cssi/SciSciGPT-SciSciNet huggingface dataset:
Suppressors of mdm20 in Yeast Identify New Alleles of ACT1 and TPM1 Predicted to Enhance Actin-Tropomyosin Interactions

The actin cytoskeleton is required for many aspects of cell division in yeast, including mitochondrial partitioning into growing buds (mitochondrial inheritance). Yeast cells lacking MDM20 function display defects in both mitochondrial inheritance and actin organization, specifically, a lack of visible actin cables and enhanced sensitivity to Latrunculin A. mdm20 mutants also exhibit a temperature-sensitive growth phenotype, which we exploited to isolate second-site suppressor mutations. Nine dominant suppressors selected in an mdm20/mdm20 background rescue temperature-sensitive growth defects and mitochondrial inheritance defects and partially restore actin cables in haploid and diploid mdm20 strains. The suppressor mutations define new alleles of ACT1 and TPM1, which encode actin and the major form of tropomyosin in yeast, respectively. The ACT1 mutations cluster in a region of the actin protein predicted to contact tropomyosin, suggesting that they stabilize actin cables by enhancing actin-tropomyosin interactions. The characteristics of the mutant ACT1 and TPM1 alleles and their potential effects on protein structure and binding are discussed.
Ages at menopause and menarche in a high-altitude Himalayan population

Women in a Tibetan speaking population living at 3250-3560 m in Upper Chumik, Nepal, have median ages at menopause and menarche of 46.8 and 16.2 years, respectively, assessed by the status quo technique. Recalled ages at menopause and menarche yield similar results and suggest a long-term existence of a pattern of relatively accelerated age at menopause and delayed age at menarche. Variation in the length of the calculated biological reproductive span in this sample is more strongly associated with recalled age at menopause than recalled age at menarche. The age at menopause in Upper Chumik is accelerated relative to that reported for Western industrial populations; however, these data do not permit drawing conclusions about the reasons underlying the acceleration.
Potential Role of Endotoxin as a Proinflammatory Mediator of Atherosclerosis

Atherosclerosis is increasingly recognized as a chronic inflammatory disease. Although a variety of inflammatory markers (ie, C-reactive protein) have been associated with atherosclerosis and its consequences, it is important to identify principal mediators of the inflammatory responses. One potentially important source of vascular inflammation in atherosclerosis is bacterial endotoxin. Mutations in Toll-like receptor 4 (TLR-4), an integral component of the endotoxin signaling complex, are fairly common in the Caucasian population and have recently been associated with reduced incidence of atherosclerosis and other cardiovascular diseases in some studies. Moreover, epidemiological studies suggest that endotoxemia at levels as low as 50 pg/mL constitutes a strong risk factor for the development of atherosclerosis. Endotoxin concentrations in this range may be produced by a variety of common subclinical Gram-negative infections. In this article, we outline the main elements of the endotoxin signaling receptor complex that initiates proinflammatory signaling (lipopolysaccharide binding protein [LBP], CD14, TLR-4, and MD-2) and discuss how changes in expression of these molecules may affect proatherogenic responses in the vessel wall. We also describe some of the proinflammatory effects of endotoxin that may be relevant to atherosclerosis, and discuss how serum lipoproteins, especially high-density lipoprotein, may modulate endotoxin-induced inflammatory responses. Further, we discuss recent findings suggesting that the lipid-lowering statins may have an additional protective role in blocking at least some of these proinflammatory signaling pathways. Finally, we discuss species diversity with regard to endotoxin signaling that should be considered when extrapolating experimental data from animal models to humans.
Design Structure Matrices to Improve Decentralized Urban Transportation Systems

Managing large, complex urban transportation systems involves numerous stakeholders because of decentralized ownership and operation of distinct pieces of the physical network and services. To deliver better service to users, many urban regions are adopting technological and operational solutions, both of which necessitate interaction among the decentralized organizations. This research applies systems engineering analysis techniques—design structure matrix and clustering—to improve efficiency and effectiveness of organizational interactions between agencies as they deploy intelligent transportation systems (ITS) and attempt to integrate their operations. Specifically, this paper examines the application of clustering to the institutional structure set forth by the regional ITS architecture for metropolitan Seattle, Washington. Clustering of Seattle area organizations noted previously unidentified multilateral relationships that offer potential for more efficient interagency interactions and, ultimately b...
Predator discrimination and ‘personality’ in captive Vancouver Island marmots (Marmota vancouverensis)

A major impediment to recovering declining populations successfully is the mortality of reintroduced or translocated animals. We generally assume that captive-born animals may lose their antipredator behaviour abilities in captivity, but studies rarely compare predator recognition abilities of captive-born and wildcaptured animals to test this. To identify whether predator discrimination abilities of the critically endangered Vancouver Island marmots Marmota vancouverensis were lost in captivity, we presented wild-captured and captive-born marmots with taxidermic mounts of predators (a cougar Felis concolor and wolf Canis lupus) together with control stimuli (marmot, domestic goat Capra aegagrus, the cart on which all stimuli were presented and a ‘blank’ no-stimulus control). Regardless of specific predator discrimination abilities, for some species overall ‘personality’ may be associated with response to predators and subsequent survival. Thus, to quantify overall reactivity in the presence of a predator, we also conducted a mirror-image stimulus (MIS) presentation experiment where marmots were videorecorded with or without the presence of a wolf. Marmots discriminated among these stimuli, responding the most to the wolf and cougar. The MIS results suggest that marmots varied along a continuum of reactivity. The amount of reactivity was unaffected by the presence of a wolf, and was correlated with our highest level of responsiveness (vigilance at the burrow and time within the burrow) to the wolf. Taken together, we conclude that marmots differentiate predators from nonpredators and that this ability has not been lost under the conditions in which they have been reared.
Pralatrexate alone or in combination with bexarotene: long-term tolerability in relapsed/refractory mycosis fungoides.

Abstract Background This study aimed to assess the long-term tolerability of pralatrexate alone or in combination with oral bexarotene for relapsed or refractory mycosis fungoides (MF). Patients and Methods Patients with MF in this report were participants in 1 of 2 multicenter trials. During the dose-ranging phase I/II study, participants were treated with pralatrexate alone for 3 of 4 weeks. During a second phase I/II dose-ranging combination trial, participants were treated with pralatrexate at 15 mg/m 2 /wk for 3 of 4 weeks combined with 150 to 300 mg/m 2 of daily oral bexarotene. Results Twenty-six patients were enrolled at our center, including 12 receiving pralatrexate and 14 receiving pralatrexate plus bexarotene. Four of 12 patients (33%) treated with pralatrexate alone responded. Of 14 patients treated with bexarotene plus pralatrexate, 7 (50%) responded. Ten participants, with a median age of 71 years (range, 41-82 years), received more than 9 cycles of pralatrexate, including 3 receiving pralatrexate and 7 receiving combination therapy. Median time to response was 15.75 weeks (range, 4-24 weeks), and the median duration of response was 26.75 weeks (range, 8.5-49.5 weeks). The most common adverse event (AE) was mucositis in 8 (80%) patients. Other AEs of any grade included arthralgias (n = 1), headache (n = 1), neutropenia (n = 5), and skin necrosis (n = 2). Two patients initially had lower leg tumors that responded to therapy, leaving residual chronic leg ulcers. Conclusion Pralatrexate alone or in combination with low-dose oral bexarotene is well tolerated and capable of providing long-term responses in patients of advanced age with advanced-stage MF.
Stratocumulus-Topped Atmospheric Planetary Boundary Layer

Marine stratocumulus often occurs over the subtropical oceans off the west coasts of the major continents throughout most of the summertime season when the large-scale subsiding motion is strong and the ocean surface is cold. This large-scale condition leads to a very moist, shallow planetary boundary layer (PBL). The lifting condensation level is below the top of the mixed layer, so an uniform layer of cloud can form in the upper part of the PBL.
Compaction of Cohesionless Foundation Soils by Explosives

The method of compacting loose, cohesionless foundation soils in their natural state by detonating buried charges of explosives has been used successfully at Franklin Falls Dam, Denison Dam, and Al...
Insights into the Neural and Genetic Basis of Vocal Communication

The use of vocalizations to communicate information and elaborate social bonds is an adaptation seen in many vertebrate species. Human speech is an extreme version of this pervasive form of communication. Unlike the vocalizations exhibited by the majority of land vertebrates, speech is a learned behavior requiring early sensory exposure and auditory feedback for its development and maintenance. Studies in humans and a small number of other species have provided insights into the neural and genetic basis for learned vocal communication and are helping to delineate the roles of brain circuits across the cortex, basal ganglia, and cerebellum in generating vocal behaviors. This Review provides an outline of the current knowledge about these circuits and the genes implicated in vocal communication, as well as a perspective on future research directions in this field.
(Na+,K+)-activated adenosinetriphosphatase and hypertension in DAHL salt- sensitive and -resistant rats.

(Na+K+)-ATPase activity was compared in Dahl salt-sensitive (S) and salt-resistant (R) rats. When S and R rats were maintained on 1% NaCl diet their blood pressures at 5 weeks of age were similar and their renal micro-somal (Na+K+)-ATPase activities were also similar. At 6 months of age, on 1% NaCl diet, S rats have markedly elevated blood pressure compared to R and renal microsomal (Na+K+)-ATPase activity was suppressed in S compared to R. Feeding 8% NaCl diet for 5 weeks induced hypertension in young S rats but failed to alter renal or brain (Na+K+)-ATPase activity. Heart (Na+K+)-ATPase activity was elevated in S compared to R rats regardless of salt intake or blood pressure. It appears unlikely that mutations in the structural locus for the renal (Na+K+)-ATPase molecule are involved in the strain specific differences in susceptibility to salt-induced hypertension since the physical-chemical properties of the enzyme from the two strains were found to be similar. Since renal (Na+K+)-ATPase activities wer...
760PDNEUROENDOCRINE PROSTATE CANCER (NEPC) IN PATIENTS (PTS) WITH METASTATIC CASTRATION RESISTANT PROSTATE CANCER (MCRPC) RESISTANT TO ABIRATERONE (ABI) OR ENZALUTAMIDE (ENZ): PRELIMINARY RESULTS FROM THE SU2C/PCF/AACR WEST COAST PROSTATE CANCER DREAM TEAM (WCDT)

ABSTRACT Aim: The mechanisms of resistance to androgen signaling inhibitors such as Abi or Enz are poorly understood. A growing proportion of these pts are developing treatment resistant NEPC. Progressive mCRPC has historically been challenging to biopsy and characterize on a molecular basis because of its bone tropism. As part of the WCDT project, which aims to identify genetic pathways underlying primary and acquired resistance to Abi and Enz, RNA sequencing (RNAseq) was used to develop a NEPC expression signature in mCRPC biopsies. Methods: Following central radiologic review, eligible mCRPC pts underwent a metastasis (met) biopsy at one of 5 WCDT clinical sites, using a uniform biopsy protocol. Tissue was both frozen, and formalin fixed/paraffin embedded (FFPE). Frozen specimens underwent laser capture micro-dissection, RNA isolation, library preparation and RNAseq. Machine learning was used to derive NEPC markers from mCRPC adenocarcinoma and met NEPC RNAseq data. FFPE tissue was evaluated histologically, including NEPC markers. Results: 85 of 300 planned mCRPC pts have undergone a met biopsy. To date, 53 specimens have been evaluated histologically. Histologically identified NEPC was present in 17 (32%) of biopsies overall, 12% of bone biopsies, 64% of lymph nodes, and 27% of liver biopsies. To date RNAseq data are available on 20 pts, including 6 with NEPC. A106 gene signature for met NEPC was developed from this learning set. Conclusions: Genomic sequencing and expression analysis can be accomplished in small bone and soft tissue mCRPC biopsies. The development of NEPC is a common event in mCRPC resistant to ABi or Enz. The majority of liver metastases are not NEPC. A 106 gene signature was derived from this met NEPC learning set and has identified a number of genes that provide insight into the biology and potential treatment of NEPC. Disclosure: All authors have declared no conflicts of interest.
Synthesis and Ring Structure of 7-Acetamido-7-deoxy-L-galacto-heptulose.

7-Acetamido-7-deoxy-L-galacto-heptulose was prepared by oxidation of l-acetamido-l-deoxy-D-glycero-D-galacto-heptitol with Acetobacter suboxydans. The new acetamido-deoxy-L-heptulose was shown to be a pyranose by comparison with β-D-fructopyranose. The following equations represent the optical rotation of 7-acetamido-7-deoxy-α-L-galacto-heptulopyranose in water at 20 °C and 3.5 °C, respectively: [ α ] 20 D = - 15.5 e - .0396 t - 97.1 , [ α ] 3.5 D = - 11.9 e - .0101 t - 105.8 where t is the time in minutes after dissolution of the sample.
Diode Laser Absorption Spectroscopy Measurements in a Gaseous Hydrogen / Oxygen Rocket

Tunable diode laser absorption spectroscopy (TDLAS) has been used to make pathintegrated temperature measurements in a gaseous oxygen / gaseous hydrogen uni-element rocket chamber with hot background flow. Four mixture conditions were studied at a nominal chamber pressure of 100 psia. Near infrared diode lasers were utilized to target rovibrational transitions of water vapor combustion product. Both direct absorption spectroscopy and wavelength modulation spectroscopy with second harmonic normalized by first harmonic (1f-normalized WMS-2f) techniques were applied, with the harmonic detection technique found to yield the best results. Illustrative examples of time-resolved measurements of temperature in the rocket chamber are presented.
Technology, Ideology, and Societal Development:

To address the question of whether ideology or technology has been the more powerful force shaping societies and their development, log-linear models are used to assess the association of typologie...
Marilyn E. Phelan. Museum Law: A Guide for Officers, Directors, and Counsel. 4th edition. Lanham: Rowman & Littlefield Publishers, 2014. 514 p. ISBN 978-0759124349. $95

Museum Law: A Guide for Officers, Directors, and Counsel , 4th edition, by Marilyn E. Phelan, provides relevant and useful information for professionals in museum administration. The fourth edition is structured into three parts, a change in organization from past editions, which had topics grouped into chapters. The three parts in the current edition are “Operations,” “Museum Collections,” and “Heritage.” Within each part are multiple sections with which readers of past editions would be familiar; however, some topics have been rearranged, allowing for better organization. This edition is also improved by placing all citations and notes at the end of chapters . . .
Excellence Redefined for the 21st Century

Based on the perspectives of our symposium contributors, certain twenty-first century themes have become increasingly important in a global economy: 1) individuality; 2) connectedness; and 3) non-cognitive attributes. Individuals are asserting their influence in ways never seen before, thanks in part to technology and democracy. The innovators aren’t doing it alone ironically; they are collaborating, or connecting, with like-minded peers and thinking across disciplines. They also possess certain non-cognitive attributes like motivation, perseverance, and adaptability that employers are increasingly looking for. Recognizing these three themes and their place in education is, therefore, critical to twenty-first century excellence. In this concluding article, the author illuminates each theme and offers a more fitting education approach that hopefully reflects an evolved perspective since A Nation at Risk was first published.
Posterior Distal Clavicle Beveling for Chronic Nonincarcerated Type IV Acromioclavicular Separations: Surgical Technique and Early Clinical Outcomes.

Purpose To describe the arthroscopic partial posterior distal clavicle beveling technique for treatment of chronic nonincarcerated type IV acromioclavicular (AC) separations and report clinical outcomes and return to sport. Methods All patients who underwent the arthroscopic partial distal clavicle beveling technique and met eligibility criteria were identified and retrospectively reviewed. Inclusion criteria included the clinical diagnosis of a chronic nonincarcerated type IV AC separation and a minimum follow-up period of 24 months. Subjects completed the American Shoulder Elbow Surgeons shoulder assessment and a study-designed questionnaire. Radiographic images and clinical charts were also reviewed. Results This study identified 15 consecutive patients with 2 lost to follow-up, resulting in inclusion of 13 subjects (9 males and 4 females). Dominant arm was involved in 77% of cases. Mean age at operation was 33.2 years (range, 19-56 years). The mean period between injury and operation was 12.5 months (range, 3-37 months), and follow-up was 48.5 months (range, 24-126 months). The mean preoperative ASES score was 46.6 ± 16.9 (range, 33-68), and the mean postoperative ASES score was 87.3 ± 17.4 (range, 50-100) ( P Conclusions The arthroscopic partial distal clavicle beveling procedure for nonincarcerated type IV AC separations resulted in a significant reduction in pain, improved daily function, and early return to sport. Level of Evidence Level IV, therapeutic case series.
Intergrating the Concept of Marketing: The Environment-Organization Marketing Interface

Underlying market theory and practice is the neoclassical economic paradigm. The firm is viewed as a rational, profit maximizing entity which operates in a closed system, akin to Emery and Trist’s (1965) placid-randomized environment. Profit maximization is indicated to be accomplished through emphasizing consumer sovereignty (the marketing concept). The tradition, however, represents unrealistic behavioral assumptions which fail to capture the complexity and dynamic nature of the modern organization-environment interaction (see Cyert and March 1963).
Memory and Countermemory: For an Open Future

Something fundamentally new is taking place in forms of memorialization that impacts post-Holocaust, trauma, postcolonial, and post-Wall (1989) research on memory by creating shared transdisciplinary spaces for conversations.
Comparison of Sterile vs Nonsterile Gloves in Cutaneous Surgery and Common Outpatient Dental Procedures: A Systematic Review and Meta-analysis

Importance Whether the use of sterile vs nonsterile gloves in outpatient cutaneous procedures affects the rate of postoperative wound infection is unknown. Objective To explore rates of surgical site infection (SSI) with the use of sterile vs nonsterile gloves in outpatient cutaneous surgical procedures. Data Sources This systematic review and meta-analysis identified studies from Ovid MEDLINE (1946 to present), Ovid Cochrane Central Register of Controlled Trials (1991 to present), Ovid EMBASE (1988 to present), EBSCO Cumulative Index to Nursing and Allied Health Literature (1980 to present), Scopus (1996 to present), and Web of Science (1975 to present). Study Selection Studies with information on sterile vs nonsterile gloves in outpatient surgical procedures were retrieved. Only randomized clinical trials and comparative studies were included for final analysis. Data Extraction Data of trial design, surgery characteristics, and outcomes from published manuscripts and unpublished data were independently extracted. Main Outcomes and Measures Randomized clinical trials were considered high quality if randomization, allocation concealment, blinding, and follow-up completeness were appropriate. Relative risk and 95% CIs were derived for postoperative wound infections. Results Fourteen articles met eligibility and inclusion criteria for systematic review; they included 12 275 unique patients who had undergone 12 275 unique outpatient procedures with sterile or nonsterile gloves and had follow-up regarding SSI. With the exclusion of 1 single-arm observational study of 1204 patients, 11 071 patients from 13 studies remained in the meta-analysis. Of these, 228 patients were documented as having postoperative SSI (2.1%), including 107 of 5031 patients in the nonsterile glove group (2.1%) and 121 of 6040 patients in the sterile glove group (2.0%). Overall relative risk for SSI with nonsterile glove use was 1.06 (95% CI, 0.81-1.39). Conclusions and Relevance No difference was found in the rate of postoperative SSI between outpatient surgical procedures performed with sterile vs nonsterile gloves.
Energy band alignment of high-k oxide heterostructures at MoS2/Al2O3 and MoS2/ZrO2 interfaces

Substrate-induced electron energy band alignments of ultrathin molybdenum disulfide (MoS2) films are investigated using photoemission spectroscopy. Thin layer MoS2/Al2O3 and MoS2/ZrO2 interfaces show valence band offset (VBO) values of 3.21 eV and 2.77 eV, respectively. The corresponding conduction-band offset (CBO) values are 3.63 eV and 1.27 eV. Similarly, the calculated VBO and CBO values for an ultrathin layer of MoS2/SiO2 are estimated to be 4.25 and 2.91 eV, respectively. However, a very thick layer of MoS2 on Al2O3 and ZrO2 layers increases the CBO and VBO values by 0.31 eV and 0.2 eV, respectively, due to the shifting of the Mo 4dz2 band toward the Fermi level. The atomic force microscopy images show that the films are atomically smooth and favor the formation of a high-quality interface between the substrate and the film. The investigated luminescence spectra reveal that the MoS2 films show very strong interactions with different high-k surfaces, whereas the Raman spectrum is only weakly influenc...
Principles of Cancer Rehabilitation

The central tenet of cancer rehabilitation is to help cancer patients and survivors regain and improve their physical, psychosocial, and vocational functioning within the limitations imposed by the disease and its treatment. As the number of survivors have increased dramatically over the last 20 years, issues related to quality of life (QoL) and function have become increasingly important. Many of the toxicities and complications of cancer and its treatment can be mitigated by rehabilitation interventions. This review outlines the role of rehabilitation in a number of common cancer rehabilitation challenges, including cancer-related fatigue, lymphedema, and peripheral neuropathy.
Push-and-Pull (MRP-JIT) Systems

This chapter covers detailed production planning methods when product demands are known. The two most important production planning approaches are push systems (known as materials requirement planning, MRP) and pull systems (known as just-in-time, JIT). Figure 5.1 presents an overview of the production planning process as related to MRP and/or JIT. Production planning is performed by using information from the master production schedule (MPS), the product processing plan, bills of material (BOMs), available inventory, outstanding purchase orders, and lead times for components (items) of the product.
High post-natal mortality associated with defects in lung maturation and reduced adiposity in mice with gestational exposure to high fat and N-acetylcysteine☆

Studies have demonstrated that maternal consumption of a high fat diet (HFD) increases offspring susceptibility to metabolic disease. This study was initiated to identify the mechanistic contribution of oxidative stress on this phenomenon. Two weeks prior to mating, dams were fed either HFD or Control diet with or without supplementation with the anti-oxidant N-acetylcysteine (NAC). Pups born to HFD dams had reduced crown rump length (CRL) at birth and higher neonatal mortality compared to pups from Control dams. Supplementation with NAC normalized CRL in pups from HFD dams, but notably increased mortality. Histological examination of the lungs postnatally and prenatally, revealed normal branching morphogenesis but delayed alveolarization in pups from dams fed HFD+NAC. Discontinuation of NAC at ED17.5 with re-introduction at PD3 improved offspring survival and lung maturation. Additionally, interscapular brown adipose tissue (BAT) was reduced in ED18.5 embryos from HFD dams. These findings suggest that increased mortality in offspring from dams fed HFD+NAC during pregnancy may in part be the result of delayed pulmonary alveolarization and decreased BAT.
Diurnal cortisol slopes and mental and physical health outcomes: A systematic review and meta-analysis

Changes in levels of the stress-sensitive hormone cortisol from morning to evening are referred to as diurnal cortisol slopes. Flatter diurnal cortisol slopes have been proposed as a mediator between chronic psychosocial stress and poor mental and physical health outcomes in past theory and research. Surprisingly, neither a systematic nor a meta-analytic review of associations between diurnal cortisol slopes and health has been conducted to date, despite extensive literature on the topic. The current systematic review and meta-analysis examined associations between diurnal cortisol slopes and physical and mental health outcomes. Analyses were based on 179 associations from 80 studies for the time period up to January 31, 2015. Results indicated a significant association between flatter diurnal cortisol slopes and poorer health across all studies (average effect size, r=0.147). Further, flatter diurnal cortisol slopes were associated with poorer health in 10 out of 12 subtypes of emotional and physical health outcomes examined. Among these subtypes, the effect size was largest for immune/inflammation outcomes (r=0.288). Potential moderators of the associations between diurnal cortisol slopes and health outcomes were examined, including type of slope measure and study quality indices. The possible roles of flatter slopes as either a marker or a mechanism for disease etiology are discussed. We argue that flatter diurnal cortisol slopes may both reflect and contribute to stress-related dysregulation of central and peripheral circadian mechanisms, with corresponding downstream effects on multiple aspects of biology, behavior, and health.
The scope of thromboembolism.

Why, the question may be appropriately asked, should there be, in 1986, a 3-day symposium on warfarin prophylaxis—a drug, after all, that was introduced into clinical medicine 45 years ago?
Blood from the Sky: Miracles and Politics in the Early American Republic

Early nineteenth-century Americans might not have lived in the “world of wonders” of their seventeenth-century forbears, argues Adam Jortner, associate professor of history at Auburn University, bu...
A hybrid gene selection approach to create the S1500+ targeted gene sets for use in high-throughput transcriptomics.

Changes in gene expression can help reveal the mechanisms of disease processes and the mode of action for toxicities and adverse effects on cellular responses induced by exposures to chemicals, drugs and environment agents. The U.S. Tox21 Federal collaboration, which currently quantifies the biological effects of nearly 10,000 chemicals via quantitative high-throughput screening(qHTS) in in vitro model systems, is now making an effort to incorporate gene expression profiling into the existing battery of assays. Whole transcriptome analyses performed on large numbers of samples using microarrays or RNA-Seq is currently cost-prohibitive. Accordingly, the Tox21 Program is pursuing a high-throughput transcriptomics (HTT) method that focuses on the targeted detection of gene expression for a carefully selected subset of the transcriptome that potentially can reduce the cost by a factor of 10-fold, allowing for the analysis of larger numbers of samples. To identify the optimal transcriptome subset, genes were sought that are (1) representative of the highly diverse biological space, (2) capable of serving as a proxy for expression changes in unmeasured genes, and (3) sufficient to provide coverage of well described biological pathways. A hybrid method for gene selection is presented herein that combines data-driven and knowledge-driven concepts into one cohesive method. Our approach is modular, applicable to any species, and facilitates a robust, quantitative evaluation of performance. In particular, we were able to perform gene selection such that the resulting set of “sentinel genes” adequately represents all known canonical pathways from Molecular Signature Database (MSigDB v4.0) and can be used to infer expression changes for the remainder of the transcriptome. The resulting computational model allowed us to choose a purely data-driven subset of 1500 sentinel genes, referred to as the S1500 set, which was then augmented using a knowledge-driven selection of additional genes to create the final S1500+ gene set. Our results indicate that the sentinel genes selected can be used to accurately predict pathway perturbations and biological relationships for samples under study.
Do CRISPR Germline Ethics Statements Cut It

Abstract The extraordinary wave of genomic-engineering innovation, driven by CRISPR-Cas9, has sparked worldwide scientific and ethical uncertainty. Great concern has arisen across the globe about whether heritable genome editing should be permissible in humans—that is, whether it is morally acceptable to modify genomic material such that the “edit” is transferable to future generations. Here I examine 61 ethics statements released by the international community within the past 3 years about this controversial issue and consider the statements' overarching positions and limitations. Despite their inability to fully address all important considerations, many of the statements may advance debate and national and international law and public policy.
Identification of avian vasotocin receptor subtype-specific antagonists involved in the stress response of the chicken, Gallus gallus.

Vasotocin 1a and 1b receptors (V1aR and V1bR) have been shown to play important roles in the neuroendocrine regulation of stress responses via the anterior pituitary (AP) of birds. To identify effe...
Animal Models in the Understanding of Human Disease

In disorders such as hypertension, animal studies have contributed to knowledge about the psychosocial as well as the physiological causes. Studies with gastric erosion in rats have provided a model for the study of how psychological processes influence the severity of disease.
Implicit negative link detection on online political networks via matrix tri-factorizations

ABSTRACTPolitical conversations have become a ubiquitous part of social media. When users interact and engage in discussions, there are usually two mediums available to them; textual conversations ...
A Late Glacial Readvance Moraine in the Central Chilean Fjords

During the 1993 cruise of R/V Polar Duke, seismic data were collected from Seno De Las Montanas (Fig. 1), a fjord that is isolated from outflow of the South Patagonia Ice Cap by a prominent bedrock ridge and contains significant deposits from late glacial readvances which flowed into the fjord from the south.
Other Genetic Syndromes (TSC, VHL, NF1, etc.)

Neuroendocrine tumors (NETs) are the main feature of a few hereditary cancer syndromes, classically Multiple Endocrine Neoplasias. In this chapter, other rare cancer syndromes that may display NETs as a part of the syndrome’s ­phenotype repertoire are reviewed. In some of them, such as pheochromocytoma-­paraganglioma, the presence of NET is crucial for the syndrome diagnosis. In others, such as von Hippel Lindau or Neurofibromatosis, NETs are found in a minorirty of the cases, but their frequency is much higher than seen in the general population, which means that NETs can be the tip of the iceberg of a hereditary cancer syndrome in these families.
Editing the Epigenome to Tackle Brain Disorders

Genetic studies of epigenetic modifiers such as DNA methyltransferases and histone acetyltransferases have revealed a critical role for epigenetic regulation during brain development and function. Alteration of epigenetic modifications have been documented in a variety of brain disorders, including neurodevelopmental, psychiatric, and neurodegenerative diseases. Development of epigenome editing tools enables a functional dissection of the link between altered epigenetic changes and disease outcomes. Here, we review the development of epigenome editing tools, summarize proof of concept applications focusing on brain disease-associated genes, and discuss the promising application and challenges of epigenome editing to tackle brain disorders.
Perceived Applicability of a Big Five Personality Inventory for Computers

Anthropomorphism is the assignment of human traits to the behavior of computers. This may occur because humans are projecting their own mind onto the device. To measure this requires a direct compa...
The Incorporation of Surgical Education into Clinical Practice

A central and hugely gratifying pillar of academic surgery is the education of learners across multiple tiers of training. Surgical training is in continuous evolution. Traditional surgical education placed emphasis on (1) obtaining information about diseases and (2) the development of technical abilities by primarily observation and by then operating on patients. The changing landscape of surgery that increasingly emphasizes quality and patient-centered care with shared decision making coupled with growing technology, educational aids (e.g., simulation) and the incorporation of ‘adult learning’ methods have defined modern surgical training as the ‘production of competent surgeons that display cognitive, technical and personal skills required to meet the needs of society’ [1]. It is no surprise that the meaningful incorporation of surgical students, residents, and fellows into clinical practice requires a sincere commitment, time, advanced planning, and system level support. This chapter proposes lessons for their efficient, safe, effective training, and mentorship while also offering current opportunities for professional educational development.
Glutathione-responsive biodegradable polyurethane nanoparticles for lung cancer treatment.

Lung cancer is one of the major causes of cancer-related deaths worldwide. Stimuli-responsive polymers and nanoparticles, which respond to exogenous or endogenous stimuli in the tumor microenvironment, have been widely investigated for spatiotemporal chemotherapeutic drug release applications for cancer chemotherapy. We developed glutathione (GSH)-responsive polyurethane nanoparticles (GPUs) using a GSH-cleavable disulfide bond containing polyurethane that responds to elevated levels of GSH within lung cancer cells. The polyurethane nanoparticles were fabricated using a single emulsion and mixed organic solvent method. Cisplatin-loaded GSH-sensitive nanoparticles (CGPU) displayed a GSH-dose dependent release of cisplatin. In addition, a significant reduction in in vitro survival fraction of A549 lung cancer cells was observed compared to free cisplatin of equivalent concentration (survival fraction of ~0.5 and ~0.7, respectively). The in vivo biodistribution studies showed localization of fluorescently labeled GPUs (~7% of total injected dose per gram tissue) in the lung tumor regions after mouse-tail IV injections in xenograft A549 lung tumor models. The animals exposed to CGPUs also exhibited the inhibition of lung tumor growth compared to animals administered with saline (tumor growth rate of 1.5 vs. 13 in saline) and free cisplatin (tumor growth rate of 5.9) in mouse xenograft A549 lung tumor models within 14 days. These nanoparticles have potential to be used for on-demand drug release for an enhanced chemotherapy to effectively treat lung cancer.
Methods, Recruitment, and Sampling in Research with LGBTQ-Parent Families

In this chapter, we consider the methodological needs of the field of LGBTQ-parent families. Our goal with this chapter is to engage in a transparent discussion of the methods used in LGBTQ-parent research—a discussion often reduced to a few sentences in journal publications. Currently, the field has two main methodological-related endeavors. The first is the dedication to the further inclusion of underrepresented populations in LGBTQ-parent research. The second is the need for more nationally representative research. In this chapter, we put forward ideas for improving measurement, thoroughly discuss methods and recruitment strategies that hold promise for including traditionally underrepresented populations in LGBTQ-parent research, and discuss pros and cons of different sampling methods in studying LGBTQ-parent families. We end the chapter with recommendations for future methodological endeavors from LGBTQ-parent scholars and a summary of the practical implications of methodological issues.
Improved contrast and noise of megavoltage computed tomography (MVCT) through cycle-consistent generative machine learning.

Purpose Megavoltage computed tomography (MVCT) has been implemented on many radiation therapy treatment machines as a tomographic imaging modality that allows for three-dimensional visualization and localization of patient anatomy. Yet MVCT images exhibit lower contrast and greater noise than its kilovoltage CT (kVCT) counterpart. In this work, we sought to improve these disadvantages of MVCT images through an image-to-image based machine learning transformation of MVCT and kVCT images. We demonstrated that by learning the style of kVCT images, MVCT images can be converted into high quality synthetic kVCT (skVCT) images with higher contrast and lower noise, when compared to the original MVCT. Methods kVCT and MVCT images of 120 head and neck (H&N) cancer patients treated on an Accuray TomoHD system were retrospectively analyzed in this study. A cycle-consistent generative adversarial network (CycleGAN) machine learning, a variant of the generative adversarial network (GAN), was used to learn Hounsfield Unit (HU) transformations from MVCT to kVCT images, creating skVCT images. A formal mathematical proof is given describing the interplay between function sensitivity and input noise and how it applies to the error variance of a high-capacity function trained with noisy input data. Finally, we show how skVCT shares distributional similarity to kVCT for various macro-structures found in the body. Results Signal to noise ratio (SNR) and contrast to noise ratio (CNR) were improved in skVCT images relative to the original MVCT images and were consistent with kVCT images. Specifically, skVCT CNR for muscle - fat, bone - fat and bone - muscle improved to 14.8 ± 0.4, 122.7 ± 22.6, and 107.9 ± 22.4 compared with 1.6 ± 0.3, 7.6 ± 1.9, and 6.0 ± 1.7, respectively, in the original MVCT images and was more consistent with kVCT CNR values of 15.2 ± 0.8, 124.9 ± 27.0, and 109.7 ± 26.5, respectively. Noise was significantly reduced in skVCT images with SNR values improving by roughly an order of magnitude and consistent with kVCT SNR values. Axial slice mean (S-ME) and mean absolute error (S-MAE) agreement between kVCT and MVCT/skVCT improved, on average, from -16.0 and 109.1 HU to 8.4 and 76.9 HU, respectively. Conclusions A kVCT-like qualitative aid was generated from input MVCT data through a CycleGAN instance. This qualitative aid, skVCT, was robust towards embedded metallic material, dramatically improves HU alignment from MVCT, and appears perceptually similar to kVCT with SNR and CNR values equivalent to that of kVCT images.
Challenges and opportunities of building an entrepreneurial discovery process through university–industry interaction: A Norwegian case study:

This study provides new insights into the entrepreneurial role of universities in an entrepreneurial discovery process. Over the past decades, European policies have encouraged universities to iden...
Foresight: Analysis That Matters for Data Reduction

As the computation power of supercomputers increases, so does simulation size, which in turn produces orders-of-magnitude more data. Because generated data often exceed the simulation’s disk quota, many simulations would stand to benefit from data-reduction techniques to reduce storage requirements. Such techniques include autoencoders, data compression algorithms, and sampling. Lossy compression techniques can significantly reduce data size, but such techniques come at the expense of losing information that could result in incorrect post hoc analysis results. To help scientists determine the best compression they can get while keeping their analyses accurate, we have developed Foresight, an analysis framework that enables users to evaluate how different data-reduction techniques will impact their analyses. We use particle data from a cosmology simulation, turbulence data from Direct Numerical Simulation, and asteroid impact data from xRage to demonstrate how Foresight can help scientists determine the best data-reduction technique for their simulations.
Corset Autodermis External Obliqueplasty Reinforcement of Rectus Diastasis and Umbilical Hernia Repairs during Abdominoplasty.

SUMMARY Abdominoplasty is among the most commonly performed aesthetic operations and is frequently combined with rectus abdominis musculoaponeurotic plication of rectus diastasis and repair of umbilical and ventral hernias. The authors present a spare parts technique to assist in reinforcement of both rectus diastasis plication and hernia repair during abdominoplasty operations using an autodermis onlay reinforcement graft. The graft is harvested from the excess abdominal pannus normally discarded during abdominoplasty and is inset on tension between the bilateral semilunar lines and plicated along a concave "corset" contour. This reduces distracting forces on the hernia and diastasis repairs and further augments abdominal contour. This technique has been performed for 8 years on 82 low-surgical-risk patients, without any noted increase in complications. The corset autodermis external obliqueplasty is a spare parts technique that may reduce recurrence of rectus diastasis and abdominal hernias repaired at the time of abdominoplasty and is an alternative strategy to mesh placement in this risk-averse aesthetic surgery population.
A mechanistic survey of Alzheimer's disease

Abstract Alzheimer's disease (AD) is the most common, age-dependent neurodegenerative disorder. While AD has been intensively studied from different aspects, there is no effective cure for AD, largely due to a lack of a clear mechanistic understanding of AD. In this mini-review, we mainly focus on the discussion and summary of mechanistic causes of Alzheimer's disease (AD). While different AD mechanisms illustrate different molecular and cellular pathways in AD pathogenesis, they do not necessarily exclude each other. Instead, some of them could work together to initiate, trigger, and promote the onset and development of AD. In a broader viewpoint, some AD mechanisms (e.g., amyloid aggregation mechanism, microbial infection/neuroinflammation mechanism, and amyloid cross-seeding mechanism) could also be applicable to other amyloid diseases including type II diabetes, Parkinson's disease, and prion disease. Such common mechanisms for AD and other amyloid diseases explain not only the pathogenesis of individual amyloid diseases, but also the spreading of pathologies between these diseases, which will inspire new strategies for therapeutic intervention and prevention for AD.
IPC driven dynamic associative cache architecture for low energy

Existing schemes for cache energy optimization incorporate a limited degree of dynamic associativity: either direct mapped or full available associativity (say 4-way). In this paper, we explore a more general design space for dynamic associativity (for a 4-way associative cache, consider 1-way, 2-way, and 4-way associative accesses). The other major departure is in the associativity control mechanism. We use the actual instruction level parallelism exhibited by the instructions surrounding a given load to classify it as an IPC k load (for 1/spl les/k/spl les/IW with an issue width of IW) in a superscalar architecture. The lookup schedule is fixed in advance for each IPC classifier 1/spl les/k/spl les/IW. The schedules are as way-disjoint as possible for load/stores with different IPC classifications. The energy savings over SPEC2000 CPU benchmarks average 28.6% for a 32 kB, 4-way, L-1 data cache. The resulting performance (IPC) degradation from the dynamic way schedule is restricted to less than 2.25%, mainly because IPC based placement ends up being an excellent classifier.
Computing array shapes in MATLAB

This paper deals with the problem of statically inferring the shape of an array in languages such as MATLAB. Inferring an array's shape is desirable because it empowers better compilation and interpretation; specifically, knowing an array's shape could permit reductions in the number of run-time array conformability checks, enable memory preallocation optimizations, and facilitate the in-lining of "scalarized" code. This paper describes how the shape of a MATLAB expression can be determined statically, based on a methodology of systematic matrix formulations. The approach capitalizes on the algebraic properties that underlie MATLAB's shape semantics and exactly captures the shape that the MATLAB expression assumes at run time. Some of the highlights of the approach are its applicability to a large class of MATLAB functions and its uniformity. Our methods are compared with the previous shadow variable scheme, and we show how the algebraic view allows inferences not deduced by the traditional approach.
Effects of 4-Hydroxy-Nonenal and Amyloid-β on Expression and Activity of Endothelin Converting Enzyme and Insulin Degrading Enzyme in SH-SY5Y Cells

The cerebral accumulation of amyloid-beta (Abeta) is a consistent feature of and likely contributor to the development of Alzheimer's disease (AD). In addition to dysregulated production, increasing experimental evidence suggests reduced catabolism plays an important role in Abeta accumulation. Although endothelin converting enzyme (ECE) and insulin degrading enzyme (IDE) degrade and thus contribute to regulating the steady-state levels of Abeta, how these enzymes are regulated remain poorly understood. In this study, we investigated the effects of 4-hydroxy-nonenal (HNE) and Abeta on the expression and activity of ECE-1 and IDE in human neuroblastoma SH-SY5Y cells. Treatment with HNE or Abeta upregulated ECE-1 mRNA and protein, while IDE was unchanged. Although both ECE-1 and IDE were oxidized within 24 h of HNE or Abeta treatment, ECE-1 catalytic activity was elevated while IDE specific activity was unchanged. The results demonstrated for the first time that both ECE-1 and IDE are substrates of HNE modification induced by Abeta. In addition, the results suggest complex mechanisms underlying the regulation of their enzymatic activity.