cssi/SciSciGPT-SciSciNet huggingface dataset:
Direct Myosin Activation by Omecamtiv Mecarbil for Heart Failure with Reduced Ejection Fraction

Myosin is the indispensable molecular motor that utilizes chemical energy to produce force for contraction within the cardiac myocyte. Myosin activity is gated by intracellular calcium levels which are regulated by multiple upstream signaling cascades that can be altered for clinical utility using inotropic medications. In contrast to clinically available cardiac inotropes, omecamtiv mecarbil is a novel direct myosin activator developed to augment left ventricular systolic function without the undesirable secondary effects of altered calcium homeostasis. Its identification and synthesis followed high-throughput screening of a reconstituted sarcomere, deliberate optimization, exquisite biochemical evaluation, and subsequently promising effects in animal models were demonstrated. Physiologically, it prolonged the duration of left ventricular systole in animal models, healthy adults, and patients with heart failure with reduced ejection fraction (HFrEF) without changing the velocity of pressure development, as assessed in animal models. It has been formulated for both intravenous and oral administration, and in both acute and chronic settings produced similar alterations in the duration of systole associated with beneficial increases in cardiac output, improvements in left ventricular volumes, and reductions in heart rate and often of natriuretic peptides. Small, asymptomatic increases in troponin were also observed in the absence of clinically evident ischemia. Clinically, the question remains as to whether the possible harm of this minimal troponin release is outweighed by the potential benefits of reduced neurohormonal activation, increased stroke volume and cardiac output, and improved ventricular remodeling in patients treated with omecamtiv mecarbil. The resolution of this question is being addressed by a phase III outcomes trial of this potential novel therapy for heart failure.
Hypoxia inducible factor-1 alpha stabilization for regenerative therapy in traumatic brain injury

Mild traumatic brain injury (TBI), also called concussion, initiates sequelae leading to motor deficits, cognitive impairments and subtly compromised neurobehaviors. While the acute phase of TBI is associated with neuroinflammation and nitroxidative burst, the chronic phase shows a lack of stimulation of the neurorepair process and regeneration. The deficiency of nitric oxide (NO), the consequent disturbed NO metabolome, and imbalanced mechanisms of S-nitrosylation are implicated in blocking the mechanisms of neurorepair processes and functional recovery in the both phases. Hypoxia inducible factor-1 alpha (HIF-1α), a master regulator of hypoxia/ischemia, stimulates the process of neurorepair and thus aids in functional recovery after brain trauma. The activity of HIF-1α is regulated by NO via the mechanism of S-nitrosylation of HIF-1α. S-nitrosylation is dynamically regulated by NO metabolites such as S-nitrosoglutathione (GSNO) and peroxynitrite. GSNO stabilizes, and peroxynitrite destabilizes HIF-1α. Exogenously administered GSNO was found not only to stabilize HIF-1α and to induce HIF-1α-dependent genes but also to stimulate the regeneration process and to aid in functional recovery in TBI animals.
"Nothing to Hide, Nothing to Fear: The Effect of Scrutiny on Policy Implementation"

Theory and research suggest that once formal structures become institutionalized, economic needs become poor predictors of adoption. Relatively little is known, however, about the implementation of...
Novel Method of Measuring Canal Dehiscence and Evaluation of its Potential as a Predictor of Symptom Outcomes After Middle Fossa Craniotomy

Background Superior semicircular canal dehiscence (SSCD) is an osseous defect of the arcuate eminence of the petrous temporal bone. Strategies for measuring dehiscence size are variable, and the usefulness of such parameters remains in clinical equipoise. Objective To present a novel method of measuring dehiscence volume and to evaluate its potential as a predictor of symptom outcomes after surgical repair of SSCD. Methods High-resolution computed tomographic temporal bone images were imported into a freely available segmentation software. Dehiscence lengths and volumes were ascertained by independent authors. Inter-rater observer reliability was assessed using Cronbach's alpha. Correlation and regression analyses were performed to evaluate for relationships between dehiscence size and symptoms (pre- and post-operative). Results Thirty-seven dehiscences were segmented using the novel volumetric assessment. Cronbach's alpha for dehiscence lengths and volumes were 0.97 and 0.95, respectively. Dehiscence lengths were more variable as compared to dehiscence volumes (σ2 8.92 vs σ2 0.55, F = 1.74). The mean dehiscence volume was 2.22 mm3 (0.74, 0.64-0.53 mm3). Dehiscence volume and headache at presentation were positively correlated (Rpb = 0.67, P = .03). Dehiscence volume and vertigo improvement after surgery were positively correlated, although this did not reach statistical significance (Rpb = 0.46, P = .21). Conclusion SSCD volumetry is a novel method of measuring dehiscence size that has excellent inter-rater reliability and is less variable compared to dehiscence length, but its potential as a predictor of symptom outcomes is not substantiated. However, the study is limited by low power.
A T7 RNA Polymerase Mutant Enhances the Yield of 5′‐Thienoguanosine‐Initiated RNAs

Spectroscopic methods, which are used to establish RNA structure-function relationships, require strategies for post-synthetic, site-specific incorporation of chemical probes into target RNAs. For RNAs larger than 50 nt, the enzymatic incorporation of a nucleoside or nucleotide monophosphate guanosine analogue (G analogue) at their 5'-end is routinely achieved by T7 RNA polymerase (T7RNAP)-mediated in vitro transcription (IVT) of the appropriate DNA template containing a GTP-initiating class III Φ6.5 promoter. However, when high G analogue:GTP ratios are used to bias G analogue incorporation at the 5'-end, RNA yield is compromised. Here, we show that the use of a T7RNAP P266L mutant in IVT with 10:1 thienoguanosine (th G):GTP increased the percent incorporation and yield of 5'-th G-initiated precursor tRNA for a net ≈threefold gain compared to IVT with wild-type T7RNAP. We also demonstrated that a one-pot multienzyme approach, consisting of transcription by T7RNAP P266L and post-transcriptional cleanup by polyphosphatase and an exonuclease, led to essentially near-homogeneous 5'-th G-modified transcripts. This approach should be of broad utility in preparing 5'-modified RNAs.
Abstract 108: Imaging Renin Granule Exocytosis by Total Internal Reflection (TIRF) Microscopy in Mouse Juxtaglomerular Cells: Effect of cAMP and Beta Adrenergic Stimulation

Renin is stored in dense core granules in juxtaglomerular (JG) cells. Renin release is highly regulated. However, the kinetics of renin release and mode of granule exocytosis remains unexplored. We...
Does Intravenous Acetaminophen Improve Postoperative Pain Control after Laparoscopic Appendectomy for Perforated Appendicitis? A Prospective Randomized Trial

Introduction The recent increased awareness of the dangers of opioids in the United States has highlighted the need to minimize narcotics and identify nonopioid options for pain control after surgery. With evidence suggesting that intravenous acetaminophen (IVA) can be an opioid sparing option, we conducted a prospective, randomized trial that evaluated the effect of IVA on the postoperative pain course of children with perforated appendicitis. Materials and Methods After IRB approval, children with perforated appendicitis were randomized to receive postoperative IVA with the standard patient/nurse-controlled analgesia (PCA) or to receive the PCA alone. All patients were treated according to an evidence-based treatment protocol. The primary outcome was duration of time on PCA. Results Eighty-two patients were analyzed from 7/14 to 11/15. There was no statistically significant difference in the time to transition from the PCA to oral pain medications for children given IVA compared with children not receiving IVA (76.4 ± 32.5 versus 86.7 ± 49.3 hours; p = 0.73). Children in the IVA group had no statistically significant difference in intravenous narcotics delivered and pain scores compared with the non-IVA group. There was no significant difference in the amount of oral narcotics between both groups (2.8 ± 2.4 versus 2.9 ± 2.5; p = 0.88). Patients who received IVA had higher medication charges ($3752.7 ± 1618.3 vs. $1198.19 ± 521.51; p Conclusion Children given IVA showed no difference in the transition time off the PCA and to oral pain medications after laparoscopic appendectomy for perforated appendicitis.
A Study on the Effects of Strain Rates on Characteristics of Brain Tissue

Traumatic brain injury (TBI) often happens when the brain tissue undergoes a high rate mechanical load. Although numerous research works have been carried out to study the mechanical characterization of brain matter under quasi-static (strain rate ≤ 100 S−1) loading but a limited amount of experimental studies are available for brain tissue behavior under dynamic strain rates (strain rate ≥ 100 S−1). In this paper, the results of a study on mechanical properties of ovine brain tissue under unconfined compression tests are to be presented. The samples were compressed under uniaxial strain rates of 0.0667, 3.33, 6.667, 33.33, 66.667 and 200 S−1. The brain tissue presents a stiffer response with increasing strain rate, showing a time-dependent behavior. So the hyperelastic-only models are not adequate to exhibit the brain viscoelasticity. Therefore, two hyper-viscoelastic constitutive equations based on power function model and Mooney-Rivlin energy function are applied to the results with quasi-static strain rate (≤ 100 S−1). Good agreement of experimental and theoretical has been achieved for results of the low strain rates. It is concluded that the obtained material parameters from quasi-static tests are not appropriate enough to fit the result with the high strain rate of 200 S−1. The study will further provide new insight into a better understanding of the rate-dependency behavior of the brain tissue under dynamic conditions. This is essential in the development of constitutive material characteristics for an efficient human brain finite element models to predict TBI under impact condition or high motion.© 2017 ASME
Electromigration-lifetime constrained power grid optimization considering multi-segment interconnect wires

Electromigration (EM) remains the top killer of copper-based damascene interconnects in 10nm and beyond technologies. On-chip power/ground (P/G) networks are most vulnerable to EM failures due to large and unidirectional current flows, thus proper sizing and even routing of power grid networks are critical for the full-chip EM sign-off. In this paper, we propose a new P/G network sizing technique based on recently proposed fast EM immortality check method for general multi-segment interconnect wires and physics-based EM assessment technique for fast time to failure analysis. We first show that the new P/G optimization problem subjected to voltage IR drop and new EM constraints can still be formulated as a sequence of linear programming (SLP) problem. The new optimization will ensure that all the wires will not fail if all the constraints are satisfied. To consider EM-induced aging effects on power supply networks for the target lifetime and mitigate the over-conservation of the first optimization formulation, we further propose an aging-aware P/G optimization method, which allows some short-lived wires to fail or to age and optimizes the rest of the wires considering resistance increase of those failed wire segments. In this way, the P/G networks can be optimized more effectively and become more robust and aging-aware. Numerical results on a number of IBM and self-generated power supply networks show that the new approach can effectively reduce the area of the network while ensuring immortality or improving target lifetime of all the wires, which is not the case for the existing current density constrained optimization method.
Marcuse’s Hegel: Hope and Despair in the Logic of Negation

Marcuse’s Reason and Revolution found a rich reception in the 1960’s field of Hegel/Marx commentary. This rereading challenges Marcuse’s reduction of Hegel’s dialectical logic to a logic of negation. It describes weaknesses in Marcuse’s Hegel paraphrases, and argues that Marcuse’s bold leap to a Revolutionary logic rejects Hegel’s method: turning instead to Kant’s transcendental logic, and leading his readers into an antinomy of hope and despair.
Illuminating women’s hidden contribution to the foundation of theoretical population genetics

Plentiful evidence shows an historic and continuing gender gap in participation and success in scientific research. However, less attention has been directed at clarifying obscured contributions of women to scientific research. The lack of visible women role models in science (particularly in computational fields) contributes to a reduced sense of belonging and retention among women at early stages in their scientific careers [Steele 1997]. We seek to counteract this cycle by illuminating the contribution of women programmers to the foundation of our own fields — population and evolutionary genetics. We consider past 9acknowledged programmers9 (APs), who developed, ran, and sometimes analyzed the results of early computer programs. Due to authorship norms at the time, these programmers were credited in the acknowledgments sections of manuscripts, rather than being recognized as authors. For example, one acknowledgement reads "I wish to thank Mrs. Jennifer Smith for ably programming and executing all the computations" (Supplemental Table 1). In this study, we documented acknowledgment sections and identified APs in Theoretical Population Biology ( TPB ) articles published between 1970 and 1990. While only 7% of authors were women, 43% of APs were women. This significant difference (p = 4.0×10-10) demonstrates a substantial proportion of women9s contribution to foundational computational population genetics has been unrecognized. We additionally observed a decrease over time in the proportion of women APs, as well as number of APs generally These observations correspond to the masculinization of computer programming, and the probable shifting of programming responsibilities to individuals credited as authors (likely graduate students). Finally, we note recurrent APs who contributed to several manuscripts. We conclude that, while previously overlooked, historically, women have made substantial contributions to computational biology.
A Novel Energy Efficient Communication Architecture for Bluetooth Ad Hoc Networks

Bluetooth is a promising wireless technology aiming at supporting electronic devices to be instantly interconnected into short-range ad hoc networks. The Bluetooth medium access control protocol is based on the Master/Slave concept wherein any communication between slave devices has to go through the Master. While this model provides for simplicity, it incurs a longer delay between any two slave devices due to far from optimal packet forwarding, the use of double the bandwidth, and also additional energy wastage at the Master. Moreover, if more than two devices want to communicate as a group, this can only be achieved by either multiple unicast transmissions or a piconet-wide broadcast, clearly resulting in inefficiency. In this paper, we propose a novel Dynamic Slot Assignment (DSA) scheme whereby the Master device dynamically assigns slots to Slaves so as to allow them to communicate directly with each other without any Master intervention. This proposed communication architecture also provides for Quality of Service (QoS) requests, admission control, and multi-device conversation by which a multicast-like communication is implemented within a piconet. Through extensive simulation, we observe that DSA drastically enhances Bluetooth performance in terms of delay and throughput, while significantly reducing power consumption at the master and also of the overall piconet.
Reducing the ATHENA WFI background with the science products module: lessons from Chandra ACIS

The Wide Field Imager (WFI) on ESA’s Athena X-ray observatory will include the Science Products Module, a secondary CPU that can perform special processing on the science data stream. Our goal is to identify on-board processing algorithms that can reduce WFI charged particle background and improve knowledge of the background to reduce systematics. Telemetry limitations require discarding most pixels on-board, keeping just candidate X-ray events, but information in the discarded data may be helpful in identifying background events masquerading as X-ray events. We present full frame data from CCDs on-board Chandra, in high-Earth orbit, and the results of our search for phenomenological correlations between particle tracks and background events that would otherwise be categorized as X-rays. In addition to possibly reducing the Athena instrumental background, these results are applicable to understanding the particle component in any X-ray Silicon-based detector in space.
Reticulocytes I. Isolation and In Vitro Maturation of Synchronized Populations

Studies of reticulocyte maturation have been limited by the inability to obtain pure populations of age-synchronized reticulocytes and by the absence of well-defined methods for the maturation of reticulocytes in vitro. Many of these problems were overcome using temporary suppression of erythropoiesis with thiamphenicol and phlebotomy resulting in a highly reproducible reticulocyte response, Percoll density gradient separation of cells yielding essentially pure populations of age-synchronized reticulocytes, and liquid culture techniques where cell lysis is minimal. The system allows reproducible study of well-defined cohorts of reticulocytes as they mature into erythrocytes. During in vitro maturation we serially monitored changes in reticulocyte count, glucose consumption, 125I-transferrin binding, fluorescein (FITC)-labeled transferrin binding, the activities of four erythrocyte enzymes (glucose-6-phosphate dehydrogenase, pyruvate kinase, phosphofructokinase, and lactate dehydrogenase) and the appearance of cells on scanning electron microscopy. These variables changed at different rates suggesting that multiple mechanisms underlie these maturational events. Transferrin binding and reticulocyte count decreased most rapidly and reached values near zero after three to four days in culture. The four enzyme activities decreased much more slowly, and only two reached pretreatment values after seven days in culture. In contrast to the findings of others, scanning electron microscopy suggested that cells do not assume the normal biconcave shape in this system. The methods described make it feasible to study the process of reticulocyte maturation in vitro. The data presented represent a first step in the study of the coordination and interrelationships of various maturational processes.
Mid-IR (8–13µm) Images of Proto-Planetary Nebulae

We present mid-IR (8–13µm) images of dust in seven proto-planetary nebulae (PPN), GL2343, HD 161796, 89 Her, OH 0739–1435, CRL2688, IRAS 22272+5435, and CRL618. The images were taken at UKIRT and the IRTF with the Berkeley mid-IR camera which was developed at the Space Sci. Lab, in UC Berkeley and is supported by IGPP and LEA, LLNL. The results presented here are part of an on-going mid-IR imaging project to study the morphological development of a star as it evolves from the Asymptotic Giant Branch (AGB) to the planetary nebula (PN) stage. In particular, we aim to establish when non-spherical symmetry which is evident in so many PN arises. Four of the objects are oxygen rich. Of these, GL2343 (Fig. 1) and HD161796 are found to have spherical dust shells in the mid-IR with diameters of 6.“ 7 and 3” , respectively. OH 0739 is marginally resolved, but has a hint of elongation that is aligned with the bipolar nebula evident in the near-IR. 89 Her is unresolved at 1.“ 1 resolution. 89 Her, HD 161796 and GL2343, all high latitude supergiants, appear to form an evolutionary sequence as evidenced by the size of their circumstellar dust shells. Three of the objects are carbon rich. CRL2688 and IRAS 22272 +5435 are found to have elongated structures which suggest a bipolar morphology. CRL 618 is unresolved at 1.” 7, but is known to be bipolar from optical studies. Hence, with the exception of OH 0739, a known binary, the oxygen rich PPN have spherical dust shells while the carbon rich have bipolar dust shells. Our small number of observations do not provide solid statistics; however, this trend suggests that nebula bipolarity is linked to carbon-rich chemistry.
Management of Patients with Failure Following Definitive Radiotherapy

The therapeutic efficacy of all definitive treatments of clinically localized, invasive bladder cancer centers on its ability to control the local-regional disease and relieve symptoms. Various approaches using single or integrated therapy have been reported (Blandy et al. 1980; Batata et al. 1981; Smith and Whitmore 1981; Abratt et al. 1984; Hope Stone et al. 1984; Schaeffer et al. 1984; Shipley et al. 1985; Matthews et al. 1987; Rotman et al. 1987; Villar et al. 1987; Zincke et al. 1988; Nissenkorn et al. 1990; Plzzocaro et al. 1990; Abratt et al. 1991; Kragelj et al. 1992; Abratt et al. 1993a; Kaufman et al. 1993; Abratt et al. 1994; Herr and Scher 1994; Srougi and Simon 1994; Given et al. 1995; Orsatti et al. 1995), with several different strategies demonstrating similar survival outcomes. Surgical intervention consisting of radical cystectomy and pelvic lymph node dissection has been the treatment of choice, particularly with physicians in the United States. Definitive local-regional treatment with radical radiation therapy is also widely used as primary therapy, definitive treatment after chemosensitization, and neoadjuvantly prior to cystectomy ar. The ongoing desire to develop effective bladder-sparing therapies has led to several treatment regimens which take advantage of these multimodality approaches.
Mitofusin 2 regulates neutrophil adhesive migration via suppressing Rac activation

Neutrophils rely on glycolysis for energy production. How mitochondria regulate neutrophil function is not fully understood. Here, we report that mitochondrial outer membrane protein Mitofusin 2 (Mfn2) regulates neutrophil homeostasis in vivo. Mfn2-deficient neutrophils are released from the hematopoietic tissue and trapped in the vasculature in zebrafish embryos. Human neutrophil-like cells deficient with MFN2 fail to arrest on activated endothelium under sheer stress or perform chemotaxis. Deletion of Mfn2 results in a significant reduction of neutrophil infiltration to the inflamed peritoneal cavity in mice. Mfn2, but not Mfn1, -null mouse embryonic fibroblast cells have altered actin structure and are impaired in wound closure. MFN2-deficient neutrophil-like cells display heightened intracellular calcium levels and Rac activation after chemokine stimulation. Mechanistically, MFN2 maintains mitochondria-ER interaction. Restoring mitochondria-ER tether rescues the chemotaxis defect and Rac activation resulted from MFN2 depletion. Finally, inhibition of Rac restores chemotaxis in MFN2-deficient neutrophils. Altogether, we identified that MFN2 regulates neutrophil migration via suppressing Rac activation and uncovered a previously unrecognized role of MFN2 in regulating the actin cytoskeleton.
Racing “return”: the diasporic return of U.S.-raised Korean Americans in racial and ethnic perspective

Despite the growing body of research on ethnic return migrants originating from the U.S., few have situated this practice within sociological framings of U.S. race relations or immigrant assimilati...
Halide metathesis in overdrive: mechanochemical synthesis of a heterometallic group 1 allyl complex.

As a synthesis technique, halide metathesis (n RM + M'X n → R n M' + n MX) normally relies for its effectiveness on the favorable formation of a metal halide byproduct (MX), often aided by solubility equilibria in solution. Owing to the lack of significant thermodynamic driving forces, intra-alkali metal exchange is one of the most challenging metathetical exchanges to attempt, especially when conducted without solvent. Nevertheless, grinding together the bulky potassium allyl [KA']∞ (A' = [1,3-(SiMe3)2C3H3]-) and CsI produces the heterometallic complex [CsKA'2]∞ in low yield, which was crystallographically characterized as a coordination polymer that displays site disorder of the K+ and Cs+ ions. The entropic benefits of mixed Cs/K metal centers, but more importantly, the generation of multiple intermolecular K…CH3 and Cs…CH3 interactions in [CsKA'2]∞, enable an otherwise unfavorable halide metathesis to proceed with mechanochemical assistance. From this result, we demonstrate that ball milling and unexpected solid-state effects can permit seemingly unfavored reactions to occur.
Interleukin-15 Enhances Anti-GD2 Antibody-Mediated Cytotoxicity in an Orthotopic PDX Model of Neuroblastoma.

Purpose: Immunotherapy with IL2, GM-CSF, and an anti-disialoganglioside (GD2) antibody significantly increases event-free survival in children with high-risk neuroblastoma. However, therapy failure in one third of these patients and IL2-related toxicities pose a major challenge. We compared the immunoadjuvant effects of IL15 with those of IL2 for enhancing antibody-dependent cell-mediated cytotoxicity (ADCC) in neuroblastoma. Experimental Design: We tested ADCC against neuroblastoma patient-derived xenografts (PDX) in vitro and in vivo and examined the functional and migratory properties of NK cells activated with IL2 and IL15. Results: In cell culture, IL15-activated NK cells induced higher ADCC against two GD+ neuroblastoma PDXs than did IL2-activated NK cells (P Conclusions: The substitution of IL15 for IL2 leads to significant tumor regression in vitro and in vivo and supports clinical testing of IL15 for immunotherapy in pediatric neuroblastoma.
Can an Imaging Marker of Consistency Predict Intraoperative Experience and Clinical Outcomes for Vestibular Schwannomas? A Retrospective Review.

Objective The main purpose of this article is to determine if vestibular schwannoma consistency as determined by tissue intensity on T2-weighted magnetic resonance imagings (MRIs) is predictive of intraoperative experience and postoperative clinical outcomes. Study Design Retrospective chart review. Setting Tertiary referral center. Patients Seventy-seven patients diagnosed with vestibular schwannomas who were treated with microsurgical resection. Intervention Diagnostic. Main Outcome Measures Intraoperative measures include totality of resection, surgical time and cranial nerve VII stimulation and postoperative measures include House–Brackmann grade and perioperative complications. Results Tumor consistency determined via tissue intensity on MRI was only found to correlate with surgical time, with a softer tumor being associated with a longer surgical time (p Conclusions Tumor consistency determined by MRI is not predictive of intraoperative experience or postoperative outcomes in vestibular schwannomas. Tumor volume is the strongest driver of these outcome measures as opposed to tumor consistency.
The epidemiology and biology of pulmonary metastases

Our goal in this chapter is to explore the complex processes of metastasis and why there is a predisposition for this to occur in the lung. In addition, we aim to describe the incidence of pulmonary metastases in various contexts and based on the origin of the primary tumor. There are unique characteristics of the pulmonary system that make metastases more likely to occur in the lung than anywhere else in the body. Some of these characteristics include receiving the entire cardiac output every minute, having the densest capillary bed in the body, and being the first reservoir of most lymphatic drainage entering the venous system. There are multiple postulated routes of metastasis to the pulmonary system including hematogenous and lymphatic routes with early or late dissemination. The vascularization of pulmonary metastases is variable and complex, often recruiting supply from bronchial and pulmonary origin. There are also many biochemical factors in the tumor microenvironment that play a key role in the development of lung metastases including vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), very late antigen 4 (VLA-4) and intercellular adhesion molecule 1 (ICAM-1). Studies vary widely in reported rates of pulmonary metastases due to differences in clinical study design, however, it is commonly accepted that up to half of autopsies performed on patients who died of malignancy have pulmonary metastases. In a surgical series describing the incidence of primary cancer types with resected pulmonary metastases the most common sites were thyroid, colon, breast, genitourinary tract, skin, liver, breast, and adrenal glands.
Trends in Appendicitis Among Pregnant Women, the Risk for Cardiac Arrest, and Maternal–Fetal Mortality

Appendicitis is the most common extra-uterine surgical emergency requiring immediate intervention during pregnancy. However, risks for mortality and morbidity among pregnant women with appendicitis remain poorly understood. This study was conducted to determine the temporal trends of appendicitis in pregnant women, and to calculate the risk of maternal–fetal mortality and near-miss marker (i.e., cardiac arrest) among pregnant women in general, and by race/ethnicity. We conducted this retrospective study using data from the Nationwide Inpatient Sample (NIS) from January 1, 2002, through December 31, 2015. Joinpoint regression was used to estimate and describe temporal changes in the rates of all and acute appendicitis during the 14-year study period. We also estimated the risk of cardiac arrest, maternal, and fetal mortality among mothers of various racial/ethnic groups with a diagnosis of acute appendicitis. Within each group, patients without acute appendicitis were the referent category. Out of the 58 million pregnancy hospitalizations during the study period, 63,145 cases (10.74 per 10,000 hospitalizations) were for acute appendicitis. There was a 5% decline (95% CI: − 5.1, − 5.0) in the rate of appendicitis hospitalizations over the period of the study. After adjusting for covariates, pregnant mothers with acute appendicitis had increased likelihood when compared to those without acute appendicitis to suffer fetal loss (OR: 2.05, 95% CI: 1.85–2.28) and nearly fivefold increase for inpatient maternal death. In conclusion, appendicitis during pregnancy remains an important cause of in-hospital maternal–fetal mortality overall and regardless of race/ethnicity.
Phosphorylation on PstP regulates cell wall metabolism and antibiotic tolerance in Mycobacterium smegmatis

ABSTRACT Mycobacterium tuberculosis and its relatives, like many bacteria, have dynamic cell walls that respond to environmental stresses. Modulation of cell wall metabolism in stress is thought to be responsible for decreased permeability and increased tolerance to antibiotics. The signaling systems that control cell wall metabolism under stress, however, are poorly understood. Here, we examine the cell wall regulatory function of a key cell wall regulator, the serine/threonine phosphatase PstP, in the model organism Mycobacterium smegmatis. We show that the peptidoglycan regulator CwlM is a substrate of PstP. We find that a phosphomimetic mutation, pstP T171E, slows growth, misregulates both mycolic acid and peptidoglycan metabolism in different conditions, and interferes with antibiotic tolerance. These data suggest that phosphorylation on PstP affects its activity against various substrates and is important in the transition between growth and stasis. IMPORTANCE Regulation of cell wall assembly is essential for bacterial survival and contributes to pathogenesis and antibiotic tolerance in mycobacteria, including pathogens such as Mycobacterium tuberculosis. However, little is known about how the cell wall is regulated in stress. We describe a pathway of cell wall modulation in Mycobacterium smegmatis through the only essential Ser/Thr phosphatase, PstP. We showed that phosphorylation on PstP is important in regulating peptidoglycan metabolism in the transition to stasis and mycolic acid metabolism in growth. This regulation also affects antibiotic tolerance in growth and stasis. This work helps us to better understand the phosphorylation-mediated cell wall regulation circuitry in Mycobacteria.
Building a System to Engage and Sustain Research Careers for Physicians.

There are increasing needs for physician-investigators to translate the rapid expansion of knowledge, technology/interventions, and big data into the clinical realm at a time of increasing age-related disabilities and communicable diseases. Yet, the number of physician-investigators has continued to decline, and only a small number of medical school graduates in the United States are actively engaged in research. This problem may be particularly pronounced in small- and medium-sized academic institutions due to more limited educational and mentoring infrastructure. Neither efforts by the federal government nor isolated institutional programs alone have been effective yet in solving this problem. This article describes an integrated institutional strategy undertaken at Penn State College of Medicine that is focused on developing and sustaining a physician-investigator workforce. Key elements of this strategy are new programs to close gaps in the professional life cycle of physician-investigators, dedicated senior leaders collaborating with an experienced and diverse advisory committee, and a data-driven approach to programmatic evaluation. In this article, the implementation of integrated institutional programs including Institutional Mock Review for evaluation of grant proposals before submission, physician-scientist faculty mentoring, and effort matching programs are described. Detailed tactics are offered for tailoring these programs to a particular institution's background to maximize both efficiency and sustainability. The overarching strategy includes engaging multidisciplinary faculty as mentors and mentees, partnering with both clinical and basic science departments, integrating new programs with established approaches, and cultivating an emerging generation of physician-investigators as near-peer mentors and future leaders. This approach may serve as a useful paradigm for building an environment to nurture junior physician-investigators at other mid-sized academic institutions and may also have value for larger institutions in which there is fragmentation of the efforts to sustain the research careers of physicians.
The Effect of Education on Symptom Onset and Severity of Huntington's Disease

Background Huntington disease (HD) is an inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive symptoms. Little is known about the effects of environmental factors on HD symptom onset and severity. Objective To evaluate the relationship between education level and age of diagnosis, symptom onset, and symptom severity in HD. Methods This study evaluated 4537 adult-onset, motor-manifest HD participants from the Enroll-HD global registry. Education level was assessed using International Standard Classification of Education categories, stratified into three education groups corresponding to pre-secondary, secondary, and post-secondary educational attainment. Motor and behavioral symptoms of HD, cognition, and functional capacity were measured using baseline Unified Huntington's Disease Rating Scale (UHDRS), Mini-Mental State Exam (MMSE), Symbol Digit Modalities Test (SDMT), verbal fluency, and Stroop assessments. Results After adjusting for CAG repeats, higher level of education predicted lower age of onset of motor symptoms, depression, irritability, and cognitive impairment (all P-values < 0.001). After adjusting for age of enrollment and CAG repeats, the highest education level predicted the lowest UHDRS motor scores, higher UHDRS total functional capacity and functional assessment scores, and higher SDMT, MMSE, verbal fluency, and Stroop assessment scores (all P-values < 0.001). Conclusions HD participants with higher education levels have earlier age of diagnosis and age of symptom onset, but lower motor exam scores and higher functional assessment scores. Earlier recognition of symptoms in more highly educated participants may explain earlier symptom onset and diagnosis. Better performance on motor and functional assessments may be explained by higher cognitive reserve in those with greater education.
Curriculum and Competency Evaluation in Respiratory Entry to Practice Programs

Background: Essential skills for respiratory therapists (RTs) now extend beyond the traditional scope of therapy. Department leaders are under increasing pressure to hire appropriately trained staff, maximize orientation time, and positively affect patient outcomes. The RT is expected to communicate effectively, provide education, and practice in interprofessional (IP) teams. Use of technology, including telehealth, for patient interaction is increasing. Accreditation standards require evaluation of student competence in communication and IP practice. No literature was found on how degree programs teach or evaluate these skills. Our objectives were to determine if program curricula include communication, patient education, telehealth, and formal IP activities apart from clinical rotations; identify related experiences; and explore how programs conduct evaluation of essential skills. Methods: Directors of accredited respiratory programs were invited by email to anonymously complete a survey regarding curriculum. Survey domains were oral communication, patient education, learning strategies, telehealth, and IP activities. Master’s programs were excluded from analysis due to small numbers. Chi-square analysis and Fisher’s exact tests were used to compare program types. Descriptive statistics were used to summarize results. P Results: Response rate was 37% (136/370): Associate (AS) Conclusions: More BS programs included patient education, telehealth, and IP activities than AS programs. Telehealth is rarely included or evaluated at any degree level. Programs should evaluate the need for enhanced patient education and telehealth instruction.
Lactic Streptococcal Agglutinins: A Review

Agglutinins that cause clumping and settling of lactic streptococci are reviewed. Evidence defining the role played by agglutinins in sedimentation defects occurring during cottage cheese manufacture is presented. The needs for a fast, simple and reliable agglutination test, and additional research on the influence of agglutinins on other fermented milk products, are noted.
Proactive Strategies to Safeguard Young Adolescents in the Cyberage.

(2009). Proactive Strategies to Safeguard Young Adolescents in the Cyberage. Middle School Journal: Vol. 41, Fostering Good Decisions, pp. 28-34.
Horse spleen hemosiderin

Abstract A method is described for the isolation of hemosiderin granules from horse spleen; it is based on differential centrifugation in concentrated aqueous potassium iodide solutions. This method achieves a good yield of hemosiderin granules that are free of any visible contamination. Chemical analysis of some of the components of the granules is reported.
Chapter 4 Alchemical Free Energy Calculations: Ready for Prime Time?

Publisher Summary In an alchemical transformation, a chemical species is transformed into another via a pathway of nonphysical (alchemical) states. Many physical processes, such as ligand binding or transfer of a molecule from gas to solvent, can be equivalently expressed as a composition of such alchemical transformations. Often, these alchemical processes are much more amenable to computational simulation than the physical process itself, especially in complex biochemical systems. A relative ligand-binding affinity, for example, may be computed via a thermodynamic cycle by alchemically transforming one ligand to another both bound to a receptor and in solution. There are other successful nonalchemical approaches for the computation of free energy differences, such as phase equilibrium Monte Carlo methods for modeling multicomponent fluids and potential of mean force methods. Alchemical approaches, however, generally allow for the larger range of conformational complexity typical of biochemical systems. This chapter discusses the efficiency and convergence of free energy methods rather than on accuracy, which is a function of the force field.
Processes of Self-Management in Chronic Illness

Chronic illnesses, such as cardiovascular disease, cancer, and diabetes, are among the most prevalent and costly of all global health problems (World Health Organization, 2011). They are the primary reason adults seek health care and are the leading cause of death and disability in the United States (U.S. Centers for Disease Control and Prevention, 2011). Chronic illnesses are long term, uncertain, and can be very intrusive to individuals' everyday lives (Larsen, 2009). Often, chronic illnesses have a course that varies over time specific to the etiology and physiology of the particular illness. However, there are common challenges across chronic illnesses, which include recognizing symptoms and taking appropriate actions, using medications effectively, managing complex regimens, developing strategies to deal with the psychological consequences of the illness, and interacting with the healthcare system over time (Wagner et al., 2001; U.K. Department of Health, 2003). Chronic illness management has been recognized as an important component of health care, and there is increasing awareness that similar strategies can be effective across different types of chronic illnesses (Dowrick, Dixon-Woods, Holman, & Weinman, 2005; Harvey et al., 2008; Swendeman, Ingram, Rotheram-Borus, 2009).
Review of Virus and Virus-Like Diseases of Pome and Stone Fruits : by Ahmed Hadidi, Marina Barba, Thierry Candresse, and Wilhelm Jelkmann (Eds.). St. Paul, MN: American Phytopathological Society, 2011

Previous texts on the topic of fruit diseases have focused either on pome fruits (apple, pear, quince) or stone fruits (cherry, peach, plum, apricot). Because there are a number of viral diseases w...
The Effect of Conservation Priority Areas on Bidding Behavior in the Conservation Reserve Program

We explore how a landowner's bid to enroll in the Conservation Reserve Program (CRP) is influenced by his parcel's designation as a Conservation Priority Area (CPA). A theoretical model of a landowner's optimal bid is presented, and we demonstrate the ambiguity in a landowner's optimal bid response to CPA designations. The bid choice is analyzed using a data set of accepted and unaccepted offers during three CRP sign-up periods. We focus empirically on a subset of offers from the Prairie Pothole CPA to identify whether bid responses to exogenous location factors differ across landowners with varying opportunity costs to enrollment. ( JEL Q15, Q18 )
Comparison of routine urinalysis and urine Gram stain for detection of bacteriuria in dogs.

Objective To determine the utility of performing urine Gram stain for detection of bacteriuria compared to routine urine sediment examination and bacterial aerobic urine culture. Design Prospective, observational study. Setting University teaching hospital. Animals Urine samples acquired via cystocentesis through convenience sampling from 103 dogs presenting to a tertiary referral institution. Interventions All samples underwent routine urinalysis, including sediment examination, as well as urine Gram stain and quantitative bacterial aerobic urine culture. Measurements and Main Results The urine Gram stain demonstrated improved sensitivity (96% versus 76%), specificity (100% versus 77%), positive predictive value (100% versus 83%), and negative predictive value (93% versus 69%) when identifying bacteriuria, compared to routine urine sediment examination. Conclusions The urine Gram stain is highly sensitive and specific when detecting the presence of bacteria in canine urine samples. Gram staining should be considered when bacteriuria is highly suspected and requires rapid identification while bacterial culture is pending.
The two-dimensional cubic sensor problem

For the two-dimensional cubic sensor problem, the unnormalized conditional probability measures do not have versions that are continuous as functions of the sample paths of the observation process.
A Novel Algorithm for Designing the PID Controllers of High-speed Flywheels for Traction Applications

High speed flywheel energy storage system (FESS) is one of the most energy dense storage technologies proposed for traction applications. In this paper, performance of a high speed and high power FESS using a permanent magnet synchronous machine (PMSM) is evaluated during both charging (motoring) and discharging (generating) modes of operations. A PWM inverter (rectifier) interfaces between the DC bus and the PMSM. During charging an inner current loop controller and outer speed loop controller regulate the whole system performance and during discharging operation the outer speed loop controller is inactive and instead a DC bus voltage regulator controls the FESS. Current, speed, and DC bus voltage regulations are realized by PI/PID controllers. These types of controllers have been used in motor drives industries for several decades. However, traditional methods based on simplifications, approximations, try and error are used to tune the gains of the controllers. The PI controllers achieved in this way do not guarantee optimal performance of the system. In this paper, the transfer functions of the current loop and speed loop are derived. Then, a novel design algorithm [1] is used to generate the entire set of stabilizing PI/PID controllers for the current and speed loops of the FESS. The algorithm is presented step by step for both current and speed controllers and a 70 kW, 36000 RPM FESS is simulated in PSIM to verify the consistency of the algorithm.
Elastoplastic medium for foundation settlements and monotonic soil–structure interaction under combined loadings

Foundation settlements and soil–structure interaction are important problems to structural and geotechnical engineers. This study introduces a novel elastoplastic three-degree-of-freedom medium which models foundations settlements under combined loadings. A soil–structure interaction problem can then be solved by replacing the soil mass with this three-degree-of-freedom elastoplastic medium, thus reducing significantly the size of the problem. The model was developed by extending the classical plasticity concepts to the force-deformation level. Its ability to predict foundation deformations was evaluated using finite element solutions of a typical shallow foundation problem and was found reasonably accurate while producing significant time savings. Copyright © 2006 John Wiley & Sons, Ltd.
Getting into chromatin: how do transcription factors get past the histones?

Transcriptional activators and the general transcription machinery must gain access to DNA that in eukaryotes may be packaged into nucleosomes. In this review, I discuss this problem from the stand...
Maya urban genesis reconsidered: Trade and intensive agriculture as primary factors

Abstract Maya scholarship, from its inception, has been characterized by a perspective that has stressed the uniqueness of Maya civilization. Specifically, it was assumed that cities did not emerge until the Post-Classic and that intensive agriculture was not practised. Attempts to explain the assumed uniqueness of Maya civilization have usually stressed religious traits. In contrast, geographers and archaeologists have recently demonstrated that the lowland Maya practised intensive agriculture and had well-developed local trade patterns. The notion that the lowland Classic Maya civilization was “non-urban” and “unique” is re-examined.