cssi/SciSciGPT-SciSciNet huggingface dataset:
College Students’ Perceptions of Positive and Negative Effects of Social Networking

The aim of this study was to examine college students’ perceptions of social networking in the United States. A secondary purpose was to determine whether differences in gender and age were prevalent. One hundred and twenty eight (N = 128) students were surveyed online. Data showed that social networking was helpful for communication, information gathering, and that it positively influenced their academic work. However, students also reported that social networking had a negative impact on their social interactions, emotional health and work completion, with younger participants reporting greater negative effects of social networking on work completion. Students also reported that social networking can be addictive, distractive, and a threat to their privacy. Although no significant gender differences emerged in students’ perceptions, numerically females viewed social networking in more positive terms. Educational implications and future directions for research are discussed.
Thermal resistance of nonproteolytic type B and type E Clostridium botulinum spores in phosphate buffer and turkey slurry.

The heat resistance of nonproteolytic type B and type E Clostridium botulinum spores in phosphate buffer and turkey slurry was determined from 70 to 90°C. Thermal-death times were determined in vials heated using a water bath. Recovery of heat-injured spores was on reinforced clostridial medium (RCM) and tryptic soy agar (TSA) with and without added lysozyme (10 μg/ml). Decimal-reduction times (D-values) were determined by fitting a survival model to the data using a curve-fitting program. The apparent or measured heat resistance was maximum with RCM supplemented with lysozyme. The D-values at 80°C for type E spores in buffer ranged from 1.03 min for strain Whitefish to 4.51 min for strain Saratoga. The D-value for the most heat-resistant nonproteolytic type B strain KAP B5 in buffer was 4.31 min at 80°C. The z-values in buffer for all strains were very similar, ranging from 8.35 to 10.08°C.Turkey slurry offered protection to the spores with a concomitant increase in heat resistance. The D-values in turke...
Prodigious Effects of Concentration Intensification on Nanoparticle Synthesis: A High-Quality, Scalable Approach

Realizing the promise of nanoparticle-based technologies demands more efficient, robust synthesis methods (i.e., process intensification) that consistently produce large quantities of high-quality nanoparticles (NPs). We explored NP synthesis via the heat-up method in a regime of previously unexplored high concentrations near the solubility limit of the precursors. We discovered that in this highly concentrated and viscous regime the NP synthesis parameters are less sensitive to experimental variability and thereby provide a robust, scalable, and size-focusing NP synthesis. Specifically, we synthesize high-quality metal sulfide NPs ( 200 g) relative to the current field of large-scale (0.1–5 g yields) and laboratory-scale (<0.1 g) efforts. Compared to conventional synthesis methods (hot injection with dilute precursor concentration) characterized by rapid growth and low yield, our highly c...
Microwave Impedance Studies on High Temperature Superconductors Using a Dielectric Sapphire Resonator in High Magnetic Fields

The vortex dissipation in an N4-Ce-Cu-O1 epitaxial film is measured at microwave frequencies using the high-Q modes of a sapphire ring resonator, over a large range of temperatures and external DC magnetic fields. The results are qualitatively consistent with a generalized thermally-activated flux-flow (TAFF) model.
Complexes with FeIII2(μ-O)(μ-OH), FeIII2(μ-O)2, and [FeIII3(μ2-O)3] Cores: Structures, Spectroscopy, and Core Interconversions

We have synthesized the first complexes with bis(μ-oxo)diiron(III) and (μ-oxo)(μ-hydroxo)diiron(III) cores (1 and 2, L = TPA (a), 5-Et3-TPA (b), 6-Me3-TPA (c), 4,6-Me6-TPA (d), BQPA (e), BPEEN (f), and BPMEN (g)) and found them to have novel structural properties. In particular, the presence of two single-atom bridges in these complexes constrains the Fe−Fe distances to 2.7−3.0 A and the Fe−μ-O−Fe angles to 100° or smaller. The significantly acute Fe−O−Fe angles (e.g., 92.5(2)° for 1c and 100.2(2)° for 2f) enforced by the Fe2O2(H) core endow these complexes with UV−vis, Raman, and magnetic properties quite distinct from those of other (μ-oxo)diiron(III) complexes. Complex 1c exhibits visible absorption bands at 470 (e = 560 M-1 cm-1) and 760 nm (e = 80 M-1 cm-1), while complexes 2 show features at ca. 550 (e ≈ 800 M-1 cm-1) and ca. 800 nm (e ≈ 70 M-1 cm-1), all of which are red shifted compared to those of other (μ-oxo)diiron(III) complexes. These complexes also exhibit distinct νFe-O-Fe vibrations at ca....
3-Hydroxykynurenine, 3-hydroxyanthranilic acid, and o-aminophenol inhibit leucine-stimulated insulin release from rat pancreatic islets.

AbstractIndividual islets were isolated from rat pancreas to study the effects of tryptophan and its metabolites on leucine-stimulated release of insulin. 3-Hydroxykynurenine, 3-hydroxyanthranilic acid, and o-aminophenol were inhibitors at concentrations below 10 mM whereas tryptophan, kynurenine, kynurenic acid, xanthurenic acid, and anthranilic acid were ineffective inhibitors at concentrations up to 10 mM. A structure-activity analysis of these metabolites demonstrated that vicinal aromatic hydroxy and amino groups with their concomitant electron donating properties are required for inhibition of insulin release. Inhibition of islet insulin release by the three kynurenine metabolites may be involved in the depressed insulin levels found in vitamin B6-deficient rats by other workers.
Automated Transient Input Stimuli Generation for Analog Circuits

We present an automated directed random input stimulus generation algorithm with high coverage for nonlinear analog circuits. Our methodology is able to generate input stimuli to meet two kinds of objectives: 1) to reach user-defined goal regions and 2) increased coverage of state space. The principal benefit of our approach is that it can provide directed input stimulus generation, as opposed to the randomly generated input stimulus by Monte Carlo-based methods. The methodology introduces multiobjective rapidly-exploring random trees (MORRTs), which add a bias and a feedback loop to the standard rapidly-exploring random trees algorithm. The biasing is provided by a statistical inference algorithm. Simultaneous biasing toward goal regions and coverage is possible in MORRT to a user-defined extent. Our methodology generates several input stimuli that are concentrated in the goals or relevant operating regions, while providing high coverage of the state space. We demonstrate the efficiency and scalability of our approach on high-dimensional analog case studies.
182 PERINATAL OUTCOMES AMONG INFANTS 24-32 WEEKS GESTATION DELIVERED BETWEEN 1/1998 AND 12/2003 ± ANTENATAL MATERNAL TOBACCO EXPOSURE

Tobacco use during pregnancy continues to be a significant public health problem. Maternal smoking during pregnancy is a well documented risk factor for LBW infant births. Mothers who smoke are 2× as likely to have a LBW infant, and tobacco use during pregnancy is responsible for 20-30% of all LBW infants. We looked at perinatal outcomes among preterm infants between 24-32 weeks gestation delivered between 1/98012/03 at JCMCH by retrospective chart analysis. (Table) Among those who died, average GA ˜ 26 weeks; among those exposed to tobacco who died (n = 6), average BW ˜ 664 g, while those unexposed (n = 20), average BW ˜ 806 g. No untoward short-term morbidity associated with antenatal exposure to by-products of maternal tobacco use.
Current factors in the causation of tubal pregnancy. A prospective clinicopathologic study.

The threat, morbidity, and high incidence of tubal pregnancy are widely recognized. The etiologic factors have not been clearly identified in the past. This study was initiated to survey possible causative factors in this antibiotic era. Sixty-four cases were studied prospectively and 84 others reviewed retrospectively. Tubal pathology, history, and clinical and operative findings were critically reviewed. This report indicates that chronic follicular salpingitis is the most common single morphologic finding. There was a striking absence of any other abnormal histologic finding. In addition, there is a significant relationship to age, parity, and abortion. Women in the older reproductive age groups, with high parity or with a history of one or more abortions, appeared to have greater predisposition to tubal pregnancy in this study. Relationship of chronic follicular salpingitis to other probable etiologic factors and specific clinical findings is presented.
The effects of pentoxifylline on the prevention of cyclosporine-induced nephrotoxicity in cardiac transplant patients

The objective of this trial was to determine if oral pentoxifylline (PTX) reduced cyclosporine (CSA)-induced renal dysfunction in cardiac transplant patients in the 8 months following transplantation. The study was a prospective, open-label, crossover trial evaluating the renal effects of PTX in nine postcardiac transplant patients. Patients received PTX 2 weeks posttransplant and continued therapy for 4 months. Patients were evaluated for an additional 4 months thereafter. During the trial, various renal function tests were performed and CSA concentrations were measured at set intervals. Baseline measurements were compared with all subsequent measurements. In addition, "on-PTX" data were compared with "off-PTX" data. Significant alterations in results of renal function tests were not seen during the trial when compared with baseline values. Although no significant changes in renal function were observed during the study, no patient developed CSA-induced acute renal failure during the 4 months posttransplant. This finding suggests that PTX may offer a nephroprotective effect against CSA-induced toxicity.
Microtubular proteins and concanavalin A receptors.

The inherent topographical distribution of Con A binding sites (CABS) is disperse or random in all cell types studied using hemocyanin to mark CABS in surface replicas. In virally transformed cells, the addition of Con A leads to the formation of clusters (CABS). A role for microtubules is suggested in this process since colchicine treatment of transformed cells and Con A addition lead to the aggregation of Con A into a “cap.” During phagocytosis CABS are selectively removed from the surface. This selective movement is abolished by drugs that disrupt microtubules. Binding of Con A or RCA to intact cells at 37°C leads to the removal of their receptors from the surface, presumably by “micropinocytosis.”
Evidence-Based Assessment of ADHD in Youth Using a Receiver Operating Characteristic Approach

Guidelines exist for the assessment of attention deficit/hyperactivity disorder (ADHD), but they are often unclear as to how a clinician should consider multiple informants, methods, and co-occurring symptoms to reach an overall diagnostic probability for an individual patient. The current study used receiver operating characteristic analyses and evidence-based medicine methods to evaluate the Achenbach System of Empirically Based Assessment measures and the Conners’ Continuous Performance Test for ADHD diagnosis in youth. Children (n = 379) and their parent(s) presented at an outpatient clinic for a psychoeducational assessment. Analyses examined the diagnostic efficiency and utility of study measures for predicting a best-estimate ADHD diagnosis. The Child Behavior Checklist Attention Problems construct, Teacher Report Form Attention Problems construct, and Hit Reaction Time Standard Error showed adequate diagnostic efficiency and unique contributions to the prediction of ADHD, Combined Type diagnosis. ...
Secure IoT architecture for integrated smart services environment

Internet of Things [IoT] is an emerging technology today after internet and mobile network. IoT enables the user with several smart applications by connecting millions of devices and sensors. The IoT infrastructure is larger than the conventional network and thus the security challenges are more while connecting the heterogeneous devices to infer information for smart services anywhere anytime from the integrated smart environment. As the services and applications are realized in Integrated IoT smart services environment, the raising security issues of different nature must be addressed properly. This paper proposes a novel security architecture for integrated IoT Smart Services Environment which could resolve the security problems. The proposed security architecture has four levels of security namely user and device authentication, sensor network security, cloud and internet security, applications and services security. This security architecture will enable the public to access the diversified services and applications anywhere and anytime using the underlying technologies of integrated smart services environment in the protected manner.
Science and Sensibility: Negotiating an Ecology of Place

The present age is characterized by complex social and ecological risks, resulting from human activities that are irreversibly altering ecosystems and the climate. Michael Vincent McGinnis calls fo...
A survey of single nucleotide polymorphisms identified from whole-genome sequencing and their functional effect in the porcine genome.

Summary Genetic variants detected from sequence have been used to successfully identify causal variants and map complex traits in several organisms. High and moderate impact variants, those expected to alter or disrupt the protein coded by a gene and those that regulate protein production, likely have a more significant effect on phenotypic variation than do other types of genetic variants. Hence, a comprehensive list of these functional variants would be of considerable interest in swine genomic studies, particularly those targeting fertility and production traits. Whole-genome sequence was obtained from 72 of the founders of an intensely phenotyped experimental swine herd at the U.S. Meat Animal Research Center (USMARC). These animals included all 24 of the founding boars (12 Duroc and 12 Landrace) and 48 Yorkshire–Landrace composite sows. Sequence reads were mapped to the Sscrofa10.2 genome build, resulting in a mean of 6.1 fold (×) coverage per genome. A total of 22 342 915 high confidence SNPs were identified from the sequenced genomes. These included 21 million previously reported SNPs and 79% of the 62 163 SNPs on the PorcineSNP60 BeadChip assay. Variation was detected in the coding sequence or untranslated regions (UTRs) of 87.8% of the genes in the porcine genome: loss-of-function variants were predicted in 504 genes, 10 202 genes contained nonsynonymous variants, 10 773 had variation in UTRs and 13 010 genes contained synonymous variants. Approximately 139 000 SNPs were classified as loss-of-function, nonsynonymous or regulatory, which suggests that over 99% of the variation detected in our pigs could potentially be ignored, allowing us to focus on a much smaller number of functional SNPs during future analyses.
Hot-Carrier-Mediated Photon Upconversion in Metal-Decorated Quantum Wells

Manipulating the frequency of electromagnetic waves forms the core of many modern technologies, ranging from imaging and spectroscopy to radio and optical communication. The process of converting photons from higher to lower energy is easily accomplished and technologically widespread. However, upconversion, which is the process of converting lower-energy photons into higher-energy photons, is still a growing field of study with nascent applications and burgeoning interest. Here, we experimentally demonstrate a new photon upconversion technique mediated by hot carriers in plasmonic nanostructures. Hot holes and hot electrons generated via plasmon decay in illuminated metal nanoparticles are injected into an adjacent semiconductor quantum well where they radiatively recombine to emit higher-energy photons. Using GaN/InGaN quantum wells decorated with gold and silver nanoparticles, we show photon upconversion from 2.4 to 2.8 eV. The process scales linearly with illumination power and enables both geometry- ...
Strengthening Students’ Self-Efficacy Through Reacting to the Past

This chapter calls on a two-year data collection to assess the impact of the RTTP pedagogy on student engagement and self-concept. Adapting Barry and Finney’s (Meas Eval Couns Dev 42:197–222, 2009) College Self-Efficacy Survey, which measures students’ confidence in their ability to successfully accomplish various tasks facing college students, both social and academic, the authors asked open-ended questions about how the course changed the students and who was responsible for the students’ learning. Comparing students’ experiences across five Reacting-based courses, the authors found significant increase in students’ confidence on multiple measures. This increase was especially strong for women, who reported lower levels of overall confidence than men in pre-tests, but showed no differences in the post-test.
Periodic structures for scalable high-power microwave transmitters

High-power microwave (HPM) sources play an important role in applications including RF acceleration, radar, and telecommunications. However, these applications are often limited by weight and the cost. A novel highly scalable two-dimensional high-power microwave source is proposed in this paper. The idea is to first charge the periodic resonating structure with a DC source. Then, using fast high-power switches, the DC source is replaced with a short-circuit leading to an oscillating state in the structure. These oscillations coherently radiate into the far-field, converting the stored DC energy into the desired microwave frequency.
The Tie that Binds? A Case Study of Student Perceptions of their Recreation-related Majors

AbstractAcademic departments change to meet university and social demands. The dynamic nature of higher education leads to discourse among park and recreation educators over the unifying purpose th...
Transgenic Animals and their Applications

Abstract Transgenic animals are the result of manipulation of specific genes of interest by creating animal models and bioreactors to (for example) produce vaccines and antibodies that can be used to help save millions of lives. These animals with altered genomes must therefore be used under strict ethical control.
The Growth of Children’s Rights

A right, as I conceive it, is a system of autonomy. A legal right is a structure of legal liberties, claims, powers and immunities. Each right has one or more core elements that define its essential content but it also contains a number of associated elements that give its possessor freedom and control with respect to that core. Thus, the essential function of a right is to allocate autonomy within some defined sphere to one party vis-a-vis second parties in the event of any conflict of wills or confrontation between these parties (Wellman, 1978).
Machine Site Preparation Improves Seedling Performance on a High-Elevation Site in Southwest Oregon

Douglas-fir (Pseudotsuga menziesii) seedlings planted on areas receiving one of four site-preparation treatments (scarify, scarify/till, soil removal, and soil removal/till) and on unprepared control areas were compared for 5 yr at a high-elevation, nutrient-poor site in the western Siskiyou Mountains of southwest Oregon. Fifth-year survival of seedlings was at least 85% among machine-prepared plots, compared to 42% on control plots. Cover of competing vegetation remained less than 25% during the period for all machine treatments. In contrast, vegetation cover on control plots was 30% at the time of planting and increased to nearly 75% after 5 yr. Competing vegetation clearly impeded seedling performance. The effects of unusually droughty conditions at the time of planting in 1982 were examined further by interplanting additional seedlings in the soil-removal treatment in 1985. The interplanting was followed by more normal spring precipitation, and seedlings grew better over 5 yr than those planted in 1982. The slow recovery of competing vegetation and generally poor seedling growth on all treatments during both planting years are attributed to low soil fertility.
Chromosome Analysis in Cancer Patients: Applications and Limitations

Since altered genetic mechanisms lead to the development of cancer, chromosome analysis plays a very important role in diagnosis and treatmentmonitoring of patients with various types of cancer. The precise methodology involves several steps. Short-term cell culture, arrest of cell division in metaphase, hypotonic treatment, and cell harvest help in getting a cell suspension rich in metaphase cells. Slide preparation and staining protocols (G-banding) allow microscopic analysis and precise identification of the chromosome complement. Malignant growth involving the hematopoietic system is categorized as myeloid or lymphoid, depending upon the origin of the cells. The myeloid neoplasms are further subgrouped into myeloproliferative disorders, myelodysplastic syndromes, and acute myeloid leukemia (AML). In the leukemic cells of a chronic myeloid leukemia (CML) patient, the presence of t(9;22)(q34;q11.2) determines the diagnosis. Just like CML, very specific chromosome abnormalities help in diagnosis of different types of myeloid leukemias. The lymphoid neoplasms include acute lymphoblastic leukemia (ALL), chronic lymphoproliferative disorders, and lymphoma. The detection of t(12;21)(p13;q22) or a chromosome count of more than 50 chromosomes is considered a good prognosis in children with ALL. Similarly, the presence of a specific chromosome abnormality helps in the classification of and treatment for lymphoma. The information on chromosome abnormalities in solid tumors has also been gaining importance in recent years. To address the limitation of resolution and to bridge the gap between classical cytogenetic analysis and molecular diagnosis, techniques such as fluorescence in situ hybridization (FISH), comparative genomic hybridization, multiplex FISH, and spectral karyotyping are now available and are discussed briefly in this chapter.
Abstract 1661: Discovery of potent Abelson kinase inhibitors from the scaffold of pyrano[2,3-d]pyrimidin-7-one

Tyrosine kinases regulate cell proliferation, survival, invasion and angiogenesis during tumor initiation and progression. The Abelson (ABL) family of protein kinases comprises ABL1 and ABL2, which link diverse extracellular stimuli to signaling pathways that control cell growth, survival, invasion, adhesion and migration. Inhibition of ABLs has been implied in many type of hematopoietic malignancies and solid tumors. The compound PD173955 is a potent ABL kinase inhibitor. It was developed from the scaffold pyrido[2,3-d]pyrimidin-7-one by Parke-Davis (Pfizer). To discover novel ABL inhibitors, we investigated the scaffold pyrano[2,3-d]pyrimidin-7-one, which is structurally analogous to pyrido[2,3-d]pyrimidin-7-one. This novel scaffold has not been extensively studied in synthetic chemistry and pharmacology. The compound LDK1504 generated from this scaffold is a close analog of PD173955. It was synthesized as a prototypical compound from the pyrano[2,3-d]pyrimidin-7-one scaffold. In the enzymatic assays, LDK1504 was demonstrated with an inhibitory activity comparable to PD173955 for ABL1 kinase. It can inhibit the ABL1 kinase with an IC50 of 18.7 nM. Further optimization leads to the identification of LDK1512 (Kd = 0.38 nM; IC50 = 1.27 nM) against ABL1. The preparation of this class of compounds was achieved through a facile synthesis of 6-bromo-2-(methylthio)-7H-pyrano[2,3-d]pyrimidin-7-one followed by Suzuki coupling reaction and derivatization of the C-2 position of the pyrimidine ring. In this presentation, our synthesis, preliminary SAR of this class of compounds, and kinase selectivity profiling will be discussed. Citation Format: Zhixing Wu, Boqiao Fu, Changjiang Qiao, Ashila Nagaraju, Dai Lu. Discovery of potent Abelson kinase inhibitors from the scaffold of pyrano[2,3-d]pyrimidin-7-one [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1661.
High-speed polarization imaging of dynamic collagen fiber realignment in tendon-to-bone insertion region.

A high-speed polarization imaging instrument is demonstrated to be capable of measuring the collagen fiber alignment orientation and alignment strength during high-displacement rate dynamic loading at acquisition rates up to 10 kHz. The implementation of a high-speed rotating quarter wave plate and high-speed camera in the imaging system allows a minimum measurement acquisition time of 6 ms. Sliced tendon-to-bone insertion samples are loaded using a modified drop tower with an average maximum displacement rate of 1.25 m / s, and imaged using a high-speed polarization imaging instrument. The generated collagen fiber alignment angle and strength maps indicate the localized deformation and fiber realignment in tendon-to-bone samples during dynamic loading. The results demonstrate a viable experimental method to monitor collagen fiber realignment in biological tissue under high-displacement rate dynamic loading.
Follicular Lymphoma: Diagnostic and Prognostic Considerations in Initial Treatment Approach

Follicular lymphoma is a diverse disease, with a diverse variable biology, clinical presentation, and prognosis. The identification of factors that can predict the specific outcome of follicular lymphoma patients remains an area of need. Here, we review the significant advances made in follicular lymphoma prognosis in the last two decades, particularly with the advent of new genetic models. Tumor burden remains an important predictor of prognosis and is still a standard upon which treatment initiation decisions are made. Clinical prognostic indices, including the follicular lymphoma international prognostic index (FLIPI) and FLIPI-2, are validated to predict overall survival and progression-free survival, respectively. However, clinical decisions are rarely made based on these and other indices. Recently described molecular abnormalities in follicular lymphoma include those involving epigenetic regulation, cell-surface receptor signaling, and those controlling the interactions of the follicular lymphoma cell with the microenvironment. Clinicogenetic indices, such as the m7-FLIPI, take into account molecular information and provide a more accurate prognostic prediction than clinical indices. Significant advances have been made in the development of predictive models of risk in follicular lymphoma, in particular with the incorporation of genetic information to predict risk. New models are capable of identifying groups of patients at highest risk of progression. However, it is not yet possible to predict the specific clinical course of a particular patient based on baseline factors. Continued research is needed to identify patients at highest risk of failing initial therapy and the therapeutic approaches to improve their outcomes.
The Siena College Medical Information Retrieval System (MIRS)

Abstract : The work done by our MIRS team of three students and two faculty mentors resulted in a baseline system for content-based medical record retrieval. We also made significant progress on an alternative system based on neural computing concepts. The task for the Medical Records TREC in 2012 was to process a list of thirty-four randomly selected queries against a large medical records database to simulate searches for patients who meet the criteria for participating in various clinical trials. The task was to analyze a data set of over 100,000 reports associated with hospital visits and identify patients whose situations were relevant to the queries. Our text retrieval process was done in two separate ways: one used an index created from standard Information Retrieval (IR) software called Lucene and an alternate method based on principles of neural computing. We submitted three runs to the TREC competition, two using our standard Lucene-based approach and one that used elements of neural network analysis.
Abstract 4074: Heat shock protein 90 inhibitors alter pancreatic stellate cell cytokine production and enhances the efficacy of immune checkpoint blockade in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) has a prominent fibrotic stroma, which is a result of interactions between tumor, immune and pancreatic stellate cells (PSC). Prior work from our laboratory has defined a role for stroma-derived cytokines such as IL-6 as a significant barrier restraining immunity against PDAC. Our group is pursuing novel approaches to target pathways in the tumor microenvironment (TME), in an effort to improve access of effector immune cells to PDAC and response to immunotherapy. Heat shock protein-90 (Hsp90), is a chaperone protein and a versatile target in pancreatic cancer. Hsp90 regulates a diverse array of cellular processes of relevance to both the tumor and the immune system. However, to date the role of Hsp90 in PSC has not been explored in detail. We hypothesize that targeting Hsp90 can modulate the TME, through its ability to target inflammatory signaling and cytokine production by PSC and enhance the efficacy of immunotherapy. Treatment of immortalized and primary patient PSC with the Hsp90 inhibitor XL888 led to decreased IL-6 at the transcript and protein level in vitro. XL888 directly limited PSC growth, and reduced expression of alpha-SMA, Jak/STAT and MAPK signaling intermediates as determined via immunoblot. Combined therapy with XL888 and anti-PD-1 was efficacious in C57BL/6 mice bearing syngeneic subcutaneous (Panc02) or orthotopic (KPC-Luc) tumors, as compared to treatment with either agent alone. The treatment was well-tolerated, with no difference in body weight observed in either model. Laboratory studies are assessing immune and stromal biomarkers to define the impact on PSC, cytokines and T-cell biomarkers in the TME. Finally, we have completed the dose escalation phase of a Phase Ib/II clinical trial of XL888 (Hsp90i) and pembrolizumab (anti-PD-1) at our institution. Expansion cohorts of patients with metastatic pancreatic cancer (n=16) or colorectal cancer (n=16) are now accruing, with paired biopsy and peripheral blood samples to address the impact of Hsp90 inhibition on anti-PD-1 mediated T cell proliferation, cytokine production, and PSC-derived cytokine signatures. Citation Format: Mohammad Zaidi, Yuchen Zhang, Michael B. Ware, Matthew R. Farren, Hannah Komar, Brian Olson, Ganji P. Nagaraju, Mehmet Akce, Olatunji Alese, Shishir Maithel, Juan Sarmiento, Walid Shaib, Christina Wu, Bassel El-Rayes, Gregory B. Lesinski. Heat shock protein 90 inhibitors alter pancreatic stellate cell cytokine production and enhances the efficacy of immune checkpoint blockade in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4074.
Mast Cells, Stress, Fear and Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is a developmental condition characterized by impaired communication and obsessive behavior that affects 1 in 59 children. ASD is expected to affect 1 in about 40 children by 2020, but there is still no distinct pathogenesis or effective treatments. Prenatal stress has been associated with higher risk of developing ASD in the offspring. Moreover, children with ASD cannot handle anxiety and respond disproportionately even to otherwise benign triggers. Stress and environmental stimuli trigger the unique immune cells, mast cells, which could then trigger microglia leading to abnormal synaptic pruning and dysfunctional neuronal connectivity. This process could alter the "fear threshold" in the amygdala and lead to an exaggerated "fight-or-flight" reaction. The combination of corticotropin-releasing hormone (CRH), secreted under stress, together with environmental stimuli could be major contributors to the pathogenesis of ASD. Recognizing these associations and preventing stimulation of mast cells and/or microglia could greatly benefit ASD patients.
Sarcopenia Is a Risk Factor for Infection for Patients Undergoing Abdominoperineal Resection and Flap-based Reconstruction.

Abdominoperineal resection (APR) carries a high risk of morbidity. Preoperative risk assessment can help with patient counseling, minimize adverse outcomes, and guide surgeons in their choice of reconstruction. This study examined the impact of sarcopenia (low lean muscle mass) on postoperative complications after APR. Methods One hundred seventy-eight patients who underwent APR between May 2000 and July 2017 were retrospectively analyzed. Sarcopenia was identified on preoperative computed tomography scans using the Hounsfield Unit Average Calculation. Two cohorts were compared (group 1: primary perineal closure; group 2: flap-based perineal reconstruction). Multivariable analysis evaluated predictors of complications. Results Sarcopenia was an independent risk factor for postoperative surgical site infection in patients undergoing APR (odds ratio [OR] = 2.9, P = 0.04). The risk for sarcopenic patients who underwent flap-based perineal reconstruction was even higher (OR = 8.9, P < 0.01). Male sex was also found to be a risk factor for infection (OR = 3.5, P < 0.01). Perineal flap-based reconstruction was a risk factor for delayed wound healing (OR = 3.2, P < 0.01). Conclusions Sarcopenia was an independent risk factor for infection in patients undergoing APR. This risk was even greater in patients undergoing flap-based perineal reconstruction. Sarcopenia can be identified on preoperative imaging and inform surgeons on risk stratification and surgical plan.
Hindu Nation and its Queers: Caste, Islamophobia, and De/coloniality in India

The 2018 Indian Supreme Court judgement decriminalizing homosexuality has been marked as a “decolonial act.” Section 377, which criminalized homosexuality, was a colonial law introduced by the Brit...
A physician-pharmacist collaborative care model to prevent opioid misuse.

PURPOSE Clinical pharmacists in primary care clinics can potentially help manage chronic pain and opioid prescriptions by providing services similar to those provided within their scope of practice to patients with diabetes and hypertension. We evaluated the feasibility and acceptability of a pharmacist-physician collaborative care model for patients with chronic pain. METHODS The program consisted of an in-person pharmacist consultation and optional follow-up visits over 4 months in 2 primary care practices. Eligible patients had chronic pain and a long-term prescription for opioids or buprenorphine or were referred by their primary care physician (PCP). Pharmacist recommendations were communicated to PCPs via the electronic medical record (EMR) and direct communication. Mixed-methods evaluation included baseline and follow-up surveys with patients, EMR review of opioid-related clinical encounters, and provider interviews. RESULTS Between January and October 2018, 47 of the 182 eligible patients enrolled, with 46 completing all follow-up; 43 patients (91%) had received opioids over the past 6 months. The pharmacist recommended adding or switching to a nonopioid pain medication for 30 patients, switching to buprenorphine for pain and complex persistent opioid dependence for 20 patients, and tapering opioids for 3 patients. All physicians found the intervention acceptable but wanted more guidance on prescribing buprenorphine for pain. Most patients found the intervention helpful, but some reported a lack of physician follow-up on recommended changes. CONCLUSION The study demonstrated that comanagement of patients with chronic pain is feasible and acceptable. Policy changes to increase pharmacists' authority to prescribe may increase physician willingness and confidence to carry out opioid tapers and prescribe buprenorphine for pain.
Pathological angiogenesis is induced by sustained Akt signaling and inhibited by rapamycin.

5706 Pathological blood vessels, such as those found in cancer, differ from their normal counterparts in both structure and function. We found that sustained endothelial cell Akt activation was sufficient to recapitulate many aberrant features of tumor blood vessels in a non-tumor microenvironment. Notably, the blood vessels were enlarged, torturous, hyperpermeable and deficient in pericyte coverage. Mice with endothelial cell Akt expression develop generalized edema, and pleural effusion. These pathological changes were reversible upon withdrawal of sustained Akt signaling, demonstrating their ongoing requirement for Akt signaling as well as the “plasticity” of the adult vasculature. Furthermore, rapamycin inhibition of mTOR, a downstream effector of Akt, blocked the development of pathological blood vessels and inhibited VEGF-induced vascular permeability. Investigation into the mechanism of rapamycin action in this model revealed that in addition to S6 kinase, rapamycin also blocked Akt phosphorylation in both cultured endothelial cells and tissues, suggesting that rapamycin inhibition of Akt signaling may account for its anti-angiogenic properties. These findings indicate a possible clinical utility of rapamycin as an angiogenesis inhibitor and support a novel pathway for rapamycin action via Akt inhibition.
Propagule pressure and the establishment of emergent polyploid populations.

BACKGROUND Whereas the incidence or rate of polyploid speciation in flowering plants is modest, the production of polyploid individuals within local populations is widespread. Explanations for this disparity primarily have focused on properties or interactions of polyploids that limit their persistence. HYPOTHESIS The emergence of local polyploid populations within diploid populations is similar to the arrival of invasive species at new, suitable sites, with the exception that polyploids suffer interference from their progenitor(s). The most consistent predictor of successful colonization by invasive plants is propagule pressure, i.e. the number of seeds introduced. Therefore, insufficient propagule pressure, i.e. the formation of polyploid seeds within diploid populations, ostensibly is a prime factor limiting the establishment of newly emergent polyploids within local populations. Increasing propagule number reduces the effects of genetic, environmental and demographic stochasticity, which thwart population survival. As with invasive species, insufficient seed production within polyploid populations limits seed export, and thus reduces the chance of polyploid expansion. CONCLUSION The extent to which propagule pressure limits the establishment of local polyploid populations remains to be determined, because we know so little. The numbers of auto- or allopolyploid seed in diploid populations rarely have been ascertained, as have the numbers of newly emergent polyploid plants within diploid populations. Moreover, seed production by these polyploids has yet to be assessed.
Surveillance testing reveals a significant proportion of hospitalized patients with SARS-CoV-2 are asymptomatic.

Background The proportion of positive patients admitted to acute-care hospitals for reasons other than coronavirus disease-19 (COVID-19) is unknown. These patients potentially put other patients and healthcare workers at risk of infection. Objective The objective of this study was to define the proportion of asymptomatic patients admitted with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Secondary objectives were to define the positivity rate, reasons for admission, and the geographic distribution in the region. Methods Universal surveillance testing for SARS-CoV-2 was performed on patients admitted to this hospital over a 12-week period from April 9, 2020 to July 1, 2020. Positive patients were categorized as either symptomatic or asymptomatic as defined by the 11 criteria per the Centers for Disease Control and Prevention. The positivity rate, proportion with and without symptoms, reasons for admission, and geographic distribution in the region were recorded. Results The positivity rate ranged from 0.8% to 6.2%. The proportion of asymptomatic patients with SARS-CoV-2 was 37%. Asymptomatic patients primarily presented to the hospital because of either trauma or labor. Some clusters in the region were identified of both symptomatic and asymptomatic patients. Conclusions The proportion of asymptomatic patients admitted with SARS-CoV-2 was significant. Identifying and isolating asymptomatic patients likely prevented exposure and development of hospital-acquired COVID-19 cases among healthcare workers and other patients, supporting the universal surveillance of all admitted patients.
Survival auctions

Dynamic clock auctions with drop-out information typically yield outcomes closer to equilibrium predictions than do comparable sealed-bid auctions. However, clock auctions require congregating bidders for a fixed time interval, which has limited field applicability and introduces inefficiencies of its own given the time cost of congregating bidders. In this experiment we explore the effects of removing these inefficiencies through survival auctions—a multi-round sealed-bid auction which is theoretically isomorphic to the dynamic clock auction with drop-out information.
MicroRNA-detargeting proves more effective than leader gene deletion for improving safety of oncolytic Mengovirus in a nude mouse model

A dual microRNA-detargeted oncolytic Mengovirus, vMC24NC, proved highly effective against a murine plasmacytoma in an immunocompetent syngeneic mouse model; however, there remains the concern of escape mutant development and the potential for toxicity in severely immunocompromised cancer patients when it is used as an oncolytic virus. Therefore, we sought to compare the safety and efficacy profiles of an attenuated Mengovirus containing a virulence gene deletion versus vMC24NC in an immunodeficient xenograft mouse model of human glioblastoma. A Mengovirus construct, vMC24ΔL, wherein the gene coding for the leader protein, a virulence factor, was deleted, was used for comparison. The vMC24ΔL induced significant levels of toxicity following treatment of subcutaneous human glioblastoma (U87-MG) xenografts as well as when injected intracranially in athymic nude mice, reducing the overall survival. The in vivo toxicity of vMC24ΔL was associated with viral replication in nervous and cardiac tissue. In contrast, microRNA-detargeted vMC24NC demonstrated excellent efficacy against U87-MG subcutaneous xenografts and improved overall survival significantly compared to that of control mice without toxicity. These results reinforce microRNA-detargeting as an effective strategy for ameliorating unwanted toxicities of oncolytic picornaviruses and substantiate vMC24NC as an ideal candidate for clinical development against certain cancers in both immunocompetent and immunodeficient hosts.
FACTORS AFFECTING THE NUMBER OF ARMS ON A SAGUARO (CARNEGIEA GIGANTEA)

The average number of arms on a saguaro (Carnegiea gigantea) increases with saguaro height, but there is considerable variation among saguaros for any given height. This variation has been largely attributed to variation in water availability among individual plants. To test this hypothesis, I recorded the height and number of arms of a sample of 425 saguaros within Organ Pipe Cactus National Monument along with values of three variables that should affect arm production through their effect on water availability: (1) the number of neighboring saguaros under the same nurse tree canopy, (2) the presence of a wash within 5 m, and (3) the presence and identity of any living or dead plant associate. Deviation from the number of arms expected for a given saguaro height was negatively related to the number of saguaro neighbors and positively related to the presence of a nearby wash. Saguaros growing with live associates also had fewer arms than those growing alone, and saguaros growing with dead associates had more arms than those growing alone. Each of these results is consistent with the idea that arm production is affected by water availability.
Microfluidic Systems to Study Neutrophil Forward and Reverse Migration

During infection, neutrophils are the most abundantly recruited innate immune cells at sites of infection, playing critical roles in the elimination of local infection and healing of the injury. Neutrophils are considered to be short-lived effector cells that undergo cell death at infection sites and in damaged tissues. However, recent in vitro and in vivo evidence suggests that neutrophil behavior is more complex and that they can migrate away from the inflammatory site back into the vasculature following the resolution of inflammation. Microfluidic devices have contributed to an improved understanding of the interaction and behavior of neutrophils ex vivo in 2D and 3D microenvironments. The role of reverse migration and its contribution to the resolution of inflammation remains unclear. In this review, we will provide a summary of the current applications of microfluidic devices to investigate neutrophil behavior and interactions with other immune cells with a focus on forward and reverse migration in neutrophils.
A Contact Mechanics Formulation for Predicting Dishing and Erosion CMP Defects in Integrated Circuits

A three-dimensional contact mechanics formulation is presented for chemical mechanical polishing applications. The formulation is coupled with the Preston material removal equation in order to simulate the evolution of pressure and wafer height. The physics-based formulation allows the pressure and height to evolve such that dishing and erosion appear seamlessly. Results are compared against another feature-scale model and experiment. The methodology and model offer physics-based results that further the understanding of chemical mechanical polishing for a given layout.
RAS mutations affect pattern of metastatic spread and increase propensity for brain metastasis in colorectal cancer

BACKGROUND RAS and PIK3CA mutations in metastatic colorectal cancer (mCRC) have been associated with worse survival. We sought to evaluate the impact of RAS and PIK3CA mutations on cumulative incidence of metastasis to potentially curable sites of liver and lung and other sites such as bone and brain. METHODS We performed a computerized search of the electronic medical record of our institution for mCRC cases genotyped for RAS or PIK3CA mutations from 2008 to 2012. Cases were reviewed for patient characteristics, survival, and site-specific metastasis. RESULTS Among the 918 patients identified, 477 cases were RAS wild type, and 441 cases had a RAS mutation (394 at KRAS exon 2, 29 at KRAS exon 3 or 4, and 18 in NRAS). RAS mutation was significantly associated with shorter median overall survival (OS) and on multivariate analysis independently predicted worse OS (HR, 1.6; P < .01). RAS mutant mCRC exhibited a significantly higher cumulative incidence of lung, bone, and brain metastasis and on multivariate analysis was an independent predictor of involvement of these sites (HR, 1.5, 1.6, and 3.7, respectively). PIK3CA mutations occurred in 10% of the 786 cases genotyped, did not predict for worse survival, and did not exhibit a site-specific pattern of metastatic spread. CONCLUSIONS The metastatic potential of CRC varies with the presence of RAS mutation. RAS mutation is associated with worse OS and increased incidence of lung, bone, and brain metastasis. An understanding of this site-specific pattern of spread may help to inform physicians' assessment of symptoms in patients with mCRC. Cancer 2015;121:1195–1203. © 2014 American Cancer Society.