cssi/SciSciGPT-SciSciNet huggingface dataset:
On the Response of Viscoelastic Materials to Triangle Pulse and Delta Function Excitations

The stress-strain constitutive relation for linear viscoelastic materials may be expressed on the real time axis by any of several convolution integral formulations. It has been pointed out by Tsch...
Identification of Source Lithology in the Hawaiian and Canary Islands: Implications for Origins

Results are reported of an exploration of mantle source lithology for intraplate magmas using whole-rock and olivine phenocryst compositions.This analysis includes modern mid-ocean ridge basalts and Archean komatiites as low- and high-temperature reference frames. It is shown that the Ni, Ca, Mn, and Fe/Mn contents of olivine phenocrysts in modern mid-ocean ridge basalts and Archean komatiites are consistent with a normal peridotite source. In contrast, olivine phenocrysts in shield-building lavas on Hawaii are higher in Ni and Fe/ Mn, and lower in Mn and Ca than those expected to crystallize from meltsofa normal peridotite source, and point tothe importance ofpyroxenite as proposed by Sobolev and co-workers. Hawaiian shield stage lavas and their olivine phenocrysts are similar to those expected from partial melts of a 100% stage 2 pyroxenite source. Such a source might form from a variety of melt^rock, melt^melt, and rock^rock reactions. Primary pyroxenite-derived magmas have a range of SiO2 contents that are positively correlated with 187 Os/ 188 Os and negatively correlated with 3 He/ 4 He.These results are consistent with a Hawaiian plume containing recycled crust within a peridotite matrix.Variable amounts of free silica are inferred in Hawaiian pyroxenite sources, which contribute to the production of SiO2-rich magmas. In contrast, peridotite and olivine pyroxenite melting are inferred to produce SiO2-poor pre-shield magmas at Loihi.The interaction of SiO2-rich and -poor magmas in the Hawaiian plume will trigger crystallization, not mixing. Mixing is permitted at low pressures in melt conduits and magma chambers, and work on olivine-hosted melt inclusions will be useful to evaluate its importance. In contrast to Hawaii, many ocean island basalts in localities such as the Canary Islands are deficient in SiO2, and may have been generated by partial melting of olivine pyroxenites that formed by solid-state reaction between recycled crust þ peridotite in the lower mantle. There is likely to be a wide range of whole-rock pyroxenite compositions in the mantle, as well assignificant variability in Mn and Fe/Mn in both peridotite partial melts and their olivine phenocrysts. In general, there are not likely to be welldefined end-member peridotite and pyroxenite sources in the mantle. Nevertheless, taxonomical difficulties encountered in source lithology identification may yield rich rewards, such as a better understanding of the relationship between lithological diversity in the lower mantle and its petrological expression in intraplate magmatism.
Nonpharmacologic management of osteoporosis to minimize fracture risk

The traditional management of osteoporosis has focused on the pharmacologic aspects of treatment. Nonpharmacologic approaches, such as the use of orthoses, exercise programs, calcium and vitamin D supplementation, fall prevention, and kyphoplasty have largely been overlooked. Evidence for an essential contribution of nonpharmacologic treatments in the management of osteoporotic patients is increasing, particularly for patients who cannot, or will not, comply with medication regimens. This Review highlights the most important aspects of nonpharmacologic management of osteoporosis.
A study parallel disk organizations

In this paper, several issues related to designing a parallel disk system are discussed. Results of performance evaluation of several parallel disk organizations are presented. A characterization of the disk systems is also presented. Issues such as scalability, networking etc. are discussed. Several problems for future research on improving the I/O performance are pointed out.
Fouling behavior of a pilot scale inside-out hollow fiber UF membrane during dead-end filtration of tertiary wastewater

A series of pilot-scale filtration experiments were performed systematically under various operating conditions to investigate the fouling behavior of ultrafiltration (UF) membranes to treat tertiary wastewater for resuse. All experiments were conducted using a pilot system, which consisted of six inside-out capillary polyether sulfone UF membrane modules (molecular-weight cutoff = 150,000 Da), arranged in parallel configuration. The pilot unit was operated in dead-end filtration mode and the membranes were frequently backwashed with chlorinated water. Results of this research clearly indicated that the productivity of the UF membranes, measured by the specific water flux (Kw), declined much faster as operating flux increased. This observation was attributed to enhanced solid and organic loading to the membrane surface at higher operating fluxes. Furthermore, the analysis of Kw variation against filtrate volume showed larger productivity reduction per foulant mass loading during operation at high flux rates, suggesting the formation of more compact cake layers which were not easily removed during backwashing. Pilot study results also demonstrated that increasing backwashing with chlorine addition significantly improved membrane productivity, primarily due to enhanced foulant removal by organic oxidation and biogrowth control. In addition, flux enhancement per backwashing volume increased with decreasing time between backwashing events. Ferric chloride pretreatment also markedly enhanced membrane productivity by increasing particle floc size, which led to decreased pore plugging, reduced cake layer resistance, and enhanced backwashing efficiency. © 2001 Elsevier Science B.V. All rights reserved.
Is scientific theory change similar to early cognitive development? Gopnik on science and childhood

I offer a two-part critique of one prominent version of the “theory theory,” advocated by Alison Gopnik, according to which early cognitive development is highly similar to scientific theory change. In the first part, I criticize the “strong” thesis that scientific inference and early cognitive development are subserved by the very same mental mechanisms. I contend that Gopnik has failed to distinguish among several different types of theories of scientific inference—including population-level, normative, competence, and performance theories—and that the strong thesis fails to hold for any of them. In the second part, I argue that even a weaker analogy between childhood cognitive development and scientific inference has severe limitations. In particular, I maintain that scientific inference is subserved by significant levels of cross-domain processing while early cognitive development is not. The hope is that the inadequacies in Gopnik's position are instructive. For one, they suggest a tighter analogy, w...
A Compartment Model of VEGF Distribution in Humans in the Presence of Soluble VEGF Receptor-1 Acting as a Ligand Trap

Vascular endothelial growth factor (VEGF), through its activation of cell surface receptor tyrosine kinases including VEGFR1 and VEGFR2, is a vital regulator of stimulatory and inhibitory processes that keep angiogenesis – new capillary growth from existing microvasculature – at a dynamic balance in normal physiology. Soluble VEGF receptor-1 (sVEGFR1) – a naturally-occurring truncated version of VEGFR1 lacking the transmembrane and intracellular signaling domains – has been postulated to exert inhibitory effects on angiogenic signaling via two mechanisms: direct sequestration of angiogenic ligands such as VEGF; or dominant-negative heterodimerization with surface VEGFRs. In pre-clinical studies, sVEGFR1 gene and protein therapy have demonstrated efficacy in inhibiting tumor angiogenesis; while in clinical studies, sVEGFR1 has shown utility as a diagnostic or prognostic marker in a widening array of angiogenesis–dependent diseases. Here we developed a novel computational multi-tissue model for recapitulating the dynamic systemic distributions of VEGF and sVEGFR1. Model features included: physiologically-based multi-scale compartmentalization of the human body; inter-compartmental macromolecular biotransport processes (vascular permeability, lymphatic drainage); and molecularly-detailed binding interactions between the ligand isoforms VEGF121 and VEGF165, signaling receptors VEGFR1 and VEGFR2, non-signaling co-receptor neuropilin-1 (NRP1), as well as sVEGFR1. The model was parameterized to represent a healthy human subject, whereupon we investigated the effects of sVEGFR1 on the distribution and activation of VEGF ligands and receptors. We assessed the healthy baseline stability of circulating VEGF and sVEGFR1 levels in plasma, as well as their reliability in indicating tissue-level angiogenic signaling potential. Unexpectedly, simulated results showed that sVEGFR1 – acting as a diffusible VEGF sink alone, i.e., without sVEGFR1-VEGFR heterodimerization – did not significantly lower interstitial VEGF, nor inhibit signaling potential in tissues. Additionally, the sensitivity of plasma VEGF and sVEGFR1 to physiological fluctuations in transport rates may partially account for the heterogeneity in clinical measurements of these circulating angiogenic markers, potentially hindering their diagnostic reliability for diseases.
Can in situ floats and satellite altimeters detect long‐term changes in Atlantic Ocean overturning?

[1] Global warming has been predicted to slow the Atlantic Meridional Overturning Circulation (AMOC), resulting in significant regional climate impacts across the North Atlantic and beyond. Here, satellite observations of sea surface height (SSH) along with temperature, salinity and velocity from profiling floats are used to estimate changes in the northward-flowing, upper limb of the AMOC at latitudes around 41°N. The 2004 through 2006 mean overturning is found to be 15.5 ± 2.4 Sv (106 m3/s) with somewhat smaller seasonal and interannual variability than at lower latitudes. There is no significant trend in overturning strength between 2002 and 2009. Altimeter data, however, suggest an increase of 2.6 Sv since 1993, consistent with North Atlantic warming during this same period. Despite significant seasonal to interannual fluctuations, these observations demonstrate that substantial slowing of the AMOC did not occur during the past 7 years and is unlikely to have occurred in the past 2 decades.
The Question of “Individuality” in Life History Interpretation

One of the most intriguing, indeed troublesome, questions that bedevils life history research in anthropology has to do with making interpretive statements about the individuality of the life history subject. Since, as a rule, notions of individuality also imply uniqueness, the problem is further compounded and raises a number of complex epistemological and methodological issues. We take individuality to refer to judgments about a complex of features or attributes that distinguish an individual from others. Uniqueness, on the other hand, is a judgment that such a complex is nonreplicable (in that population or humanity); it appears only once in its special form. What, we ask, is epistemologically at stake in the actual rendering of statements about individuality (or individual uniqueness) based on an interpretation of the life history text of a particular subject? How is it possible to arrive at such statements in the first place? And what, if anything, gives us confidence that they mean anything? Methodologically, what factors help or hinder us in making an interpretation that defines individuality as a central element?
Is Dentistry at Risk? A Case for Interprofessional Education

The goal of interprofessional education (IPE) is to bring various professional groups together in the educational environment to promote collaborative practice and improve the health care of patients. Interest in IPE has been sparked by several factors in the health care system, including the increased awareness of oral-systemic connections, an aging population, the shift of the burden of illness from acute to chronic care, and lack of access to basic oral care. Increasingly, since the publication of the U.S. surgeon general's report in 2000, the dialogue surrounding IPE in dentistry has escalated. But how has dentistry changed regarding IPE since the report was released? This position paper argues that little has changed in the way dental students are taught and prepared to participate in IPE. The authors contend that academic dentistry and organized dentistry must take the lead in initiating and demanding IPE if dental students are to be prepared to work in the health care environment of the twenty-first century. Included are reasons why IPE is necessary and why dentistry must lead the conversation and participate in the solution to the oral health care crisis. It explores existing models and alternate approaches to IPE, barriers to implementation, and proposed strategies for academic institutions.
The prevalence of elder self-neglect in a community-dwelling population: hoarding, hygiene, and environmental hazards.

Objectives: To examine the prevalence of self-neglect and its specific behaviors in a community-dwelling population of older adults. Method: A population-based cohort study conducted between 2007 and 2010 rated participant’s personal and home environment, particularly with regard to hoarding, personal hygiene, house in need of repair, unsanitary conditions, and inadequate utility. Prevalence estimates were presented across health-related variables of health status, physical function, and cognitive function. Results: There were 4,627 older adults (1,645 men and 2,982 women). Prevalence of self-neglect in older adults increased with lower health status in both men (4.7% in very good/excellent health, 7.9% in good health, and 14.9% in fair/poor health) and women (4.5% in very good/excellent health, 7.9% in good health, and 10.6% in fair/poor health). For those with ≥3 Katz impairments, the prevalence of self-neglect in older adults was 12.8% in men and 13.8% in women. For those with MMSE (Mini-Mental State E...
Two-year migration of adult female white sharks ( Carcharodon carcharias ) reveals widely separated nursery areas and conservation concerns

Satellite tagging programs have provided detailed information about the migratory patterns of northeastern Pacific white sharks, revealing a seasonal migration between a vast offshore region and coastal aggregation sites. Although adult males undergo annual round-trip migrations, photo-identification programs have noted that sexually mature females may only visit coastal aggregation sites once every 2 years, a behavior that is presumably linked to an estimated 18-month gestation period. The whereabouts of females during their full 2-year migration were previously unknown, because of the limited battery capacity of satellite pop-up tags. Through the use of satellite-linked radio-telemetry tags with multi-year tracking capability, we describe the 2-year migratory pattern for four mature female white sharks tagged at Guadalupe Island, Mexico. The 2-year migration comprised four phases: 1) an Offshore Gestation Phase (which had an average duration of 15.5 months; 2) a Pupping Phase, which occurred along the Mexican coast between the months of April and August; 3) a Pre-Aggregation Phase (when the females were in transition between the Pupping Phase and Guadalupe Island; and 4) the Guadalupe Island Aggregation Phase, which began when the mature females arrived at Guadalupe Island between late September and early October. Long-term satellite tracking of mature female white sharks highlighted the connectivity between a single presumed mating site at Guadalupe Island, and two widely separated pupping sites along the Mexican coast. The Offshore Gestation Phase provided evidence that the females remained offshore for up to 16 months during their 2-year migration cycle. The Pupping Phase along the Mexican coast coincided with the seasonal presence of young-of-the-year white sharks along the coast of North America, and with a presumed gestation period of 18 months, this placed mating between October and January, during the period when white sharks are known to be at Guadalupe Island. Tracking data during the time sharks were offshore showed that mature males and females are spatially segregated, except for their concurrent seasonal presence at Guadalupe Island. These discoveries provide important new details about the complete life history of northeastern Pacific white sharks while identifying crucial regions in which young-of-the-year, juveniles and adult females are most vulnerable.
Science Signaling Podcast: 10 December 2013

This is an interview with Judith Davie, senior author of a Research Article published in the 10 December 2013 issue of Science Signaling , about how an inflammatory cytokine interferes with muscle repair. Inflammatory cytokines are produced at sites of infection and tissue damage, and they promote the inflammatory processes that fight pathogens and initiate tissue repair. When skeletal muscles are damaged, they secrete the inflammatory cytokine interferon-γ (IFN-γ), which helps muscles heal. Although transient production of IFN-γ is required for repairing damaged muscle, too much of it hinders repair. Priya Londhe and Judith Davie report that excess IFN-γ represses the expression of muscle-specific genes that are required for the differentation of new muscle cells.
The Energy Landscape Analysis of Cancer Mutations in Protein Kinases

The growing interest in quantifying the molecular basis of protein kinase activation and allosteric regulation by cancer mutations has fueled computational studies of allosteric signaling in protein kinases. In the present study, we combined computer simulations and the energy landscape analysis of protein kinases to characterize the interplay between oncogenic mutations and locally frustrated sites as important catalysts of allostetric kinase activation. While structurally rigid kinase core constitutes a minimally frustrated hub of the catalytic domain, locally frustrated residue clusters, whose interaction networks are not energetically optimized, are prone to dynamic modulation and could enable allosteric conformational transitions. The results of this study have shown that the energy landscape effect of oncogenic mutations may be allosteric eliciting global changes in the spatial distribution of highly frustrated residues. We have found that mutation-induced allosteric signaling may involve a dynamic coupling between structurally rigid (minimally frustrated) and plastic (locally frustrated) clusters of residues. The presented study has demonstrated that activation cancer mutations may affect the thermodynamic equilibrium between kinase states by allosterically altering the distribution of locally frustrated sites and increasing the local frustration in the inactive form, while eliminating locally frustrated sites and restoring structural rigidity of the active form. The energy landsape analysis of protein kinases and the proposed role of locally frustrated sites in activation mechanisms may have useful implications for bioinformatics-based screening and detection of functional sites critical for allosteric regulation in complex biomolecular systems.
Comparison of single-ISA heterogeneous versus wide dynamic range processors for mobile applications

Mobile computing devices demand processors to offer a wide range of performance/power trade-offs so that they can provide much needed high performance or low power consumption depending on a given operating requirement. While dynamic voltage/frequency scaling (DVFS) has been the most powerful technique to provide such trade-offs, few processor vendors have the capability to provide a sufficient DVFS range requiring joint optimization of devices and circuits. Facing such a challenge, two promising approaches are proposed: scaling the amount of processor resources such as on-chip memory and execution units, i.e., dynamic resource scaling (DRS) and switching between big out-of-order (OoO) and little in-order cores in a single-ISA heterogeneous processor such as ARM's big. LITTLE. In this paper, we compare a single-ISA heterogeneous processor with a wide dynamic range (WDR) processor augmented with DRS in terms of (1) device-, circuit-, architecture-level implications, (2) design challenges, (3) area, (4) performance, and (5) energy efficiency. We evaluate a big. LITTLE processor (as a representative of single-ISA heterogeneous processor) based on Cortex-A15/A7 and a WDR processor based on Cortex-A15 running various mobile and SPEC2006 benchmarks. Our experiments demonstrate that the WDR processor combined with DRS can deliver energy efficiency close to the single-ISA heterogeneous processor, depending on the power overhead of circuit implementation to provide the wide DVFS range.
Original article: Treatment of epidemic Kaposi's sarcoma with combination chemotherapy (vincristine and bleomycin) and zidovudine

Summary Advanced AIDS-associated Kaposi's sarcoma often requires systemic cytotoxic chemotherapy. Despite high response rates, the majority of the patients die of opportunistic infections (OIs). Effective anti-retroviral agents in combination with cytotoxic chemotherapy may be useful in preventing the development of OIs in addition to increasing the tumor response. Twelve patients with extensive EKS were treated with a non-myelosuppressive drug regimen consisting of bleomycin and vincristine (BV) in combination with the anti-retroviral agent, zidovudine (ZDV). The dose of ZDV was 200 mg orally every four hours (full dose) in eight patients (Group I) or 100 mg orally every four hours (half dose) in four patients (Group IT). Toxicity was acceptable with only 3 patients (all from Group I) requiring blood transfusions. ZDV dose reduction due to granulocytopenia was required in 6 patients (5 in Group I and 1 in Group II). Only two patients developed OIs during 27.5 cumulative months of therapy. The overall response rate was 83% in both groups with 4 patients achieving complete remission (CR) and 6 patients achieving a partial remission (PR). We conclude that a combination of (BV) chemotherapy and ZDV can be used safely with high response rates. Prospective studies of such combination regimens are currently in progress.
Abstract 232: Postgraduate Education in Quality Improvement Methods: Initial Results of the Fellows’ Applied Quality Training Curriculum

Background: Formal training in quality improvement (QI) methods is sporadic in medical educational settings. QI is a growing expectation for individual professional certifications and facility accreditations; future physicians will need to understand and apply QI methods as part of their practice. We developed a curriculum with both didactic and applied components to teach QI methods to cardiology fellows. Methods: The Fellows Applied Quality Training (FAQT) curriculum started in July 2013 with an initial cohort of 23 postgraduate trainees in general and subspecialty cardiovascular medicine fellowships. The FAQT is a multifaceted QI curriculum consisting of online learning modules, didactic training, and the start-to-finish completion of a team-based, self-directed quality improvement project under supervision of a faculty mentor. Trainees completed selected modules from the Institute of Healthcare Improvement Open School including basic terminology and background of QI methods. Trainees were assigned to small groups and challenged to identify an area in need, design an intervention to improve quality or safety, select an appropriate metric to measure, determine how to acquire the necessary data, implement their plan, analyze data to measure their success, and formally present the results. Prior to, during, and at the completion of the FAQT, trainees completed the 13 question self-assessment from the Quality Assessment and Improvement Curriculum. This assessment asks participants to rate their confidence to perform QI activities independently. The primary outcome of our investigation was an increase in the median confidence score reported on a 4 point scale (1=not at all confident, 2=slightly confident, 3=moderately confident, 4=extremely confident) compared by Wilcoxon signed rank test. Results: Prior to the FAQT, 15 trainees reported no prior formal QI training. Of those with prior training, 4 were practical and 4 had only didactic training. At baseline, the median score given on the assessment was 3.0. After completion of online training modules, the median score did not increase (3.0, p=0.51). At the conclusion of the self-directed projects, average confidence was higher (3.27, p=0.004). The proportion of fellows reporting they were “extremely” confident about using quality assessment and improvement in your future career increased from15% to 50% while the proportion reporting “slight” confidence decreased from 30% to 5%. Conclusion: At our institution, the majority of post-graduate medical trainees had no formal exposure to QI training. After completing a curriculum with practical application of QI methods, trainees reported an increase in their self-confidence to independently conduct QI; no increase was observed with didactic training alone.
Empirical and fully Bayesian approaches for random effects models in microarray data analysis

A linear model involving a mixture distribution is considered for the comparison of normalized microarray data from two treatment groups. Model fitting using an empirical Bayes approach has been sh...
Why are some STEM fields more gender balanced than others

Women obtain more than half of U.S. undergraduate degrees in biology, chemistry, and mathematics, yet they earn less than 20% of computer science, engineering, and physics undergraduate degrees (National Science Foundation, 2014a). Gender differences in interest in computer science, engineering, and physics appear even before college. Why are women represented in some science, technology, engineering, and mathematics (STEM) fields more than others? We conduct a critical review of the most commonly cited factors explaining gender disparities in STEM participation and investigate whether these factors explain differential gender participation across STEM fields. Math performance and discrimination influence who enters STEM, but there is little evidence to date that these factors explain why women's underrepresentation is relatively worse in some STEM fields. We introduce a model with three overarching factors to explain the larger gender gaps in participation in computer science, engineering, and physics than in biology, chemistry, and mathematics: (a) masculine cultures that signal a lower sense of belonging to women than men, (b) a lack of sufficient early experience with computer science, engineering, and physics, and (c) gender gaps in self-efficacy. Efforts to increase women's participation in computer science, engineering, and physics may benefit from changing masculine cultures and providing students with early experiences that signal equally to both girls and boys that they belong and can succeed in these fields. (PsycINFO Database Record
Medicine: The Decisive Test of Anticipation

Given the life and death extremes at which medicine operates, no other human activity is of higher significance to members of society, and to society itself. Therefore, it is surprising that, instead of aligning itself with the anticipatory condition of life, medical practitioners at all levels approach health from the physics perspective of reaction and reductionism. On the other hand, anticipation—definitory of the living—could prove to be consequential if the perspective it opens would become the backbone of medicine. The study discusses the reported negative effects of healthcare and medical practice based on the mechanical model provided by physics-dominated science. Acknowledging technological progress in medicine, the study also provides actual expressions of anticipation important for the theory and practice of medicine. Complexity is examined as a characteristic of anticipatory systems. Lastly, the study suggests concrete steps towards an anticipation-grounded medical education.
Studies of electrochemical interfaces by broadband sum frequency generation

Abstract We present a perspective on the use of potential-dependent broadband multiplex vibrational sum-frequency generation spectroscopy (hereafter SFG) to study electrochemical systems. In SFG, a broadband mid-infrared (IR) pulse is combined with a narrowband visible pulse, generating a pulse at the sum frequency, which contains a spectrum that, due to the principles of nonlinear optics, originates solely from the electrified interface. Our SFG spectrometer can obtain one hundred or more spectra during a routine cyclic voltammetry (CV) measurement. We used SFG to study a model for a Li-ion battery anode and a low-overpotential CO 2 reduction reactor based on a room-temperature ionic liquid (RTIL). SFG spectra from these complex systems were difficult to interpret, in part due to the organic electrolytes that have a forest of infrared vibrational transitions. Here we discuss a rubric for experimental measurement and interpretation with such systems. We describe the electrified interface, or double layer, as consisting of the electrode surface, a region of adsorbed molecules and an outer diffuse electric double layer. We combined resonant SFG, where the IR pulses were tuned to vibrational transitions of adsorbates, with nonresonant SFG where the IR pulses were tuned away from all vibrational transitions. The former provides information about chemistry on the electrode surface and the latter about the potential-dependent response of the double layer. We show how this rubric can be used to understand solid-electrolyte interphase formation on a model for the Li-ion electrode, and how low-overpotential CO 2 reduction on Ag is controlled by potential-driven structural transitions of the RTIL electrolyte.
Preparation of Protective Nanocomposite Coatings by Ultra-Fast Gas-Dynamic Formation Using Hard Alloy Electro-Erosion Powders

Results are presented for a study of protective nanocomposite coating properties prepared by ultra-fast gasdynamic formation using hard alloy electro-erosion powders.
Defining a Novel Role for the Pdx1 Transcription Factor in Islet β-Cell Maturation and Proliferation During Weaning.

The transcription factor encoded by the Pdx1 gene is a critical transcriptional regulator, as it has fundamental actions in the formation of all pancreatic cell types, islet β-cell development, and adult islet β-cell function. Transgenic- and cell line-based experiments have identified 5'-flanking conserved sequences that control pancreatic and β-cell type-specific transcription, which are found within areas I (bp -2694 to -2561), II (bp -2139 to -1958), III (bp -1879 to -1799), and IV (bp -6200 to -5670). Because of the presence in area IV of binding sites for transcription factors associated with pancreas development and islet cell function, we analyzed how an endogenous deletion mutant affected Pdx1 expression embryonically and postnatally. The most striking result was observed in male Pdx1ΔIV mutant mice after 3 weeks of birth (i.e., the onset of weaning), with only a small effect on pancreas organogenesis and no deficiencies in their female counterparts. Compromised Pdx1 mRNA and protein levels in weaned male mutant β-cells were tightly linked with hyperglycemia, decreased β-cell proliferation, reduced β-cell area, and altered expression of Pdx1-bound genes that are important in β-cell replication, endoplasmic reticulum function, and mitochondrial activity. We discuss the impact of these novel findings to Pdx1 gene regulation and islet β-cell maturation postnatally.
De novo assembly and characterization of breast cancer transcriptomes identifies large numbers of novel fusion-gene transcripts of potential functional significance

Gene-fusion or chimeric transcripts have been implicated in the onset and progression of a variety of cancers. Massively parallel RNA sequencing (RNA-Seq) of the cellular transcriptome is a promising approach for the identification of chimeric transcripts of potential functional significance. We report here the development and use of an integrated computational pipeline for the de novo assembly and characterization of chimeric transcripts in 55 primary breast cancer and normal tissue samples. An integrated computational pipeline was employed to screen the transcriptome of breast cancer and control tissues for high-quality RNA-sequencing reads. Reads were de novo assembled into contigs followed by reference genome mapping. Chimeric transcripts were detected, filtered and characterized using our R-SAP algorithm. The relative abundance of reads was used to estimate levels of gene expression. De novo assembly allowed for the accurate detection of 1959 chimeric transcripts to nucleotide level resolution and facilitated detailed molecular characterization and quantitative analysis. A number of the chimeric transcripts are of potential functional significance including 79 novel fusion-protein transcripts and many chimeric transcripts with alterations in their un-translated leader regions. A number of chimeric transcripts in the cancer samples mapped to genomic regions devoid of any known genes. Several ‘pro-neoplastic’ fusions comprised of genes previously implicated in cancer are expressed at low levels in normal tissues but at high levels in cancer tissues. Collectively, our results underscore the utility of deep sequencing technologies and improved bioinformatics workflows to uncover novel and potentially significant chimeric transcripts in cancer and normal somatic tissues.
Socioeconomic status and breast cancer treatment

Evidence suggests substantial disparities in breast cancer survival by socioeconomic status (SES). We examine the extent to which receipt of newer, less invasive, or more effective treatments—a plausible source of disparities in survival—varies by SES among elderly women with early-stage breast cancer. Multivariate regression analyses applied to 11,368 women (age 66–90 years) identified from SEER-Medicare as having invasive breast cancer diagnosed in 2006–2009. Socioeconomic status was defined based on Medicaid enrollment and level of poverty of the census tract of residence. All analyses controlled for demographic, clinical health status, spatial, and healthcare system characteristics. Poor and near-poor women were less likely than high SES women to receive sentinel lymph node biopsy and radiation after breast-conserving surgery (BCS). Poor women were also less likely than near-poor or high SES women to receive any axillary surgery and adjuvant chemotherapy. There were no significant differences in use of aromatase inhibitors (AI) between poor and high SES women. However, near-poor women who initiated hormonal therapy were more likely to rely exclusively on tamoxifen, and less likely to use the more expensive but more effective AI when compared to both poor and high SES women. Our results indicate that SES disparities in the receipt of treatments for incident breast cancer are both pervasive and substantial. These disparities remained despite women’s geographic area of residence and extent of disease, suggesting important gaps in access to effective breast cancer care.
Availability of Pharmacist-Prescribed Contraception in California, 2017

This survey study estimates the extent to which pharmacies in California are making pharmacist-prescribed contraception available since it was permitted, but not required, in April 2016.
Impact of loading and work rest intervals on muscle micro-trauma

Abstract Purpose To examine whether rest intervals of different durations (“High Rest, Low Frequency” v. “Low Rest, High Frequency”), and load at different force exertion levels with different repetition frequencies (“High Load, Low Repetition” v. “Low Load, High Repetition”) have an impact on muscle micro-trauma, as such micro-trauma over repetitive loading and long-term muscle overuse can lead to musculoskeletal disorders (MSDs). Method Twenty-four adult males (mean age: 24.1 years; 3.6 SD) were randomly assigned to one of 4 bicep muscle eccentric exercise treatment groups (n = 6; “High Load, Low Repetition; High Rest, Low Frequency”, “High Load, Low Repetition; Low Rest, High Frequency”, “Low Load, High Repetition; High Rest, Low Frequency”, or “Low Load, High Repetition; Low Rest, High Frequency”) with non-dominant arm to induce muscle micro-trauma reactions in serum. Subjects in all treatment groups had equivalent total work volume, total rest duration and total work duration for comparison of muscle micro-trauma between and within the treatment groups. Muscle micro-trauma biomarker serum Creatine Kinase (CK) level was measured pre-exercise (Day 0) and post-exercise on Days 1, 2, 4, and 8. ANOVA with repeated measures was used to examine significance of rest and load-repetition combination over pre and post experiment days, as well as possible interactions. Result CK levels fluctuated significantly across different “Day” (P = 0.0115). Interaction was disordinal and significant between “Day” and “Rest” (P = 0.0000), and “Load” and “Rest” (P = 0.0322). Under “High Load, Low Repetition” condition, CK levels on Day 4 were significantly higher than on Days 0 and 2; CK levels on Day 8 were significantly higher than Day 0. CK level peaked on Day 4. Under “Low Rest” Condition, CK level on Days 4 and 8 are significantly higher than Day 0. Conclusion Shorter but more frequent rest intervals led to more extreme muscle micro-traumatic responses than the longer but less frequent ones, especially under “High Load, Low Repetition” condition when non-dominant bicep brachii was subscribed with eccentric exercise regimen. Relevance to industry The exploration of how rest scheduling affects progression of microtrauma from a biomechanical and molecular level in this study furthers current understanding of the early stage development of WMSDs. With future studies’ further research and confirmation, the findings of this study may be able to serve as a first attempt to guide shift scheduling and job design at manufacturing facilities.
Epigenetics, Alcohol, and Cancer

Chronic or excessive alcohol consumption often leads to various medical disorders, including liver cirrhosis, pancreatitis, cardiomyopathy, fetal abnormalities, brain damage, and various cancers. To effectively prevent or treat these disorders, a better understanding of their underlying mechanisms is pivotal. Alcohol and its metabolites alter cellular functions through changes at the levels of DNA, RNA, protein, and metabolites, resulting in pathophysiological changes. Although the amount of RNA, protein, or metabolites is determined by dynamic processes of synthesis and degradation with many regulators involved, it is initially predominantly determined by the activity of the genes involved. Two major mechanisms of gene regulation involve genetic and epigenetic controls of gene expression. In the past half century, research and technological innovations have led to a remarkable progress in understanding the genetic controls of gene activities. However, only in recent years, epigenetic controls of gene expression drew immense interest, especially in the biomedical fields of cancer and ageing. To date, research efforts to understand effects of alcohol on regulation of gene activity have been primarily focused on genetic factors. The mechanisms of epigenetic modifications in alcohol-induced organ damage, including cancers, have only started to be tackled in the past few years.
Linear Differential Equations and Kronecker's Canonical Form

Publisher Summary This chapter describes the linear differential equations and Kroneckers canonical form. It presents a solution of an explicit system of linear differential equations of first order with constant coefficients. The general solution may be given in terms of quadratures. It involves three arbitrary constants and the initial values may be prescribed arbitrarily and no relations are required for the solution to exist. The relevance to the general solution of the explicit system is almost universally appreciated by numerical analysts. The differential equations rarely arise in the explicit form. Much more commonly they arise in the implicit form. The relevant algebraic theory in this case is provided by the work on the matrix pencil. The transformation to will usually take place in a number of elementary steps in some of which selected variables will remain unchanged. The corresponding matrix involved in the change of variables in such a stage will be block diagonal, the diagonal block being the identity matrix for the variables which are unchanged. The associated variables are uniquely determined and cannot prescribe their initial values arbitrarily.
Crystallization of non-fullerene acceptor might cause catastrophic failure in ductile organic solar cells (Conference Presentation)

Organic solar cell (OSC) technology has recently achieved over 13% efficiency through the synthesis of novel non-fullerene small molecule acceptors (NFAs), which can be processed from benign solvents as low-cost third generation photovoltaics[1,2]. Of critical importance to OSCs is understanding the morphological and thermal stability of the active layers governed by thermodynamics and kinetics as an intrinsic stability process which cannot be controlled by encapsulation[3,4]. Here we highlight the importance of ductility of donor polymers on nucleation and growth of micro-size small molecule crystals which leads to the catastrophic failure of the solar cells in the long-term operating condition We consider three high performance polymers P3HT, PBnDBT-FTAZ, and PffBT4T-C9C13 blended with EH-IDTBR as the model systems to investigate the thermal stability of state of the art non-fullerene OSCs, where elevated temperatures were used to accelerate the crystal formation and imitate the long-term operation conditions of OCSs. We also propose an easy accessible method using differential scanning calorimetry (DSC) to investigate the thermal behavior of NFA in the blends. Although non-fullerene solar cells have shown to have better overall morphological stability compared to their fullerene counterparts, our results suggest that catastrophic failure due to micro-size crystal formation in non-fullerene systems can happen at a rate similar to fullerene systems unless the right donor polymer is chosen to suppress the crystallization of small molecule. It is also shown and argued that the growth rate of small molecule crystals can be reduced upon mixing of NFAs with semi-crystalline polymers, such as P3HT with a higher overall density compared to amorphous donor polymers, i.e. PBnDT-FTAZ. Our findings may pave a way to understand and predict the morphological stability of non-fullerene OSCs. References [1] L. Ye, Y. Xiong, Q. Zhang, S. Li, C. Wang, Z. Jiang, J. Hou, W. You, H. Ade, Adv. Mater. 2017, DOI: 10.1002/adma.201705485. [2] S. Holliday, R. S. Ashraf, A. Wadsworth, D. Baran, S. A. Yousaf, C. B. Nielsen, C.-H. Tan, S. D. Dimitrov, Z. Shang, N. Gasparini, M. Alamoudi, F. Laquai, C. J. Brabec, A. Salleo, J. R. Durrant, I. McCulloch, Nat. Commun. 2016, 7, 11585. [3] M. Ghasemi, L. Ye, Q. Zhang, L. Yan, J. H. Kim, O. Awartani, W. You, A. Gadisa, H. Ade, Adv. Mater. 2017, 29, 1604603. [4] L. Ye, H. Hu, M. Ghasemi, T. Wang, B. A. Collins, J.-H. Kim, K. Jiang, J. Carpenter, H. Li, Z. Li, T. McAfee, J. Zhao, X. K. Chen, J. Y. L. Lai, T. Ma, J.-L. Bredas, H. Yan, H. Ade, Nat. Mater. 2018, DOI: 10.1038/s41563-017-0005-1.
Storied Places: Pilgrim Shrines, Nature, and History in Early Modern France

Pilgrim shrines were places of healing, holiness, and truth in early modern France. By analyzing the creation of these pilgrim shrines as natural, legendary, and historic places whose authority provided a new foundation for post-Reformation Catholic life, Virginia Reinburg examines the impact of the Reformation and religious wars on French society and the French landscape. Divided into two parts, Part I offers detailed studies of the shrines of Sainte-Reine, Notre-Dame du Puy, Notre-Dame de Garaison, and Notre-Dame de Betharram, showing how nature, antiquity, and images inspired enthusiasm among pilgrims. These chapters also show that the category of 'pilgrim' included a wide variety of motivations, beliefs, and acts. Part II recounts how shrine chaplains authored books employing history, myth, and archives in an attempt to prove that the shrines were authentic, and to show that the truths they exemplified were beyond dispute.
Sensitivity of Fusarium oxysporum f. sp. niveum to Prothioconazole and Pydiflumetofen In Vitro and Efficacy for Fusarium Wilt Management in Watermelon

Field experiments were conducted in 2015 and 2016 to determine the effects of drench or drench-plus-foliar applications of prothioconazole and pydiflumetofen on Fusarium wilt (caused by Fusarium ox...
ARF suppresses 5’-terminal oligopyrimidine mRNA translation

Tumor cells require nominal increases in protein synthesis in order to maintain high proliferation rates. As such, tumor cells must acquire enhanced ribosome production. How many of the mutations in tumor cells ultimately achieve this aberrant production is largely unknown. The gene encoding ARF is the most commonly deleted gene in human cancer. ARF plays a significant role in regulating ribosomal RNA synthesis and processing, ribosome export into the cytoplasm, and global protein synthesis. Utilizing ribosome profiling, we show that ARF is a major suppressor of 59-terminal oligopyrimidine mRNA translation. Genes with increased translational efficiency following loss of ARF include many ribosomal proteins and translation factors. Knockout of p53 caused a similar increase in 59-TOP mRNA translation. The 59-TOP regulators mTORC1, eIF4G1 and LARP1 are dysregulated in ARF and p53 null cells.
Anaplastic Lymphoma Kinase Mutation–Positive Non–Small Cell Lung Cancer

The treatment of patients with advanced non-small cell lung cancer with anaplastic lymphoma kinase chromosomal rearrangements has been revolutionized by the development of tyrosine kinase inhibitors (TKIs). Excellent progress has been made over the past decade, with 4 TKIs now approved in the front-line setting. Alectinib is the preferred first-line option based on its efficacy and side-effect profile. The central nervous system (CNS) activity of alectinib and brigatinib has allowed for treatment of CNS metastases with TKI therapy. Once resistance inevitably develops, newer therapies such as lorlatinib can be considered.
“Is There a Self in This Text? Satire, Passing, and Life in Danzy Senna’s Caucasia”

In this paper, I argue that Danzy Senna’s Caucasia is a satirical passing narrative that exposes the tragedy of traditional passing novels as archaic for relying on racial binaries and perpetuating...
Urban Vegetation Slows Down the Spread of Coronavirus Disease (COVID-19) in the United States

Key Points: Urban vegetation can well explain the large spatial variability of the COVID-19 incidence and can slow down the spread of COVID-19 Population density and the timing of government intervention on COVID-19 are strongly associated with the spread of COVID-19 There is no evidence that warm weather would curb the spread of COVID-19
3D-printed assistive pipetting system for gel electrophoresis for technicians with low acuity vision

In molecular biology laboratories, many tasks require fine motor control and high acuity vision. For example, lab technicians with visual impairment experience difficulty loading samples into the small wells of a horizontal agarose gel. We have developed a 3D-printable gel loading system which allows technicians with low-contrast vision to load gels correctly. It includes a casting tray, a bridge, and a modified comb. The system provides a high-contrast visual field to improve visibility, and the bridge allows pipette tips to be inserted at the correct location and only to the correct depth. The necessary computer files for printing this device are freely available to increase the accessibility of molecular biology laboratories to people with visual impairment.