cssi/SciSciGPT-SciSciNet huggingface dataset:
The aerodynamic effect of surface wetting characteristics on a laminar flow airfoil in simulated heavy rain

Wind tunnel experiments have been conducted on a natural laminar flow airfoil in a simdated heavy rain of 440 m/hr at a Reynolds number of 310,000 to assess the effect of surface wettability on the performance degradation due to rain. A significant loss of performance was observed fur each of the three surfaces tested with the nonwettable, waxed, surface being the most degraded (75% reduction in maximum LID) and the incompletely wettable epoxy gel coat being the least (45% reduction). Accompanying the LID loss was an effective reduction in angle of attack of up to 2' resulting from a downward translation of the C polar. In photographic L observations, the runback water layer was found to bead on the wax surface and to sheet on the wettable surfaces. The strong dependence on surface wettability of both the airfoil performance and the w a t e r behavior indicates that the degradation due to heavy rain is primarily a result of the roughenir-gofthe airfoil surface by the runback water layer. The observed performance loss could only be partially emulated by causing premature transition from a laminar to turbulent boundary layer.
2011 CUSHMAN AWARD TO CHRISTOPH HEMLEBEN

Christoph Hemleben received his Masters Degree in Geology and Paleontology from the University of Munich in 1964 under the direction of Herbert Hagn, with a thesis on Oligocene Foraminifera and Ostracoda. He then completed his Ph.D. on the morphogenesis of planktonic foraminifera with Adolf Seilacher as his advisor at the University of Tuebingen in 1969. This led him to a career studying the evolution and biology of Foraminifera. Early in his career, Christoph was a principal investigator of the joint US-American German project (Lamont-Doherty Geological Laboratories of Columbia University and Woods Hole Oceanographic Institution) on foraminiferal biology. In this program he worked with Allan Be, Roger Anderson, and Michael Spindler, carrying out numerous field studies and pioneering laboratory experiments on test ultrastructure, morphogenesis, geochemistry, and ecology. Among others, they established the lunar periodicity of reproduction in many planktonic foraminiferal species. In 1979, Christoph was tenured (Habilitation) comprising a sedimentological study on “Fossillagerstatten”. This led to intensive studies …
The Enduring Social Psychology of Robert K. Merton: Motivating Sentiments, Reference Groups and Self-Fulfilling Prophecies

Robert K. Merton (1910–2003) gained renown as a distinguished sociologist, especially in connection with the paradigm of “structural-functionalism” and he publicly self-identified as a “structuralist.” This paper calls attention to an emphasis in Merton’s work that sociologists have often overlooked, namely, his social psychology. I argue that, throughout his long career, Merton consistently pursued social psychological issues, including how non-logical action, appeals to shared sentiments and collective definitions of situations affect life in organized groups. I shall characterize his earlier analyses as “Harvard style,” and his later social psychological works as “Chicago style,” as a heuristic means of calling attention to interesting variations in framing. Merton’s formulations have impacted numerous subfields of sociology, and some (e.g., “self-fulfilling prophecies,” “the Matthew Effect”) remain influential even today. Examining Merton’s social psychology will contribute both to a fuller appreciation of his career and also to a more complete history of social science in the United States.
Early quit days among methadone-maintained smokers in a smoking cessation trial.

INTRODUCTION Methadone maintenance treatment (MMT) patients have an exceedingly high prevalence of tobacco use, and interventions that have been specifically developed for this vulnerable subpopulation have struggled to attain even modest rates of cessation. A significant barrier has been an inability to initiate a quit attempt early in the treatment process and adherence to treatment. METHODS This study examined the extent to which self-efficacy, medication adherence, and other demographic and smoking variables predicted an early quit day in a sample of MMT smokers (n = 315) enrolled in a smoking cessation pharmacotherapy trial. Using logistic regression, we estimated the association of having an early quit day-24hr without smoking during the first month of treatment. RESULTS Only 35.2% of participants reported a successful early quit day. The likelihood of an early quit day increased significantly (odds ratio [OR] = 1.39, 95% CI = 1.04-1.86, p < .05) with education level and if a quit attempt was made in the past year (OR = 2.27, 95% CI = 1.33-3.87, p < .01). Compared to the placebo arm, those randomized to either nicotine replacement therapy (OR = 3.25, 95% CI = 1.30-8.10, p < .01) or varenicline (OR = 3.16, 95% CI = 1.26-7.92) were significantly more likely to have an early quit day. The likelihood of an early quit day was also positively associated with adherence to the medication protocol (OR = 2.05, 95% CI = 1.52-2.76). CONCLUSIONS Difficulty in achieving an early quit attempt may help explain the very low cessation rates found in studies of MMT smokers.
A Historical Perspective on the Toughness of Ceramics

In this paper, we discuss fracture problems experienced by engineers early in the twentieth century, before fracture mechanics was developed and before we had a systematic way to characterize the fracture resistance of ceramic materials. Universal mechanical test machines and standard methods of establishing material performance under mechanical loads did not exist. Yet the needs for mechanical reliability were there, just as they are today. We review some of the problems encountered by engineers in designing with ceramic materials at the beginning of the twentieth century that are still problems today, but on materials with very different use. We shall show how the development of fracture mechanics and modern techniques of microstructural analysis enabled the solution of mechanical problems associated with the ceramics in modern applications. In the course of the paper we will trace the development of fracture mechanics from the early twentieth century to the present day and the replacement of performance tests with design criteria based on fracture mechanics analysis.
Mesenchymal stem cells suppress cardiac alternans by activation of PI3K mediated nitroso-redox pathway.

BACKGROUND The paracrine action of non-cardiac progenitor cells is robust, but not well understood. Mesenchymal stem cells (MSC) have been shown to enhance calcium (Ca(++)) cycling in myocytes. Therefore, we hypothesized that MSCs can suppress cardiac alternans, an important arrhythmia substrate, by paracrine action on Ca(++) cycling. METHODS AND RESULTS Human cardiac myocyte monolayers derived from iPS cells (hCM) were cultured without or with human MSCs (hMSC) directly or plated on a transwell insert. Ca(++) transient alternans (Ca(++) ALT) and Ca(++) transient duration (CaD) were measured from hCM monolayers following application of 200μM H2O2. Ca(++) ALT in hCM was significantly decreased when cultured with hMSCs directly (97%, p<0.0001) and when cultured with hMSC in the transwell insert (80%, p<0.0001). When hCM with hMSCs were pretreated with PI3K or eNOS inhibitors, Ca(++) ALT was larger than baseline by 20% (p<0.0001) and 36% (p<0.0001), respectively. In contrast, Ca(++) ALT was reduced by 89% compared to baseline (p<0.0001) when hCM monolayers without hMSCs were pretreated with 20μM GSNO. In all experiments, changes in Ca(++) ALT were mirrored by changes in CaD. Finally, real time quantitative PCR revealed no significant differences in mRNA expression of RyR2, SERCA2a, and phospholamban between hCM cultured with or without hMSCs. CONCLUSION Ca(++) ALT is suppressed by hMSCs in a paracrine fashion due to activation of a PI3K-mediated nitroso-redox pathway. These findings demonstrate, for the first time, how stem cell therapy might be antiarrhythmic by suppressing cardiac alternans through paracrine action on Ca(++) cycling.
Ethical Choices in Contemporary Medicine: The predicaments of contemporary medicine

The debate over the nature and definition of medicine is as old as our recorded western history. Eighteen hundred years ago, Galen defined medicine as an art ( techne ) and tried to distinguish between the empiricist and rationalist trends in the field. How much should experience (collected empirical data) influence the practice of medicine? Should reason (rational and logical deduction of effects from a set of causes) play an important role in the theoretical construction of a medical model? Depending on how these two questions are answered, we will have a better idea about how to train students of medicine. These questions have reappeared at the dawn of the twenty-first century because of our increased reliance on technoscience, the confluence and interwoven emergence of scientific theories and models and technological instruments and innovations. This reliance, as we shall explain in the second section, is not limited to specific breakthroughs in biochemistry or genetics, but is pervasive in the atmosphere in which we come across public health issues. Questions about medicine as art and as science, as the third section will illustrate, are also tied to changing public expectations with regard to the promises of democracy and capitalism. And finally, the questions raised and answered here bring together a multidisciplinary or integrative approach to the widening field of medicine in the twenty-first century.
Achieving low anastomotic leak rates utilizing clinical perfusion assessment

Background Anastomotic leak after colorectal resection increases morbidity, mortality, and in the setting of cancer, increases recurrences rates and reduces survival odds. Recent reports suggest that fluorescence evaluation of perfusion after colorectal anastomosis creation is associated with low anastomotic leak rates (1.4%). The purpose of this work was to evaluate whether a similar low anastomotic leak rate after left-sided colorectal resections could be achieved using standard assessment of blood flow to the bowel ends. Methods We performed a retrospective chart review at an academic tertiary referral center, evaluating 317 consecutive patients who underwent a pelvic anastomosis after sigmoid colectomy, left colectomy, or low anterior resection. All operations were performed by a single surgeon from March 2008 to January 2015 with only standard clinical measures used to assess perfusion to the bowel ends. The primary outcome measure was the anastomotic leak rate as diagnosed by clinical symptoms, exam, or routine imaging. Results The average patient age was 59.7 years with an average body mass index of 28.8 kg/m 2 . Rectal cancer (128, 40.4%) was the most common indication for operation while hypertension (134, 42.3%) was the most common comorbidity. In total, 177 operations were laparoscopic (55.8%), 13 were reoperative resections (4.1%), and 108 were protected with a loop ileostomy (34.1%). Preoperative chemotherapy was administered to 25 patients (7.9%) while preoperative chemo/radiation was administered to 64 patients (20.2%). The anastomotic leak rate was 1.6% (5/317). Conclusion Our data suggests that standard, careful evaluation of adequate blood flow via inspection and confirmation of pulsatile blood flow to the bowel ends and meticulous construction of the colorectal or coloanal anastomoses can result in very low leak rates, similar to the rate reported when intraoperative imaging is used to assess perfusion.
Investigation of the stability of a tapered gyro-TWT amplifier

The stability of a wideband single-stage tapered gyrotron traveling wave tube amplifier (gyro-TWT) operating in Ka-band (27-38 GHz) has been investigated. The amplifier operates at 33 kV, 1.6 A in the TE/sub 10/ rectangular waveguide mode at the fundamental cyclotron frequency. Small signal gain in excess of 20 dB has been demonstrated over a wide (33%) frequency range with this device. Recent narrowband large signal measurements have demonstrated a saturated efficiency of around 10%, corresponding to a peak power of 5 kW at 35 GHz. Attempts to increase the amplifier gain and efficiency further have been limited, however, by the onset of oscillations due to insufficient output circuit match. A stability study has been performed to assist in the optimization of the present device, and to aid in the design of a follow-on two-stage experiment. The study has focused on the parametric dependence of the start oscillation current threshold on the velocity ratio, the magnetic field detuning, and the output port reflection coefficient. >
Polarization-controlled modulation doping of a ferroelectric from first principles

In a ferroelectric field effect transistor (FeFET), it is generally assumed that the ferroelectric gate plays a purely electrostatic role. Recently it has been shown that in some cases, which could be called ``active FeFETs,'' electronic states in the ferroelectric contribute to the device conductance as the result of a modulation doping effect in which carriers are transferred from the channel into the ferroelectric layers near the interface. Here we report first-principles calculations and model analysis to elucidate the various aspects of this mechanism and to provide guidance in materials choices and interface termination for optimizing the on-off ratio, using $\mathrm{BaTi}{\mathrm{O}}_{3}/n\ensuremath{-}\mathrm{SrTi}{\mathrm{O}}_{3}$ (electron-doped $\mathrm{SrTi}{\mathrm{O}}_{3}$) and $\mathrm{PbTi}{\mathrm{O}}_{3}/n\ensuremath{-}\mathrm{SrTi}{\mathrm{O}}_{3}$ as prototypical systems. It is shown that the modulation doping is substantial in both cases, and that the electrostatic model developed in previous work can be used to predict electron transfer. This model can thus be used to suggest additional materials heterostructures for the design of active FeFETs.
The male gaze is more relevant, and more dangerous, than ever

In her canonical essay ‘Visual Pleasure and Narrative Cinema’ Laura Mulvey follows Freud in identifying activity with masculinity and passivity with femininity. Following Freud, she also makes a di...
Use of a mechanical thrombectomy device to treat early hepatic artery thrombosis after orthotopic liver transplant.

Abstract Hepatic artery thrombosis (HAT) is a major cause of morbidity and mortality after orthotopic liver transplantation, occurring in 5% of cases (Piardi et al, 2016). HAT is the second main cause of graft loss after primary nonfunction, the leading cause of graft failure in the immediate postoperative period (
Structure–Activity Relationship Studies of Vitamin D3 Analogues Containing an Ether or Thioether Linker as Hedgehog Pathway Inhibitors

The Hedgehog (Hh) signaling pathway is critical for embryonic patterning and postembryonic tissue regeneration. Constitutive pathway activation has also been linked to human malignancies such as basal cell carcinoma (BCC) and medulloblastoma; therefore, multiple small-molecule scaffolds that inhibit Hh signaling are in development. Previously, Grundmann's alcohol, also known as the "northern region" of vitamin D3 (VD3), has been identified as a moderate Hh pathway inhibitor. In this study, isomers of Grundmann's alcohol with different orientations of the C4 hydroxy group and C3α proton were investigated to determine the optimal configuration for this hexahydroindane scaffold with respect to Hh inhibition. A series of analogues containing Grundmann's alcohol linked to a substituted phenyl or benzyl ring through an ether or thioether linker were synthesized and evaluated for their anti-Hh activity. Of these, analogue 17 ((1R,3aR,4R,7aR)-1-[(R)-1,5-dimethylhexyl]-4-(4-aminophenoxy)-7a-methyloctahydro-1H-indene) demonstrated potent anti-Hh activity in Hh-dependent BCC cells and did not activate canonical vitamin D receptor signaling, demonstrating its selective nature for the Hh signaling pathway.
System level design considerations in imaging ISR systems

Development and implementation of an effective imaging ISR system involves multiple design tradeoffs and proper specification of many interdependent system parameters. This paper discusses some of the trades and design considerations that are integral to the development of an optimized imaging ISR system. System parameters such as Atmospheric Effects, Waveband, Field of View, Resolution, proper Eye‐to‐Display Matching, and Size, Weight, Power‐Cost (SWAP‐C) will be discussed.
Systems Theory and Discrete Linear Control Systems

This chapter presents the concept of a system and then define the basic terms of discreteness, etc., in the context of a system. A discrete event is a specific happening that is distinguishable from other events. A discrete system is one whose output occurs naturally on a discretized time scale, often referred to as discrete time. The discreteness of the process output, however, is not the only factor that determines the discreteness of a system. A Fourdrinier machine produces paper in a continuous sheet. The quality characteristics, such as density and moisture content are determined; however, by moving a gage across the bed of the machine. At the completion of a scan, the gage signals are analyzed and a discrete-control action initiated to adjust for any noted deviations from standard. Thus, the control of this continuous product is accomplished by a discrete-control system. Similarly, a central computer that sequentially monitors a number of processes on a time-shared basis supplies each unit in turn with a discrete-control signal regardless of the nature of the processes or their outputs.
Seasonal Implications of Maya Eclipse and Rain Iconography in the Dresden Codex

L'implication des saisons est demontree par l'iconographie de la pluie et des eclipses dans l'almanach des civilisations Mayas qui enregistraient preferentiellement les phenomenes d'eclipses durant les saisons pluvieuses
Komplikationsmanagement nach winkelstabiler Plattenosteosynthese am proximalen Humerus

In einer prospektiven Studie sollen die Komplikationen nach winkelstabiler Plattenosteosynthese („locking proximal humeral plate“, LPHP®) am proximalen Humerus differenziert analysiert und spezifische Therapien abgeleitet werden. Funfzig Patienten im Alter von median 65 (25–84) Jahren (39 weiblich, 11 mannlich) mit dislozierter proximaler Humerusfraktur (7 2-Segment-, 36 3-Segment- und 7 4-Segment-Frakturen) wurden nach winkelstabiler Plattenosteosynthese 3, 6 und 12 Monate postoperativ anhand eines Standardprotokolls nachuntersucht. Der alters- und geschlechtsadaptierte Constant Score nach 12 Monaten betrug fur 2-/3- und 4-Segment-Frakturen median 86/87/55 Punkte. Die Komplikationsrate lag abhangig von der Frakturkomplexitat fur die 2-/3- und 4-Segment-Frakturen bei 14/19/100%. Es fanden sich 7 primare und 7 sekundare Implantatfehllagen, 5 Humeruskopfnekrosen, 4 ossare Fehlstellungen, 2 Pseudarthrosen, 2 Infekte sowie eine heterotope Ossifikation; 9 Revisionsoperationen (3 Implantatentfernungen, 2 Implantat-, 2 Pseudarthrose-, 2 Infektrevisionen) waren notwendig. Eine differenzierte Komplikationsanalyse und ein Ableiten gezielter Praventions- und Behandlungsstrategien ermoglicht unter Beachtung von Uberlegungen um Operationstechnik, Implantat, Frakturmorphologie und Humeruskopfperfusion eine Minimierung der Komplikationsrate nach winkelstabiler Plattenosteosynthese am proximalen Humerus.
Occupational knowledge in college students: Examining relations to career certainty, career decision-making self-efficacy, and interest congruence

Several career decision-making models describe an ongoing career decision evaluation process in which career decisions are constantly being re-assessed as individuals gain occupational information and self-awareness. However, the relation between career decision certainty and knowledge of one’s chosen career has not yet been adequately examined; in part due to the difficult nature of assessing the latter construct in large samples. The present study objectively measured occupational knowledge in 316 college students; specifically regarding the career each student had reportedly been considering. Objective occupational knowledge of participants’ chosen careers significantly related to interest congruence only, and neither variable significantly contributed to variance in career certainty. Results indicated career decision-making self-efficacy partially drives participation in career exploration activities and perceived occupational knowledge, and all three variables in turn contributed to the prediction of career certainty through direct and/or indirect effects. This study was the first to objectively assess college students’ knowledge of the careers they were actively pursuing, and the first to examine that construct along with other important career decision-making variables. Implications and future research directions are discussed.
HISTAMINE RELEASE BY COMPOUND 48/80 AND TEXTILE DUSTS FROM LUNG TISSUE IN VITRO

Abstract Extracts of cotton, flax and hemp dusts, and of the bracts of the cotton boll do not release histamine from guinea pig, rat, cat, sheep and pig lung tissue in vitro. They do, however, release significant amounts of histamine from human lung tissue in vitro , under similar experimental conditions. Extracts of pericarps, another component of the cotton boll, were without effect in both animal and human lung tissue. The results suggest that the histamine-releasing activity of cotton dust is due to the presence of bract fragments in the cotton processed in the mills.
New view on the initial development site and radiographic classification system of osteoarthritis of the knee based on radiographic analysis.

Introduction: radiographic pathology of severe osteoarthritis of the knee (OAK) such as severe osteo phyte at tibial spine ( ts), compartment narrowing, marginal osteophyte, and subchondral sclerosis is well known. Kellgren-Lawrence grading system, which is widely used to diagnose OAK, describes narrowingmarginal osteophyte in 4-grades but uses osteophyte at ts only as evidence of OAK without detailed-grad ing. However, kinematically the knee employs medial ts as an axis while medial and lateral compartments carry the load, suggesting that early OAK would occur sooner at ts than at compartment. t hen, KellgrenLawrence system may be inadequate to diagnose early-stage OAK manifested as a subtle osteophyte at ts without narrowing-marginal osteophyte. t his undiagnosed-OAK will deteriorate becoming a contributing factor in an increasing incidence of OAK. Methods: this study developed a radiographic OAK-marker based on both osteophyte at ts and compartment narrowing-marginal osteophyte and graded as normal, mild, moderate, and severe. With this marker, both knee radiographs of 1,728 patients with knee pain were ana lyzed. Results: Among 611 early-stage mild OAK, 562 or 92% started at ts and 49 or 8% at compartment. It suggests the initial development site of OAK, helping develop new site-specific radiographic classification system of OAK accurately to diagnose all severity of OAK at early, intermediate, or late-stage. It showed that Kellgren-Lawrence system missed 92.0% of early-stage mild OAK from diagnosis. Conclusions: A subtle osteophyte at TS is the earliest radiographic sign of OAK. A new radiographic classification system of OAK was suggested for accurate diagnosis of all OAK in severity and at stage. ( Int J Biomed Sci 2012; 8 (4): 233-243)
Colonoscopic Polypectomy: Silent Perforation

Abstract The management of colon polyps has been completely revolutionized since the introduction of colonoscopic polypectomy. 1–3 The reductions in patient time, cost, morbidity, and mortality are major advantages. Reported complications include primarily hemorrhage (1.7%) and frank clinical perforation (0.32%). 4 This report describes a silent perforation after the removal of a broad based polyp through the colonscope.
Impact of Variation of Corticosteroid Dose, Injection Site, and Multiple Injections on Blood Glucose Measurement in Diabetic Patients.

Purpose This study examined how corticosteroid dose, injection site location, and patient demographics affect blood glucose level after corticosteroid injection in diabetic patients. Methods We prospectively enrolled 70 patients with diabetes mellitus requiring upper- and/or lower-extremity corticosteroid injections. Patients measured fasting and postprandial blood glucose for 14 days after the injection. Blood glucose from days 1 through 7 was compared with the average of days 10 through 14, acting as control. Changes in blood glucose were compared by corticosteroid dose, injection location, patient demographics, and insulin use. Results Patients who underwent shoulder, wrist, or hand injections and patients who received multiple injections had no significant elevations in fasting or postprandial blood glucose, whereas those with knee injections had a significant increase in fasting blood glucose on postinjection days 1 and 2. Preinjection hemoglobin A1C had a significant effect on postinjection blood glucose whereas corticosteroid dose, body mass index, insulin use, and the number of injections had no significant effect on the elevation of blood glucose. There were no cases of diabetic ketoacidosis in any subjects. Conclusions Patients receiving corticosteroid injections in the upper extremity did not experience significant increases in blood glucose whereas those undergoing knee corticosteroid injections demonstrated elevated blood glucose levels. Because poorer glucose control was associated with greater elevations in blood glucose after injection, patients with higher hemoglobin A1C should be counseled to monitor postinjection glucose more closely. Type of study/level of evidence Therapeutic II.
Unexpectedly High Prevalence of Cystoisospora belli Infection in Acalculous Gallbladders of Immunocompetent Patients.

Objectives Indications for cholecystectomy have changed dramatically over the past three decades. Cystoisospora belli has been reported in cholecystectomy specimens of immunocompetent patients. The present study was designed to determine the prevalence and clinical association of C belli in the gallbladder. Methods The study included retrospective review of cholecystectomy specimens (n = 401) removed for various indications, and a prospective cohort of cholecystectomy specimens (n = 22) entirely submitted for histologic evaluation. Correlations of presence of C belli with age, sex, clinical indication, and abnormalities of preoperative laboratory values were assessed by Fisher exact test. Results C belli was identified in 39/401 (9.7%) of the retrospective cohort, and 6/22 (27.3%) of the entirely submitted specimens. The presence of C belli showed no correlation with age, sex, clinical indication, or laboratory abnormalities. Conclusions C belli resides in a latent state in the gallbladder and may be best considered a commensal organism.
Effects of regional dialect on oral-nasal balance and nasality perception.

While cross-dialectal variations in nasalance have been investigated in previous studies, the influence of regional dialect on listeners' perceptual ratings of nasality has received limited research attention. This study explored cross-dialectal differences in the production of oral-nasal balance and the perception of nasality, with special emphasis on Inland North (IN) and Midland (M) dialects in the USA. Twenty-six adults representing the IN (n = 15) and M (n = 11) dialects participated in the study. Oral-nasal balance characteristics and nasality perception were compared between dialects using mean nasalance of various speech stimuli, measured via nasometry, and perceptual ratings of nasality of synthetic vowel stimuli, measured using direct magnitude estimation (DME). Despite similar mean nasalance scores between two regional dialects for standardized passage readings and sustained vowels, IN and M groups significantly differed in their perceptual ratings of nasality, with the DMEs of IN listeners being consistently and significantly higher, i.e. more nasal, than those of M listeners. Our findings provide evidence for perceptual variations of nasality that may exist at a dialectal level in addition to cross-linguistic variations in the perception of nasality as reported by Lee et al. (2008). Further research is needed to determine to what extent perceptual variations of nasality exist in other dialects and how these variations manifest in perceptual judgments of hypernasality and its severity ratings.
The Importance of Oral Communication Skills and a Graduate Course to Help Improve These Skills

This article addresses the importance of oral communication and many of its fundamental underlying principles. Emphasis is placed on oral presentations, particularly those used in science and engineering. Following this, the author provides a brief outline of an elective graduate level oral communications course that was developed and utilized to improve the presentation skills of the participants.
High-Throughput Single-Molecule R-loop Footprinting Reveals Principles of R-loop Formation

ABSTRACT R-loops are a prevalent class of non-B DNA structures that form during transcription upon reannealing of the nascent RNA to the template DNA strand. R-loops have been profiled using the S9.6 antibody to immunoprecipitate DNA:RNA hybrids. S9.6-based DNA:RNA immunoprecipitation (DRIP) techniques revealed that R-loops form dynamically over conserved genic hotspots. We developed an orthogonal profiling methodology that queries R-loops via the presence of long stretches of single-stranded DNA on the looped-out strand. Non-denaturing sodium bisulfite treatment catalyzes the conversion of unpaired cytosines to uracils, creating permanent genetic tags for the position of an R-loop. Long read, single-molecule PacBio sequencing allows the identification of R-loop ‘footprints’ at near nucleotide resolution in a strand-specific manner on single DNA molecules and at ultra-deep coverage. Single-molecule R-loop footprinting (SMRF-seq) revealed a strong agreement between S9.6-and bisulfite-based R-loop mapping and confirmed that R-loops form from unspliced transcripts over genic hotspots. Using the largest single-molecule R-loop dataset to date, we show that individual R-loops generate overlapping sets of molecular clusters that pile-up through larger R-loop-prone zones. SMRF-seq further established that R-loop distribution patterns are driven by both intrinsic DNA sequence features and DNA topological constraints, revealing the principles of R-loop formation.
Development of segmental tonic-clonic activity following subarachnoid phenol injection

Three cases of segmental tonic-clonic activity occurring several hours after subarachnoid phenol rhizotomies are reported as a probable complication of the technique. All patients had experienced incomplete cord transections above the level at which the blocks were performed long before the performance of the block. Management of the complication and suggested etiologies are discussed.
Epigenetic field cancerization in breast cancer using subject-matched tumor, ipsilateral-normal, and contralateral-normal tissues

Abstract Background Emerging work has demonstrated that histologically normal (non-tumor) tissue adjacent to breast tumor tissue shows evidence of molecular alterations related to tumorigenesis, referred to as field cancerization effects. Although changes in DNA methylation are known to occur early in breast carcinogenesis and the landscape of breast tumor DNA methylation is profoundly altered compared with normal tissue, there have been limited efforts to identify DNA methylation field cancerization effects in histologically normal breast tissue adjacent to tumor. Methods Matched tumor, histologically normal tissue of the ipsilateral breast (ipsilateral-normal), and histologically normal tissue of the contralateral breast (contralateral-normal) were obtained from nine women undergoing bilateral mastectomy. Laser capture microdissection was used to select breast epithelial cells from normal tissues, and neoplastic cells from tumor specimens for genome-scale measures of DNA methylation with the Illumina HumanMethylationEPIC array. Results We identified substantially more CpG loci that were differentially methylated between contralateral-normal breast and tumor tissue (63,271 CpG loci q Conclusions Our results indicate that early hypermethylation events in breast carcinogenesis are more likely to occur in the regions immediately surrounding CpG islands than CpG islands per se, reflecting a field effect of the tumor on surrounding histologically normal tissue. This work offers an opportunity to focus investigations of early DNA methylation alterations in breast carcinogenesis and potentially develop epigenetic biomarkers of disease risk.
Interaction of heat shock protein 90 with hypoxia inducible factor and signal transducer and activator of transcription in colon cancer

Abstract Hypoxia inducible factor (HIF)-1α and signal transducer and activator of transcription 3 (STAT-3) promote angiogenesis through transcriptional control of angiogenic cytokines such as vascular endothelial growth factor (VEGF). HIF-1α and STAT-3 represent clients of heat shock protein 90 (HSP90). We hypothesize that HSP90 inhibition can impair STAT-3 and HIF-1α activation, resulting in reduced VEGF expression in colorectal cancer (CRC). Protein levels and mRNA levels were measured using western blot and QRT-PCR, respectively, in CRC cell lines. Stable transfection and knockdown of HIF-1α, HSP90 and STAT-3 was performed in the two cell lines. Biologic effects following transfection were confirmed by chemical stimulation of STAT-3 with interleukin 6 (IL-6) and HIF-1α with hypoxia, respectively. HSP90 inhibition blocks the activation of its clients, HIF-1α and STAT-3, and inhibits VEGF transcription. HIF-1α is located downstream of HSP90 and the two molecules are co-dependent. Finally, STAT-3 inhibition affects VEGF expression only, thus disrupting angiogenesis. Inhibiting HSP90 is an effective approach to indirectly limit activity via HIF-1 α/STAT-3 and subsequent angiogenesis in CRC.
Inequality and Opportunity in a Perfect Storm of Graduate Student Debt.

Recent efforts to understand aggregate student loan debt have shifted the focus away from undergraduate borrowing and toward dramatically rising debt among graduate and professional students. We su...
How to Perfect the Transfer-Pricing Tax of China

With China entry into WTO, it is becoming more important for China to do more study on tax evasion, which aims at preventing the foreign-investment enterprises from evading tax. China should establish a consummate, comprehensive, authoritative and specific transfer-pricing -tax law to deal with such problems. This law will establish some special clauses and basic principles.
SOD1 Suppression with Adeno-Associated Virus and MicroRNA in Familial ALS

Two patients with familial amyotrophic lateral sclerosis (ALS) and mutations in the gene encoding superoxide dismutase 1 (SOD1) were treated with a single intrathecal infusion of adeno-associated virus encoding a microRNA targeting SOD1. In Patient 1, SOD1 levels in spinal cord tissue as analyzed on autopsy were lower than corresponding levels in untreated patients with SOD1-mediated ALS and in healthy controls. Levels of SOD1 in cerebrospinal fluid were transiently and only slightly lower in Patient 1 but were not affected in Patient 2. In Patient 1, meningoradiculitis developed after the infusion; Patient 2 was pretreated with immunosuppressive drugs and did not have this complication. Patient 1 had transient improvement in the strength of his right leg, a measure that had been relatively stable throughout his disease course, but there was no change in his vital capacity. Patient 2 had stable scores on a composite measure of ALS function and a stable vital capacity during a 12-month period. This study showed that intrathecal microRNA can be used as a potential treatment for SOD1-mediated ALS.
ACR Guideline for Managing Patients with Degenerative Joint Disease of the Hand, Knee, and Hip.

This meta-analysis found no evidence that the monoclonal antibody denosumab reduces the risk of fracture more than bisphosphonates.
Numerical Modelling for Slope Stabilizations in Modern Geotechnical Practice

Until recently geomechanical numerical modelling of slopes and landslides was mostly performed for academic research purposes and for the engineering design of high earth embankments. In recent years, the use of Finite Element and Finite Difference modelling packages has become commonplace, and allowed complex analyses to be performed by practicing engineers in firms of all sizes. Although these software packages have widespread use in geotechnical engineering, there are two applications that are particularly well-suited for slope stability and landslide modelling. The first one, is the analysis of slope repairs and landslide stabilizations that combine multiple structural elements (e.g., several rows of piles with tiebacks). The second is the seismic performance of slopes, e.g., designs where dynamic amplification and permanent seismic displacements are a major concern. This paper presents recent advancements for the practical design of slopes, the advantages for designers of performing geomechanical modelling, and provides guidelines for their use in modern slope engineering and landslide stabilization practice.
38460 Independent Investigator Incubator (I3) yields external funding within three years for the majority of junior faculty

ABSTRACT IMPACT: The Independent Investigator Incubator program provides 1:1 mentoring from ‘super-mentors’ to enhance junior faculty careers in research. OBJECTIVES/GOALS: In 2014, the Indiana University School of Medicine (IUSM) in collaboration with the Indiana CTSI established the Independent Investigator Incubator (I3) Program. The I3 Program is designed to provide 1:1 mentoring for new research faculty during the crucial early years of their careers. Our goal is to provide an overview of the I3 design and 5-year data. METHODS/STUDY POPULATION: The I3 Program employs a resource-sharing, centralized design that provides concentrated 1:1 mentorship from a senior faculty ‘super mentor’ as well as other resources, such as grant writing support. Unlike many mentorship programs, I3 mentors closely interact with the mentees within the School and are compensated for their efforts (5% full-time equivalency per mentee, max of 15%). The number of ‘super mentors’ has grown from 6 to 15 faculty over 5 years, and mentors typically serve 4 to 5 mentees. Mentee applications are accepted on a rolling enrollment basis. The I3 mentees represent a diverse group based on sex, ethnicity, terminal degree, academic track, and discipline. Mentors and mentees have annual reviews through the program. RESULTS/ANTICIPATED RESULTS: In five years, 110 mentees have enrolled in the I3 program. Upon entering, 53% had no external funding, 28% had internal funding, 12% had K-awards, 7% had R03/R21 awards. Over the first five years, 75% have received extramural funding. The median funding was 300K direct costs) was 2.2 years (median - 2.6 years). Nearly all mentees were satisfied with their mentor pairing based on the mentor’s ‘availability’ and ‘valuable feedback,’ and all mentees wanted the mentoring relationship to continue DISCUSSION/SIGNIFICANCE OF FINDINGS: Since 2014, the I3 Program has had a positive impact on the careers of junior faculty at IUSM as determined by faculty satisfaction and funding metrics. Future focus areas will include developing criteria/models for graduating from the program to balance fiscal sustainability with mentee needs during their transition to mid-career.
Association of Quality of Life Measures and Otolaryngologic Care in Cystic Fibrosis Patients.

Objectives:Appropriate management of chronic rhinosinusitis (CRS) among patients with cystic fibrosis (CF) is important in improving quality of life. Otolaryngologists play a critical role in reduc...
A theoretical interpretation of learning vs. Memorizing text

Learning and memory have been studied by researchers throughout psychological history, however similar tasks have been used to measure them. Dependence upon recall and recognition memory is a result of both the list learning tradition in psychology and the efficient and objective scoring for which they provide. Several studies are described which point out the differences between memory and learning and the shortcomings of using recall and recognition to measure both. Results regarding differential effects of independent variables on learning and memory are interpreted in terms of the van Dijk and Kintsch (1983) theory of text comprehension. Si l’apprentissage et la memoire ont ete etudies depuis les debuts de la psychologie, ce sont les memes tâches — le rappel et la reconnaissance — qui ont ete utilisees pour les mesurer. L’utilisation de ces epreuves resulte a la fois de la tradition d’apprentissage de listes et des possibilites de notation aisee et objective qu’elles permettent. Dans cet article, plusieurs recherches qui montrent des differences entre l’apprentissage et la memorisation et, par consequent, les inconvenients a assimiler les deux activites, sont decrites. Les effets differentiels de plusieurs variables independantes sur les performances d’apprentissage et de memorisation a partir de textes sont interpretes dans le cadre du modele de comprehension propose par van Dijk et Kintsch (1983).
Cumulative Innovation and Antitrust Policy

We develop a stylized model of a Schumpeterian industry, characterized by cumulative innovation and a succession of incumbent monopolists, to address issues in competition policy toward abuse of dominance. Incumbents’ R&D investments increase future social surplus flows as well as the incumbents’ tenure in the market, thus generating both positive and negative intertemporal externalities. We find that conduct that appropriates surplus (“extraction”) increases innovation and surplus growth. By contrast, conduct that lengthens incumbent tenure (“extension”) increases innovation and surplus growth when the net intertemporal externality is positive but decreases innovation and surplus growth when the net intertemporal externality is negative.
History of Endocrine Surgery

The science of endocrinology began relatively recently, at the beginning of the twentieth century. At that time, physiological theories were dominated by the Russian Ivan Pavlov, who argued that the nervous system primarily controlled all bodily activities. Because of this, few thought that ductless glands existed. However, in 1902 William Bayliss and Ernest Starling made a simple discovery that gave birth to the science of endocrinology. They demonstrated that acid in the gut stimulated the secretion of pancreatic juice when all connections from both organs to the nervous system were severed. They postulated that a “chemical” rather than a “nervous” substance is responsible for pancreatic secretion, and named the substance secretin.1 This finding of secretin represented a whole new class of body messenger. In 1905 Starling proposed the term hormone from a Greek word meaning “to excite” for substances that mediate messages through the circulation.2 Langerhans had previously attributed an endocrine function to the islets of the pancreas, and the science of endocrinology was born.
Invasive fungal sinusitis in a healthy athlete due to long-term anabolic steroid use.

Invasive fungal rhinosinusitis is a potentially fatal infection that affects immunocompromised patients. Prognosis is generally poor despite aggressive medical and surgical treatments. We present the first reported case of invasive fungal sinusitis in a healthy 18-year-old male athlete who was taking anabolic androgenic steroids (AAS). The effects of excessive AAS use on the immune system are not fully understood, but there may be consequences at supraphysiological concentrations. This case demonstrates potential immunomodulatory effects of anabolic steroids and highlights a previously unknown cause of invasive fungal sinusitis. Laryngoscope, 124:1756–1759, 2014
The Methylation of Histones during Regeneration of the Liver

Abstract Histones are methylated after synthesis by a transfer of methyl groups (derived from methionine) to the free e-amino groups of lysine residues in the polypeptide chain. The time courses of histone synthesis and methylation have been compared during regeneration of the liver in the rat. Uniformly labeled arginine-14C and methionine-(methyl-14C) were used as precursors, and the e-N-methyllysines were separated from the other amino acids in the protein digest. The histones were fractionated by differential acetone precipitation to yield an "arginine-rich" fraction containing 0.91 mole per 100 moles of e-N-methyllysines. e-N-Dimethyllysine is the predominant form of the modified amino acid. Its concentration exceeds that of the monomethyl derivative by a factor of 3. Histone methylation is a relatively late event in the course of cell division after partial hepatectomy. The peak in methylation occurs at a time when the rates of histone synthesis and DNA synthesis have already begun to decline. Methylation of histones does not correlate with an increase in DNA template activity for RNA synthesis, nor with the initiation of histone, nonhistone protein, or DNA synthesis. It may correlate with structural and functional changes known to occur in the nucleus prior to mitosis, which involve a condensation of the chromatin and a curtailment of nucleic acid synthesis.
Studies of Semiconductor Surfaces and Interfaces by Three-Wave Mixing Spectroscopy

The surface-sensitive nonlinear optical processes of second-harmonic generation (SHG) and sum-frequency generation (SFG) are powerful tools for investigating the structural and electronic properties of semiconductor surfaces and interfaces. Information about the symmetry and structural properties of the surface or interface can be obtained from an analysis of the polarization dependence of the nonlinear optical response, as has been illustrated for clean Si(111) surfaces prepared with different surface reconstructions. The approach has been applied to real-time, in-situ studies of thin film growth and annealing, from which barriers for adatom motion can be inferred. Information concerning the electronic properties of surfaces and interfaces can be obtained from spectroscopic measurements of resonant three-wave mixing (SHG or SFG). The method has been utilized, for example, to probe electronic transitions at the insulator/semiconductor interface formed by CaF2/Si(111). These measurements led to a determination of the “interface” band gap, i.e. the minimum energy separation between filled and empty interface states. The interface band gap is found to differ strongly from that of either of the bulk materials, highlighting our ability to probe the distinctive properties of this quasi-two-dimensional region.
Physical Examination of Patients With Cerebrospinal Fluid Shunts: Is There Useful Information in Pumping the Shunt?

To assess the value of the information derived from pumping the shunt valve in hydrocephalic patients with cerebrospinal fluid shunts, the findings on examination of 200 consecutive patients were recorded prospectively. The status of each shunt was determined on the basis of all available clinical data, and the results of the shunt pumping test were compared to the final status of each shunt for various subsets of the study group. In the most clinically pertinent subsets, the sensitivity of the shunt pumping test in the detection of shunt obstruction was 18% to 20%, and the predictive value of a negative shunt pumping test, indicating shunt patency, was only 65% to 81%. For the hydrocephalic patient with symptoms of shunt malfunction, definitive imaging studies must not be deferred because of reassuring findings on examination of the shunt valve.