cssi/SciSciGPT-SciSciNet huggingface dataset:
Magmatic problems of the Aleutians

So little is actually known about the igneous rocks of the Aleutian Islands that it might seem as if there were little more to say on the subject of magmatic problems than that the whole field lies before the investigator. That can indeed be said, and it can be said further that the region is especially favorable for investigation because of the great number of active and extinct volcanoes situated along this chain of islands; but it is possible to suggest two or three more specific problems.
Power and the Changing Environment

The exercise presented integrates the basic power model and environmental change drivers. The exercise incorporates an innovative teaching approach to demonstrate how power is gained and lost as the organization’s environment changes. In addition to developing students’ interpersonal group skills and reinforcing the theories of power and change, the exercise bridges the organizational behavior and organizational theory concepts of power and the changing environment. This article provides a brief summary of the power model, a brief review of the four environmental change drivers, instructions for facilitating and processing the exercise, and a classroom handout.
Dietary Energy Restriction Modulates the Activity of AMP-Activated Protein Kinase, Akt, and Mammalian Target of Rapamycin in Mammary Carcinomas, Mammary Gland, and Liver

Dietary energy restriction (DER) inhibits mammary carcinogenesis yet mechanisms accounting for its protective activity have not been fully elucidated. In this study we tested the hypothesis that DER exerts effects on intracellular energy sensing pathways resulting in alterations of phosphorylated proteins that play a key role in the regulation of cancer. Experiments were conducted using the 1-methyl-1-nitrosourea-induced mammary cancer model in which rats were 0, 20, or 40% energy restricted during the post initiation stage of carcinogenesis. Parallel experiments were done in non carcinogen treated rats in which effects of DER at 0, 5, 10, 20, or 40% in liver were investigated. In a DER dose dependent manner, levels of Thr-172 phosphorylated AMP-activated protein kinase (AMPK) increased in mammary carcinomas with a concomitant increase in phosphorylated acetyl-CoA-carboxylase, a direct target of AMPK, the phosphorylation of which is regarded as an indicator of AMPK activity. Levels of phosphorylated mTOR decreased with increasing DER and down regulation of mTOR activity was verified by a decrease in the phosphorylation state of two mTOR’s targets, 70-kDa ribosomal protein S6 kinase (p70S6K) and 4E-binding protein 1 (4E-BP1). Coincident with changes in mTOR phosphorylation, levels of activated protein kinase B (Akt) were also reduced. Similar patterns were observed in mammary gland and in liver of non carcinogen treated rats. This work identifies components of intracellular energy sensing pathways, specifically mTOR, its principal up-stream regulators, AMPK and Akt, and its downstream targets, p70S6K and 4E-BP1 as candidate molecules on which to center mechanistic studies of DER.
Corrigendum to ‘Sex modulates approach systems and impulsivity in substance dependence’ [Drug Alcohol Depend. 133 (2013) 222–227]

The authors regret that an error was present in Table 1 of the above published article. The main findings of this paper are the significant group by sex interactions on measures of personality whereby female SDI showed he highest approach tendencies and impulsivity, followed by male SDI, male controls, and finally female controls. Table 1, which shows he correlation matrix of demographic and personality variables across all groups, was found to have an error in one value. The correlation etween education and BAS (Table 1: last column, 2nd row) should be −0.19 rather than −0.17. With this correction, the correlation ecomes significant at the 0.05 level and so this value should correctly display −0.19 superscripted with “a”. We feel that this error does ot impact the interpretation of our findings because all analyses were adjusted for education level, and the group by sex interaction results re unchanged. The authors would like to apologise for any inconvenience caused.
Open-Label Trial of Recombinant Human Insulin-like Growth Factor 1/Recombinant Human Insulin-like Growth Factor Binding Protein 3 in Myotonic Dystrophy Type 1

Myotonic dystrophy type 1 (DM1) is a progressive multisystem degenerative disorder caused by expansion of a CTG repeat in the dystrophia myotonica protein kinase (DMPK) gene.(1) Currently there is no known treatment capable of modifying the progressive myopathy of DM1. IGF-1 is a potent regulator of muscle differentiation and growth. This peptide hormone acts in an autocrine and paracrine fashion to promote the proliferation and differentiation of muscle precursor cells and to induce the hypertrophy of muscle fibers. IGF-1 can also enhance muscle regeneration. Forced overexpression of IGF-1 in muscle fibers can ameliorate disease in mouse models of muscular dystrophy.(2, 3) Evidence has suggested a potential role for IGF-1 in the treatment of DM1. Previous work has shown that IGF-1 can increase the protein synthesis and differentiation competence of DM1 muscle cells in tissue culture.(4) In addition, during a small clinical study of nine patients with DM1, four months of twice daily subcutaneous rhIGF-1 resulted in improved insulin action, increased muscle protein synthesis, decreased body fat, and increased plasma testosterone.(5) Compared to rhIGF-1 alone, the circulating half-life of rhIGF-1/rhIGFBP-3 following subcutaneous injection is extended and side effects related to peak activity, mainly hypoglycemia, may be reduced.(6) rhIGF-1/rhIGFBP-3 is currently approved for children with severe primary IGF-1 deficiency, and has been studied as a therapeutic agent for hip fractures, diabetes, and severe burns.(7–10) This two-component preparation of recombinant proteins may offer advantages for increasing the effects of rhIGF-1 on muscle while reducing peak-dose side effects. Its use for DM1 patients has not yet been described. Here we examined the safety, tolerability, and skeletal muscle effects of rhIGF-1/rhIGFBP-3 for DM1.
Prophylactic pinning of the contralateral hip after unilateral slipped capital femoral epiphysis.

Background: The management of the contralateral hip after unilateral slipped capital femoral epiphysis is controversial. The purpose of this study was to determine, with use of expected-value decision analysis, the optimal management strategy—prophylactic in situ pinning versus observation—for the contralateral hip. Methods: Outcome probabilities were determined from a systematic review of the literature. Utility values were obtained from a questionnaire on patient preferences completed with use of a visual analog scale by twenty-five adolescent male patients without slipped capital femoral epiphysis. A decision tree was constructed, fold-back analysis was performed to determine the optimal treatment, and one and two-way sensitivity analyses were performed to determine the effect on decision-making of varying outcome probabilities and utilities. Results: Observation was the optimal management strategy for the contralateral hip given the outcome probabilities and utilities that we studied (the expected value was 9.5 for observation and 9.2 for prophylactic in situ pinning, with a marginal value of 0.3). Increased rates of a late second slip favored prophylactic in situ pinning (the threshold probability was 27%). Risk-taking patients with a high utility for uncomplicated prophylactic in situ pinning favored prophylaxis (the threshold utility was 9.8). Conclusions: The iatrogenic risks of treating a healthy patient or an uninvolved body part rarely outweigh the potential benefits unless the probability of the adverse event is likely and the consequences of the adverse event are very severe. In this decision analysis, the optimal decision was observation. In cases where the probability of contralateral slipped capital femoral epiphysis exceeds 27% or in cases where reliable follow-up is not feasible, pinning of the contralateral hip is favored. For a given individual patient, the optimal strategy depends not only on probabilities of the various outcomes but also on personal preference. Thus, we advocate a model of doctor-patient shared decision-making in which both the outcome probabilities and the patient preferences are considered in order to optimize the decision-making process. Level of Evidence: Economic and decision analysis, Level III-1 (limited alternatives and costs; poor estimates). See Instructions to Authors for a complete description of levels of evidence.
Spatio-Temporal Heterogeneity: Concepts and Analyses by DUTILLEUL, P.R.L.

EDITOR: TAESUNG PARK Spatio-Temporal Heterogeneity: Concepts and Analyses (P.R.L. Dutilleul) Jun Zhu Programming Graphical User Interfaces (M.L. Lawrence and J. Verzani) Fernando Tusell Simultaneous Inference in Regression (W. Liu) Aldo Solari
Topic-Segmentation of Dialogue

We introduce a novel topic segmentation approach that combines evidence of topic shifts from lexical cohesion with linguistic evidence such as syntactically distinct features of segment initial and final contributions. Our evaluation shows that this hybrid approach outperforms state-of-the-art algorithms even when applied to loosely structured, spontaneous dialogue. Further analysis reveals that using dialogue exchanges versus dialogue contributions improves topic segmentation quality.
Experimental Study of Magnetorheological Dampers and Application to Cable Vibration Control

As primary members of cable-stayed bridges, cables are susceptible to vibrations because of their low intrinsic damping. Mechanical dampers have been used to improve cable damping. Magnetorheological (MR) dampers have been proven efficient for seismic applications because of their large output damping forces, stable performance, low power requirement, and quick response from bot hl aboratory research and field practice. In this paper, experimental work was carried out to demonstrate that MR dampers are also suitable for cable vibration control. First, a MR damper was tested with various test parameters to obtain the performance curves of the MR damper under different loading conditions, including different electric currents, loading frequencies, loading wave types, and working temperatures. The MR damper was then installed on a cable to reduce the cable vibration. A 7.16 m long stay cable with a prototype-to-model scale factor of 8 was established for this study. The frequencies of the stay cable under different tension forces were measured and compared with those obtained through theoretical calculations. Then, a free vibration control test was carried out with the MR damper being installed at the 1/4 point of the cable. In the forced vibration test, a shaker was installed at 0.18 m from the lower end of the cable. The measured data show that the damper is efficient for cable vibration control within its working current range (zero to maximum) although there is a saturation effect. It was also observed that the damper could reduce cable vibration under a variety of excitation frequencies, especially for resonant vibrations.
Adolescent and Young Adult Suicide: A 10‐Year Retrospective Review of Kentucky Medical Examiner Cases

The compilation of all suicidal causes of death attained the third highest ranking of mortality between the ages of 15 and 24 following unintentional deaths and homicide in the United States, accounting for approximately 4000 deaths in 2002. A variety of biopsychosocial factors may contribute to adolescent suicidal behavior, including psychiatric disorders, risk-taking behaviors, and lack of a cohesive family unit. The authors conducted a 10-year (1993-2002) retrospective review of 108 Medical Examiner cases of suicide ages 11-17 and 358 cases ages 18-24 in Kentucky, which represents two thirds of the Coroner cases in the state. The majority of victims were male and Caucasian. The major causes of death were the same for the two age groups, specifically, firearm injury (72.2% and 70.7%), hanging (22.2% and 18.7%), and drug intoxication (2.8% and 5.3%). An integrated Coroner-Medical Examiner system profits in the public health arena by providing collaborative research data for policy decisions. The prevalence of youth suicide by firearm should prompt further discussion regarding ways to better identify high-risk adolescents and young adults and restrict pediatric access to unsecured household firearms.
Reduced Voltage Scaling in Clock Distribution Networks

We propose a novel circuit technique to generate a reduced voltage swing (RVS) signals for active power reduction on main buses and clocks. This is achieved without performance degradation, without extra power supply requirement, and with minimum area overhead. The technique stops the discharge path on the net that is swinging low at a certain voltage value. It reduces active power on the target net by as much as 33% compared to traditional full swing signaling. The logic 0 voltage value is programmable through control bits. If desired, the reduced-swing mode can also be disabled. The approach assumes that the logic 0 voltage value is always less than the threshold voltage of the nMOS receivers, which eliminate the need of the low to high voltage translation. The reduced noise margin and the increased leakage on the receiver transistors using this approach have been addressed through the selective usage of multithreshold voltage (MTV) devices and the programmability of the low voltage value.
An imprint and merge algorithm incorporating geometric tolerances for conformal meshing of misaligned assemblies

A size tolerant algorithm for imprinting and merging adjacent part geometries is presented in this paper. This approach cleans up misaligned and dirty assembly geometry that is intended for conformal mesh generation. The algorithm first discretizes the boundary edges of adjacent faces into linear segments. The segments are then intersected and a partial intersection graph is calculated from the intersection results. The intersections are calculated by accounting for size tolerances to minimize the effect of misaligned parts on the meshing process. The partial intersection graph is next used to imprint the adjacent faces as appropriate. The imprints are generated using virtual geometry so that the tolerant topology created therein can be employed. Several examples are given to demonstrate the resulting improvement in the mesh quality of conformal meshes. The approach is shown to work robustly with misaligned and poorly defined parts.
Loss of giant obscurins promotes breast epithelial cell survival through apoptotic resistance

Obscurins (∼70 - 870 kDa), encoded by the single OBSCN gene, are cytoskeletal proteins originally identified in striated muscles with structural and regulatory roles. Recently, analysis of 13,023 genes in breast and colorectal cancers identified OBSCN as one of the most frequently mutated genes, implicating it in cancer formation. Herein we studied the expression profile of obscurins in breast, colon, and skin cancer cell lines and their involvement in cell survival. Immunoblot analysis demonstrated significant reduction of obscurin proteins [corrected] in cancer cells, resulting from decreased mRNA levels and/or the presence of mutant transcripts. In normal epithelium, obscurins localize in cytoplasmic puncta, the cell membrane, and the nucleus. Accordingly, subcellular fractionation demonstrated the presence of 2 novel nuclear isoforms of ∼110 and ∼120 kDa. Nontumorigenic MCF10A breast epithelial cells stably transduced with shRNAs targeting giant obscurins exhibited increased viability (∼30%) and reduced apoptosis (∼20%) following exposure to the DNA-damaging agent etoposide. Quantitative RT-PCR further indicated that the antiapoptotic genes BAG4 and HAX1 were up-regulated (1.5- and 1.4-fold, respectively), whereas initiator caspase-9 and death caspase-3 transcripts were down-regulated (0.8- and 0.6-fold, respectively). Our findings are the first to pinpoint critical roles for obscurins in cancer development by contributing to the regulation of cell survival.
EUS diagnosis of a primary pancreatic metastasis of alveolar rhabdomyosarcoma.

Context Alveolar rhabdomyosarcoma are rare malignancies. These lesions typically metastasize to the lungs, liver, and bone marrow. Pancreatic metastases from alveolar rhabdomyosarcoma are exceptionally uncommon. Case report An 18-year-old man with a history of right orbital alveolar rhabdomyosarcoma, which had been treated with neoadjuvant therapy, surgery and adjuvant chemotherapy developed an episode of pancreatitis. CT at that time demonstrated acute pancreatitis with no mass lesions. Two months later, the patient developed abdominal pain and an MRI documented a 6.4 cm mass in the pancreatic body and tail. EUS guided FNA confirmed the diagnosis of alveolar rhabdomyosarcoma metastatic to the pancreas. Conclusion To our knowledge this is the first reported case of EUS guided FNA diagnosis of alveolar rhabdomyosarcoma metastatic to the pancreas. This is also the only case report of a primary pancreatic metastasis of this type of tumor in a male patient (which occurs less commonly than in females).
Specific depletion of body fat in parabiotic partners of tube-fed obese rats

One member in each of 15 parabiosed pairs of rats was fed twice its normal food intake as four tube-fed meals per day. Seven other pairs ate ad libitum. Partners of overfed rats ate approximately 90% of the intake of individual members of ad libitum pairs. After 46 days of overfeeding, blood samples were taken and the rats were killed for carcass analysis. Tube-fed parabiotic rats had gained a considerable amount of fat and some protein. Their partners had a normal lean body mass but very little fat. Serum corticosterone, reverse triiodothyronine, free fatty acids, and beta-hydroxybutyrate were the same in all parabionts. Serum triiodothyronine and insulin were increased and growth hormone was decreased in obese rats. Serum thyroxine and triiodothyronine were increased and glucose was decreased in their parabiotic partners. The results are discussed as evidence for a humoral factor that crossed the parabiotic union and acted as a "lipid-depleting" agent in the partners of overfed rats.
Social and Environmental Barriers to Nutrition Therapy for Diabetes Management Among Underserved Pregnant Women: A Qualitative Analysis

Abstract Objective To identify social and environmental barriers to nutrition therapy for diabetes management during pregnancy among a population of low-income, minority pregnant women. Design Prospective, in-depth, semi-structured interviews performed serially during pregnancy and continued until thematic saturation was reached. Setting Urban academic medical center. Participants Ten pregnant low-income, minority women with gestational diabetes and type 2 diabetes mellitus. Phenomenon of Interest Social and environmental barriers to nutrition therapy for diabetes management during pregnancy. Analysis Qualitative analysis of interview data using electronic coding software was performed using theme analysis. Results Participants perceived limited ability and self-efficacy to adopt nutrition recommendations. Specific themes identified as barriers included (1) feeling overwhelmed by the unfamiliar; (2) using and decoding nutrition labels; (3) managing nutrition choices and seeking control in the setting of food insecurity; (4) experiencing lack of control and motivation, and limited self-efficacy; (5) balancing recommendations with taste preferences and cultural food norms; (6) maintaining a healthy eating schedule; and (7) accommodating diabetes in family and social life. Conclusions and Implications Pregnant women with diabetes encounter a number of knowledge-based, attitudinal, and resource-related barriers that reduce capacity for nutrition therapy adherence. Provision of culturally informed, practical nutrition support that addresses the needs of women in low-resource communities is an important component of comprehensive diabetes care during pregnancy.
The 3 "Rs"-Relax, Reflect, and Regroup: Avoiding Burnout During Cardiology Fellowship.

Whether you believe that the Creator created the 24-h, 7-day, or 365-day cycle for a reason or that evolution selected cycles for a specific purpose, the fact remains that cycles are essential for optimal operation of any system. Only systems with set cycles or checkpoints for replenishing can
Boron and Hydrogen in NI3AL: Part II. Mechanical Testing of Bicrystals

To provide a sensitive measurement of the effect of boron segregation on the strength and ductility of Ni3Al grain boundaries, bicrystal tensile tests were performed on small specimens of boron doped Ni76Al24 cut from extremely large-grained boules. Five specimens with the same “random” or low-symmetry grain boundary (disorientations measured by means of backscattered Kikuchi patterns) and two specimens with a second random grain boundary were tested in quenched and slow-cooled conditions. Duplicate tests performed in a low (7 ppm) water-vapor environment showed that the fracture mode and the stress and strain at fracture are altered by environmental embrittlement at individual, partially strengthened grain boundaries.
Posterior Reversible Encephalopathy Syndrome after Surgical Resection of a Giant Vestibular Schwannoma: Case Report and Literature Review.

Background Posterior reversible encephalopathy syndrome (PRES) is a constellation of neurologic symptoms—seizures, headaches, altered mental status, and visual changes—associated with characteristic brain magnetic resonance imaging findings seen on T2 and fluid-attenuated inversion recovery sequences. Classically, this condition is caused by hypertension, but several other risk factors have been described. The development of PRES after surgical resection of posterior fossa tumors has mostly been linked to the pediatric neurosurgical practice. Case Report We report the first case of PRES after resection of a giant vestibular schwannoma in an adult patient. This 57-year-old female patient underwent a retrosigmoid approach for total resection of her left-sided giant tumor. On the second postoperative day, she developed the classic clinical and radiologic characteristics of PRES. She was treated aggressively with antihypertensive and anticonvulsant medications and showed complete recovery without sequelae. Conclusion PRES is a potential yet rare complication of surgeries to posterior fossa tumors that are compressing the brainstem. Rapid diagnosis and aggressive management are essential for achieving the best outcome.
A mutant of Nicotiana sylvestris deficient in serine glyoxylate aminotransferase activity : Callus induction and photorespiratory toxicity in regenerated plants.

A photorespiration mutant of Nicotiana sylvestris lacking serine: glyoxylate aminotransferase activity was isolated in the M2 generation following EMS mutagenesis. Mutants showing chlorosis in air and normal growth in 1% CO2 were fed [14C]-2-glycolate to examine the distribution of 14C among photorespiratory intermediates. Mutant strain NS 349 displayed a 9-fold increase in serine accumulation relative to wild-type controls. Enzyme assays revealed an absence of serine: glyoxylate aminotransferase (SGAT) activity in NS 349, whereas other peroxisomal enzymes were recovered at normal levels. Heterozygous siblings of NS 349 segregating air-sensitive M3 progeny in a 3∶1 ratio were shown to contain one half the normal level of SGAT activity, indicating that air sensitivity in NS 349 results from a single nuclear recessive mutation eliminating SGAT activity. Since toxicity of the mutation depends on photorespiratory activity, callus cultures of the mutant were initiated and maintained under conditions suppressing the formation of functional plastids. Plantlets regenerated from mutant callus were shown to retain the SGAT deficiency and conditional lethality in air. The utility of photorespiration mutants of tobacco as vehicles for genetic manipulation of ribulose bisphosphate carboxylase/oxygenase at the somatic cell level is discussed.
Inhibition of slow-wave repolarization and Ca(2+)-activated K+ channels by quaternary ammonium ions.

We studied the effects of the K+ channel blocker tetrapentylammonium (TPeA) on the electrical activity of intact circular smooth muscle from canine colon. TPeA (10 and 20 microM) increased slow-wav...
Unresolved Tensions in the Study of Meaning in Life

In an effort to provide some integration to the commentaries in this special issue on existential meaning, this article explores some of the tensions expressed within and across the commentaries regarding how conceptualization and research on meaning should proceed. These tensions include (a) mystery versus science, (b) situational versus global focus, (c) boundaries versus boundlessness, (d) subjective versus objective phenomena, (e) cognitive versus affective aspects, and (f) universal versus culturespecific meanings. Each of these tensions warrants considerable exploration and discussion; future advances in our understanding of existential meaning depend on our successful resolution of these tensions. The commentaries in this special issue on the prospects for advancing our understanding of meaning in life contain many great insights and ideas. Collectively, these commentaries provide much wisdom and many directions for future theory development and empirical research. To provide some integration, I hi...
Previewing as a Principle for Motivating Interpersonal Communication

Most practitioners would concur that working with caregivers and their infants is rewarding in a way that is dramatically different from the treatment of other adult patients. This experience of professional satisfaction arises for several reasons. First, in contrast to the treatment of adult psychopathology, if psychopathology threatens the interaction between the caregiver and infant, it is, more often than not, susceptible to intervention. This is primarily because the relationship between caregiver and infant is relatively fresh, and aberrant patterns have not yet had an opportunity to become entrenched. Therefore the potential for instilling adaptive patterns of interaction is enhanced.
Gynecologic Brachytherapy: Endometrial Cancer

The management of endometrial cancer generally involves surgical extirpation of tumor as a primary therapeutic endeavor. Following surgery, and in some cases in lieu of surgery (in medically inoperable patients), brachytherapy is frequently required as part of the definitive treatment scheme. We present management guidelines and techniques in this chapter to aid in the therapeutic management of these patients.
Developing Safe and Effective Antidementia Drugs

Within the United States, most activities related to the development, clinical testing, and marketing of new drug products are subject to the provisions and requirements of the Federal Food, Drug and Cosmetic Act. The Act is enforced by the Food and Drug Administration [FDA], an administrative agency within the Executive Branch of America’s Federal Government.
Tropical SNO comparisons of AIRS and CrIS calibration for windows

AIRS on EOS-Aqua and CrIS on Suomi NPP are two hyperspectral infrared sounders with similar capabilities and orbits, so there is a great opportunity to compare their absolute calibration while they are both in orbit. This insures that long-term climate record can be created by concatenating the two instrument records. There are significant differences in instrument architecture which may lead to subtle differences and complicate attempts to combine the records. We use Tropical Simultaneous Nadir Observations (TSNOs), cases where both instruments are looking nearly at the same place at the same time, to explore the differences. Due to the presence of cold clouds and clear hot desert surface, the data cover a brightness temperature range from 190 K to 340 K. We concentrate on the differences between the mean of the two instruments using atmospheric window channels as function of brightness temperature in 20-K wide bins. With the currently available AIRS and CrIS official calibrated data, radiometric differences as large as 0.3 K are seen at the extreme temperatures. These differences may be reduced in future releases of the AIRS and CrIS calibration.
“I’m not gonna be another statistic”: The imagined futures of former foster youth

This article reports results from a qualitative study of former foster youth attending a 4-year university, focusing on the process by which these students construct and communicate imagined futures. Drawing on 30 in-depth interviews and sixteen months of participant observation at an on-campus support program, this study empirically illustrates how aspirations can be constructed through a complex process that involves individual biography, cultural notions of morality, and imagination. I argue that analysis of former foster youths’ imagined futures reveals how ambitious educational and professional aspirations serve as moral assertions of identity that separate this group from the negative stereotypes they feel have been projected onto them. Finally, I show how support programs for marginalized populations are critical not just for the resources they provide, but also for their role in expanding worldviews.
126. Identification of Human Papillomavirus Entry Receptors with CRISPR-Cas9 Library

Human papillomaviruses (HPVs) are a family of small nonenveloped viruses that induce mostly benign papillomas. However, infection of several high-risk HPV types, most prominently HPV 16 and 18, can cause cervical cancer and other epithelial tumors. The cell biology of HPV entry is still a subject of scientific debate, and in particular, the cellular receptors for HPV infection have not been firmly determined. The present study was designed to use CRISPR-Cas9 gene knock-out library to identify cellular proteins that may be used by HPV for entry. HEK293 cells were initially transduced with CRISPR-Cas9 knockout screening libraries, and then selected with puromycin for two weeks. The cells were then transduced with HPV-16 pseudoviruses containing the GFP marker gene, and GFP-negative cells were subsequently selected by flow cytometry. This process was repeated multiple rounds to enrich the GFP− cell population, and the percentage of GFP+ cells went down from over 90% to less than 10% during this enrichment process. A combination of PCR and DNA sequencing was then used to determine the genes that had been knocked out from this cell population. Our data show that solute carrier family 35 (adenosine 3’-phospho 5’-phosphosulfate transporter) member B2 (SLC35B2), malectin (MLEC), xylosylprotein beta 1,4-galactosyltransferase and transmembrane protein 8C (TMEM8C) were the most frequently knocked out genes in these cells. We then validated the involvement of one of these genes, SLC35B2 in HPV entry, by either deleting genes from fresh HEK293 cells or by reintroducing the gene back to the cells that had it knocked out. Interestingly, SLC35B2 knockout was found to affect entry of some other viruses such as herpes simplex viruses. In conclusions, CRISPR-Cas9 knockout screening system is a useful tool for identifying cellular receptors for viruses such as HPV, in which the entry mechanism has not been fully elucidated.
Transient Performance Analysis of Closed Production Lines With Bernoulli Machines, Finite Buffers, and Carriers

In many manufacturing systems, each piece of intermediate product is attached to a dedicated carrier (e.g., pallet, skid, fixture, etc.) throughout the entire process for material handling and/or transportation purposes. Once a part finishes all processing steps, the associated carrier will be removed and returned to the front of the production process to pick up new incoming parts. We referred to production systems operating in such manner as “closed.” In the current literature, available results on closed production systems are very limited. In this paper, we study transient performance of closed serial lines with machines that operate according to the Bernoulli reliability model. Specifically, exact mathematical model for the system considered is derived based on Markov analysis. Then, formulas for calculating the system's performance measures during transients are obtained based on the model. An approximation method is proposed to estimate a closed Bernoulli line's performance in completing a finite production run. Finally, properties of finite production run-based closed Bernoulli lines during transient are investigated.
Reversible Cluster Aggregation and Growth Model for Graphene Suspensions

We present a reversible cluster aggregation model for 2-dimensional macromolecules represented by line segments in 2-dimensions; and, we use it to describe the aggregation process of functionalized graphene particles in an aqueous SDS surfactant solution. The model produces clusters with similar sizes and structures as a function of SDS concentration in agreement with experiments and predicts the existence of a critical surfactant concentration (Ccrit) beyond which thermodynamically stable graphene suspensions form. Around Ccrit, particles form dense clusters rapidly and sediment. At C ≪ Ccrit, a contiguous ramified network of graphene gel forms which also densifies, but at a slower rate, and sediments with time. The deaggregation-reaggregation mechanism of our model captures the restructuring of the large aggregates towards a graphite-like structure for the low SDS concentrations. This article is protected by copyright. All rights reserved.
DOSE DEPENDENT EFFECT OF INTRAVENOUS FENTANYL ADMINISTRATION ON TICAGRELOR ABSORPTION AND PLATELET INHIBITION IN PATIENTS RECEIVING PERCUTANEOUS CORONARY INTERVENTION: A SECONDARY-ANALYSIS OF THE PACIFY RANDOMIZED CLINICAL TRIAL

Rapid platelet inhibition is essential during percutaneous coronary intervention (PCI). We recently demonstrated that fentanyl, an intravenous opiate commonly administered during PCI, delays gastrointestinal absorption of oral P2Y12 inhibitors and attenuates platelet inhibition. In this post-hoc
Leadership Mentoring: A Survey of Early Career Psychologist Leaders.

Health service psychology has been slow to create a leadership mentoring model. A survey of former chairs of the American Psychological Association of Graduate Students and American Psychological A...
Pharyngeal reconstruction after total laryngectomy with preservation of phonation.

The goal of pharyngeal reconstruction after laryngectomy is to prevent fistulization and to permit rapid resumption of satisfactory deglutition. Alaryngeal speech acquisition by the traditional method of esophageal speech is effective if insufflation is rapidly learned and tolerated by the pharyngoesophageal segment. Experience with tracheoesophageal phonation revealed an incidence of pharyngoesophageal spasm in 40 % of an esophageal speech failure population which prevented useful air flow for speech production. This is related to esophageal distention and reflexive upper esophageal sphincter hypertension. It is suggested that pharyngeal reconstruction after total laryngectomy may permit higher wall tension than is desirable for speech acquisition. The problem of post laryngectomy pharyngoesophageal spasm may be reduced by myotomy of the pharyngeal constrictors with resultant higher air flows in the residual vocal tract for speech. Alterations in the pharyngeal wall tonicity will affect the pitch of the speech and listener acceptability. Recently identification and division of the pharyngeal plexus has produced a similar result in improved phonatory air flows with subjective vocal pitch approximating more normal voices. The above mentioned techniques are readily applied to the laryngectomy procedure and enhance the likelihood of alaryngeal speech acquisition.
Bio-Inspired Nanocatalysis

In response to increasing energy concerns, new materials are required that efficiently use and/or produce energy for a variety of applications. One specific and important area would be for catalytic applications that typically are energy intensive, but extremely important. In this regard, biomimetic methods have recently been studied for such reactivity, where the effects of the biointerface on the catalytic functionality have begun to be examined. This chapter focuses on these materials, typically prepared with peptides and viral templates, for a selection of important catalytic processes.
Rebelocracy: social order in the Colombian Civil War

Ana Arjona’s ambitious book, Rebelocracy: Social Order in the Colombian Civil War, starts with a simple insight: rather than the chaos most often associated with civil war, combat zones usually exh...
White Integration or Segregation? The Racial and Ethnic Transformation of Rural and Small Town America

Rural America has seemingly been “left behind” in an era of massive immigration and growing diversity. The arrival of new immigrants has exposed many rural whites, perhaps for the first time, to ra...
Subcentimeter epilepsy surgery targets by resting state functional magnetic resonance imaging can improve outcomes in hypothalamic hamartoma.

OBJECTIVE The purpose of this study is to investigate the outcomes of epilepsy surgery targeting the subcentimeter-sized resting state functional magnetic resonance imaging (rs-fMRI) epileptogenic onset zone (EZ) in hypothalamic hamartoma (HH). METHODS Fifty-one children with HH-related intractable epilepsy received anatomical MRI-guided stereotactic laser ablation (SLA) procedures. Fifteen of these children were control subjects (CS) not guided by rs-fMRI. Thirty-six had been preoperatively guided by rs-fMRI (RS) to determine EZs, which were subsequently targeted by SLA. The primary outcome measure for the study was a predetermined goal of 30% reduction in seizure frequency and improvement in class I Engel outcomes 1 year postoperatively. Quantitative and qualitative volumetric analyses of total HH and ablated tissue were also assessed. RESULTS In the RS group, the EZ target within the HH was ablated with high accuracy (>87.5% of target ablated in 83% of subjects). There was no difference between the groups in percentage of ablated hamartoma volume (P = 0.137). Overall seizure reduction was higher in the rs-fMRI group: 85% RS versus 49% CS (P = 0.0006, adjusted). The Engel Epilepsy Surgery Outcome Scale demonstrated significant differences in those with freedom from disabling seizures (class I), 92% RS versus 47% CS, a 45% improvement (P = 0.001). Compared to prior studies, there was improvement in class I outcomes (92% vs 76%-81%). No postoperative morbidity or mortality occurred. SIGNIFICANCE For the first time, surgical SLA targeting of subcentimeter-sized EZs, located by rs-fMRI, guided surgery for intractable epilepsy. Our outcomes demonstrated the highest seizure freedom rate without surgical complications and are a significant improvement over prior reports. The approach improved freedom from seizures by 45% compared to conventional ablation, regardless of hamartoma size or anatomical classification. This technique showed the same or reduced morbidity (0%) compared to recent non-rs-fMRI-guided SLA studies with as high as 20% permanent significant morbidity.
Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy describes a variety of neuropathic conditions caused by diabetes mellitus. It is a common complication of the disease. The pathophysiology is incompletely understood but involves multifactorial mechanisms of nerve injury that lead to a painful disease state. Multiple pharmacologic treatments exist which may reduce the symptoms of disease. These include anticonvulsants, antidepressants, opioids, and topical medications. Little can be done to reverse the progression of disease, and ultimately good glycemic control is the cornerstone of prevention.
Abstract 277: Inhibition of protein arginine methylation alters RNA metabolism and DNA damage response providing a new therapeutic strategy in pancreatic ductal adenocarcinoma

With limited therapeutic options, poor overall 5-year survival rates, and increasing incidence, pancreas cancer is estimated to become the second leading cause of cancer deaths by 2030. Recognizing the need for transformative advances in pancreas cancer management, we developed an in vivo target discovery platform to uncover molecular vulnerabilities in patient-derived pancreatic ductal adenocarcinoma (PDAC) xenografts to identify and rapidly translate novel therapeutic concepts to the clinic. We identified protein arginine methyltransferase 1 (PRMT1) as a dependency in PDAC required for disease maintenance and progression. Extensive genetic and pharmacological studies support PRMT1 as a novel vulnerability, which prompted our design and synthesis of proprietary series of potent, selective PRMT Type I inhibitors (PRMTi) with compelling in vivo activity. While advancing the project in drug discovery, we deployed a comprehensive approach to elucidate the mechanism of action of PRMTi. We characterized the PRMT1 interactome via PRMT1 immunoprecipitation followed by LC/MS and observed that PRMT1 binding partners were significantly enriched in RNA-binding and -processing genes. In addition, because methylation of arginine residues is a common post-translational modification regulating protein function, we identified substrates differentially methylated upon PRMT inhibition. Integrating these results with the PRMT1 interactome confirmed a strong correlation between PRMT1 substrates and complexes that are physically associated and linked to RNA metabolism. Transcriptome assays demonstrated that PRMT inhibition globally impaired RNA metabolism, including but not limited to RNA splicing, transcription termination, and R-loop formation. In addition, PRMTi caused a profound down-regulation of multiple pathways involved in the DNA damage response (DDR) promoting genomic instability. Taken together, these data support PRMT1 as a compelling target in an area of high unmet medical need and inform a mechanism-based translational strategy for future clinical development. Citation Format: Virginia Giuliani, Alessandro Carugo, Meredith Miller, Lionel Sanz, Chiu-Yi Liu, Christopher A Bristow, Erika Suzuki, Caleb A Class, Stella R. Hartono, Guang Gao, Ningping Feng, Jason P Gay, Bhavatarini Vangamudi, Joseph R Marszalek, Jeffrey Kovacs, Maria Emilia Di Francesco, Frederic Chedin, Philip Jones, Giulio Draetta, Timothy Heffernan. Inhibition of protein arginine methylation alters RNA metabolism and DNA damage response providing a new therapeutic strategy in pancreatic ductal adenocarcinoma [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 277.
On classification of rational vertex operator algebras with central charges less than 1

Abstract The rational and C 2 -cofinite simple vertex operator algebras whose effective central charges c ˜ and the central charges c are equal and less than 1 are classified. Such a vertex operator algebra is zero if c ˜ 0 and C if c ˜ = 0 . If c ˜ > 0 , it is an extension of discrete Virasoro vertex operator algebra L ( c p , q , 0 ) by its irreducible modules. It is also proved that for any rational and C 2 -cofinite simple vertex operator algebra with c = c ˜ , the vertex operator subalgebra generated by the Virasoro vector is simple.
Comparisons of genetic and morphological distance with heterosis between Medicago sativa subsp. sativa and subsp. falcata

Biomass yield heterosis has been shown to exist between Medicago sativasubsp. sativa and Medica gosativa subsp. falcata. The objective of this study was to gain a better understanding of what morphological and genetic factors were most highly correlated with total biomass yield heterosis. We calculated genetic distances among nine sativa and five falcate genotypes based on amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) DNA markers. Genetic distance did not correlate with specific combining ability (SCA) or mid-parent heterosis. In contrast, a morphological distance matrix based on seventeen agronomic and forage quality traits was significantly correlated with heterosis; the agronomic traits of maturity, midseason regrowth, and autumn regrowth showed strong association with heterosis. Heterosis was also correlated with subspecies. We suggest that in many cases progeny heterosis can be accounted for by the interaction of genes controlling morphologically divergent traits between the parents. In other cases, progeny heterosis could also be due to divergence between the parents at particular genetic loci that do not control field-level phenotypic differences. Genetic distanceper se between parental genotypes, based on neutral molecular markers, however, does not reflect the potential of individual genotypes to produce heterosis in their progeny.
First record of the non-indigenous parasitic copepod Neoergasilus japonicus (Harada, 1930) in the Lake Ontario Watershed: Oneida Lake, New York

Abstract Four specimens of the Asiatic parasitic copepod Neoergasilus japonicus (Harada, 1930) were collected from Oneida Lake, New York in September 2018; one specimen was from a white sucker Catostomus commersonii, another from a green sunfish Lepomis cyanellus, and two from a bluegill Lepomis macrochirus. The four adult female specimens were found attached to the base of the gills of their respective hosts along with other ergasilid species. The average total length of the adult female N. japonicus specimens we found was 0.609 mm. These detections represent the first known occurrence of this non-native species in the state of New York, extends the easternmost distribution of this parasite over 400 miles, and now includes the Lake Ontario watershed for the first time. It is commonly believed that the international aquaculture industry and aquarium fish trade are the most likely vectors of dispersal for N. japonicus. Monitoring the spread of non-indigenous aquatic species is an important step towards the development of management plans and mitigation efforts with regards to the anthropogenic causes of dispersal, and fish parasites are no exception.
A 7-Year Report of Spectrum of Inborn Errors of Metabolism on Full-Term and Premature Infants in a Chinese Neonatal Intensive Care Unit

Inborn errors of metabolism (IEMs) have great repercussions in neonatal intensive care units (NICUs). However, the integrative analysis of the incidence for full-term and premature neonates of IEMs in NICUs have not been reported. In this study, we aimed to estimate the incidence of IEMs in the NICU population so as to better evaluate the impact of IEMs on Chinese NICUs. A total of 42,257 newborns (proportion of premature as 36.7%) enrolled to the largest Chinese NICU center for a sequential 7 years screen, and 66 were diagnosed with IEMs. The prevalence of IEMs in total, full-term, and premature infants was 1:640, 1:446, and 1:2,584, respectively. In spectrum of our NICU, diseases that cause endogenous intoxication like methylmalonic acidemia accounted for 93.9% (62/66), and this ratio was higher in full-term infants with 98.3% (59/60), while the most prevalent disease in premature newborn was hyperphenylalaninemia (50%, 3/6), respectively. The genetic analysis of 49 cases revealed 62 potentially pathogenic mutations in 10 well-documented pathogenic genes of IEMs, among which 21 were novel. In conclusion, differences in incidence and spectrum of full-term and premature births we obtained in NICU will provide diagnostic guidelines and therapeutic clues of neonatal IEMs for pediatricians.