such as many in the aeronautical industry, occur under conditions of consequential uncertainty, i.e. risk. Risk is manifest with respect to project cost, schedule, and technical performance. These risks need to be managed in relation to each other as well as to the project schedule, budget, and technical requirements. This chapter presents an integrated model to plan and monitor project value in terms of all of these areas. The model complements conventional approaches such as earned value management, which does not directly account for technical performance or any kind of risk. The model allows a user to quantify a project's overall value, the portion of that value at risk, and the respective contributions of cost, schedule, and technical performance to that value and risk.
Abstract 3641: ReCapSeg: Validation of somatic copy number alterations for CLIA whole exome sequencing

The presence of specific somatic copy number alterations (SCNAs) in tumor genomes can be used to predict sensitivity to specific treatments and to predict outcomes. CapSeg Revised (ReCapSeg) detects SCNAs from tumor sequencing data. The Broad Institute is integrating ReCapSeg into the Clinical Research Sequencing Platform (CRSP), a CLIA-certified platform, to enable physicians to use detected SCNAs in treatment decisions. By using sequencing data CRSP can produce SCNA reports using the same data being generated for other reports (e.g. somatic single nucleotide variants). ReCapSeg produces copy ratio estimates for regions of the genome and includes a caller that labels regions as amplified, deleted, or neutral. ReCapSeg leverages a panel of normals (PoN), which obviates the need for the matched normal for a given tumor sample. Validation for ReCapSeg, in CRSP, is repeatable and standardized with a process for creating a PoN and gathering performance metrics from case samples. Additional QC metrics and criteria on input sequencing data were identified and included, so that reports can indicate when reduced performance can be expected. Citation Format: Lee Lichtenstein, Betty Woolf, Alyssa MacBeth, Ozge Birsoy, Niall Lennon. ReCapSeg: Validation of somatic copy number alterations for CLIA whole exome sequencing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3641.
A Better Understanding of the Deaf Through a Public Relations Program

“One of the best exhibits a school for the deaf can put on is a demonstration by the pupils in the school … No school will farm out deaf pupils to a public relations firm. This responsibility belongs to the schools.”
Fluorescent and Colorimetric Probes for Carbohydrates: A Second Decade’s Worth of Bright Spies for Saccharides

This review provides a chronological survey of 95 fluorescent chemosensors for carbohydrates from 2005 to the present. The review describes molecular probes that are synthetic or chemosensory and utilize monoboronic acids, bisboronic acids, and alternative receptor groups such as lanthanides and platinum. In each probe description, attempts have been made to highlight the unique features of each system, their solvation characteristics, and the relevant optical absorption and emission wavelengths. In cases involving fluorescence, the signaling switch of either ON–OFF or OFF–ON is indicated as well as molecular fluorescence quantum yields. In addition, the selectivity of each chemosensor is provided with saccharide affinity trends in binding constants. Following this outline of various carbohydrate probes, the applications of these molecular probes are presented in polymeric, well plate, and sensor arrays. We conclude the review with a discussion on the commercial successes such as continuous glucose monitoring and potential future directions that readers may come to expect in the coming decade.
AGFusion: annotate and visualize gene fusions

The discovery of novel gene fusions in tumor samples has rapidly accelerated with the rise of next-generation sequencing. A growing number of tools enable discovery of gene fusions from RNA-seq data. However it is likely that not all gene fusions are driving tumors. Assessing the potential functional consequences of a fusion is critical to understand their driver role. It is also challenging as gene fusions are described by chromosomal breakpoint coordinates that need to be translated into an actual amino acid fusion sequence and predicted domain architecture of the fusion proteins. Currently there are no easy-to-use tools that can automatically reconstruct and visualize fusion proteins from genomic breakpoints. To facilitate the functional interpretation of gene fusions, we developed AGFusion, available as an online web tool that can be readily used by non-computational researchers as well as a python package that can be built into computational pipelines. With minimal input from the user, AGFusion predicts the cDNA, CDS, and protein sequences of all gene fusion products based on all combinations of gene isoforms. For protein coding fusions, AGFusion can annotate and visualize the protein domain architecture. AGFusion currently supports Homo sapiens (genome builds GRCh37 and GRCh38) and Mus musculus (genome build GRCm38) and new genomes can easily be added.
IoTSAT: A formal framework for security analysis of the internet of things (IoT)

The new attack surface being crafted by the huge influx of IoT devices is both formidable and unpredictable, as it introduces a rich set of unexplored attack techniques and unknown vulnerabilities. These new attack techniques are hard to perceive through traditional means, owing to concealed and cascaded inter-device, inter-system and device-environment dependencies. In this paper, we present IoTSAT, a formal framework for security analysis of IoT. IoTSAT formally models the generic behavior of IoT system of systems, based on device configurations, network topologies, user policies and IoT-specific attack surface. The model is then used to measure system's resilience against potential attacks and identify threat vectors and specific attack techniques, which can be used to achieve higher-level adversary's objectives. We evaluate IoTSAT over realistic IoT networks, which concludes that our approach is scalable and highly beneficial for uncovering complex attack vectors of IoT systems.
Fault-Tolerant Adaptive Model Inversion Control for Vision-Based Autonomous Air Refueling

The practical autonomous air refueling of unmanned air system tanker aircraft to unmanned air system receiver aircraft will require an integrated relative navigation system and controller that is t...
El neutro de materia en asturiano: Un acercamiento sintáctico al fenómeno en cuanto a la especificidad, genericidad y la posición del adjetivo

La lengua asturiana muestra el fenomeno llamado neutro de materia, que se genera cuando un sustantivo incontable precede a un adjetivo neutro, el cual es representado por la terminacion -o. Esta estructura crea una lectura generica; y asi, ‘l’arroz blanco’ se refiere a cualquier arroz de ese color. Este adjetivo neutro no se puede manifestar en posicion prenominal, porque el resultado seria agramatical. Es decir que el adjetivo prepuesto tiene que concordar en genero con el sustantivo, en general para los masculinos la terminacion -u, y -a para los femeninos. El ejemplo‘el blancu arroz’ muestra esta concordancia completa del adjetivo prepuesto. Ademas, el adjetivo pospuesto tiene la opcion de generar el neutro, o tambien concordar con el genero del sustantivo que lo precede. Se ve lo segundo en el ejemplo ‘l’arroz blancu’. Los adjetivos antepuesto y pospuesto, los cuales tienen una concordancia completa, conllevan una lectura especifica, por la que el hablante se refiere a la realidad que tiene ante si. Este trabajo pretende examinar la posibilidad de un DegP (Degree Phrase) presente en la estructura sintactica del asturiano con posibles rasgos de [EPP] y [+ESP(ecificidad)] o solo los de [+ESP(ecificidad)], enconjuncion con movimiento adjetival o sin el, para explicar los contextos en los cuales el neutro de materia no se puede generar gramaticalmente.The Asturian language demonstrates a phenomena so called the mass neuter. This characteristic of the language contains a mass noun that precedes a neuter adjective, which is represented by the morphological ending -o. This structure creates a generic reading, as the example ‘l’arroz blanco’ is semantically interpreted as any rice that is white. This neuter adjective cannot be in a prenominal position, as this would be ungrammatical. It is to say, that the prenominal adjective must agree in gender with the noun. The adjective is therefore generally marked by themorphological ending -u and the morphological ending -a is for the feminine one. For example, ‘el blancu arroz’ shows this agreement of the prenominal adjective. In addition to the previously mentioned, the postnominal adjective has the option of either taking on the neuter gender or agreeing with the gender of the noun that precedes it. This is shown with the example ‘l’arroz blancu’. Both the prenominal and postnominal adjective, which have complete gender agreement, cause a specific reading. That is to say that the speaker has the white rice in frontof him. This work aims to examine the possibility of a DegP (Degree Phrase) that is present in the syntactic structure of Asturian, which can contain possible [EPP] and [+ESP(ecificity)] features or only [+ESP(ecificity)] features, in conjunction with adjectival movement or lack thereof, in order to explain the contexts in which the mass neuter cannot appear grammatically.
Metropolitan Business Cycle Analysis for Lubbock

Abstract. This study develops a business cycle index (BCI) for Lubbock Metropolitan Statistical Area (MSA). The Stock & Watson ( 1989 ; 1991 ; 1993 ) methodology is used to develop the BCI and assumes that the co-movements of key economic indicators have a single underlying, unobservable factor. This factor is extracted from the indicators and used to calculate an index that represents economic conditions through an econometric approach. The model uses the Kalman filter smoothing approach which smooths across variables and over time. This results in an index that is smoother with less pronounced expansions and recessions. Indicator series used for the study are: establishment employment, unemployment, real retail sales and real wages that begin in 1990 and include complete data through the end of 2015. Results indicate that the Lubbock business cycle has peaks and troughs that occur later than those for the national economy. Keywords. Regional Economics; Business Cycles; Economic Indicators. JEL. R15, E32.
UMLS visualization for biomedical and health science classroom teaching and student learning

The primary goal of Unified Medical Language System (UMLS) is to unify disparate medical standards for uniform and unambiguous semantic interpretation. For the past two decades, UMLS is used in research ranging from biomedical natural language processing to electronic health record and even enhancing UMLS metathesaurus itself. However, only few research efforts have focused on its visualization and none of them are designed for classroom and student learning environment. In this research effort, we have implemented a visualization framework for UMLS using datadriven technologies. We also present a proposed evaluation framework adapted from Unified Technology Acceptance and Use Theory (UTAUT) for its impact.
Impact of Pharmacogenetics on Efficacy and Safety of Statin Therapy for Dyslipidemia

Interindividual variability in response to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, with regard to both efficacy and safety is an obvious target for pharmacogenetic research. Many genes have been identified as possible contributors to variability in statin response and safety. Genetic polymorphisms may alter the structure or expression of coded proteins, with potential impacts on lipid and statin absorption, distribution, metabolism, and elimination as well as response pathways related to the pharmacologic effect. Many studies have explored the variation in statins' pharmacokinetic and pharmacodynamic parameters; however, to our knowledge, few have established definitive relationships between the genetic polymorphisms and patient outcomes, such as cardiovascular events. In this review article, we provide a statin-based summary of available evidence describing pharmacogenetic associations that may be of clinical relevance in the future. Although currently available studies are often small or retrospective, and may have conflicting results, they may be useful in providing direction for future confirmatory studies and may point to associations that could be confirmed in the future when more patient outcomes-based studies are available. We also summarize the clinically relevant evidence currently available to assist clinicians with providing personalized pharmacotherapy for patients requiring statin therapy.
Fifth Metatarsal Fracture Treated with Intramedullary Screw Fixation

Fifth metatarsal fractures can occasionally require surgical fixation if found in the proximal meta-diaphyseal junction. Intramedullary screw fixation has become the standard fixation method for initial management of many acute fractures. This chapter describes a surgical technique for intramedullary fixation.
A Compact Kinetic Model for Biomass Pyrolysis at Gasification Conditions

Computational fluid dynamics (CFD) tools are increasingly gaining importance to obtain detailed insight into biomass gasification. A major shortcoming of the current CFD tools to study biomass gasification is the lack of computationally affordable chemical kinetic models, which allows detailed predictions of the yield and composition of various gas and tar species in complex reactor configurations. In this work, a detailed mechanism is assembled from the literature and reduced to a compact model describing the gas-phase reactions of biomass gasification in the absence of oxygen. The reduction procedure uses a graph-based method for unimportant kinetic pathways elimination and quasi-steady-state species selection. The resulting reduced model contains 39 gas species and 118 reactions and is validated against the detailed model and two experimental configurations: the pyrolysis of volatile species, such as levoglucosan, in a tubular reactor, and the fast pyrolysis of biomass particles in a drop tube reactor....
The effect of verified pediatric trauma centers, state laws, and crash characteristics on time trends in adolescent motor vehicle fatalities, 1999-2015.

BACKGROUND Motor vehicle crashes are a leading cause of adolescent death from trauma. A recent study found American College of Surgeons-verified pediatric trauma centers (vPTC) were inversely correlated with pediatric mortality, but the analysis was limited to a single year. This study assesses the contribution of vPTCs, crash characteristics, and state driver laws on 15- to 17-year-old motor vehicle crash mortality for all 50 states from 1999 to 2015. METHODS Prospective data on motor vehicle fatalities, crash characteristics, state driving laws, and American College of Surgeons-verified trauma centers were collected from publicly available sources for 50 US states from 1999 to 2015. A mixed fixed/random effects multivariate regression model was fitted to assess the relative contribution of crash characteristics, state laws, and vPTCs while controlling for state variation and time trends. RESULTS The final regression model included driver and crash characteristics, verified trauma centers, and state laws. Camera laws ([B = -0.57 [p 90 mph (B = 0.004 [p < 0.001]), rural roads (B = 0.002 [p < 0.002], unknown seat belt compliance (B = 0.004 [p < 0.001]), and dry road surface (B = 0.005 [p < 0.001]). CONCLUSIONS State camera laws during the study time frame are associated with a 57% decrease in the rate of change in adolescent crude fatalities; vPTCs during the study time period reduced overall rate of change in the crude fatality rate by 12%. State laws, restrictions on teenage passengers and longer learner's permit periods, and seat belt laws are associated with significant decreases in the crude teen mortality rate. LEVEL OF EVIDENCE Prospective study and prevention, level III.
Calabi-Yau Spaces and Orbifolds

Although the heterotic string is a great advance over the usual formulation of string theory, the question still remains whether we can break the theory down to four dimensions and do rigorous phenomenology. The answer, unfortunately, is no.
Human internal mammary artery produces more prostacyclin than saphenous vein.

The patency rate of internal mammary artery grafts is reported to be better than that of saphenous vein grafts in myocardial revascularization operations. To identify a possible biochemical explanation for this phenomenon, we studied the production of prostacylin by the internal mammary artery and saphenous vein in 11 patients. Segments of internal mammary artery and saphenous vein from each patient were incubated in Krebs-Henseleit buffer at 37° C. After 15 minutes, the basal production of 6-keto-prostaglandin F1α (prostacyclin metabolite) by the internal mammasry artery was 152 ± 39 pg/mg wet weight (mean ± standard error of the mean), whereas the saphenous vein produced only 68 ± 17 pg/mg (p
Supplier Affiliated Extended Supply Chain Backbones

E-commerce has progressed from the preliminary stages of brochure-ware to on-line transaction management, and is entering a phase where great opportunities exist in extended supply-chain over the Internet. Currently, much of the focus is on business-to-business e-commerce, where middleman hubs perform broker functions of search and comparison. Their value is derived from providing time and cost savings to participants. As XML semantics and other information sharing technologies become more standardized, and as behavioral aspects of Internet commerce become better established, we would expect the searching and comparison mechanics to become priced at their marginal costs. Business-to-business hubs, or interorganizational systems that do not add value in another way to the chain will find very little margins. In this paper, we examine issues related to Internet extended supply chain backbones from the supplier’s viewpoint and discuss the information architecture of a third party software backbone and how it can provide value-added services to suppliers and OEMs via internetworking standards.
Pathways to Parental Engagement: Contributions of Parents, Teachers, and Schools in Cultural Context

Research Findings: This study examined correlates of parents’ reported school engagement in an ethnically diverse, rural sample (N = 346) of parents and teachers in kindergarten through Grade 2. Of...
Dimeric ferrochelatase bridges ABCB7 and ABCB10 homodimers in an architecturally defined molecular complex required for heme biosynthesis

Loss-of-function mutations in the ATP-binding cassette (ABC) transporter of the inner mitochondrial membrane, ABCB7, cause X-linked sideroblastic anemia with ataxia, a phenotype that remains largely unexplained by the proposed role of ABCB7 in exporting a special sulfur species for use in cytosolic iron-sulfur (Fe-S) cluster biogenesis. Here, we generated inducible ABCB7-knockdown cell lines to examine the time-dependent consequences of loss of ABCB7. We found that knockdown of ABCB7 led to significant loss of mitochondrial Fe-S proteins, which preceded the development of milder defects in cytosolic Fe-S enzymes. In erythroid cells, loss of ABCB7 altered cellular iron distribution and caused mitochondrial iron overload due to activation of iron regulatory proteins 1 and 2 in the cytosol and to upregulation of the mitochondrial iron importer, mitoferrin-1. Despite the exceptionally large amount of iron imported into mitochondria, erythroid cells lacking ABCB7 showed a profound hemoglobinization defect and underwent apoptosis triggered by oxidative stress. In ABCB7-depleted cells, defective heme biosynthesis resulted from translational repression of ALAS2 by iron regulatory proteins and from decreased stability of the terminal enzyme ferrochelatase. By combining chemical crosslinking, tandem mass spectrometry and mutational analyses, we characterized a complex formed of ferrochelatase, ABCB7 and ABCB10, and mapped the interfaces of interactions of its components. A dimeric ferrochelatase physically bridged ABCB7 and ABCB10 homodimers by binding near the nucleotide-binding domains of each ABC transporter. Our studies not only underscore the importance of ABCB7 for mitochondrial Fe-S biogenesis and iron homeostasis, but also provide the biochemical characterization of a multiprotein complex required for heme biosynthesis.
Academic Leaders' Response to the Volatility of Higher Education: The Influence of Institutional Logics.

The purpose of this research was to articulate the pressures faced by USA higher education leaders lived experiences and the relationship to problem definition, attention focus, and strategy choice...
Microdermal Implants Show No Effect on Surrounding Tissue During Surgery With Electrocautery.

Abstract Background Microdermal implants are an increasingly popular form of body jewelry. The potential for electrical conduction burn at the site of metal jewelry left in situ during electrosurgery has prompted surgical societies to recommend routine removal before surgery. To date, however, there is a lack of evidence to support this practice. We assessed in vivo thermal effect and tissue damage around implants during and after electrocautery. Materials and methods Stainless steel microdermal anchors were surgically implanted into four swine. After allowing for initial healing, negative controls were excised and evaluated. An electrocautery grounding pad was placed 2 cm caudal to the implant. Continuous electrocautery (coagulation/30 W) for 30 s was applied to the skin 2 cm cranial to the implant. Surface skin temperature was recorded during electrocautery using thermal imaging. Tissue damage was assessed by gross examination and histologic evaluation. The same procedure was then performed to the contralateral nonimplanted side as a sham control. Results Electrocoagulation raised skin temperature around the electrocautery tip 27.7°C (Tmax 64.8°C). Skin temperature around the dermal implant rose 1.58°C (Tmax 38.6°C) compared with 2.03°C (Tmax 39.2°C) in the nonimplanted control skin (P = 0.627). Skin temperatures at implanted and control sites showed no statistical difference at any recorded time interval. Histologic review of excised tissue samples showed no evidence of thermal injury. Conclusions Metallic implants appear to have no effect on skin temperature during the use of electrocautery even when in close proximity to both the electrocautery pen and return pad. Aggressive steps to remove microdermal implants before surgery may be unnecessary.
Increased Yogurt Intake Lowers Risk of Cardiovascular Disease among Middle-Aged Adults with High Blood Pressure

BackgroundHigh blood pressure (HBP) is a major risk factor for cardiovascular disease (CVD), the leading cause of mortality worldwide. Short-term clinical trials have found beneficial effects of hi...
Angiogenesis in osteosarcoma is regulated by tumor interstitial fluid pressure

4549 Aim: We have previously shown that osteosarcomas (OS) have states of increased interstitial fluid pressure (IFP) and that these states correlated with increased proliferation and chemosensitivity. This study investigates the effect of constitutively raised IFP on angiogenesis in OS. . Method: Sixteen patients with the clinical diagnosis of OS underwent IFP readings by the wick-in-needle method at the time of open biopsy. Blood flow readings were made in the location of the biopsy concurrently. Vascularity as determined by capillary density in the biopsied specimens was correlated with interstitial fluid pressure and blood flow. We validated these findings using immunohistochemical staining for VEGF-A, VEGF-C and TPA on paraffin-embedded tissue blocks of the biopsy samples. In addition human OS (HOS and U2OS), osteoblast (OB) and endothelial (HUVEC) cell lines were grown in a pressurized cell culture system designed to replicate the pressure readings found in the clinical study. Quantitative and qualitative PCR were performed on OS and OB samples grown at various levels of pressure. Cell cycle analysis was performed on HUVEC cells grown under pressure. . Results: Interstitial fluid pressures in the tumors (median 32 mmHg ± SD 19 mmHg) was significantly higher than that in normal tissues (3 ± 6 mmHg). Pressure readings were significantly higher in low vascularity tumors compared to high vascularity tumors (p
Advances in preclinical approaches to Chagas disease drug discovery

Introduction: Chagas disease affects 8-10 million people worldwide, mainly in Latin America. The current therapy for Chagas disease is limited to nifurtimox and benznidazole, which are effective in treating only the acute phase of the disease but with severe side effects. Therefore, there is an unmet need for new drugs and for the exploration of innovative approaches which may lead to the discovery of new effective and safe drugs for its treatment. Areas covered: The authors report and discuss recent approaches including structure-based design that have led to the discovery of new promising small molecule candidates for Chagas disease which affect prime targets that intervene in the sterol pathway of T. cruzi. Other trypanosome targets, phenotypic screening, the use of artificial intelligence and the challenges with Chagas disease drug discovery are also discussed. Expert opinion: The application of recent scientific innovations to the field of Chagas disease have led to the discovery of new promising drug candidates for Chagas disease. Phenotypic screening brought new hits and opportunities for drug discovery. Artificial intelligence also has the potential to accelerate drug discovery in Chagas disease and further research into this is warranted.
Hardware vs. software implementations for calculating roots of polynomials

This paper discusses ongoing research into the design and development of custom configurable hardware using a field programmable gate array. In particular, Newton's Method for finding roots of polynomials is investigated, and the solutions using both software and hardware techniques are presented and compared. The Principle of Equivalence of Hardware and Software for this method is verified.
CRISPR-mediated modeling and functional validation of candidate tumor suppressor genes in small cell lung cancer

Small cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer that remains among the most lethal of solid tumor malignancies. Recent genomic sequencing studies have identified many recurrently mutated genes in human SCLC tumors. However, the functional roles of most of these genes remain to be validated. Here, we have adapted the CRISPR-Cas9 system to a well-established murine model of SCLC to rapidly model loss-of-function mutations in candidate genes identified from SCLC sequencing studies. We show that loss of the gene p107 significantly accelerates tumor progression. Notably, compared with loss of the closely related gene p130, loss of p107 results in fewer but larger tumors as well as earlier metastatic spread. In addition, we observe differences in proliferation and apoptosis as well as altered distribution of initiated tumors in the lung, resulting from loss of p107 or p130 Collectively, these data demonstrate the feasibility of using the CRISPR-Cas9 system to model loss of candidate tumor suppressor genes in SCLC, and we anticipate that this approach will facilitate efforts to investigate mechanisms driving tumor progression in this deadly disease.
A holistic view of future risks

Almost everything is somehow interrelated with everything else---and that should not surprise us.
Surgical resection of early stage hepatocellular carcinoma improves patient survival at safety net hospitals

BACKGROUND AND OBJECTIVES Surgical resection is indicated for hepatocellular carcinoma (HCC) patients with Child A cirrhosis. We hypothesize that surgical intervention and survival are limited by advanced HCC presentation at safety net hospitals (SNHs) versus academic medical centers (AMCs). METHODS Patients with HCC and Child A cirrhosis in the US Safety Net Collaborative (2012-2014) were evaluated. Demographics, clinicopathologic features, operative characteristics, and outcomes were compared between SNHs and AMCs. Liver transplantation was excluded. Kaplan-Meier and Cox proportional-hazards models were used to identify the effect of surgery on overall (OS). RESULTS A total of 689 Child A patients with HCC were identified. SNH patients frequently presented with T3/T4 stage (35% vs. 24%) and metastases (17% vs. 8%; p < .05). SNH patients were as likely to undergo surgery as AMC patients (17% vs. 18%); however, SNH patients were younger (56 vs. 64 years), underwent minor hepatectomy (65% vs. 38%), and frequently harbored well-differentiated tumors (23% vs. 2%; p < .05). On multivariate analysis, surgical resection and stage, but not hospital type, were associated with improved OS. CONCLUSIONS Although SNH patients present with advanced HCC, survival outcomes for early stage HCC are similar at SNHs and AMCs. Identifying barriers to early diagnosis at SNH may increase surgical candidacy and improve outcomes.
Habitat and environmental risks of Chagas disease in low-income colonias and peri-urban subdivisions in South Texas

Abstract Both the planning and public health literature have discussed proximity to greenspaces as predominantly beneficial to health, based on studies mostly conducted in high-income regions. Understanding the health risks of proximity to greenspace and nature—where pathogens and wildlife coexist—is important, as nature-based solutions are increasingly called for to address complex urban challenges. This exploratory pilot study bridges planning and epidemiology approaches to develop a new method to analyze habitat and environmental factors associated with the risk of vector-borne Chagas disease in a low-income region, South Texas. Chagas disease is endemic in Latin America, where it affects between seven to eight million people and where environmental factors have been studied to limit the disease's spread. The disease is considered endemic in the southern United States, where little is known about environmental risks. In this pilot study, we developed a new methodology to analyze publicly available habitat and environmental secondary data, which could be used by planning departments. We applied the method to a prior pilot study, which determined a 19.6% prevalence level of T. cruzi (the agent of Chagas disease) among 209 domestic dogs. We geocoded the sample to 100 low-income residential locations, which yielded a 32% positivity rate, and collected secondary data surrounding each location. Logistical regression of factors yielded the following risks: adjacent unconstructed lots, and the presence of four or more dogs in a yard. Based on the results, we formulated vector control-based planning policy recommendations to prevent the spread of the disease.
Integration of a PQ:PMMA holographic memory device into the hybrid opto-electronic correlator for shift, scale, and rotation invariant target recognition

The hybrid optoelectronic correlator (HOC) combines optical and electronic signal processing to achieve the same functionality as traditional optical correlators but without the need for dynamic materials. Here we propose and demonstrate the integration of a PQ:PMMA holographic memory device (HMD) into the HOC as a high-speed all-optical database for reference images. Using a PQ:PMMA HMD for one of the inputs eliminates one of the key speed limitations in the HOC. The observed correlation signal agrees with simulations but highlights the need for high quality holographic substrates in this application.
Data assimilation and uncertainty assessment for complex geological models using a new PCA-based parameterization

In this paper, a recently developed parameterization procedure based on principal component analysis (PCA), which is referred to as optimization-based PCA (O-PCA), is generalized for use with a wide range of geological systems. In O-PCA, the mapping between the geological model in the full-order space and the low-dimensional subspace is framed as an optimization problem. The O-PCA optimization involves the use of regularization and bound constraints, which act to extend substantially the ability of PCA to model complex (non-Gaussian) systems. The basis matrix required by O-PCA is formed using a set of prior realizations generated by a geostatistical modeling package. We show that, by varying the form of the O-PCA regularization terms, different types of geological scenarios can be represented. Specific systems considered include binary-facies, three-facies and bimodal channelized models, and bimodal deltaic fan models. The O-PCA parameterization can be applied to generate random realizations, though our focus here is on its use for data assimilation. For this application, O-PCA is combined with the randomized maximum likelihood (RML) method to provide a subspace RML procedure that can be applied to non-Gaussian models. This approach provides multiple history-matched models, which enables an estimate of prediction uncertainty. A gradient procedure based on adjoints is used for the minimization required by the subspace RML method. The gradient of the O-PCA mapping is determined analytically or semi-analytically, depending on the form of the regularization terms. Results for two-dimensional oil-water systems, for several different geological scenarios, demonstrate that the use of O-PCA and RML enables the generation of posterior reservoir models that honor hard data, retain the large-scale connectivity features of the geological system, match historical production data, and provide an estimate of prediction uncertainty. MATLAB code for the O-PCA procedure, along with examples for three-facies and bimodal models, is included as online Supplementary Material.
College 2.0: An Entrepreneurial Approach to Reforming Higher Education - Overcoming Barriers and Fostering Innovation (Papers from the Entrepreneurship in Higher Education Retreat, December 2011)

A far-reaching discussion is taking place in the United States about the challenges facing higher education and the possible forms postsecondary learning might take in the future. Notwithstanding the strengths of our best research institutions, the shortcomings of many U.S. colleges and universities are significant. There is growing evidence that they need to focus more effectively on student learning, improve completion rates, lower costs, make much better use of technology, boost productivity, improve delivery of instruction for nontraditional students, and take innovations to scale more quickly.To make this happen - and to provide brand-new alternatives to traditional models - a more entrepreneurial approach to postsecondary education is sorely needed. But even as a period of unusual ferment in U.S. higher education gets under way, numerous barriers continue to slow innovation and thwart experimentation, both in traditional institutions and in start-up ventures.In an effort to understand the nature of those barriers and to generate ideas for overcoming them, in December 2011 the Ewing Marion Kauffman Foundation convened a diverse group of analysts and practitioners for a two-day retreat in Palm Beach, Florida. Participants included Shai Reshef, founder of the University of the People; the management editor of The Economist; the founders of startups 2tor, Inc. and StraighterLine; senior leaders of nontraditional universities such as Olin College and Western Governors University; the president and CEO of Kaplan, Inc.; the directors of education policy at the American Enterprise Institute, the Brookings Institution, and the Center for American Progress; and professors who both study and participate in postsecondary reform initiatives.The gathering, part of the Kauffman Foundation’s Law, Innovation and Growth series, was organized into panels addressing six broad themes: Tackling Campus-Level Obstacles to Innovation; Rethinking Accreditation; Streamlining State and Federal Regulations; Improving Incentives to Boost Academic Productivity; Filling Information Gaps about Student-Learning and Job-Market Outcomes; and Overcoming Barriers to Taking Innovation to Scale. The aim was not to limit discussion to these issues, but simply to provide provisional categories that might foster wide-ranging conversation.Each participant prepared a short background paper and presentation linked to one of the retreat’s themes. The resulting essays are collected in this report, organized by theme. (A full list of authors can be found on page 7.) These thoughtful analyses offer a window into how a range of articulate thinkers and doers approach the question of what is wrong with U.S. higher education, and how it ought to be fixed.
SOFTWARE ACCOUNTING POLICY: DOES IT MATTER?

II. PRIOR STUDIES OF THE EFFECT OF CERTAIN ACCOUNTING POLICIES ON BANK LENDING DECISIONS AND STOCK PRICE . . . . . . . . . . . • . . . . . . . . • . . . . . . . . . . . . . • . 706 III. RESULTS OF THE FIRST COMMERCIAL LENDING OFFICER SURVEY. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . • . . . . 709 A. Background . . . . . . . . . . . . . . . . . . . . . . . 709 B. The First Commercial Lending Officer Survey ...... 709 C. Summary and Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . 723
Explanatory model for the break of logic equivalence by irrational agents in Elkan's paradox

Fuzzy logic breaks logic equivalence of statements such as (A∧B)∨(¬A∧B)∨(A∧¬B) and A∨B. It breaks the symmetry of use of such logically equivalent statements. There is a controversy about this property. It is called a paradox (Elkan's paradox) and interpreted as a logical weakness of fuzzy logic. In the opposite view, it is not a paradox but a fundamental postulate of fuzzy logic and one of the sources of its success in applications. There is no explanatory model to resolve this controversy. This paper provides such a model using a vector/matrix logic of rational and irrational agents that covers scalar classical and fuzzy logics. It is shown that the classical logic models rational agents, while fuzzy logic can model irrational agents. Rational agents do not break logic equivalence in contrast with irrational agents. We resolve the paradox by showing that the classical and fuzzy logics have different domains of rational and irrational agents.
Heat and Water Budgets

Net radiation at the upper boundary of the planet Earth amounts to a heat gain in the tropics and a loss in higher latitudes. Redistribution of energy over the continents takes place exclusively in the atmosphere, whereas in the realm of the vast tropical oceans both atmosphere and hydrosphere cooperate in the heat export to other parts of the globe. The partitioning of atmospheric versus oceanic heat transport is of fundamental interest in global energetics. Sea-air interaction processes play an important role in this context. Because of the latent heats involved in phase changes, the continuity of water is directly related to that of energy.
A nonlinear droop method to improve voltage regulation and load sharing in DC systems

It is well-known that load sharing among paralleled sources in dc grid can be achieved by droop control. However, practical factors that influence the load sharing and voltage regulation are seldom discussed, like the sensor discrepancy and cable resistance. In this paper, the impact from cable resistance is analyzed and verified by experiment. To suppress the impact from practical factors, instead of using constant droop resistance, a nonlinear droop method is proposed. In the proposed method, the value of droop resistance is a function of output current. Its value increases when the converter's output current increases. The proposed method needs only the local output current information so the advantage of traditional droop control is preserved. Different second-order droop functions are evaluated and compared. The effectiveness of proposed droop method is verified by simulation and experiment. The experimental result proves the proposed nonlinear droop method has better load sharing at heavy load and tighter bus voltage regulation at light load. The necessary droop voltage range to fully utilize the capacity of paralleled sources is also reduced.
Advanced transport phenomena

Note: Includes bibliography and index Reference Record created on 2004-09-07, modified on 2016-08-08