cssi/SciSciGPT-SciSciNet huggingface dataset:
SUV in pelvic lymph node is a significant prognostic factor in previously untreated squamous carcinoma of the uterine cervix

5051 Background: The aim of this prospective study was to identify prognostic factors (including 18F-fluorodeoxyglucose positron emission tomography [FDG-PET] parameters) in previously untreated sq...
A META-ANALYSIS OF CARDIOVASCULAR SAFETY OF FDA APPROVED ANTI OBESITY DRUGS

Introduction: Despite FDA approval, the cardiovascular safety of anti-obesity drugs (naltrexone-bupropion, phenteramine-topiramate, liraglutide, orlistat and lorcaserin) remains unknown. This is important given the withdrawal of historical weight loss agents amidst safety concerns. Methods: Large
Revisiting the value of competition assays in folate receptor-mediated drug delivery.

Polymeric nanoparticles have been studied for gene and drug delivery. These nanoparticles can be modified to utilize a targeted delivery approach to selectively deliver their payload to specific cells, while avoiding unwanted delivery to healthy cells. One commonly over-expressed receptor which can be targeted by ligand-conjugated nanoparticles is the folate receptor alpha (FRα). The ability to target FRα remains a promising concept, and therefore, understanding the binding dynamics of the receptor with the ligand of the nanoparticle therapeutic can provide valuable insight. This manuscript focuses on the interaction between self-assembled nanoparticles decorated with a folic acid (FA) ligand and FRα. The nanoparticles consist of micelles formed with a FA conjugated triblock copolymer (PEI-g-PCL-b-PEG-FA) which condensed siRNA to form micelleplexes. By combining biological and biophysical approaches, this manuscript explores the binding kinetics and force of the targeted siRNA containing nanoparticles to FRα in comparison with free FA. We demonstrate via flow cytometry and atomic force microscopy that multivalent micelleplexes bind to FRα with a higher binding probability and binding force than monovalent FA. Furthermore, we revisited why competitive inhibition studies of binding of multivalent nanoparticles to their respective receptor are often reported in literature to be inconclusive evidence of effective receptor targeting. In conclusion, the results presented in this paper suggest that multivalent targeted nanoparticles display strong receptor binding that a monovalent ligand may not be able to compete with under in vitro conditions and that high concentrations of competing monovalent ligands can lead to measurement artifacts.
CCR6 promotes steady-state mononuclear phagocyte association with the intestinal epithelium, imprinting and immune surveillance.

The intestinal lamina propria (LP) contains antigen-presenting cells with features of dendritic cells and macrophages, collectively referred to as mononuclear phagocytes (MNPs). Association of MNPs with the epithelium is thought to play an important role in multiple facets of intestinal immunity including imprinting MNPs with the ability to induce IgA production, inducing the expression of gut homing molecules on T cells, facilitating the capture of luminal antigens and microbes, and subsequent immune responses in the mesenteric lymph node (MLN). However, the factors promoting this process in the steady state are largely unknown, and in vivo models to test and confirm the importance of LP-MNP association with the epithelium for these outcomes are unexplored. Evaluation of epithelial expression of chemoattractants in mice where MNP-epithelial associations were impaired suggested CCL20 as a candidate promoting epithelial association. Expression of CCR6, the only known receptor for CCL20, was required for MNPs to associate with the epithelium. LP-MNPs from CCR6-/- mice did not display defects in acquiring antigen and stimulating T-cell responses in ex vivo assays or in responses to antigen administered systemically. However, LP-MNPs from CCR6-deficient mice were impaired at acquiring luminal and epithelial antigens, inducing IgA production in B cells, inducing immune responses in the MLN, and capturing and trafficking luminal commensal bacteria to the MLN. These findings identify a crucial role for CCR6 in promoting LP-MNPs to associate with the intestinal epithelium in the steady state to perform multiple functions promoting gut immune homeostasis.
Online C-benevolent job scheduling on multiple machines

We consider scheduling a sequence of C-benevolent jobs on multiple homogeneous machines. For two machines, we propose a 2-competitive Cooperative Greedy algorithm and provide a lower bound of 2 for the competitive ratio of any deterministic online scheduling algorithms on two machines. For multiple machines, we propose a Pairing-m Greedy algorithm, which is deterministic 2-competitive for even number of machines and randomized $$(2+2/{\hbox {m}})$$ -competitive for odd number of machines. We provide a lower bound of 1.436 for the competitive ratio of any deterministic online scheduling algorithms on three machines, which is the best known lower bound for competitive ratios of deterministic scheduling algorithms on three machines.
“We Are All Children of God”: The Intersectionality of Religion, Race and Ethnicity, and Immigration in Chinese Churches in Memphis, Tennessee

The Chinese (including the Taiwanese) are one of the fastest growing immigrant groups in the greater Memphis area. In a southern midsize city like Memphis where Chinese are less concentrated, Chine...
Mediating Justice: Women’s Perceptions of Fairness in the Civil Protection Order Process:

Mediation use has grown rapidly in the past few decades as an efficacious method of civil dispute resolution. However, early research suggests that civil mediation may cause further harm to victims of intimate partner abuse because, based on the inherent power dynamics of abusive relationships, they are not able to effectively advocate on their own behalf. In addition, organizational efficiency concerns have led to the development of consent processes for civil protection orders (POs). However, research has yet to examine the extent to which victims of intimate partner violence who take part in these consent processes perceive the process and associated outcomes as fair. Using qualitative data (N = 19 interviews) collected from women who sought civil POs through Family Court in Delaware, this research finds that the consent process and women’s interactions with mediators reproduce power inequalities that are inherent in cases of intimate partner abuse, which shape their perceptions of fairness in the PO p...
Saracatinib and Dasatinib Fail To Prevent Heritable Pulmonary Arterial Hypertension

Evidence suggests that the deregulation of SRC Family Kinases may play a role in the development of heritable pulmonary arterial hypertension, associated with BMPR2 mutations. The truncated c-terminus of the BMPR2 protein is known to increase the phosphorylation and downstream activity of SRC tyrosine kinases. To test the hypothesis that the inhibition of SRC can prevent heritable PAH due to a BMPR2 mutation, we exposed BMPR2 mutant mice to SRC inhibitors, saracatinib and dasatinib, to block the SRC activation caused by the BMPR2 mutation. Saracatinib and dasatinib failed to prevent the development of PAH in BMPR2 mutant mice. Increased pressure in the right ventricle was not normalized and muscularization of large blood vessels was not reduced when compared to wild type mice. Inhibiting SRC9s phosphorylation does not prevent heritable PAH, and thus supports evidence that SRC9s aberrant localization and trafficking in PAH plays a more critical role in disease development.
The Role of Phosphatases in TOR Signaling in Yeast

The TOR pathway controls cellular functions necessary for cell growth and proliferation of yeast and larger eukaryotes. The search for members of the TOR signaling cascade in yeast led to the discovery of type 2A protein phosphatases (PP2A) as important players within the pathway. We describe the roles in yeast of PP2A and the closely related phosphatase, Sit4, and then focus on complexes formed between the catalytic subunit of these phosphatases and Tap42, a direct target of the Tor protein kinases in yeast. Recent results suggest that Tap42 mediates many of the Tor functions in yeast, especially those involved in transcriptional modulation. However, whether Tap42 executes its function by inhibiting phosphatase activity or by activating phosphatases is still uncertain. In addition, Tor affects some transcriptional and physiological processes through Tap42 independent pathways. Thus, Tor proteins use multiple mechanisms to regulate transcriptional and physiological processes in yeast.
The Fibrotic Substrate in Persistent Atrial Fibrillation Patients: Comparison Between Predictions From Computational Modeling and Measurements From Focal Impulse and Rotor Mapping

Focal impulse and rotor mapping (FIRM) involves intracardiac detection and catheter ablation of re-entrant drivers (RDs), some of which may contribute to arrhythmia perpetuation in persistent atrial fibrillation (PsAF). Patient-specific computational models derived from late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) has the potential to non-invasively identify all areas of the fibrotic substrate where RDs could potentially be sustained, including locations where RDs may not manifest during mapped AF episodes. The objective of this study was to carry out multi-modal assessment of the arrhythmogenic propensity of the fibrotic substrate in PsAF patients by comparing locations of RD-harboring regions found in simulations and detected by FIRM (RDsim and RDFIRM) and analyze implications for ablation strategies predicated on targeting RDs. For 11 PsAF patients who underwent pre-procedure LGE-MRI and FIRM-guided ablation, we retrospectively simulated AF in individualized atrial models, with geometry and fibrosis distribution reconstructed from pre-ablation LGE-MRI scans, and identified RDsim sites. Regions harboring RDsim and RDFIRM were compared. RDsim were found in 38 atrial regions (median [inter-quartile range (IQR)] = 4 [3; 4] per model). RDFIRM were identified and subsequently ablated in 24 atrial regions (2 [1; 3] per patient), which was significantly fewer than the number of RDsim-harboring regions in corresponding models (p < 0.05). Computational modeling predicted RDsim in 20 of 24 (83%) atrial regions identified as RDFIRM-harboring during clinical mapping. In a large number of cases, we uncovered RDsim-harboring regions in which RDFIRM were never observed (18/22 regions that differed between the two modalities; 82%); we termed such cases "latent" RDsim sites. During follow-up (230 [180; 326] days), AF recurrence occurred in 7/11 (64%) individuals. Interestingly, latent RDsim sites were observed in all seven computational models corresponding to patients who experienced recurrent AF (2 [2; 2] per patient); in contrast, latent RDsim sites were only discovered in two of four patients who were free from AF during follow-up (0.5 [0; 1.5] per patient; p < 0.05 vs. patients with AF recurrence). We conclude that substrate-based ablation based on computational modeling could improve outcomes.
Historical non-treatment of metastatic non-small cell lung cancer: Implications for evaluating novel therapies.

e18662Background: Recent immunotherapy and targeted therapy approvals for metastatic non-small cell lung cancer (NSCLC) were based on superior efficacy vs. cytotoxic chemotherapy. However, not all ...
Antenatal and Intrapartum Risk Factors for Hypoxic-Ischemic Encephalopathy in a US Birth Cohort

Objective To identify risk factors for hypoxic-ischemic encephalopathy (HIE) within a recent US birth cohort. Study design In a retrospective cohort study of 44 572 singleton infants ≥36 weeks of gestation born at Kaiser Permanente Northern California in 2008-2015, we identified all infants with HIE based on the presence of 3 inclusion criteria: clinical signs of neonatal encephalopathy, NICU admission, and either a 10-minute Apgar of ≤5 or a base excess of ≤-15 mmol/L. Neonatal acidemia was defined as a base excess of ≤-12 mmol/L. We ascertained antenatal and intrapartum complications from electronic records. Multivariable analysis was performed using logistic regression. Results There were 45 infants (1.0 per 1000) with HIE and 197 (4.4 per 1000) with neonatal acidemia. Of the infants with HIE, 64% had an intrapartum complication consisting of a sentinel event (36%), clinical chorioamnionitis (40%), or both (11%). Risk factors for HIE on multivariable analysis were sentinel event (relative risk [RR], 16.1; 95% CI, 8.4-33) and clinical chorioamnionitis (RR, 5.2; 95% CI, 2.7-9.9). After removing the 16 infants with HIE who were exposed to a sentinel event from multivariate analysis, maternal age of ≥35 years (RR, 2.5; 95% CI, 1.1-5.6) and a urinary tract infection during pregnancy (RR, 2.6; 95% CI, 1.0-6.5) emerged as potential antenatal risk factors for HIE. Conclusions A significant proportion of HIE is preceded by a sentinel event, emphasizing the importance of developing improved methodologies to predict and prevent this perinatal complication. Strategies focused on reducing other complications such as clinical chorioamnionitis and/or maternal pyrexia may also improve our ability to prevent HIE.
Implantable Direct Current Neural Modulation: Theory, Feasibility, and Efficacy

Implantable neuroprostheses such as cochlear implants, deep brain stimulators, spinal cord stimulators, and retinal implants use charge-balanced alternating current (AC) pulses to recover delivered charge and thus mitigate toxicity from electrochemical reactions occurring at the metal-tissue interface. At low pulse rates, these short duration pulses have the effect of evoking spikes in neural tissue in a phase-locked fashion. When the therapeutic goal is to suppress neural activity, implants typically work indirectly by delivering excitation to populations of neurons that then inhibit the target neurons, or by delivering very high pulse rates that suffer from a number of undesirable side effects. Direct current (DC) neural modulation is an alternative methodology that can directly modulate extracellular membrane potential. This neuromodulation paradigm can excite or inhibit neurons in a graded fashion while maintaining their stochastic firing patterns. DC can also sensitize or desensitize neurons to input. When applied to a population of neurons, DC can modulate synaptic connectivity. Because DC delivered to metal electrodes inherently violates safe charge injection criteria, its use has not been explored for practical applicability of DC-based neural implants. Recently, several new technologies and strategies have been proposed that address this safety criteria and deliver ionic-based direct current (iDC). This, along with the increased understanding of the mechanisms behind the transcutaneous DC-based modulation of neural targets, has caused a resurgence of interest in the interaction between iDC and neural tissue both in the central and the peripheral nervous system. In this review we assess the feasibility of in-vivo iDC delivery as a form of neural modulation. We present the current understanding of DC/neural interaction. We explore the different design methodologies and technologies that attempt to safely deliver iDC to neural tissue and assess the scope of application for direct current modulation as a form of neuroprosthetic treatment in disease. Finally, we examine the safety implications of long duration iDC delivery. We conclude that DC-based neural implants are a promising new modulation technology that could benefit from further chronic safety assessments and a better understanding of the basic biological and biophysical mechanisms that underpin DC-mediated neural modulation.
Primary vitreoretinal lymphoma: empowering our clinical suspicion.

Purpose of review Vitreoretinal lymphoma (VRL) is well known as a masquerade syndrome. However, delays in diagnosis are common particularly because of the small volume of tissue that is used for investigative studies. We outline the current diagnostic tests available to clinicians and provide a glimpse of possible future novel diagnostics. Recent findings The use of spectral domain ocular coherence tomography to identify subretinal lesions has proven to be a reliable ally to clinicians. Nevertheless, the diagnostic gold standard remains cytology, which requires a skilled pathologist. Molecular tests, including MYD88 polymerase chain reaction testing has further refined our diagnostic capabilities. Metagenomic deep sequencing is a newer molecular test that offers the ability to identify any mutation associated with lymphoma development and may offer more sensitive testing in the future. Summary Clinicians have developed a strong acumen for suspecting VRL based upon clinical features, which can further be supported by a variety of imaging modalities. Delays in diagnosis continue to occur particularly because of the small volume of ocular fluid available for testing and because current tests offer a biased approach in terms of limited scope of detecting a specific mutation or cytopathologic feature(s). Newer molecular techniques feature an expanded scope of detecting any mutation associated with lymphomatous development.
Religion and the Meaning of Life: An Existential Approach

As humans, we want to live meaningfully, yet we are often driven by impulse. In Religion and the Meaning of Life, Williams investigates this paradox – one with profound implications. Delving into felt realities pertinent to meaning, such as boredom, trauma, suicide, denial of death, and indifference, Williams describes ways to acquire meaning and potential obstacles to its acquisition. This book is unique in its willingness to transcend a more secular stance and explore how one's belief in God may be relevant to life's meaning. Religion and the Meaning of Life's interdisciplinary approach makes it useful to philosophers, religious studies scholars, psychologists, students, and general readers alike. The insights from this book have profound real-world applications – they can transform how readers search for meaning and, consequently, how readers see and exist in the world.
Higher-order resistivity-strain relations for self-sensing nanocomposites subject to general deformations

Abstract Nanocomposites have received enormous attention for the development of smart structures and materials with intrinsic self-sensing capabilities via the piezoresistive effect. Consequently, much work has been done to model the resistivity-strain relationship in these materials. To date, the prevailing approach to modeling nanocomposite piezoresistivity has been to track the interaction of individual nanofillers via computational micromechanics-based models or analytical homogenizations thereof. Even though such models have generated great insight into the piezoresistive effect, they are not without limitations. For example, they are computationally expensive, require extensive calibration and/or training data, and are often limited to simple deformations and microscale analyses. In light of the preceding, this work presents a novel higher-order tensor-based resistivity-strain relation that is amenable to general strains and macroscale analyses. Herein, it is shown that higher-order resistivity-strain relations can be described by three piezoresistive constants which can be determined by fitting the model to experimental data. The proposed resistivity-strain relation is applied to three different weight fractions of carbon nanofiber (CNF)-modified epoxy and validated against experimental discrete resistance changes and spatially distributed resistivity changes imaged via electrical impedance tomography (EIT) for complex strain states with good agreement. This work could be of significant impact to a wide range of engineers working with polymer, cementitious, and ceramic-based smart materials who wish to utilize the piezoresistive effect without resorting to in-depth microscale modeling.
Dielectric Response and Charge Injection Behavior for Cu/PMMA/Pt and Cu/PMMA/n-Si

Metal - Insulator - Metal (MIM) and Metal - Insulator- Semiconductor (MIS) capacitors were fabricated by spin coating poly (methyl methacrylate) (PMMA) as the insulating material. Here, we consider the effect of dissimilar contact electrodes systems (Cu/Pt and Cu/n-Si) on the dielectric and electrical response. From the frequency- and temperature- dependent dielectric measurements, it was found that Cu/PMMA/n-Si interface has an additional contribution that affects the dielectric properties. Activation energies obtained from the ohmic conduction in forward bias showed a higher value in activation energy for Cu/PMMA/n-Si compared to that for Cu/PMMA/Pt, demonstrating the possible contribution of interfacial regions. Further experiments under reverse bias were carried out to study the importance of polarization in the electrical response.
Effectiveness of Radio in Teaching Activities of Daily Living to Visually Handicapped Persons

Little research has been done on the potential effectiveness of radio as a method of educating, training, and rehabilitating blind persons. This article describes an evaluation of a training progra...
Rod and Cone Coupling Modulates Photopic ERG Responses in the Mouse Retina

Light adaptation changes both the sensitivity and maximum amplitude (Rmax) of the mouse photopic electroretinogram (ERG) b-wave. Using the ERG, we examined how modulation of gap junctional coupling between rod and cones alters the light-adapted ERG. To measure changes, a b-wave light adaptation enhancement factor (LAEF), was defined as the ratio of Rmax after 15 min light adaptation to Rmax recorded at the onset of an adapting light. For wild-type mice (WT), the LAEF averaged 2.64 ± 0.29, however, it was significantly reduced (1.06 ± 0.04) for connexin 36 knock out (Cx36KO) mice, which lack electrical coupling between photoreceptors. Wild type mice intraocularly injected with meclofenamic acid (MFA), a gap junction blocker, also showed a significantly reduced LAEF. Degeneration of rod photoreceptors significantly alters the effects of light adaptation on the photopic ERG response. Rd10 mice at P21, with large portions of their rod photoreceptors present in the retina, exhibited a similar b-wave enhancement as wildtype controls, with a LAEF of 2.55 ± 0.19. However, by P31 with most of their rod photoreceptors degenerated, rd10 mice had a much reduced b-wave enhancement during light-adaptation (LAEF of 1.54 ± 0.12). Flicker ERG responses showed a higher temporal amplitude in mesopic conditions for WT than those of Cx36KO mice, suggesting rod-cone coupling help high-frequency signals to pass from rods to cone pathways in the retina. In conclusion, our study provides a novel method to noninvasively measure the dynamics and modulation by the light adaptation for rod-cone gap junctional coupling in intact eyes.
Culture, Class, and Critical Theory: Between Bourdieu and the Frankfurt School

1. Modern Culture as Mass Unity or Ranked Diversity 2. Reification of Consumer Products: A General History Illustrated by the American Automobile 3. Culture as Class Symbolization or Mass Reification? A Critique of Bourdieu's Distinction 4. Three Ages of the Automobile: The Cultural Logics of the Car 5. Why Modern Architecture Emerged in Europe, Not America: The New Class and the Aesthetics of Technocracy 6. Bourdieu's Theory of Cultural Change: Explication, Application, Critique 7. Bourdieu and Adorno: Converging Theories of Culture and Inequality
A Virtual Book Club for Professional Development in Emergency Medicine.

Author(s): Jordan, Jaime; Bavolek, Rebecca A.; Dyne, Pamela L.; Richard, Chase E.; Villa, Stephen; Wheaton, Natasha | Abstract: Introduction: Professional development is an important component of graduate medical education, but it is unclear how to best deliver this instruction. Book clubs have been used outside of medicine as a professional development tool. We sought to create and evaluate a virtual professional development book club for emergency medicine interns.Methods: We designed and implemented a virtual professional development book club during intern orientation. Afterward, participants completed an evaluative survey consisting of Likert and free-response items. Descriptive statistics were reported. We analyzed free-response data using a thematic approach.Results: Of 15 interns who participated in the book club, 12 (80%) completed the evaluative survey. Most (10/12; 83.3%) agreed or strongly agreed that the book club showed them the importance of professional development as a component of residency training and helped them reflect on their own professional (11/12; 91.7%) and personal development (11/12; 91.7%). Participants felt the book club contributed to bonding with their peers (9/12; 75%) and engagement with the residency program (9/12; 75%). Our qualitative analysis revealed five major themes regarding how the book club contributed to professional and personal development: alignment with developmental stage; deliberate practice; self-reflection; strategies to address challenges; and communication skills.Conclusion: A virtual book club was feasible to implement. Participants identified multiple ways the book club positively contributed to their professional development. These results may inform the development of other book clubs in graduate medical education.
Fundamental studies to emerging applications of pyrrole-BF2 (BOPHY) fluorophores

BF2-based fluorophores, such as the well-known BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) dye, are prevalently used in diverse research areas (e.g., bioimaging and chemosensing) as they exhibit promising features including high quantum yields, fine-tuned absorption and emission spectra as well as good photostability and biocompatibility. While BODIPY dyes are most commonly used in such applications, other BF2-based fluorophores, such as BOPHY (bis(difluoroboron)-1,2-bis((1H-pyrrol-2-yl)methylene)hydrazine – which possess their own characteristic features – are rising in popularity and are being used in a range of applications spanning from molecular sensors to photosensitizers for solar cells. This review examines select examples of BOPHY dyes to highlight the progression of their development while detailing their syntheses and photophysical properties including structure–property relationships. Applications of a number of substituted BOPHYs made by the methods described in this review are also presented.
Electrical breakdown strength enhancement in aluminum scandium nitride through a compositionally modulated periodic multilayer structure

In this study, we report the effects of a multilayer architecture on the electrical breakdown strengths and ferroelectric characteristics of 45 nm thick aluminum scandium nitride (AlScN) films. Multilayered films (three-layer, five-layer, and seven-layer) are deposited via sequential deposition of Al0.72Sc0.28N and Al0.64Sc0.36N while maintaining constant volume ratios in all three samples. The effect of the increased number of interfaces is compared to 45 nm single layer Al0.72Sc0.28N and single layer Al0.64Sc0.36N films. The Weibull analysis shows an increase in the characteristic breakdown field from 5.99 and 5.86 MV/cm for single layer Al0.72Sc0.28N and Al0.64Sc0.36N to as high as 7.20 MV/cm in the seven-layered sample. The breakdown field to coercive field (EBD/Ec) ratios also increase from 1.37 and 1.26 in single layer Al0.72Sc0.28N and Al0.64Sc0.36N to up to 1.44 in the seven-layered sample with no significant change in remanent polarization. The enhancement of the characteristic breakdown field can be understood as the propagation of the electrical tree being deflected by multilayer interfaces and/or being slowed by the relative compressive stress in the alternating layers.
Replacement of alanine 58 by asparagine enables the melibiose carrier of Klebsiella pneumoniae to couple sugar transport to Na

Abstract The melibiose carrier of Klebsiella pneumoniae couples sugar transport to H+ and Li+, while that of Escherichia coli uses Na+ besides the other two cation species (Hama and Wilson, 1992). We have shown that the K. pneumoniae melibiose carrier is capable of recognizing Na+ when the amino-terminal 81 residues are replaced by the corresponding region of the E. coli melibiose carrier (Hama and Wilson, 1993). In this amino-terminal region there are 5 residues that are not conserved between the two carriers. In this study, we changed each of the 5 residues of the K. pneumoniae carrier to the one in the E. coli carrier. The substitutions are Ile-36-->Val, Val-43-->Leu, Leu-54-->Trp, Ala-58-->Asn, and Cys-68-->Ala. With four of the five mutants, Ile-36-->Val, Val-43-->Leu, Leu-54-->Trp, and Cys-68-->Ala, sugar accumulation was not affected by Na+. In striking contrast, melibiose and methyl-1-thio-beta-D-galactopyranoside accumulation was greatly stimulated by Na+ with the Ala-58-->Asn mutant. Furthermore, Na+ uptake coupled to downhill melibiose transport was observed with the Ala-58-->Asn mutant. These results indicate that the Ala-58-->Asn substitution enables the K. pneumoniae melibiose carrier to couple sugar transport to Na+. It is clear that the Asn-58 residue (Asn-54 in the E. coli carrier) is involved in Na+ recognition.
Fatal uterine rupture during oxytocin-augmented, saline-induced abortion

PIP: In light of the knowledge of the association between oxytocin administration and uterine rupture in late pregnancy, supraphysiologic doses of intravenous oxytocin are used by physicians to augment second trimester saline-induced abortions. According to the Center for Disease Control, this practice causing uterine rupturing is not unique to higher parities and can be fatal if not recognized. 2 case studies are reported. The 1st case, a 23-year-old woman (gravida 3, para 2), underwent saline instilled elective abortion at 18 menstrual weeks' gestation. Following removal of 200 cc of clear amniotic fluid from the uterus, an equal volume of 20% saline was instilled. 2 hours later, intravenous oxytocin was begun and an additional 400 mg of oxytocin was administered in the next 32 hours. 35 hours after instillation the patient had a thready pulse and blood pressure of 88/60, followed by stupor and cardiopulmonary arrest. After resuscitation a laparotomy disclosed an anterior paramedian laceration of the uterus. A hysterectomy was performed, the subsequent course was complicated, and the patient died on the 5th hospital day. In Case 2 a 29-year-old obese women (gravida 4, para 3) had an elective saline-instilled abortion at 20 menstrual weeks' gestation. After saline instillation the patient received intravenous oxytocin in the following amounts: 1) 60 mg; 2) 40 mg, with mild bleeding noted, and 3) 60 mg, followed by profuse vaginal bleeding. The fetus and the placenta were removed, and no detection of uterine rupture was made. The patient was transferred to another hospital, and died 5 hours later following multiple cardiopulmonary arrests. Rupture of the gravida uterus is defined as disruption of the uterine wall, occurring predominantly in the lower uterine segment. Uterine rupture and rupture during a term birth are probably analogous. The death-to-case rate for saline-induced abortions in the U.S. from 1972 to 1975 is .08 deaths/100,000, however, this rate would be higher if only saline-induced abortions receiving oxytocin were considered.
Angle-closure glaucoma in association with orbital pseudotumor.

Abstract Purpose To describe the pathophysiology of angle-closure glaucoma secondary to idiopathic inflammatory orbital pseudotumor. Design Retrospective, small noncomparative case series. Participants Three patients with angle-closure glaucoma and orbital pseudotumor. Methods The pathophysiology of this entity was investigated using magnetic resonant imaging (MRI) and ultrasound biomicroscopy (UBM). Main outcomes measures Clinical features, anterior chamber angle configuration, and intraocular pressure. Results Angle closure from anterior rotation of the ciliary body caused by choroidal effusions secondary to pseudotumor was demonstrated using MRI and UBM. Two of the three cases resolved after treatment for orbital pseudotumor. Conclusions Idiopathic orbital pseudotumor is a cause of secondary angle-closure glaucoma. The mechanism of angle closure is anterior rotation of the ciliary body secondary to choroidal effusions resulting from the orbital inflammation.
Some Thoughts on the Economic History of Early Colonial Mexico

Competitive markets reward the scarce factor of production. As a result of the Spanish Conquest, Indian labor became the scarce factor of production relative to land. But the whole point of conquest was to enrich the Spaniards, not the Indians. Therefore, the Spaniards resisted the use of the market as a device to accomplish productive economic activities. The result was an inefficient allocation of resources and a suboptimal rate of growth, not to say the structural economic distortions that resulted. The development of the economy in colonial Mexico was, in effect, given over to wholesale rent-seeking, the allocation of resources by the use of political power. If there is a conceptual basis for understanding colonial development, it is this rather than dependent capitalism.
Some effects of experimental error in fracture testing.

Effects of experimental imprecision on the stress intensity factors calculated for various practical specimen types are shown. A general form equation for the stress intensity factor is presented and a general error equation is derived. The expected error in the stress intensity factor is given in terms of the precision levels of the basic experimental measurements and derivatives of the stress intensity calibration factor. Nine common fracture specimen types are considered, and the sensitivity of the various types to experimental error is illustrated. Some implications for fracture toughness testing and crack growth rate testing are discussed and methods of analysis are proposed to compensate for the effects of experimental error.
New Directions in Eighteenth-Century Periodical Studies

The State of the Field in periodical studies is perhaps best characterized as ‘ripening’. This essay examines foundational and recent studies of 18th-century periodicals taken as their own genre; when used as supporting texts in cultural studies inquiries; and when studied because of their relationship to canonical writers, such as Addison, Steele, Johnson, Haywood, and Dunton. It suggests that due to the era of the digital humanities, the time is excellent for a renewed exploration of scholarship devoted to and using periodicals, and for expanding their presence in the classroom.
Functional mapping of quantitative trait loci underlying the character process: a theoretical framework.

Unlike a character measured at a finite set of landmark points, function-valued traits are those that change as a function of some independent and continuous variable. These traits, also called infinite-dimensional characters, can be described as the character process and include a number of biologically, economically, or biomedically important features, such as growth trajectories, allometric scalings, and norms of reaction. Here we present a new statistical infrastructure for mapping quantitative trait loci (QTL) underlying the character process. This strategy, termed functional mapping, integrates mathematical relationships of different traits or variables within the genetic mapping framework. Logistic mapping proposed in this article can be viewed as an example of functional mapping. Logistic mapping is based on a universal biological law that for each and every living organism growth over time follows an exponential growth curve (e.g., logistic or S-shaped). A maximum-likelihood approach based on a logistic-mixture model, implemented with the EM algorithm, is developed to provide the estimates of QTL positions, QTL effects, and other model parameters responsible for growth trajectories. Logistic mapping displays a tremendous potential to increase the power of QTL detection, the precision of parameter estimation, and the resolution of QTL localization due to the small number of parameters to be estimated, the pleiotropic effect of a QTL on growth, and/or residual correlations of growth at different ages. More importantly, logistic mapping allows for testing numerous biologically important hypotheses concerning the genetic basis of quantitative variation, thus gaining an insight into the critical role of development in shaping plant and animal evolution and domestication. The power of logistic mapping is demonstrated by an example of a forest tree, in which one QTL affecting stem growth processes is detected on a linkage group using our method, whereas it cannot be detected using current methods. The advantages of functional mapping are also discussed.
‘Consultations with the Poor’ from a Health Perspective

Deepa Narayan presents how we should look at health ‘through the eyes of the poor’. She argues that the body is sometimes poor people's only asset and is a major source of insecurity. New partnerships between public authorities, private sector and community groups must be formed to provide the foundation for good health.
Abstract IA05: Targeting the oxidative stress pathway in rhabdomyosarcoma

Rhabdomyosarcoma is a soft-tissue sarcoma with molecular and cellular features of developing skeletal muscle. Histologically, there are two major subtypes of rhabdomyosarcoma, embryonal and alveolar, which have distinct clinical, molecular, and genetic features. Patients with resected localized disease are highly curable, but patients with recurrent, metastatic or large unresectable tumors have a poor clinical outcome. In this study, we performed whole-genome sequencing, exome sequencing, RNA-sequencing and DNA methylation profiling of embryonal and alveolar rhabdomyosarcomas. The embryonal tumors had more structural and copy number variations than did alveolar tumors and those lesions result from the accumulation of chromosomal lesions over time. Mutations in the RAS/NF1 pathway were significantly associated with intermediate- and high-risk embryonal rhabdomyosarcoma. In contrast, alveolar rhabdomyosarcoma had fewer genetic lesions overall and there were no known cancer consensus genes that were recurrently mutated other than the PAX3/7-FOXO1translocation that is a hallmark of alveolar rhabdomyosarcoma. DNA methylation profiling and RNA-seq analysis showed that embryonal and alveolar rhabdomyosarcomas are distinct and the alveolar tumors more closely resemble normal myoblasts and myotubes. To identify novel therapeutics for embryonal rhabdomyosarcomas, we developed and characterized 6 orthotopic xenografts of tumors in our discovery cohort. High throughput screening of primary cultures derived from those xenografts identified oxidative stress as a pathway of therapeutic relevance for embryonal rhabdomyosarcoma. Citation Format: Michael A. Dyer. Targeting the oxidative stress pathway in rhabdomyosarcoma. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr IA05.
CO oxidation on nanostructured SnOx/Pt(111) surfaces: unique properties of reduced SnOx

We have investigated surface CO oxidation on “inverse catalysts” composed of SnOx nanostructures supported on Pt(111) using X-ray photoelectron spectroscopy (XPS), low-energy ion scattering spectroscopy (LEISS) and temperature-programmed desorption (TPD). Nanostructures of SnOx were prepared by depositing Sn on Pt(111) pre-covered by NO2 layers at low temperatures. XPS data show that the SnOx nanoparticles are highly reduced with Sn(II)O being the dominant oxide species, but the relative concentration of Sn(II) in the SnOx nanoparticles decreases with increasing Sn coverage. We find that the most active SnOx/Pt(111) surface for CO oxidation has smallest SnOx coverage. Increasing the surface coverage of SnOx reduces CO oxidation activity and eventually suppresses it altogether. The study suggests that reduced Sn(II)O, rather than Sn(IV)O2, is responsible for surface CO oxidation. The occurrence of a non-CO oxidation reaction path involving reduced Sn(II)O species at higher SnOx coverages accounts for the decreased CO oxidation activity. From these results, we conclude that the efficacy of CO oxidation is strongly dependent on the availability of reduced tin oxide sites at the Pt–SnOx interface, as well as unique chemical properties of the SnOx nanoparticles.
Microtubule dynamics in living cells.

Abstract Most people think of a skeleton as a solid and static framework upon which complex structures are elaborated. From what we have learned in the past decade about the cytoskeleton, it seems certain that the ‘skeleton’ part of the term is a bit misleading. It is clear now that the polymers that constitute the cytoskeleton, actin filaments, microtubules, and intermediate filaments, are all in fact ever-changing dynamic infrastructures of cells. Recently, advances have been made in the study of the cellular dynamics of one of the prominent components of the cytoskeleton, the microtubules. Observations in the past year have revealed some fundamental in vivo behaviors of these polymers, during interphase, during mitosis, and during the elaboration of postmitotic axonal microtubule arrays. These observations are important for the understanding of cytoplasmic organization in many types of cells.
Mesial Temporal Lobe Epilepsy: What Have We Learned?

Mesial temporal lobe epilepsy is the most common form of human epilepsy, and its pathophysiological substrate is usually hippocampal sclerosis, the most common epileptogenic lesion encountered in patients with epilepsy. The disabling seizures associated with mesial temporal lobe epilepsy are typically resistant to antiepileptic drugs but can be abolished in most patients by surgical treatment. Anteromesial temporal resection, therefore, is the most common surgical procedure performed to treat epilepsy, and stereotactically implanted intracerebral electrodes are required in some patients to localize the epileptogenic region. This clinical setting provides a large number of patients for invasive in vivo research with microelectrode and microdialysis techniques and in vitro research following surgical resection on a single epileptic disorder. Consequently, much has now been learned about the fundamental neuronal mechanisms underlying the epileptogenic properties of the human hippocampus in mesial temporal lobe epilepsy. Parallel reiterative studies in patients and animal models of this disorder indicate that enhanced inhibition, in addition to enhanced excitation, underlies the appearance of hypersynchronous neuronal discharges responsible for generating spontaneous seizures. Recent studies have elucidated what may be unique electrophysiological markers of epileptogenicity, which could have valuable diagnostic utility. Although basic research on mesial temporal lobe epilepsy may ultimately suggest novel approaches to treatment and prevention, attention must also be given to maximizing the application of available effective treatments. In particular, the safety and efficacy of surgical therapy has greatly improved in recent years, yet this alternative treatment remains seriously underutilized worldwide. An appropriate increase in referral of patients with this surgically remediable syndrome to epilepsy centers will not only relieve a great many patients of their disabling seizures and reduce the burden of epilepsy but will also provide increased opportunities for invasive research that could ultimately result in even more effective therapies or cures.
Secret Key Generation Via Localization and Mobility

We consider secret key generation by a pair of mobile nodes utilizing observations of their relative locations in the presence of a mobile eavesdropper. In our proposed algorithm, the legitimate node pair makes noisy observations of the relative locations of each other. Based on these observations, the nodes generate secret key bits via information reconciliation, data compression, and privacy amplification. We characterize a theoretically achievable secret key bit rate in terms of the observation noise variance at the legitimate nodes and the eavesdropper and show that the performance of our algorithm is comparable to the theoretical bounds. We also test our algorithm in a vehicular setting based on observations made using wireless beacon exchange between the legitimate nodes. To achieve this, we used TelosB wireless radios mounted on the sides of the vehicles on local roads and freeways. Note that our approach relies solely on distance reciprocity, and thus, it is not restricted to the use of wireless radios and can be used with other localization systems (e.g., infrared and ultrasound systems) as well. Overall, this study proves, via both information theoretic and practical analysis, that localization information provides a significant additional resource for secret key generation in mobile networks.
RNA stabilization by the AU‐rich element binding protein, HuR, an ELAV protein

An important paradigm for post‐transcriptional regulation is the control of cytoplasmic mRNA stability mediated by AU‐rich elements (AREs) in the 3′ untranslated region of transcripts encoding oncoproteins, cytokines and transcription factors. While many RNA‐binding proteins have been shown to bind to AREs in vitro , neither the functional consequences nor the physiological significance of their interactions are known. Here we demonstrate a role for the embryonic lethal abnormal visual (ELAV) RNA‐binding protein HuR in mRNA turnover in vivo . The ELAV family of RNA‐binding proteins is highly conserved in vertebrates. In humans, there are four members; HuR is expressed in all proliferating cells, whereas Hel‐N1, HuC and HuD are expressed in terminally differentiated neurons. We show that elevation of cytoplasmic HuR levels inhibits c‐ fos ARE‐mediated RNA decay but has little effect on rapid decay directed by c‐ jun ARE. It appears that HuR has little effect on deadenylation but delays onset of decay of the RNA body and slows down its subsequent decay. We also show that HuR can be induced to redistribute from the nucleus to the cytoplasm and that this redistribution is associated with an altered function. Modulation of the ARE‐mediated decay pathway through controlling distribution of the ELAV proteins between nucleus and cytoplasm may be a mechanism by which cell growth and differentiation is regulated.
Resting functional connectivity of language networks: characterization and reproducibility

The neural basis of language comprehension and production has been associated with superior temporal (Wernicke's) and inferior frontal (Broca's) cortical areas, respectively. However, recent resting-state functional connectivity (RSFC) and lesion studies have implicated a more extended network in language processing. Using a large RSFC data set from 970 healthy subjects and seed regions in Broca's and Wernicke's, we recapitulate this extended network that includes not only adjoining prefrontal, temporal and parietal regions but also bilateral caudate and left putamen/globus pallidus and subthalamic nucleus. We also show that the language network has predominance of short-range functional connectivity (except posterior Wernicke's area that exhibited predominant long-range connectivity), which is consistent with reliance on local processing. Predominantly, long-range connectivity was left lateralized (except anterior Wernicke's area that exhibited rightward lateralization). The language network also exhibited anti-correlated activity with auditory (only for Wernicke's area) and visual cortices that suggests integrated sequential activity with regions involved with listening or reading words. Assessment of the intra-subject's reproducibility of this network and its characterization in individuals with language dysfunction is required to determine its potential as a biomarker for language disorders.