cssi/SciSciGPT-SciSciNet huggingface dataset:
Dissociation of the Hepatic Phenotype from HNF4 and HNF1α Expression

Dedifferentiated cells have served as tools to understand the molecular consequences of the loss of tissue-specific pathways. Here we report the characterization of one of these cell lines, M29, which lacks the liver-enriched HNF4-HNF1α pathway, in order to determine if this class of variant cell lines could provide additional information regarding requirements for tissue-type expression. We report that although the liver-specific α1-antitrypsin (α1AT) gene remains silent despite reactivation of the HNF4/HNF1α pathway in the M29 cells, the frequency of activation of an integrated α1AT-APRT transgene is increased 1000-fold in response to these transcription factors. The human α1AT locus (introduced via chromosome transfer) also remained silent on these cells, despite HNF4 and HNF1α expression. Results from cell fusion experiments suggest that the defect in the M29 cells is recessive. Results suggest that the M29 cells contain a defect that represses liver gene expression despite the presence of the HNF4/HNF1α pathway.
Price Bundling and Travel Product Pricing Practices Used by Online Channels of Distribution

Price bundling is one of the most prevalent marketing practices in many industries, including hospitality and travel. Virtually all types of firms in the hospitality and travel industry, from suppliers such as hotels and airlines to intermediaries such as travel agents, are encouraging customers to purchase travel “packages” rather than a single component of travel to save money and streamline the purchasing process. The purpose of this research is to determine whether the practice of price bundling by online travel agents results in actual monetary savings for consumers (i.e., lower prices) relative to the prices charged by individual service providers (i.e., hotels and airlines) through their own online Web sites. The results indicate that there are monetary savings in the form of lower prices realized by consumers who purchase bundled offerings from online travel agents, and there is an interaction effect between channel and hotel class.
A FORMAL APPROACH TO THE ANALYSIS OF PRIORITIES OF IMPRECISE CONFLICTING REQUIREMENTS

Priority analysis is one of the most important issues in the trade-off analysis of imprecise conflicting requirements whose elasticity is captured using fuzzy logic. Requirement analysts need to know not only the relative ordering of requirements based on their importance but also how much a requirement is more important than another requirement in order to achieve an effective trade-off. This paper presents a formal approach for reasoning about the relative priority by analyzing the customer’s trade-off preference among imprecise conflicting requirements. A possibilistic reasoning framework for inferring the lower bound of relative priority from case analysis under uncertainty is also developed. Consistency and nonredundancy criteria are established to facilitate the conversion of a possibilistic statement on a lower bound of relative priority into a relative priority. Finally, relative priorities are transformed into weights of importance so that they can be used in the aggregation of conflicting requirements to resolve conflicts.
Reasons for Patient Nonattendance During Acute Partial Hospitalization

Objective:This study explored predictors and consequences of nonattendance of a brief, five-day partial hospital program (PHP).Methods:Patients (N=675; N=744 admissions) who did not attend every day of a PHP, with or without prior excuses, were considered nonattenders and were compared with patients with no missed days on clinical and demographic variables collected from their medical records. Their psychiatrists’ conclusions regarding reasons for nonattendance were also collected.Results:Nonattendance occurred in 22% of admissions (7% of patient-days) and was associated with disability, lower income, attending a program for more impaired patients, less education, more previous treatment episodes at the affiliated hospital, and co-occurring or past substance use disorders. Reasons for nonattendance were mostly related to physical or psychiatric symptoms or crucial medical appointments. Nonattendance was associated with dropping out and 30-day readmission.Conclusions:PHP nonattendance occurred frequently; ...
The Role of the Researcher

In “The Role of the Researcher,” we provide encouragement for carefully considering and defining relationships among material, audience, and scholarly venues. We hope that this discussion will prompt readers to find new avenues for capturing and documenting their work, and perhaps add a new dimension to ongoing research interests. We discuss various research methodologies, IRB guidelines, primary research methods and methodologies, research with human subjects, the scholarship of teaching, and research with students.
Classifying groupware

The definition of what groupware is can be a topic of great debate and is often very broad. This allows many types of software to earn the name groupware but makes it very difficult to compare applications and to do any kind of background research in the field. This paper attempts to bring some organization to the chaos and serve as introduction to groupware.
One-clip, one-kidney hypertension in rats with hereditary hypothalamic diabetes insipidus

An attempt was made to produce one-clip, one-kidney hypertension in the rat with diabetes insipidus (DI). Renal artery constriction in unilaterally nephrectomized DI rats (DI-clip) resulted in an increased blood pressure in all 9 rats, but this response was only transient in 3 rats. The magnitude of the hypertension was less in the DI-clip rats than in Long-Evans rats subjected to the same protocol (LE-clip). Infusion of saralasin i.v. at doses of 10 and 30 μg/kg·min. 4 to 6 weeks after surgery was without effect on mean arterial pressure in LE-clip and control DI rats, but substantially lowered blood pressure in the DI-clip rats (p < 0.05 - 0.01). It is concluded that vasopressin is not essential for the production of one-clip, one-kidney hypertension in the rat, and that, in the DI rat, the renin-angiotensin system is an important factor in this form of hypertension.
Alternative Translation of 1 Corinthians 12.2: Unreal (Contra-Factual) Sense of ἂν ἤγεσθε ἀπαγόμενοι:

Many English translations follow Blass and Debrunner, taking ἂν ἤγeσθe ἀπαγόμeνοι (1 Cor 12.2) in an iterative sense: “You know that, when you were pagans, you were (led astray) to mute idols, as y...
Diapause in Protoparce sexta (Lepidoptera: Sphingidae)1

Protoparce sexta (Johannson) exhibits facultative diapause in the pupal stage, with the incidence of diapause increasing from less than 5% in June to more than 95% in late fall. The majority of diapausing pupae are produced from mid-August to mid-September in fields with heavy sucker growth on uncut stalks. Exposure of larvae to photoperiods of 5–13 hr initiates diapause, whereas a 15-hr photoperiod or continuous light prevents it. Diapause is initiated by exposing only the 4th- and 5th-instar larvae to short photoperiods and is more intense when early-stage larvae are transferred from a long to a short photoperiod than when held constantly at a short photo-period. Developmental time of diapausing pupae decreases with an increase in temperature, and termination of diapause does not require exposure to low temperature. Diapausing pupae may be stored for 4 months or more at 55° or 65°F without adversely affecting survival but storage for 2 months at 45°F results in heavy mortality.
Construction of Parametrically-Robust CFD-Based Reduced-Order Models for PDE-Constrained Optimization

A method for simultaneously constructing a reduced-order model and using it as a surrogate model to solve a PDE-constrained optimization problem is introduced. A reducedorder model is built for the parameters corresponding to the initial guess of the optimization problem. Since the resulting reduced-order model can be expected to be accurate only in the vicinity of this point in the parameter space, emphasis is placed on constructing this model by searching for regions of high error. These are determined by solving a small, nonlinear program with the objective defined as a linear combination of a residual error indicator and the objective function of the original PDE-constrained optimization problem. The reduced-order model is updated with information from the high-dimensional model in the regions of large error, and the process is repeated with more emphasis placed on solving the PDE-constrained optimization problem. The iteration terminates when the optimality conditions of the surrogate PDE-constrained optimization problem are satisfied. Application to a standard, nonlinear CFD shape optimization problem shows that the proposed method effectively solves a PDE-constrained optimization problem with few full CFD simulation queries.
Pharmacy practice in Russia amid economic turmoil

The Pharmacy Abroad section of AJHP features brief, informal, and topical communications related to pharmacy in other countries. Contributions are welcomed from pharmacists abroad or from pharmacists who have traveled abroad. AJHP also encourages pharmacists from outside of the United States to submit traditional manuscripts (e.g., scientific studies, descriptions of practice innovations), which are evaluated for publication in the primary sections of the journal.
The effect of median eminence (ME) lesions on plasma levels of FSH, LH, and prolactin in the rat.

SummaryLesions were located in the ME of ovariectomized rats to determine their effect on plasma levels of FSH, LH, and prolactin as determined by RIA. Initial levels of FSH and LH were elevated as a result of removal of steroid feedback from the ovaries. One week after placement of lesions plasma LH levels had fallen, 32-fold, to very low values. There was a lesser, 3-fold, fall in FSH, and a dramatic, 15-fold, rise in prolactin to levels nearly as high as those observed in lactating rats and in females in proestrus. In sham-operated controls, in which the electrodes were lowered into the hypothalamus stopping short of the ME, no significant changes were seen in the plasma levels of all three hormones. The results demonstrate that the release of LH and to a lesser extent FSH is decreased after removal of hypothalamic control, whereas the release of prolactin is greatly enhanced.
Drug resistance of Helicobacter pylori in nodular gastritis in children

Objective To analyze the drug resistance of Helicobacter pylori(H.pylori) in nodular gastritis in children and to further explore the rational use of antibiotics for drug-resistant H.pylori strains. Methods A total of 473 children with upper gastrointestinal symptoms undergoing gastroscopy from January 2013 to June 2014 in our hospital were enrolled. Two pieces of gastric antral mucosa in children with nodular gastritis were collected for H.pylori rapid urease test and H.pylori culture. The resistance of H.pylori to amoxicillin, clarithromycin, metronidazole, moxifloxacin and levofloxacin was detected by agar dilution method and E-test. Results In 473 cases of nodular gastritis, 258 cases were H.pylori culture-positive. The resistance rate of H.pylori isolates to amoxicillin, clarithromycin, metronidazole, moxifloxacin, levofloxacin was 6.2%, 34.9%, 49.2%, 8.9% and 5.0%, respectively. Dual resistance to clarithromycin and metronidazole was 23.3%. Moreover, 405 cases had a family history of H.pylori infection. Conclusions Nodular gastritis is a special sign of H.pylori infection in children. H.pylori infection has obvious familial aggregation. The low resistance rate of H.pylori to amoxicillin in children with nodular gastritis indicates that amoxicillin can be used as the main drug for eradication of H.pylori. Meanwhile, clarithromycin should be applied according to the drug sensitive test due to high resistance rate of H.pylori to clarithromycin.
High temperature radiation responses of amorphous SiOC/crystalline Fe nanocomposite

Abstract The radiation tolerance of amorphous silicon oxycarbide (SiOC) and crystalline Fe nanocomposites were examined by ion irradiation and transmission electron microscopy characterization. A comparison was made between a pure Fe film and SiOC/Fe multilayers. The composites were subjected to 120 keV He + ions to average damage levels from approximately 0.5 to 10.7 displacements per atom (dpa) at 600 °C. Compared to pure Fe films, the swelling resistance in the Fe layers of thick SiOC/Fe (80/60 nm) multilayer films is improved by 2.2 times and the averaged void size is reduced to half. In some instances, a crystalline Fe x Si y O z reaction layer formed between the Fe and SiOC components of the composite, and the interface between Fe and Fe x Si y O z was observed to be incoherent. Void denuded zones were observed in the Fe layer close to the SiOC/Fe and Fe/Fe x Si y O z interfaces. For thin SiOC/Fe (14/14 nm) multilayers, layer breakdown was observed and the extent of the layer breakdown became more significant with increasing dpa values. However, there were no voids in the Fe component of the thin SiOC/Fe nanocomposites. These results suggest that the SiOC/Fe and Fe/Fe x Si y O z interfaces act as efficient defect sinks which promote point defect recombination and suppress void swelling.
The Effect of Prerequisite Pharmacodynamics Course Timing on Student Performance in Pharmacotherapy Courses.

Objective. To evaluate the impact that decreasing the time from 12 to three months between prerequisite pharmacodynamics courses and their corresponding pharmacotherapy courses had on overall student performance in the pharmacotherapy courses measured by course examination scores.Methods. Two cohorts of second-professional year (P2) and third professional year (P3) classes, respectively, following different curriculum plans, simultaneously took two pharmacotherapy courses (infectious disease and neoplastic disease). Admission data (age, gender, prior bachelor’s degree status, grade point average (GPA), Pharmacy College Admission Test (PCAT) score, and interview score) were collected to establish baseline characteristics between the two cohorts. Examination scores in the corresponding prerequisite pharmacodynamics and pharmacotherapy courses were also collected. The variable was the difference in time each cohort experienced between the prerequisite pharmacodynamics courses and the subsequent pharmacothera...
Parodies of the Pre-Raphaelite Ballad Refrain

Carolyn Williams, “Parodies of the Pre-Raphaelite Ballad Refrain” (pp. 227–255) Parodies of literary ballads changed over the course of the nineteenth century, as did their implicit commentaries on practices of poetic revival in general. In the 1870s and 1880s a focused reaction against the Pre-Raphaelite ballad refrain has much to show us about the function of the refrain, which operates as a timing device yet also guides a gradual increase in the ballad’s incrementally modulated sense of pain, making meaning by turning away from narrative progression and meaning-making. Debates about the poetics of revival, a subject across the eighteenth and nineteenth centuries, culminate in the great theorizations of Walter Pater and Oscar Wilde, who both comment on the ballad refrain. The dynamics of literary history may also be illuminated by this attention to parodies of the ballad refrain, for the role of the refrain within any given ballad may be seen as homologous to the role of parody within literary history—simultaneously interrupting, turning away, and binding a sense of continuity. This essay glances at the ballads of “Bon Gaultier” (1845) and demonstrates the general parodic interest in—and defenses of—the Pre-Raphaelite ballad refrain later in the century, before attending to parodies of D. G. Rossetti’s “Sister Helen” (1870, 1881) by Robert Buchanan in 1871 and Henry Duff Traill in 1882.
A High Voltage Power Supply That Mitigates Current Reversals in Capillary Zone Electrophoresis-Electrospray Mass Spectrometry

Capillary electrophoresis coupled with electrospray ionization typically employs two power supplies, one at each end of the capillary. One power supply is located at the proximal (injection) end of the capillary. The power supply located at the distal (detector) end of the capillary drives the electrospray. Electrophoresis is driven by the difference in potential between these power supplies. Separations that employ large capillary inner diameter, high conductivity background electrolyte, and high separation potentials generate higher current than that produced by the electrospray. Excess current flows through the electrospray power supply. Most power supplies are not designed to sink current, and the excess current will cause the electrospray voltage to deviate from its set point. We report a simple circuit to handle this excess current, allowing separations under a wide range of electrophoretic conditions. Graphical Abstract ᅟ.
The L2 Discrepancy of Irrational Lattices

It is well known that, when α has bounded partial quotients, the lattices \(\big\{\big(k/N,\{k\alpha \}\big)\big\}_{k=0}^{N-1}\) have optimal extreme discrepancy. The situation with the L 2 discrepancy, however, is more delicate. In 1956 Davenport established that a symmetrized version of this lattice has L 2 discrepancy of the order \(\sqrt{\log N}\), which is the lowest possible due to the celebrated result of Roth. However, it remained unclear whether this holds for the original lattices without any modifications. It turns out that the L 2 discrepancy of the lattice depends on much finer Diophantine properties of α, namely, the alternating sums of the partial quotients. In this paper we extend the prior work to arbitrary values of α and N. We heavily rely on Beck’s study of the behavior of the sums \(\sum \big(\{k\alpha \} -\frac{1} {2}\big)\).
Immunogenetic aspects of allotransplantation.

Histocompatibility antigens may be defined as those antigens present on various cells which evoke an immune response after transplantation of an organ or tissue from one individual into another.
Problem Formulation in Knowledge Discovery via Data Analytics (KDDA) for Environmental Risk Management.

With the growing popularity of data analytics and data science in the field of environmental risk management, a formalized Knowledge Discovery via Data Analytics (KDDA) process that incorporates all applicable analytical techniques for a specific environmental risk management problem is essential. In this emerging field, there is limited research dealing with the use of decision support to elicit environmental risk management (ERM) objectives and identify analytical goals from ERM decision makers. In this paper, we address problem formulation in the ERM understanding phase of the KDDA process. We build a DM3 ontology to capture ERM objectives and to inference analytical goals and associated analytical techniques. A framework to assist decision making in the problem formulation process is developed. It is shown how the ontology-based knowledge system can provide structured guidance to retrieve relevant knowledge during problem formulation. The importance of not only operationalizing the KDDA approach in a real-world environment but also evaluating the effectiveness of the proposed procedure is emphasized. We demonstrate how ontology inferencing may be used to discover analytical goals and techniques by conceptualizing Hazardous Air Pollutants (HAPs) exposure shifts based on a multilevel analysis of the level of urbanization (and related economic activity) and the degree of Socio-Economic Deprivation (SED) at the local neighborhood level. The HAPs case highlights not only the role of complexity in problem formulation but also the need for integrating data from multiple sources and the importance of employing appropriate KDDA modeling techniques. Challenges and opportunities for KDDA are summarized with an emphasis on environmental risk management and HAPs.
Pulmonary excretion of H2 in calves with Cryptosporidium-induced malabsorption.

Pulmonary hydrogen gas (H2) concentrations were used to assess the malabsorption of dietary nutrients in preruminating calves inoculated withCryptosporidium sp. Normal values were established in five control calves and seven calves (principals) were inoculated with 1.0 ×105 Cryptosporidium sp. oocysts. Hydrogen concentrations and wet fecal weights were measured at three stages: beforeCryptosporidium sp. inoculation (stage 1), three days after the onset of diarrhea (stage 2), and after the resolution of diarrhea (stage 3). Mean end-breath and total-breath H2 concentrations in the principal calves were higher (P<0.025 andP< it0.05) for stage 2, when compared to control values. Both end-breath and total-breath H2 concentrations were increased (P<0.001 andP<0.025, respectively) in the principal calves during stage 2 when compared to values obtained for stages 1 and 3. Concurrently,Cryptosporidium sp. infection was associated with increased (P=0.06) fecal output during stage 2, only. The increased H2 concentrations and cumulative fecal output show thatCryptosporidium sp. caused malabsorption of fermentable nutrients.
Evaluation of the Quality of Adjuvant Endocrine Therapy Delivery for Breast Cancer Care in the United States

Importance Randomized trials in breast cancer have demonstrated the clinical benefits of adjuvant endocrine therapy (AET) in preventing recurrence and death. The examination of concordance with AET guidelines at a national level as a measure of quality of care is important. Objective To investigate temporal trends and factors related to receipt of AET for breast cancer. Design, Setting, and Participants This retrospective cohort study included 981 729 women with breast cancer in the National Cancer Database from January 1, 2004, to December 31, 2013. Women with stages I to III breast cancer who received all or part of their treatment at the reporting institution were included in the analysis. Main Outcomes and Measures Temporal changes in AET receipt (estimating the annual percentage change) and AET practice patterns (using logistic regression) and the effect of AET guideline concordance on survival of women with hormone receptor–positive (HR+) breast cancer (using the multivariable Cox proportional hazards model). Results Of the 981 729 eligible patients (mean [SD] age, 60.8 [13.3] years), 818 435 had HR+ and 163 294 had HR-negative (HR−) cancer. Among the patients with HR+ cancer, receipt of AET increased over time, from 69.8% in 2004 to 82.4% in 2013. Among patients with HR− cancer, receipt decreased from 5.2% in 2004 to 3.4% in 2013. Hospital-level adherence (≥80% of patients with HR+ cancer received AET) increased from 40.2% in 2004 to 69.2% in 2013. Receipt of AET varied significantly by age (lower in patients ≥80 years), race (lower in African American and Hispanic participants), geographic location (lower in West South Central, Mountain, and Pacific census regions), and receptor status (lower in patients with estrogen receptor–negative and progesterone receptor–positive cancer). Surgery and radiotherapy were the factors most significantly associated with appropriate AET receipt (only 45.0% in patients who received lumpectomy without radiotherapy). Receipt of AET was associated with a 29% relative risk reduction in mortality. Based on this effectiveness estimate, if all patients with HR+ cancer received AET, approximately 14 630 lives would have been saved over 10 years. Conclusions and Relevance From 2004 to 2013, underuse and misuse of AET have decreased for patients with breast cancer, but optimal use has not been achieved, and significant variation in care remains. The involvement of surgery and radiotherapy were among the most significant factors associated with optimal use, which underscores the benefits of team-based care to support guideline-concordant therapy.
Challenges in Recruiting, Retaining and Promoting Racially and Ethnically Diverse Faculty

Abstract Background Despite individual and institutional awareness of the inequity in retention, promotion and leadership of racially and ethnically underrepresented minority faculty in academic medicine, the number of such faculty remains unacceptably low. The authors explored challenges to the recruitment, retention and promotion of underrepresented faculty among a sample of leaders at academic medical centers. Methods Semi-structured interviews were conducted from 2011 to 2012 with 44 senior faculty leaders, predominantly members of the Group on Diversity and Inclusion (GDI) and/or the Group on Women in Medical Sciences (GWIMS), at the 24 randomly selected medical schools of the National Faculty Survey of 1995. All institutions were in the continental United States and balanced across public/private status and geographic region. Interviews were audio-taped, transcribed, and organized into content areas before conducting inductive thematic analysis. Themes expressed by multiple informants were studied for patterns of association. Results The climate for underrepresented minority faculty was described as neutral to positive. Three consistent themes were identified regarding the challenges to recruitment, retention and promotion of underrepresented faculty: 1) the continued lack of a critical mass of minority faculty; 2) the need for coordinated programmatic efforts and resources necessary to address retention and promotion; and 3) the need for a senior leader champion. Conclusion Despite a generally positive climate, the lack of a critical mass remains a barrier to recruitment of racially and ethnically underrepresented faculty in medicine. Programs and resources committed to retention and promotion of minority faculty and institutional leadership are critical to building a diverse faculty.
Bilingual experience shapes language processing: Evidence from codeswitching

Abstract We report three experiments on two groups of Spanish–English bilinguals who differed in codeswitching experience (codeswitchers and non-codeswitchers) to examine how different production choices predict comprehension difficulty. Experiment 1 examined the processing of gender congruent and gender incongruent determiner-noun switches in sentential contexts using event-related potentials. While codeswitchers demonstrated N400 sensitivity to congruency manipulations, non-codeswitchers showed a modulation of early frontal EEG activity to switching, regardless of switch type. Experiment 2 validated the translation-equivalent target words compared in Experiment 1. In Experiment 3, the bilinguals who participated in Experiment 1 completed a task that elicited naturally-produced codeswitched speech. Codeswitchers switched more often than non-codeswitchers, and their switches robustly reflected the conditions that were more easily processed in Experiment 1. Together, the results indicate the comprehension system becomes optimally attuned to variation in the input, and demonstrate that switching costs depend on the type of codeswitch and bilinguals’ language experience.
Optical frequency comb generation by pulsed pumping

A synchronously pumped Kerr cavity is proposed and studied for power-efficient frequency comb generation in optical microring resonators. The system is modeled using the Lugiato-Lefever equation. Analytical solutions are provided for an ideal case and extended by numerical methods to account for optical loss and higher orders of dispersion. It is shown that the average power requirement is reduced by the duty cycle of the pulse with respect to the conventional continuous-wave-pumped microrings, and it is significantly lower than the pulsed pumping of straight waveguides.
Heterogeneous content caching in wireless networks

This work develops a cooperative content caching framework for Social Wireless Networks (SWNETs) in which content demands are hierarchically heterogeneous. The heterogeneous request model incorporates user preference for different categories/genres, and contents under each category, both following power law distributions at local as well as global levels. Based upon such request generation model, an optimal Heterogeneous Split Caching (HSC) algorithm is proposed which can minimize electronic content provisioning cost using cooperative caching policies. Detailed simulation experiments for functional validation and performance evaluation with respect to traditional caching strategies are then performed under various protocol and network parameters. The baseline HSC mechanism is also tested against a special benchmark situation that provides a steady state performance bound, which can occur after an infinite request horizon.
Molecular moieties masking Ca2+-dependent facilitation of voltage-gated Cav2.2 Ca2+ channels

Voltage-gated Cav2.1 (P/Q-type) Ca2+ channels undergo Ca2+-dependent inactivation (CDI) and facilitation (CDF), both of which contribute to short-term synaptic plasticity. Both CDI and CDF are mediated by calmodulin (CaM) binding to sites in the C-terminal domain of the Cav2.1 α1 subunit, most notably to a consensus CaM-binding IQ-like (IQ) domain. Closely related Cav2.2 (N-type) channels display CDI but not CDF, despite overall conservation of the IQ and additional sites (pre-IQ, EF-hand-like [EF] domain, and CaM-binding domain) that regulate CDF of Cav2.1. Here we investigate the molecular determinants that prevent Cav2.2 channels from undergoing CDF. Although alternative splicing of C-terminal exons regulates CDF of Cav2.1, the splicing of analogous exons in Cav2.2 does not reveal CDF. Transfer of sequences encoding the Cav2.1 EF, pre-IQ, and IQ together (EF-pre-IQ-IQ), but not individually, are sufficient to support CDF in chimeric Cav2.2 channels; Cav2.1 chimeras containing the corresponding domains of Cav2.2, either alone or together, fail to undergo CDF. In contrast to the weak binding of CaM to just the pre-IQ and IQ of Cav2.2, CaM binds to the EF-pre-IQ-IQ of Cav2.2 as well as to the corresponding domains of Cav2.1. Therefore, the lack of CDF in Cav2.2 likely arises from an inability of its EF-pre-IQ-IQ to transduce the effects of CaM rather than weak binding to CaM per se. Our results reveal a functional divergence in the CDF regulatory domains of Cav2 channels, which may help to diversify the modes by which Cav2.1 and Cav2.2 can modify synaptic transmission.
Emerging Adults and Criminal Offending

Studies suggest emerging adulthood impacts offending in young adults This chapter presents evidence exploring the influence emerging adulthood has on criminal offending including the role of turning points and social bonds (e.g., marriage, parenthood, military service). Continuity and persistence in offending are also explored.
Lactoferrin: a promoter of polymorphonuclear leukocyte adhesiveness.

Polymorphonuclear leukocytes (PMN) degranulate, adhere to vascular endothelium, or aggregate to each other following exposure of the cells to high concentrations of chemotactic stimuli such as formyl-methionyl- leucyl phenylalanine (FMLP). PMN released the specific granule product lactoferrin more readily in response to chemotactic stimuli, which correlated with promotion of PMN aggregation as measured by light transmission and enhanced PMN adherence. Both concanavalin A (Con-A) and phorbol myristate acetate (PMA), agents that lead to specific granule discharge, induced and sustained human PMN aggregation. Similarly, supernatants, generated from Con-A-treated PMN, aggregated fresh PMN in the presence of alpha-methylmannoside, a competitive inhibitor of the lectin. Anti-human lactoferrin IgG but not normal goat IgG blunted the aggregation elicited by both PMA and FMLP. Both human milk lactoferrin and rabbit PMN lactoferrin aggregated human lactoferrin promoted PMN adherence to endothelial cells. The enhanced PMN stickiness was correlated with the early phase of degranulation. Thus, PMN lactoferrin serves an autoregulatory role to retain PMN at inflammatory sites to amplify the inflammatory response.
Pathogenesis of Mycoplasma pneumoniae infections:adaptive immunity, innate immunity, cell biology, and virulence factors

Mycoplasmas represent the smallest self-replicating organisms. They are unique among bacteria in that they lack a cell wall and require sterols for growth. The limited metabolic and biosynthetic activities of mycoplasmas have complicated development of accurate means for laboratory detection and hampered understanding of their roles as human pathogens. Mycoplasma pneumoniae was first identified and characterized in the 1960s and shown to be a common cause of upper and lower respiratory disease in children and adults. Serious infections requiring hospitalization, while rare, occur in persons of all age groups, and may affect multiple organ systems. Severity of disease appears to be related to the degree to which the host immune response reacts to the infection. Extrapulmonary complications involving all of the major organ systems can occur in association with M. pneumoniae infection as a result of direct invasion and/or autoimmune response. Evidence is accumulating for this organism’s contributory role in chronic lung conditions such as asthma. Serology has been the most common means for laboratory detection of M. pneumoniae infection due to the slow growth that makes culture impractical. Newer diagnostic methods utilizing nucleic acid amplification offer the advantages for rapid detection and are likely to become increasingly important in the future, but these techniques have not achieved widespread utilization thus far due to the lack of commercially sold products and non-standardized methodology. Management of M. pneumoniae infections can usually be achieved with macrolides, ketolides, tetracyclines, or fluoroquinolones. As more is learned about pathogenesis and immune response elicited by M. pneumoniae, improved methods for diagnosis and prevention of disease due to this organism are anticipated.
Scaling Up In-Memory-Computing Classifiers via Boosted Feature Subsets in Banked Architectures

In-memory computing is an emerging approach for overcoming memory-accessing bottlenecks, by eliminating the costs of explicitly moving data from point of storage to point of computation outside the array. However, computation increases the dynamic range of signals, such that performing it via the existing structure of dense memory substantially squeezes the signal-to-noise ratio (SNR). In this brief, we explore how computations can be scaled up, to jointly optimize energy/latency/bandwidth gains with SNR requirements. We employ algorithmic techniques to decompose computations so that they can be mapped to multiple parallel memory banks operating at chosen optimal points. Specifically focusing on in-memory classification, we consider a custom IC in 130-nm CMOS IC and demonstrate an algorithm combining error-adaptive classifier boosting and multi-armed bandits, to enable segmentation of a feature vector into multiple subsets. The measured performance of 10-way MNIST digit classification, using images downsampled to $16{\times }16$ pixels (mapped across four separate banks), is 91%, close to that simulated using full unsegmented feature vectors. The energy per classification is 879.7 pJ, $14.3{\times }$ lower than that of a system based on separated memory and digital accelerator.
Genetic linkage of Beckwith-Wiedemann syndrome to 11p15.

Beckwith-Wiedemann syndrome (BWS), characterized by multiorgan developmental abnormalities and predisposition to cancer, usually occurs sporadically, but small apparently dominant pedigrees have been described. Since rare patients show varying karyotypic abnormalities on the short arm of chromosome 11, it has been suggested that BWS may be related to the Wilms tumor gene on 11p13 or, alternatively, to growth factor genes on 11p15. We performed genetic linkage analysis on two BWS kindreds, using RFLPs for loci on 11p. BWS was linked to the insulin gene (11p15.5), with an overall maximum lod score of 3.60 (recombination fraction = .00). Linkage to D11S16 (11p13) could be excluded for recombination fractions less than or equal to .03. These results suggest that BWS defines a tumor-predisposition gene on 11p15.
Shock Tunnel Noise Measurement with Resonantly Enhanced Focused Schlieren Deflectometry

The character of the boundary layer noise and ambient tunnel noise are of interest in the experimental study of laminar to turbulent transition. The instability mechanism in hypersonic flow over slender bodies is the acoustic mode. A number of investigations of flow over a slender cone in high-enthalpy facilities have been performed; however, measurements of the boundary layer noise and ambient tunnel noise have not been made. In cold hypersonic facilities the frequency range of the acoustic mode typically lies below 500 kHz; in high-enthalpy facilities, 5-20 MJ/kg, the most strongly amplified acoustic mode frequency is approximately 1-3 MHz. These high frequencies are well beyond the reach of the piezo-electric pressure transducers typically used in cold hypersonic facilities. A logical approach is to investigate the use of optical methods. Measurements of the boundary layer noise and ambient tunnel noise on a five degree half angle cone in the Caltech T5 hypervelocity shock tunnel are made with a single point focused schlieren system and a resonantly enhanced focused schlieren system.
Mind, medicine, and metaphysics: reflections on the reclamation of the human spirit.

Following the publication of such works as Auguste Comte’s Cour de Philosophic Positive (1830-1842), in which he argued the inherent immaturity of metaphysical discourse, metaphysics, for Western i...
Next generation pathways into biomedical informatics: lessons from 10 years of the Vanderbilt Biomedical Informatics Summer Internship Program.

Objectives To examine roles for summer internship programs in expanding pathways into biomedical informatics, based on 10 years of the Vanderbilt Department of Biomedical Informatics (DBMI) Summer Research Internship Program. Materials and methods Vanderbilt DBMI's internship program is a research-intensive paid 8-10 week program for high school, undergraduate, and graduate students. The program is grounded in a "Windows, Mirrors, and Open Doors" educational framework, and is guided by an evolving set of design principles, including providing meaningful research experiences, applying a multi-factor approach to diversity, and helping interns build peer connections. Results Over 10 years, 90 individuals have participated in the internship program, with nine students participating for more than one summer. Of 90 participants, 38 were women and 52 were men. Participants represented a range of racial/ethnic groups. A total of 39 faculty members have served as primary mentor for one or more interns. Five key lessons emerged from our program experience: Festina Lente ("Make haste slowly"), The Power of Community, Learning by Doing, Thoughtful Partnerships Lead to Innovation, and The Whole is More Than the Sum of Its Parts. Discussion Based on our experience, we suggest that internship programs should become a core element of the biomedical informatics educational ecosystem. Continued development and growth of this important educational outreach approach requires stable funding sources and building connections between programs to share best practices. Conclusion Internship programs can play a substantial role in the biomedical informatics educational ecosystem, helping introduce individuals to the field earlier in their educational trajectories.
Effects of Estrogens on Central Nervous System Neurotransmission: Implications for Sex Differences in Mental Disorders

Nearly one of every five US individuals aged 12 years old or older lives with certain types of mental disorders. Men are more likely to use various types of substances, while women tend to be more susceptible to mood disorders, addiction, and eating disorders, all of which are risks associated with suicidal attempts. Fundamental sex differences exist in multiple aspects of the functions and activities of neurotransmitter-mediated neural circuits in the central nervous system (CNS). Dysregulation of these neural circuits leads to various types of mental disorders. The potential mechanisms of sex differences in the CNS neural circuitry regulating mood, reward, and motivation are only beginning to be understood, although they have been largely attributed to the effects of sex hormones on CNS neurotransmission pathways. Understanding this topic is important for developing prevention and treatment of mental disorders that should be tailored differently for men and women. Studies using animal models have provided important insights into pathogenesis, mechanisms, and new therapeutic approaches of human diseases, but some concerns remain to be addressed. The purpose of this chapter is to integrate human and animal studies involving the effects of the sex hormones, estrogens, on CNS neurotransmission, reward processing, and associated mental disorders. We provide an overview of existing evidence for the physiological, behavioral, cellular, and molecular actions of estrogens in the context of controlling neurotransmission in the CNS circuits regulating mood, reward, and motivation and discuss related pathology that leads to mental disorders.
Venous thromboembolism after total joint arthroplasty: Risk stratification and prophylaxis

Abstract Venous thromboembolic disease (VTE) is an infrequent but serious complication after total joint arthroplasty. The selection of an appropriate prophylaxis regimen is a balance between efficacy and safety. Risk stratification is the key to the selection of an appropriate prophylaxis regimen, but there is no ideal risk stratification protocol available today.
Factor one, familiarity and frontal cortex: a challenge to the two-factor theory of delusions.

Introduction: Two-factor theory suggests delusions require two neuropsychological impairments, one in perception (which furnishes content), and a second in belief evaluation (that augers formation ...
Accelerating Hyperdimensional Classifier on Multiple GPUs

Among brain-inspired computing paradigms, hyperdimensional (HD) computing is based on mathematical properties of high-dimensional spaces which show remarkable agreement with brain-controlled behaviors [1] . In [2] , the authors present an HD classifier for the task of identifying the language of text samples based on letter N -grams. They describe a computing architecture in which an encoding module generates a hypervector for each text sample and a search module compares the generated vector with a set of trained hypervectors. They provide an open-source implementation of their HD classifier written in hardware description language (HDL). In addition, they implemented the classifier with the 65-nm technology library, and evaluated the efficiency and accuracy of the classifier.
Characterizing Colonization Patterns of Clavibacter michiganensis During Infection of Tolerant Wild Solanum Species

Clavibacter michiganensis is the Gram-positive causal agent of bacterial canker of tomato, an economically devastating disease with a worldwide distribution. C. michiganensis colonizes the xylem, leading to unilateral wilt, stem canker, and plant death. C. michiganensis can also infect developing tomato fruit through splash dispersal, forming exterior bird's eye lesions. There are no documented sources of qualitative resistance in Solanum spp.; however, quantitative trait loci conferring tolerance in Solanum arcanum and Solanum habrochaites have been identified. Mechanisms of tolerance and C. michiganensis colonization patterns in wild tomato species remain poorly understood. This study describes differences in symptom development and colonization patterns of the wild type (WT) and a hypervirulent bacterial expansin knockout (ΔCmEXLX2) in wild and cultivated tomato genotypes. Overall, WT and ΔCmEXLX2 cause less severe symptoms in wild tomato species and are impeded in spread and colonization of the vascular system. Laser scanning confocal microscopy and scanning electron microscopy were used to observe preferential colonization of protoxylem vessels and reduced intravascular spread in wild tomatoes. Differences in C. michiganensis in vitro growth and aggregation were determined in xylem sap, which may suggest that responses to pathogen colonization are occurring, leading to reduced colonization density in wild tomato species. Finally, wild tomato fruit was determined to be susceptible to C. michiganensis through in vivo inoculations and assessing lesion numbers and size. Fruit symptom severity was in some cases unrelated to severity of symptoms during vascular infection, suggesting different mechanisms for colonization of different tissues.
Estudiantes universitarias chilenas: discursos y prácticas contra la violencia sexista

espanolEl trabajo da cuenta del itinerario que siguen las estudiantes universitarias, para visibilizar y contrarrestar el acoso sexual dentro de la institucion educativa, durante las movilizaciones por una educacion no sexista en Chile en el 2018. El analisis es realizado desde el corpus teorico del feminismo y la accion colectiva, enfatizando la mirada situada desde la etnografia dialogica y el analisis de documentos y prensa. Evidencia desplazamientos en las relaciones de poder desde practicas y discursos que cuestionan el dispositivo de genero y las formas tradicionales de participacion democratica representativa. EnglishThe work gives an account of the itinerary that female university students followed during the mobilizations for a non-sexist education in Chile in 2018. They were aiming at raising awareness and counteracting sexual harassment within the educational institution. Feminism and collective action make up the theoretical corpus for the analysis, giving emphasis to the situated perspective of dialogic ethnography and the analysis of records and press. It shows displacements in power relations within practices and discourses that question the gender device and the traditional forms of representative democratic participation. portuguesO traballio descreve o itinerario que os estudantes universitarios seguem, para tornar visivel e neutralizar o assedio sexual dentro da instituigno educacional, durante as mobilizagoes para uma educagno nao sexista no Chile em 2018. A analise e realizada a partir do corpus teorico do feminismo e agao coletiva, enfatizando a perspectiva da etnografia dialogica e a analise de documentos e imprensa. Evidencias de deslocamentos nas relagdes de poder com base em praticas e discursos que questionam o dispositivo de genero e as formas tradicionais de participagao democratica representativa.
Omaveloxolone and TX63682 are hepatoprotective in the STAM mouse model of nonalcoholic steatohepatitis.

Omaveloxolone is a potent activator of Nrf2, a master transcriptional regulator of a multitude of cytoprotective functions, including antioxidative, anti-inflammatory, and mitochondrial bioenergetic effects. Some of the most potent known effects of Nrf2 involve hepatoprotective functions. The purpose of this study was to evaluate the effects of omaveloxolone and TX63682, a closely related structural analog with similar oral bioavailability, in the STAM mouse model of nonalcoholic steatohepatitis (NASH). C57Bl/6 mice received a single subcutaneous injection of streptozotocin two days after birth and were fed a high-fat diet from 4 to 9 weeks of age. Omaveloxolone and TX63682 were orally administered at doses of 1, 3, and 10 mg/kg/d from 6 to 9 weeks of age. Consistent with the beneficial effects of Nrf2 on hepatoprotection and improved lipid handling, both omaveloxolone and TX63682 decreased hepatic fat deposition, hepatocellular ballooning, inflammatory cell infiltration, and collagen deposition. Omaveloxolone and TX63682 also improved blood glucose control, as evidenced by reductions in nonfasting blood glucose and glycated hemoglobin A1C concentrations. Reductions in liver and serum triglycerides with omaveloxolone and TX63682 treatment were also observed. Both omaveloxolone and TX63682 decreased leptin and increased adiponectin in serum, which is consistent with the anti-inflammatory and antifibrotic effects observed in the liver. These results were associated with significant induction of Nrf2 target gene expression in the liver, including NAD(P)H:quinone oxidoreductase 1, sulfiredoxin 1, and ferritin heavy chain 1. Overall, these data suggest that omaveloxolone and related Nrf2 activators may be useful for the treatment of NASH.