cssi/SciSciGPT-SciSciNet huggingface dataset:
Artificial neural network subgrid models of 2D compressible magnetohydrodynamic turbulence

We explore the suitability of deep learning to capture the physics of subgrid-scale ideal magnetohydrodynamics turbulence of 2D simulations of the magnetized Kelvin-Helmholtz instability. We produce simulations at different resolutions to systematically quantify the performance of neural network models to reproduce the physics of these complex simulations. We compare the performance of our neural networks with gradient models, which are extensively used in the magnetohydrodynamic literature. Our findings indicate that neural networks significantly outperform gradient models in accurately computing the subgrid-scale tensors that encode the effects of magnetohydrodynamics turbulence. To the best of our knowledge, this is the first exploratory study on the use of deep learning to learn and reproduce the physics of magnetohydrodynamics turbulence.
"Residents as Teachers" Workshop Improves Knowledge, Confidence, and Feedback Skills for General Surgery Residents.

Objective Surgical residents receive limited formal training in education, yet they are expected to teach medical students and one another. A “Residents as Teachers” curriculum was developed and implemented to improve residents’ knowledge of educational strategies, confidence in teaching abilities, and quality of feedback given to learners. Design A 6-hour workshop was delivered at an academic general surgery residency program. It included 3 interactive sessions: “Teaching on the wards”, “How to give and receive feedback”, and “Teaching in the operating room (OR)”. Pre- and postsession surveys were administered to evaluate participants’ knowledge and confidence regarding teaching skills. Standard statistical analyses were used to compare pre- and postcurriculum scores. Setting General surgery residents at Case Western Reserve University/University Hospitals Cleveland Medical Center Program attended a 6-hour educational seminar entitled “Residents as Teachers”. Three attending surgeons with expertise in surgical education administered the curriculum. Participants Twenty-four residents completed the course and surveys (5 PGY-5s, 6 PGY-4s, 4 PGY-3s, 5 PGY-2s, and 4 PGY-1s). Results On a 5-point Likert scale, residents' self-rating of teaching skills (pre = 1.8, post = 3.04, p Conclusions A “Residents as Teachers” workshop improved resident confidence in teaching and feedback skills, particularly for intraoperative instruction, and improved knowledge in the 3 specific educational domains included in the session.
Self-advocacy is associated with lower likelihood of living donor kidney transplantation

Abstract Background The Living Donor Navigator (LDN) Program pairs kidney transplant candidates (TC) with a friend or family member for advocacy training to help identify donors and achieve living donor kidney transplantation (LDKT). However, some TCs participate alone as self-advocates. Methods In this retrospective cohort study of TCs in the LDN program (04/2017-06/2019), we evaluated the likelihood of LDKT using Cox proportional hazards regression and rate of donor screenings using ordered events conditional models by advocate type. Results Self-advocates (25/127) had lower likelihood of LDKT compared to patients with an advocate (adjusted hazard ratio (aHR): 0.22, 95% confidence interval (CI): 0.03–1.66, p = 0.14). After LDN enrollment, rate of donor screenings increased 2.5-fold for self-advocates (aHR: 2.48, 95%CI: 1.26–4.90, p = 0.009) and 3.4-fold for TCs with an advocate (aHR: 3.39, 95%CI: 2.20–5.24, p Conclusions Advocacy training was beneficial for self-advocates, but having an independent advocate may increase the likelihood of LDKT.
Adaptive Plasticity as a Fitness Benefit of Mate Choice

Phenotypic plasticity and sexual selection can each promote adaptation in variable environments, but their combined influence on adaptive evolution is not well understood. We propose that sexual selection can facilitate adaptation in variable environments when individuals prefer mates that produce adaptively plastic offspring. We develop this hypothesis and review existing studies showing that diverse groups display both sexual selection and plasticity in nonsexual traits. Thus, plasticity could be a widespread but unappreciated benefit of mate choice. We describe methods and opportunities to test this hypothesis and describe how sexual selection might foster the evolution of phenotypic plasticity. Understanding this interplay between sexual selection and phenotypic plasticity might help predict which species will adapt to a rapidly changing world.
Impact of COVID-19 Governmental Restrictions on Emergency General Surgery Operative Volume and Severity.

BACKGROUND: To describe the effect of the COVID-19 pandemic on emergency general surgery operative volumes during governmental shutdowns secondary to the pandemic and characterize differences in disease severity, morbidity, and mortality during this time compared to previous years. METHODS: This retrospective cohort study compares patients who underwent emergency general surgery operations at a tertiary hospital from March 1st to May 31st of 2020 to 2019. Average emergent cases per day were analyzed, comparing identical date ranges between 2020 (pandemic group) and 2019 (control group). Secondary analysis was performed analyzing disease severity, morbidity, and mortality. RESULTS: From March 1st to May 31st, 2020, 2.5 emergency general surgery operations were performed on average daily compared to 3.0 operations on average daily in 2019, a significant decrease (P = .03). No significant difference was found in presenting disease severity, morbidity, or mortality between the pandemic and control groups. DISCUSSION: This study demonstrates a decrease of 65% in emergency general surgery operations during governmental restrictions secondary to the COVID-19 pandemic. This decrease in operations was not associated with worse disease severity, morbidity, or mortality.
Human Rights 2030: Existential Challenges and a New Paradigm for the Field

This chapter proposes disruptive interventions in human rights practice that address the existential challenges to the field: a more collaborative mode of operation, greater sense of time (both long term and short term), and heightened attention to narratives, emotions, and frames capable of connecting with larger constituencies and other social justice movements. The traditional paradigm of human rights is inadequate to deal with the simultaneity, speed, and depth of the ecological, technological, geopolitical, and socio-economic challenges of the 2020s. Against the despair of critics who announce the ‘endtimes’ of human rights and the defensiveness of traditional advocates who double down on conventional tactics, this chapter proposes ideas and strategies for the next decade that draw on lessons from other fields of knowledge and practice.
Intracranial Pressure and Cerebral Hemodynamic Monitoring After Cardiac Arrest in Pediatric Pigs Using Contrast Ultrasound-Derived Parameters

Objectives We explore the correlation of contrast-enhanced ultrasound (CEUS) parameters to intracranial pressure (ICP) in a porcine experimental model of pediatric cardiac arrest. Methods Eleven pediatric pigs underwent electrically induced cardiac arrest followed by cardiopulmonary resuscitation. ICP was measured using intracranial bolt monitor and CEUS was monitored through a cranial window. Various CEUS parameters were monitored at baseline, immediately post return of spontaneous circulation (ROSC), 1 hour-post ROSC, and 3 hours post-ROSC. Results There was significant ICP correlation with wash-out slope assessed by CEUS time intensity curve analysis at immediate post-ROSC. At 3 hours post-ROSC there was also significant negative correlation between ICP and peak enhancement which may be due to the evolution of anoxic injury. Conclusion The use of CEUS in assessing disruption of cerebral hemodynamics and ICP post cardiac arrest will need future validation and comparison to other imaging modalities. The correlation between CEUS parameters and ICP may be due to the alterations in cerebral autoregulation that result from anoxic brain injury.
Symbolic Interaction and Applied Social Research: A FOCUS ON TRANSLATIONAL SCIENCE RESEARCH 1

In symbolic interaction, a traditional yet unfortunate and unnecessary distinction has been made between basic and applied research. The argument has been made that basic research is intended to generate new knowledge, whereas applied research is intended to apply knowledge to the solution of practical (social and organizational) problems. I will argue that the distinction between basic and applied research in symbolic interaction is outdated and dysfunctional. The masters of symbolic interactionist thought have left us a proud legacy of shaping their scholarly thinking and inquiry in response to and in light of practical issues of the day (e.g., Znaniecki, and Blumer). Current interactionist work continues this tradition in topical areas such as social justice studies. Applied research, especially in term of evaluation and needs assessment studies, can be designed to serve both basic and applied goals. Symbolic interaction provides three great resources to do this. The first is its orientation to dynamic sensitizing concepts that direct research and ask questions instead of supplying a priori and often impractical answers. The second is its orientation to qualitative methods, and appreciation for the logic of grounded theory. The third is interactionism's overall holistic approach to interfacing with the everyday life world. The primary illustrative case here is the qualitative component of the evaluation of an NIH-funded, translational medical research program. The qualitative component has provided interactionist-inspired insights into translational research, such as examining cultural change in medical research in terms of changes in the form and content of formal and informal discourse among scientists; delineating the impact of significant symbols such as "my lab" on the social organization of science; and appreciating the essence of the self-concept "scientist" on the increasingly bureaucratic and administrative identities of medical researchers. This component has also contributed to the basic social scientific literature on complex organizations and the self.
The impact of frequency of behavior and type of contact on judgments involving a criminal stalking case.

We investigated mock juror perceptions of the frequency of behavior and type of contact in an ex-intimate stalking case. We used a mock-juror methodology, in which 204 community members (129 women) read a stalking trial summary, rendered a verdict, and evaluated the intent of the defendant to cause the victim fear and distress, as well as the victim's experience with these emotions. The trial varied as to whether there were 5 or 30 stalking incidents and whether the stalking involved personal contact or stalking via text message. RESULTS showed that females were more likely to render a guilty verdict when the victim had been stalked 30 times rather than 5 times while males were equally likely to render a guilty verdict regardless of the frequency. Mock jurors were significantly more likely to render guilty verdicts in the personal contact condition than in the text message condition. Females' perceptions of the victim's fear and distress mediated the frequency of incidents x gender interaction. The victim's fear and the defendant's intentions mediated the main effect of type of contact on verdict. Cognitive network analyses showed that victim fear and the defendant's intent to cause fear were central to participant verdict decision making. We discuss these results in terms of the implications, specifically that victim fear should be a primary focus in stalking legislation. (PsycINFO Database Record Language: en
Annual and Interannual Behavior of Solar Ultraviolet Irradiance Revealed by Broadband Measurements

This research examines the behavior of ground-level solar UV radiation as measured by eight broadband meters in the continental United States during the period from late 1994 to late 1998. The goal is to define the variability that occurs in UV irradiance over time scales ranging from one to several years. The monthly integrated irradiances, from latitude 32 8 Nt o 47 8N, contain large annual cycles and latitudinal gradients which depend on season. Seven of the eight sites show a maximum in July, a behavior related to proximity to the summer solstice, with modifications associated with the annual cycle in column ozone. A large interannual variability in monthly integrated irradiance appears over the 4 year period studied. A comparison of corresponding months during different years shows differences in irradiance of 20% or more in one-third of the cases analyzed. When the solar zenith angle (SZA) is held fixed in the range 60‐65 8, a substantial annual cycle in UV irradiance remains where the maximum monthly mean irradiance is 1.4‐1.9 times the minimum, depending on location. Furthermore, the annual cycle at fixed SZA is not in phase with the normal seasonal cycle. Maximum irradiances at fixed SZA tend to occur in the October to December period, while minima cluster in April through July. The annual cycle in ozone, with maximum column values in spring and minima in autumn, explains the general character of the fixed-SZA data, although changes in cloudiness are significant contributors to interannual variability.
Clonal Evolution in a Human Neuroblastoma

Tumor samples, obtained from a single patient at two points in his illness, have enabled us to study clonal evolution in a neuroblastoma. Cells from the primary tumor demonstrated considerable heterogeneity in terms of chromosome number; cells from 4 subsequent metastases were all nearly diploid; and cells from a tumor produced in a mouse by the injection of cells from the primary tumor were hypotriploid in modal number. All of the tumor samples contained the same marker chromosome rearrangements, indicating their origin from a common precursor. Each of the cell lines analyzed (including those from the patient's metastases, those from the tumor in a mouse, and those from the primary tumor after 11 months in continuous culture) also contained different and distinguishing chromosome abnormalities. The differences in karyotype among these tumor samples and cell lines presumably reflect the different selection pressures at work in each instance.
Seasonal climatology of CO2 across North America from aircraft measurements in the NOAA/ESRL Global Greenhouse Gas Reference Network

Seasonal spatial and temporal gradients for the CO2 mole fraction over North America are examined by creating a climatology from data collected 2004–2013 by the NOAA/ESRL Global Greenhouse Gas Reference Network Aircraft Program relative to trends observed for CO2 at the Mauna Loa Observatory. The data analyzed are from measurements of air samples collected in specially fabricated flask packages at frequencies of days to months at 22 sites over continental North America and shipped back to Boulder, Colorado, for analysis. These measurements are calibrated relative to the CO2 World Meteorological Organization mole fraction scale. The climatologies of CO2 are compared to climatologies of CO, CH4, SF6, N2O (which are also measured from this sampling program), and winds to understand the dominant transport and chemical and biological processes driving changes in the spatial and temporal mole fractions of CO2 as air passes over continental North America. The measurements show that air masses coming off the Pacific on the west coast of North America are relatively homogeneous with altitude. As air masses flow eastward, the lower section from the surface to 4000 m above sea level (masl) becomes distinctly different from the 4000–8000 masl section of the column. This is due in part to the extent of the planetary boundary layer, which is directly impacted by continental sources and sinks, and to the vertical gradient in west-to-east wind speeds. The slowdown and southerly shift in winds at most sites during summer months amplify the summertime drawdown relative to what might be expected from local fluxes. This influence counteracts the dilution of summer time CO2 drawdown (known as the “rectifier effect”) as well as changes the surface influence “footprint” for each site. An early start to the summertime drawdown, a pronounced seasonal cycle in the column mean (500 to 8000 masl), and small vertical gradients in CO2, CO, CH4, SF6, and N2O at high-latitude western sites such as Poker Flat, Alaska, suggest recent influence of transport from southern latitudes and not local processes. This transport pathway provides a significant contribution to the large seasonal cycle observed in the high latitudes at all altitudes sampled. A sampling analysis of the NOAA/ESRL CarbonTracker model suggests that the average sampling resolution of 22 days is sufficient to get a robust estimate of mean seasonal cycle of CO2 during this 10 year period but insufficient to detect interannual variability in emissions over North America.
Neurological reactivity during medial prefrontal cortex stimulation: Effects of self-stimulation experience

Abstract Electrical stimulation of the medial prefrontal cortex (MFC) induced a moderate behavioral suppression in a series of neurological tests that included measures of (1) open field activity (2) righting and climbing reflexes (3) somatosensory reactivity and (4) approach-withdrawal responsivity to positive and negative stimuli. The same animals were trained to lever press for medial prefrontal cortex stimulation and after several days of self-stimulation were again tested for neurological reactivity during MFC stimulation. No habituation or lessening of behavioral suppression was evident as a result of self-stimulation experience. Therefore behavioral suppression, by itself, cannot account for the slow acquisition of MFC self-stimulation. Other data suggest that the stimulation interferes with the learning of complex operant responses and/or that the reward value of the stimulation is increased as a result of repetition.
Capillary electrophoresis as a clinical tool for the analysis of protein in serum and other body fluids

Most electrophoretic analyses of proteins in the clinical laboratory are currently carried out by electrophoresis in acrylamide or agarose gels. This labor-intensive method is now being challenged by capillary electrophoresis (CE) because of its potential for automated, rapid, high efficiency separations. The automatability of CE itself, combined with its amenability to interfacing with other robotized functions, positions this technology perfectly for the analysis of proteins in physiological matrices, such as serum, urine, and cerebrospinal fluid. The focus of this overview is to familiarize the clinical scientist with the research demonstrating the applicability of the technology to the clinical protein laboratory.
The differential contribution of premaxillary, maxillary, and palatine dimensions to sexual dimorphism in the adult olive baboon (Papio cynocephalus anubis)

Measurements of the palatal components: premaxillary, maxillary, and palatine length are made on the adult skulls of 19 male and 21 femalePapio cynocephalus anubis. The relative contributions of each of these components to overall palatal length are compared between the sexes. It is found that the proportions are the same for the two sexes and concluded that sexual dimorphism observed in the adult is not the result of differential growth of one component.
Regulating intensity using perceived exertion: effect of exercise duration

To examine whether the validity of perception-based intensity regulation would be affected by exercise duration, 20 subjects were recruited to complete a maximal exercise test (GXT) and four submaximal trials of varying duration and intensity using a cyle ergometer. During GXT, ratings of perceived exertion (RPE), oxygen uptake VO2, heart rate (HR), and power output (PO) equivalent to 50 and 75% VO2peak were determined. During each trial, subjects were to produce and maintain a workload using RPE estimated at 50 or 75% VO2peak for 20 or 40 min, and VO2, HR, and PO were measured throughout the exercise. No differences in average VO(2) were found between the estimation and production trial of either duration. However, average HR and PO were lower (P < 0.05) during the production trial of both durations. It appears that exercise duration has a minimal impact upon the accuracy of using RPE to regulate a target metabolic demand.
Singularities of the n-body problem. I

Little is known about the nature of the singularities of the n-body problem. While it is plausible to suppose that they are due to collisions, this has never been established, except when n = 2 or n = 3. In the general case the best that can be said at present is the fact, due to PAINLEV~ [5], that a singularity occurs at the time to if and only if the minimum of the mutual distances between pairs of particles approaches zero as the time t approaches to. In the present paper we shall investigate the problem of singularities due to collisions. We define a singularity at time to to be due to collisions i f as t ~ to each particle approaches a definite position in the inertial coordinate f rame. This means, in view of PAINLEV~'S theorem, that at least two particles approach the same point. In 1908 VON ZEIPEL [4] published a statement to the effect that if the system remains bounded as t--+ to, then a singularity at time t o is due to collisions. His proof is erroneous, and the assertion still stands as a conjecture. The purpose of the present paper is to obtain necessary and sufficient conditions for a singularity due to collisions. It will be supposed that the origin of coordinates is fixed at the center of mass, and that the singularity occurs as t ~ 0 +. The following notation will be used. The symbols m k, re, vk denote respectively the mass, position and velocity of the kth particle. We define further
Utilization deficiencies among children with learning disabilities

Abstract Learning Disabled (LD) and Average children in grades 3, 4, and 5 were tested on a sort/recall task consisting of 5 trials of categorizable words using different categories and different words on each trial. Strategy use was measured separately at encoding and at recall. Average children recalled more than did LD children, even when strategy use was equated, an event which was interpreted as a utilization deficiency. A pattern of increasing disparity between LD and average children with age, due to lack of progress by older LD children, was reported and explained in terms of Stanovich's (1986) Matthew effect. Average children seemed to benefit most from clustering at recall, while older LD children may have benefitted more by strategic behaviors at encoding. A discriminant analysis indicated that LD and Average children differ not only by learning ability but that the basis of their strategic behavior and memory performance may also change with age.
Relapsing diffuse idiopathic tracheal stenosis in a child: Dilemmas in management

Summary Subglottic stenosis is a common presentation of biphasic stridor in young children, however a rarer cause of biphasic stridor is tracheal stenosis. Causes of acquired non-neoplastic diffuse tracheal stenosis include Wegener's granulomatosis, sarcoidosis, TB, relapsing polychondritis, and thermal trauma. However, on occasions no pathological process or agent can be identified as the aetiological factor. In such instances this is defined as idiopathic tracheal stenosis. In this paper, we present the causes of diffuse tracheal stenosis, and propose a sensible pathway for management where a causative agent cannot be elucidated including the use of balloon dilatation within an endotracheal tube.
The right to be information literate : the core foundation of the knowledge society

This article considers the origins and essence of human rights, the requirement that people should have access to information in order to participate in society and develop their human capacity, and the relationship between information and freedom of choice. Information literacy and the right of access to information are interrelated and interconnected. Human freedom implies not only the ability to choose (formal freedom) but also the choices people are able to make (material freedom). It is argued that information literacy, and specifically the ability to evaluate, and benefit from, information, is essential to both formal and material freedom. It is furthermore seen as part of the positive dimension of the right of access to information, and as such implies that the state has a positive duty to protect and promote the right of its citizens to become information literate.
Ritual, religion and the sacred: Selections from the ‘annales: Economies, sociétés, civilisations’, volume 7

(1985). Ritual, religion and the sacred: Selections from the ‘annales: Economies, societes, civilisations’, volume 7. History of European Ideas: Vol. 6, No. 3, pp. 362-363.
Synapses, Language, and Being Human

Humans' ability to cope with the challenges they meet in life is transmitted almost exclusively through the medium of language. We have yet to fully map out the circuits of the human brain, the genes acting on them, and the processes they control that yield this distinct human quality. However, the findings of Sia et al. ( 1 ), on page 987 of this issue, bring us a step closer. The authors have determined that a secreted protein called sushi repeat–containing protein X-linked 2 (SRPX2) promotes mammalian vocalization by controlling the formation of synapses in the mouse cerebral cortex. Expression of this protein is known to be repressed by the transcription factor foxhead box protein P2 (FOXP2), which has been implicated in human language acquisition. A link between these two factors and synaptogenesis may have played a role in the evolution of the neural circuits associated with human language and cognition, as well as the pathogenesis of language disorders.
Characterization of the androgen-sensitive MDA-kb2 cell line for assessing complex environmental mixtures

Synthetic and natural steroidal androgens and estrogens and many other non-steroidal endocrine-active compounds commonly occur as complex mixtures in aquatic environments. It is important to understand the potential interactive effects of these mixtures to properly assess their risk. Estrogen receptor agonists exhibit additivity in mixtures when tested in vivo and in vitro. Little is known, however, concerning possible mixture interactions of androgen receptor agonists. In these studies we used the MDA-kb2 cell line, a human breast cancer cell line with endogenous androgen receptors and a stably transfected luciferase reporter gene construct to quantify the androgenic activity of seven natural and synthetic androgens: 17β-trenbolone, dihydrotestosterone, methyltestosterone, testosterone, trendione, 17α-trenbolone, and androstenedione. We tested combinations of these androgens and compared the observed activity to expected androgenic activity based on a concentration addition model. Our analyses support the hypothesis that androgen receptor agonists cause additive responses in a mixture. Binary mixtures of 17β-trenbolone with 17β-estradiol or triclocarban (an anti-microbial found in the environment) were also tested. 17β-Estradiol induced androgenic activity, but only at concentrations 600-fold greater than those found in the environment. Triclocarban enhanced the activity of 17β-trenbolone. Additionally, three anti-androgens were each paired with three androgens of varying potencies. The relative potencies of the antagonists were a vinclozolin metabolite (M2) > procymidone > prochloraz regardless of the androgen used. The results of our studies demonstrate the potential utility of the androgen-responsive MDA-kb2 cell line for quantifying the activity of mixtures of endocrine-active chemicals in complex wastes such as municipal effluents and feedlot discharges. Environ. Toxicol. Chem. 2010;29:1367–1376. © 2010 SETAC
Overproduction, purification and characterization of M·HinfI methyltransferase and its deletion mutant

We have used the polymerase chain reaction to alter transcriptional and translational signals surrounding the hinfIM gene [encoding M.HinfI methyltransferase (MTase)] so as to achieve overexpression in Escherichia coli. The PCR-generated hinfIM gene was subcloned in a high-expression vector under control of the hybrid trp-lac promoter. In addition, the positive retroregulator stem-loop sequence derived from the crystal protein-encoding gene of Bacillus thuringiensis was inserted downstream from hinfIM. Using a similar approach, we have also constructed overproducer clones of a deletion mutant of M.HinfI MTase that has 97 amino acids from the C terminus deleted. The plasmid from the mutant clones is fully protected from HinfI restriction endonuclease digestion. It appears that the functional properties (the recognition and catalytic functions) are encoded within this mutant gene. The overproducer clones yield the wild type (wt) and the mutant enzymes to about 10% of total cellular protein upon induction with 1 mM IPTG. The wt M.HinfI and the mutant MTase were purified to near electrophoretic homogeneity by phosphocellulose, DEAE and gel chromatography. Their monomer sizes by SDS/polyacrylamide-gel electrophoresis are 43 kDa and 31 kDa, respectively, in good agreement with that predicted from the nucleotide sequence. DNA methylation experiments with purified enzymes using single-strand and double-strand M13mp18 DNA substrates indicate that while wt enzyme methylates both forms of DNA substrates, the mutant enzyme appears to preferentially methylate ss DNA substrate.
Doped Mott insulator: Results from mean-field theory.

The Mott transition phenomena can be studied systematically in the limit of large lattice spatial coordination. We investigate the properties of doped Mott insulators with a variety of techniques and compare our results with experiments on transition-metal oxides. \textcopyright{} 1996 The American Physical Society.
Abstract 5474: The formin, DIAPH3, regulates response to MT stabilizing drugs in prostate and breast cancer

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Diaphanous-related formin-3 (DIAPH3), a cytoskeletal regulator of the formin family, is lost at high frequency in metastatic breast and prostate cancers and has characteristics of a non-canonical metastasis suppressor. We previously showed that DIAPH3 silencing evokes a transition to an “amoeboid” phenotype, characterized by rapid motility, RhoA/ROCK and ERK pathway activation, dynamic membrane blebbing and increased shedding of microvesicles. Here we demonstrate that DIAPH3 loss reduces microtubule (MT) stability in prostate and breast cancer cell lines, and increases the cells' sensitivity to the taxanes, paclitaxel and docetaxel and the non-taxane, epothilone B. DIAPH3 silencing reduces membrane localization of the multidrug resistance-associated protein, MRP1, a regulator of taxane efflux, and increases intracellular accumulation of fluorescent paclitaxel. Baseline acetylation of tubulin, which is proportional to the number of stable MT, is lower in DIAPH3-silenced cells. In contrast, the fold-increase of tubulin acetylation after treatment with MT stabilizing drugs is greater in DIAPH3 knockdown compared to control cells. Further, cytotoxicity induced by paclitaxel, docetaxel or epothilone B is enhanced by DIAPH3 silencing. Analysis of gene expression profiles of breast cancer patients treated with chemotherapeutic regimens containing taxanes in a neoadjuvant phase-2 clinical trial revealed that low DIAPH3 expression is associated with increased relapse free survival. Collectively, the data demonstrate that DIAPH3 deficiency increases responsiveness to widely used MT stabilizing drugs. These findings have implications for the inclusion of DIAPH3 in biomarker panels that stratify patients for treatment with taxanes, in particular in the neoadjuvant setting. Citation Format: Samantha Morley, Sara G. Pollan, Sungyong You, Beatrice S. Knudsen, Michael Freeman. The formin, DIAPH3, regulates response to MT stabilizing drugs in prostate and breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5474. doi:10.1158/1538-7445.AM2014-5474
Efficient global optimization algorithm assisted by multiple surrogate techniques

Surrogate-based optimization proceeds in cycles. Each cycle consists of analyzing a number of designs, fitting a surrogate, performing optimization based on the surrogate, and finally analyzing a candidate solution. Algorithms that use the surrogate uncertainty estimator to guide the selection of the next sampling candidate are readily available, e.g., the efficient global optimization (EGO) algorithm. However, adding one single point at a time may not be efficient when the main concern is wall-clock time (rather than number of simulations) and simulations can run in parallel. Also, the need for uncertainty estimates limits EGO-like strategies to surrogates normally implemented with such estimates (e.g., kriging and polynomial response surface). We propose the multiple surrogate efficient global optimization (MSEGO) algorithm, which adds several points per optimization cycle with the help of multiple surrogates. We import uncertainty estimates from one surrogate to another to allow use of surrogates that do not provide them. The approach is tested on three analytic examples for nine basic surrogates including kriging, radial basis neural networks, linear Shepard, and six different instances of support vector regression. We found that MSEGO works well even with imported uncertainty estimates, delivering better results in a fraction of the optimization cycles needed by EGO.
The public electronic library: web-menuing versus OPAC cataloging

Compares and contrasts the benefits of Web menuing against the merits of OPAC cataloging. Looks at recent electronic developments of OPAC cataloging using web interfacing and the cost implications of cataloging the large volumes of data available. Discusses new metadata formats and offers a succint definition of metadata. Considers the need for national standards in electronic data searching.
Shadows of finite sets

Abstract After a discussion of shadows in a more general setting, we prove for the immediate inclusion graph the union shadow bound theorem, on the finiteness of the bound for the shadow of the union of families of sets if a bound is given for the shadow of each family. Here each family may contain sets of specified cardinalities; for the case of a single cardinality, the same for each family, the theorem reduces to Ramsey's theorem. The proof of the union shadow bound theorem provides also a recursive inequality for the bound.
Targeted Transtracheal Stimulation for Vocal Fold Closure

Paralysis of the structures in the head and neck due to stroke or other neurological disorder often causes dysphagia (difficulty in swallowing). Patients with dysphagia have a significantly higher incidence of aspiration pneumonia and death. The recurrent laryngeal nerve (RLN), which innervates the intrinsic laryngeal muscles that control the vocal folds, travels superiorly in parallel to the trachea in the tracheoesophageal groove. This study tests the hypothesis that functional electrical stimulation (FES) applied via transtracheal electrodes can produce controlled vocal fold adduction. Bipolar electrodes were placed at 15° intervals around the interior mucosal surface of the canine trachea, and current was applied to the tissue while electromyography (EMG) from the intrinsic laryngeal muscles and vocal fold movement visualization via laryngoscopy were recorded. The lowest EMG thresholds were found at an average location of 100° to the left of the ventral midsagittal line and 128° to the right. A rotatable pair of bipolar electrodes spaced 230° apart were able to stimulate bilaterally both RLNs in every subject. Laryngoscopy showed complete glottal closure with transtracheal stimulation in six of the eight subjects, and this closure was maintained under simultaneous FES-induced laryngeal elevation. Transtracheal stimulation is an effective tool for minimally invasive application of FES to induce vocal fold adduction, providing an alternative mechanism to study airway protection.
GPU-Based Steady-State Solution of the Chemical Master Equation

The Chemical Master Equation (CME) is a stochastic and discrete-state continuous-time model for macromolecular reaction networks inside the cell. Under this theoretical framework, the solution of a sparse linear system provides the steady-state probability landscape over the molecular microstates. The CME framework can in fact reveal important insights into basic principles on how biological networks function, having critical applications in stem cell study and cancer development. However, the exploratory nature of system biology research involves the solution of the same reaction network under different conditions. As a result, the application of the CME framework is feasible only if we are able to solve several large linear systems in a reasonable amount of time. In recent years, GPU has emerged as a cost-effective high performance architecture easily available to bioscientists around the world. In this paper, we propose an efficient GPUbased Jacobi iteration for steady-state probability calculation. We provide several optimization strategies based on the problem structure with the aim of outperforming the conventional multicore implementation while minimizing the GPU memory footprint. We combine an ELL+DIAG sparse matrix format with DFS ordering to leverage the diagonal density. Moreover, we devise an improved sliced ELL sparse matrix representation based on warp granularity and local rearrangement. Experimental results demonstrate an average double-precision performance of 14.212 GFLOPS in solving the CME (a speedup of 15.67x compared to the optimized Intel MKL library). Our implementation of the warp-grained sliced ELL format outperforms the state-of-the-art in terms of SpMV performance (a speedup of 1.24x over clSpMV). Moreover, it shows consistent improvements for a wider set of application domains and a good memory footprint reduction. The results achieved in this work provide the foundation for applying the CME framework to realistic biochemical systems. In addition, our GPU-based steady-state computation can be generalized to operation on stochastic matrices (Markov models), achieving good performance with matrix structures similar to biological reaction networks.
Photophysics of Methyl-Substituted Uracils and Thymines and Their Water Complexes in the Gas Phase

We report studies on several methylated uracils and thymines and thymine−water complexes in the gas phase using resonantly enhanced multiphoton ionization (REMPI) and laser-induced fluorescence (LIF) spectroscopy. Results from two different REMPI experiments provided strong evidence that, after photoexcitation to the S1 state, bare molecules were funneled into and trapped in a dark state via fast internal conversion. Lifetimes of this dark state were determined to be tens to hundreds of nanoseconds, depending on the internal energy and the degree of methyl substitution. The mass spectra of hydrated thymine clusters demonstrated dependence on the excitation wavelength, and the gradual loss of the ion signal with increasing water content across the absorption region of the S1 state indicated a reduced lifetime of the S1 state by the water solvent. In addition, the lifetime of the dark state also decreased gradually as thymine became more hydrated. On the basis of these results, we conclude that, in water so...
Behavioral correlates of denervation and reinnervation of the hippocampal formation of the rat: open field activity and cue utilization following bilateral entorhinal cortex lesions.

Abstract Bilateral lesions of the entorhinal cortex (E.C.) of the rat result in persistent deficits in both spontaneous and reinforced alternation. The present study analyzes the nature of this impairment. To determine if changes in exploratory activity accompanied the deficits in alternation, open field activity was measured daily from 2–22 days following bilateral E.C. lesions. Such lesions resulted in a pronounced transient increase in open field activity which peaked between 5 and 7 days postlesion, but subsequently decreased to near preoperative levels at approximately 11 days postlesion. Alternation performance was also analyzed, to determine which cues are utilized to make the alternation, and whether cue utilization is affected by bilateral E.C. lesions. Utilizing a plus (+) maze, animals readily learned to alternate goal arms, but even with extensive training, failed to learn to alternate turns (left and right). However, the ability to identify the two goal arms in a nonalternation situation (which does not require short term recall of the preceding trial) was not permanently impaired by bilateral E.C. lesions. Since bilateral E.C. lesions do not result in persistent deficits in the ability to identify the two goal arms, but do disrupt alternation performance, we hypothesize that the deficit in alternation might reflect an inability to recall which arm was chosen on preceding trials. The implications of these results for an understanding of the behavioral consequences of postlesion reorganization of neuronal circuitry are discussed.
Interindividual Variability in Hepatic Expression of the Multidrug Resistance-Associated Protein 2 (MRP2/ABCC2): Quantification by Liquid Chromatography/Tandem Mass Spectrometry

Multidrug-associated protein 2 (MRP2) is an efflux transporter that is expressed at the bile canalicular membrane. To allow in vitro to in vivo extrapolation of the contribution of MRP2 toward hepatic disposition of its substrates, data on the interindividual variability of hepatic MRP2 protein expression are required. Therefore, we quantified the expression of MRP2 in the University of Washington (UW) human liver bank (n = 51) using a modified version of a previously validated liquid chromatography/tandem mass spectrometry assay. An unlabeled (LTIIPQDPILFSGSLR) and stable isotope-labeled (LTIIPQDPILFSGSL[13C615N1]R) surrogate peptide for MRP2 were used as the calibrator and internal standard, respectively. After isolation of the membrane fraction from the liver tissue, in-solution tryptic digestion was conducted. Quality control samples created by spiking human serum albumin or pooled human liver (n = 51) matrix with three different MRP2 synthetic peptide concentrations generated error and precision values of less than 15%. As determined by the surrogate peptide, the average MRP2 expression in the UW liver bank samples was 1.54 ± 0.64 fmol/μg liver membrane protein and was found to be independent of age (7–63 years) or sex. A single nucleotide polymorphism in the promoter region (rs717620), previously thought to affect MRP2 expression, did not influence hepatic expression of MRP2. In contrast, the single nucleotide polymorphism 21214G>A (V417I; rs2273697) was associated with significantly higher hepatic MRP2 expression.
The role of end-systolic pressure-volume analysis in clinical assessment of ventricular function.

Over the past two decades, the end-systolic pressure-volume relationship (ESPVR) has undergone intensive investigation assessing its role as an index of ventricular contractile function and performance. From this investigation, we have learned that the ESPVR accurately assesses acute changes in contractility and is especially useful in the research setting where cardiac load can be controlled and altered. However, the need to alter load to develop the relationship and the dependence of ESPVR on cardiac mass limits broad clinical usage of the tool.
Cross-Cultural Knowledge Sharing for Competitive Advantage: An Interview With Nigel J. Holden

The contemporary business organization functions in a global economy operating in multiple country environments and with competitive advantage based largely on the ability to develop and manage kno...
Targeting the pro-survival protein MET with tivantinib (ARQ 197) inhibits growth of multiple myeloma cells.

The hepatocyte growth factor (HGF)/MNNG HOS transforming gene (MET) pathway regulates cell growth, survival, and migration. MET is mutated or amplified in several malignancies. In myeloma, MET is not mutated, but patients have high plasma concentrations of HGF, high levels of MET expression, and gene copy number, which are associated with poor prognosis and advanced disease. Our previous studies demonstrated that MET is critical for myeloma cell survival and its knockdown induces apoptosis. In our current study, we tested tivantinib (ARQ 197), a small-molecule pharmacological MET inhibitor. At clinically achievable concentrations, tivantinib induced apoptosis by > 50% in all 12 human myeloma cell lines tested. This biologic response was associated with down-regulation of MET signaling and inhibition of the mitogen-activated protein kinase and phosphoinositide 3-kinase pathways, which are downstream of the HGF/MET axis. Tivantinib was equally effective in inducing apoptosis in myeloma cell lines resistant to standard chemotherapy (melphalan, dexamethasone, bortezomib, and lenalidomide) as well as in cells that were co-cultured with a protective bone marrow microenvironment or with exogenous cytokines. Tivantinib induced apoptosis in CD138 + plasma cells from patients and demonstrated efficacy in a myeloma xenograft mouse model. On the basis of these data, we initiated a clinical trial for relapsed/refractory multiple myeloma (MM). In conclusion, MET inhibitors may be an attractive target-based strategy for the treatment of MM.
African philosophy: a key to African innovation and development

This essay demonstrates how African philosophy can be a key to African innovation and development. Its first section illustrates how philosophy as a discipline drives innovation in science and technology. The second part proposes a new discipline linking science, engineering and technology to sustainable, ethical development. The third section proposes an ethics core derived from ancient Egyptian and Ethiopian thought. It addresses the fact that non-African principles and personnel have in some measure directed African development, resulting in unsustainable and sometimes destructive outcomes. The conclusion argues that the primary instrument for African development must be a Pan-African curriculum developed through research funded by the African Union. The curriculum's dissemination will depend on widespread broadband internet access throughout Africa. The essay's method is philosophical, deploying conceptual analysis of key terms as well as generalized descriptions of the intersections of science, techn...
Ion velocity distributions in gramicidin channels determined with laser Doppler velocimetry.

Laser Doppler scattering from TI(I) ions moving synchronously through an ensemble of gramicidin channels in a bilayer membrane gives their intrachannel velocity distribution. The observed velocity distributions are unimodal indicating that ion flow through some region or regions of the channels is relatively steady. Average intrachannel velocities range from 3.75 · 10−2 m/s to 2.38 · 10−1 m/s for transmembrane potentials between 10 mV and 150 mV, respectively.