cssi/SciSciGPT-SciSciNet huggingface dataset:
Overexpression of LMW cyclin E results in faster M phase progression via Cdc25C interaction leading to chromosome missegragation in breast cancer cells.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #5032 Cyclin E is a G (1) cyclin essential for S-phase entry and has a profound role in oncogenesis. Cyclin E is overexpressed and present in low-molecular-weight (LMW) isoforms in breast cancer cells and tumor tissues compared to normal cells and tissues. Such alteration of cyclin E is linked to poor patient outcome. We have previously shown that ectopic expression of low molecular weight of Cyclin E (LMW-E) in breast cancer cell lines induces genomicinstability by promoting aneuploidy and the formation of structuralchromosomal lesion. To determine the mechanism of induction of genomic instability by ectopic expression of LMW-E, we generated the MCF-7 cells inducibly expressing either the full length (EL) or low molecular weight (LMW-E) form of cyclin E. We observed 5.5 fold higher number of cells with centrosome defects in LMW-E induced versus EL induced cells. Notably, elevated levels of LMW-E led to a significant increase in fragmented nuclei and multinucleated cells. Immunofluorescence analysis also showed a 4-5 fold increase in the number of cells containing lagging chromosomes and anaphase bridges. Karyotype analysis for gross chromosomal aberrations metaphase preparation of the uninduced and EL and LMW induced cells showed a significantly higher percentage of chromosomal defects including dicentric chromosome and chromosomal breaks associated with LMW-E overexpression. We also show that while overexpression of EL leads to accumulation of cells in S and G2/M phases of the cell cycle, the overexpression of LMW of cyclin E causes a faster M phase progression. As a consequence, LMW-cyclin E overexpressing cells are resistant to nocodazole-induced M phase arrest. Using biochemical assays, we show that EL and LMW-E interact with the phosphatase Cdc25C and when either EL or LMW are in complex with CDK2 that they phosphorylate Cdc25C. Such association of LMW-E with Cdc25C results premature inactivation of cyclin B/CDK1 upon treatment of these cells with nocodazole. Additionally, continued induction of LMW-E results in premature inactivation of PLK1 in mitotic cells and deregulated localization of PLK1 such that it is no longer associated to central spindles during anaphase and telophase. Collectively, these results suggest that overexpression of LMW-E interferes with the activation of CDK1 during mitosis. The relatively low activity of CDK1 during the passage through prophase, prometaphase, and metaphase interferes with the regulation of the spindle checkpoint and facilitates the premature transition of dividing cells from metaphase to anaphase resulting in chromosomal instability and aneuploidy. This is the first observation of how mechanistically the overexpression of a proto-oncogene can lead to genomic instability in breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5032.
Effects of Music on the Perception of Paintings

This study tested the influence of musical style on observers' perceptions of representational and abstract paintings. Participants were thirty-six male and thirty-six female undergraduates who viewed eight paintings under one of three listening conditions: matching, non-matching, or no music. Participants rated each painting on four semantic-differential scales. Mean ratings were compared using MANOVAs. An interaction of painting style and listening condition (Wilks' lambda = .780, p < .05) showed participants' aesthetic experience of viewing the paintings was intensified when the paintings were accompanied by matching music. A main effect for music style (Wilks' lambda = .718, p < .01) showed participants thought all paintings were less active and more beautiful when accompanied by the impressionist music. There were no significant effects for gender.
Writing Womanhood in the New Brazil: Machado’s Lição de Botânica

This chapter offers an analysis of Machado’s representation of female characters through critical readings of his short stories and his understudied theatrical works, particularly Licao da Botânica(Botanical Lesson). More than mere props or foils for his more famous male characters, Machado’s fictional women possess their own narrative logic and their functions are quite distinct from those of his better-known male characters. Machado’s fictional women are also the mechanism by which he shows his reading public (made up largely of women) that a new, more socially conscious woman is part of what the new Brazil needs as it creates its post-emancipation and post-empire era.
Online parameterization for WOFOST for United States using open geospatial standards

WOFOST (WOrld FOod STudies) is a well-known, widely applied simulation model to analyze quantitatively the growth and production annual field crops that was originally developed for crops in European countries. It is the base model for Monitoring Agricultural ResourceS (MARS) Crop Growth Monitoring System (CGMS) in operational use for yield estimation in European Union. The model is of great potential in providing effective modeling of crops in the United States. The first step to adopt the model to be fit for applications to crop modeling in the US is to provide required parameters at any region and any time in the United States. In this study, several data sources have been identified and enabled to be readily fed into the models through standard, open, automatic, Web-based, online geospatial Web services. These Web services have the flexibility of accessing, re-processing, and customization to the models at different levels — from regional (i.e. counties, agricultural statistic districts) modeling to point (i.e. pixel) modeling because of their spatiotemporal capabilities. Three major data sources and parameters for WOFOST model are meteorological data, crop data, and soil data. Soil data are accessed and customized through standard Web Feature Service (WFS) request to the online services of Soil Survey Geographic Database (SSURGO). Crop data are retrieved from Web Coverage Service (WCS) from CropScape that serves Cropland Data Layer (CDL). Assimilated data from ground observations provide meteorological observations. Meteorological observations are retrieved online through public service application programming interface (API) of DayMet that provide gridded estimates of daily weather parameters for North America, including daily continuous surfaces of minimum and maximum temperature, precipitation occurrence and amount, humidity, shortwave radiation, snow water equivalent, and day length. Workflow is enabled to support the on-demand customization and live feeding to WOFOST modeling. The services enable the parameterization process in WOFOST modeling.
Regenerated Sciatic Nerve Axons Stimulated through a Chronically Implanted Macro-Sieve Electrode.

Sieve electrodes provide a chronic interface for stimulating peripheral nerve axons. Yet, successful utilization requires robust axonal regeneration through the implanted electrode. The present study determined the effect of large transit zones in enhancing axonal regeneration and revealed an intimate neural interface with an implanted sieve electrode. Fabrication of the polyimide sieve electrodes employed sacrificial photolithography. The manufactured macro-sieve electrode (MSE) contained nine large transit zones with areas of ~0.285 mm2 surrounded by eight Pt-Ir metallized electrode sites. Prior to implantation, saline or glial derived neurotropic factor (GDNF) was injected into nerve guidance silicone-conduits with or without a MSE. The MSE assembly or a nerve guidance conduit was implanted between transected ends of the sciatic nerve in adult male Lewis rats. At 3 months’ post-operation, fiber counts were similar through both implant types. Likewise, stimulation of nerves regenerated through a MSE or an open silicone conduit evoked comparable muscle forces. These results showed that nerve regeneration was comparable through MSE transit zones and an open conduit. GDNF had a minimal positive effect on the quality and morphology of fibers regenerating through the MSE; thus, the MSE may reduce reliance on GDNF to augment axonal regeneration. Selective stimulation of several individual muscles was achieved through monopolar stimulation of individual electrodes sites suggesting that the MSE might be an optimal platform for functional neuromuscular stimulation.
On the windowed encoding complexity of SC-LDGM codes for lossy source compression

It has been shown that spatially coupled low-density generator-matrix (SC-LDGM) code ensembles display distortion saturation for the lossy binary symmetric source coding problem with belief propagation guided decimation algorithms, in the sense that the distortion of the SC-LDGM code ensemble approaches the optimal distortion of the underlying (uncoupled) LDGM block code ensemble. This has also been demonstrated for the class of protograph-based SC-LDGM code ensembles with windowed encoding (WE), where distortion close to the rate distortion limit was obtained with low-latency encoding. In this paper, we propose and compare two decimation techniques for lowering the WE complexity of SC-LDGM codes that maintain distortion performance close to the rate-distortion bound.
Molluscum Contagiosum Virus MC159 Abrogates cIAP1-NEMO Interactions and Inhibits NEMO Polyubiquitination

Molluscum contagiosum virus (MCV) is a dermatotropic poxvirus that causes benign skin lesions. MCV lesions persist because of virally encoded immune evasion molecules that inhibit antiviral responses. The MCV MC159 protein suppresses NF-κB activation, a powerful antiviral response, via interactions with the NF-κB essential modulator (NEMO) subunit of the IκB kinase (IKK) complex. Binding of MC159 to NEMO does not disrupt the IKK complex, implying that MC159 prevents IKK activation via an as-yet-unidentified strategy. Here, we demonstrated that MC159 inhibited NEMO polyubiquitination, a posttranslational modification required for IKK and downstream NF-κB activation. Because MCV cannot be propagated in cell culture, MC159 was expressed independent of infection or during a surrogate vaccinia virus infection to identify how MC159 prevented polyubiquitination. Cellular inhibitor of apoptosis protein 1 (cIAP1) is a cellular E3 ligase that ubiquitinates NEMO. Mutational analyses revealed that MC159 and cIAP1 each bind to the same NEMO region, suggesting that MC159 may competitively inhibit cIAP1-NEMO interactions. Indeed, MC159 prevented cIAP1-NEMO interactions. MC159 also diminished cIAP1-mediated NEMO polyubiquitination and cIAP1-induced NF-κB activation. These data suggest that MC159 competitively binds to NEMO to prevent cIAP1-induced NEMO polyubiquitination. To our knowledge, this is the first report of a viral protein disrupting NEMO-cIAP1 interactions to strategically suppress IKK activation. All viruses must antagonize antiviral signaling events for survival. We hypothesize that MC159 inhibits NEMO polyubiquitination as a clever strategy to manipulate the host cell environment to the benefit of the virus.IMPORTANCE Molluscum contagiosum virus (MCV) is a human-specific poxvirus that causes persistent skin neoplasms. The persistence of MCV has been attributed to viral downregulation of host cell immune responses such as NF-κB activation. We show here that the MCV MC159 protein interacts with the NEMO subunit of the IKK complex to prevent NEMO interactions with the cIAP1 E3 ubiquitin ligase. This interaction correlates with a dampening of cIAP1 to polyubiquitinate NEMO and to activate NF-κB. This inhibition of cIAP1-NEMO interactions is a new viral strategy to minimize IKK activation and to control NEMO polyubiquitination. This research provides new insights into mechanisms that persistent viruses may use to cause long-term infection of host cells.
Epigenetic consequences of Epstein–Barr virus infection

The biphasic nature of the Epstein–Barr virus (EBV) life cycle is tightly regulated by epigenetic modifications. Silencing of viral gene expression associated with latency is accompanied by repressive chromatin modifications and DNA methylation. Latency is integral to the lifelong persistence of EBV, yet persistence also relies on viral replication and virus production for infection of naive hosts. Thus, EBV can overcome and disrupt the repressive epigenetic environment of the latent viral genomes. Viral modulators of the host epigenetic machinery are not only involved in establishing the latent and lytic viral epigenetic states but also reprogram the host epigenome in ways that are likely beneficial to the virus, but can carry long term consequences to the host. Here, we will review epigenetic aspects of EBV life cycle control and consequences to the host cell.
Epigenetic programming of autonomic functions in an experimental model of apnea of prematurity

Intermittent hypoxia (IH) is a hallmark manifestation of recurrent apneas, which is a major clinical problem in infants born preterm. Carotid body (CB) chemoreflex and catecholamine (CA) secretion from adrenal medullary chromaffin cells (AMCs) are two major mechanisms contributing to the maintenance of cardiorespiratory homeostasis during hypoxia. The purpose of this article is to highlight recent studies showing how neonates experiencing IH affect the CB and AMC function and their consequences in adult life. To simulate apneas, rat pups were treated with IH consisting of alternating cycles of hypoxia (1.5% O2) for 15 s and room air for 5 min, 8 h/day from ages P0–P10. Rats treated neonatal IH displayed augmented CB response to hypoxia and augmented CA secretion from AMC. Rats treated for 10 days of IH in the neonatal period were allowed to grow into adulthood. Remarkably, the effects of neonatal IH on CB and AMC persisted in the adulthood. Moreover, adult rats that were exposed to IH in neonatal period exhibited hypertension, increased incidence apnea. Analysis of the underlying molecular mechanisms revealed re-programming of the redox state by epigenetic mechanisms involving suppression of transcription of antioxidant enzyme genes by DNA hypermethylation. DNA hypomethylating agents might offer a novel therapeutic intervention to prevent early onset of cardiorespiratory morbidities caused by neonatal IH.
Selective Cervical Denervation for Cervical Dystonia: Modification of the Bertrand Procedure.

BACKGROUND Cervical dystonia, commonly referred to as spasmodic torticollis, is a neurological disorder characterized by aberrant, involuntary contraction of the muscles of the neck and shoulders. One surgical option that can be considered is selective cervical denervation. OBJECTIVE To report our modification of the Bertrand procedure for selective cervical denervation. METHODS Our modification of the Bertrand procedure for selective cervical denervation is reported with intraoperative photographs and schematic depictions of the operative steps. RESULTS We report our modification of the Bertrand procedure for selective cervical denervation, which consists of a combination of C2-6 denervation, myectomy of the splenius capitis and/or semispinalis capitis, myotomy of the levator scapulae when indicated, and myotomy and selection denervation of the sternocleidomastoid. The combination of techniques utilized depends on the subtype and severity of cervical dystonia. CONCLUSION Our modification of the original Bertrand procedure for selective cervical denervation represents an alternative surgical strategy for the treatment of cervical dystonia, with the potential advantages and disadvantages discussed.
Actively variable transmission for robotic knee prostheses

We present a novel powered knee prosthesis with an active variable transmission (AVT) that adapts motor torque and speed output based on the requirements of different ambulation activities. The AVT works in combination with a spring/damper system to allow for both active and passive operation modes. Preliminary tests performed by an able-bodied subject wearing a bypass orthosis show that the proposed knee can support walking on level ground in passive mode, as well as ambulating on stairs with a reciprocal gait pattern in active mode.
Soft Chaos and the KAM Theorem

Chaotic behavior in a dynamical system is most easily understood as a breakdown of the invariant tori due to the perturbations. The KAM theorem deals with this process of disintegration and shows that it is gradual. The resulting situation in phase space, to be called soft chaos, is smooth wherever the tori are intact, but it has many rough spots that are associated with resonances or phase-locking. This phenomenon happens when two degrees of freedom get stuck with the ratio of their frequencies given by a rational number. Soft chaos can be explained by estimating the size of the domain of phase space where phase-lock occurs as a function of the perturbation strength.
Pseudoaneurysm of the Mitral-Aortic Intervalvular Fibrosa: A Case Series with Literature Review.

Pseudoaneurysm of the mitral-aortic intervalvular fibrosa (P-MAIVF) was traditionally considered a rare, life-threatening sequela of endocarditis or valve surgery. Pseudoaneurysm is an outpouching where the aortic and mitral valves meet and forms between the aorta and the left atrium with superior and posterior extension. It is contiguous with the left ventricular outflow tract, which differentiates it from an abscess.1, 2 In this article we present three consecutive cases and one highly suspicious case of P-MAIVF diagnosed at our institution using transesophageal echocardiography and discusses the causes, presentation, diagnosis, and management of that entity.
An Introduction to Field Education in Higher Christian Education

Field education, as a key link between Christian education institutions and practical ministry experience, has expanded in recent decades. This article introduces the reader to the foundational iss...
Economic co-optimization of oil recovery and CO2 sequestration

Abstract Drawing on techniques from both petroleum engineering and economics, we analyze how oil fields that use CO2 injection to enhance oil recovery are likely to respond to CO2 storage incentives by “co-optimizing” oil recovery and CO2 sequestration. We focus specifically on predicting the CO2-injection path that co-optimizing operators will choose, and on how sensitive this path and the cumulative oil production and CO2 sequestration resulting from it are to variation in the oil price and CO2 subsidy. A study by Leach et al. (2011), which to date is the only rigorous economic study of co-optimization, addresses these questions using an ad hoc reservoir model. Our study applies Leach et al.’s analysis to dynamic reservoir-simulation models of two different oil fields. We find that, even though Leach et al.’s assumptions about how a reservoir responds to CO2 injection are quite far off the mark quantitatively, their main findings hold up remarkably well qualitatively.
Usability Heuristics for M-Commerce Apps

Usability studies found that mobile users suffer from poor user experience which might explain the low spending of mobile-based commerce (m-commerce). This study focuses on identifying the usability heuristics to apply when evaluating the usability of m-commerce mobile apps. An integrated approach is applied considering the general usability heuristics developed by Nielsen, the Google Android design guidelines and Apple human interface guidelines. The proposed 13 heuristics are: “Visibility”, “Matching-Real-World”, “User-Control”, “Error-Prevention”, “Recognition”, “Flexibility-and-Efficient Use”, “Minimal Design”, “Diagnose-and-Recover”, “Help”, “Performance”, “Information–and-Visual-Hierarchy”, “Natural-Interaction”, and “Dynamic-Engagement”. Four usability experts test empirically the developed mobile usability heuristics against two mobile apps that are used for secondhand retailing where users can sell and buy used items. Usability violations are identified and severity is ranked. Mobile apps usability is an ever evolving and dynamic research playground. Many of research challenges posed by lack of a comprehensive tool to understand the usability in the context of m-commerce. This is the contribution of the present paper.
Paracentesis in cirrhotics is associated with increased risk of 30-day readmission.

AIM To determine the readmission rate, its reasons, predictors, and cost of 30-d readmission in patients with cirrhosis and ascites. METHODS A retrospective analysis of the nationwide readmission database (NRD) was performed during the calendar year 2013. All adults cirrhotics with a diagnosis of ascites, spontaneous bacterial peritonitis, or hepatic encephalopathy were identified by ICD-9 codes. Multivariate analysis was performed to assess predictors of 30-d readmission and cost of readmission. RESULTS Of the 59597 patients included in this study, 18319 (31%) were readmitted within 30 d. Majority (58%) of readmissions were for liver related reasons. Paracentesis was performed in 29832 (50%) patients on index admission. Independent predictors of 30-d readmission included age 3 Elixhauser comorbidity (OR: 1.13; CI: 1.05-1.22), nonalcoholic cirrhosis (OR: 1.16; CI: 1.10-1.23), paracentesis on index admission (OR: 1.28; CI: 1.21-1.36) and having hepatocellular carcinoma (OR: 1.21; CI: 1.05; 1.39). Cost of index admission was similar in patients readmitted and not readmitted (P-value: 0.34); however cost of care was significantly more on 30 d readmission ($30959 ± 762) as compared to index admission ($12403 ± 378), P-value: < 0.001. CONCLUSION Cirrhotic patients with ascites have a 33% chance of readmission within 30-d. Younger patients, with public insurance, nonalcoholic cirrhosis and increased comorbidity who underwent paracentesis are at increased risk of readmission. Risk factors for unplanned readmission should be targeted given these patients have higher healthcare utilization.
Vocal Stress/Lie Detectors

It is without question that law enforcement, security, intelligence and related agencies need an effective method for the detection of deception. Incidentally, “detection of deception” is the phrase used by many professionals when they mean lying. Whether a lie detector—were it to exist—would be used effectively, legally and ethically is not the focus of our concern here (however, these issues will be discussed briefly at the end of the chapter). Rather, I will stress the need for such a system and some approaches to the problem. But first, let us consider the basic issue: can lies be detected; is there such a thing as a lie response?
COOPERATIVE ACTION OF PURIFIED BACTERICIDAL/PERMEABILITY INCREASING PROTEIN AND PHOSPHOLIPASE A2 FROM RABBIT POLYMORPHONUCLEAR LEUKOCYTES

ABSTRACT We have purified from rabbit and human polymorphonuclear leukocytes a potent bactericidal cationic membrane-active protein. These two proteins kill gram-negative bacteria only and are closely similar in molecular and biological properties. Leukocytes also contain a phospholipase A2 which we have purified to near homogeneity from rabbit leukocytes. This phospholipase A2 only degrades the phospholipids of susceptible bacteria when in combination with the rabbit leukocyte bactericidal protein. The very similar human leukocyte bactericidal protein cannot substitute in this cooperative action, nor can four other purified phospholipases A2.
BEHAVIORAL RESPONSIVITY TO TASTES IN DEVELOPING RATS

The development of taste responsivity has recently attracted considerable attention from neurophysiologists’ who have studied taste ontogeny in the sheep,2,3 an animal with a lengthy gestation period (circa 150 days) and rats,4,5,6 whose gestation period is considerably shorter, (22 days). In general, it appears that, in sheep, taste development is a prenatal phenomenon such that at birth the system is mature, morphologically and electrophysiologically at least.
An Analysis of Prospective Teachers' Dual Roles in Understanding the Mathematics of Change: Eliciting Growth with Technology

We analyze the interrelations between prospective and practicing teachers' learning of the mathematics of change and the development of their emerging understanding of effective mathematics teaching. The participants in our study, who were all interested in teaching secondary mathematics, were mathematics majors who had significant formal knowledge of the fundamental concepts of calculus prior to taking our courses, but who often experienced and expressed procedural orientations toward the teaching of mathematics. To address this difficulty, we developed novel computer-based activities to challenge the participants' mathematical understandings and required them to use technology during short teaching episodes they conducted with younger students. To analyze our participants' understandings, we developed a framework that juxtaposes the roles of the participants as students and teachers, and their understanding of mathematics and of pedagogical strategies. Our analysis of the participants' views from these different perspectives enabled us to see simultaneously the intertwined development of subject matter insights and specific views of teaching.
The Lower Paleolithic Site of Wadi Qalkha

Although isolated handaxes were found in the uplands overlooking the Wadi Judayid basin and within the deeply incised wadis north of Jebel Qalkha, the site of Wadi Qalkha (J401) represents the only discovery of concentrated Lower Paleolithic artifacts. The site is actually located in a deeply incised wadi near the extreme headwaters of the Wadi Aheimir and close to the point of an impending drainage capture of the Wadi Qalkha (Figure 4.1). During survey a light scatter of artifacts was found in the wadi bed and on the steep slopes of the east bank distributed over an area of ca. 2,300 m2. Given the steepness of the wadi banks and the low density of artifacts, this area of artifact coverage seems likely to be greatly exaggerated over the original occupation area, however.
FACTORS CONTROLLING FORAGING STRATEGIES OF INSECTIVOROUS BIRDS

Factors are reviewed which are known or suspected to exert control over the foraging techniques of insectivorous birds. Optimal foraging strategies are postulated as describing the behavioral baseline subject to proximate modification by the internal factors of sex, age, intraspecific dominance status and hunger state, and the external factors of food distribution and abundance, habitat type, weather, interspecific social environment, proximity of predators, time of day, season of the year and age of young. Future research will involve controlled studies of the effects of individual factors on foraging. Important, also, will be the effort to refine the current first-generation models of optimal foraging.
Deep Generative Adversarial Neural Networks for Compressive Sensing MRI

Undersampled magnetic resonance image (MRI) reconstruction is typically an ill-posed linear inverse task. The time and resource intensive computations require tradeoffs between accuracy and speed . In addition, state-of-the-art compressed sensing (CS) analytics are not cognizant of the image diagnostic quality . To address these challenges, we propose a novel CS framework that uses generative adversarial networks (GAN) to model the (low-dimensional) manifold of high-quality MR images. Leveraging a mixture of least-squares (LS) GANs and pixel-wise $\ell _{1}/\ell _{2}$ cost, a deep residual network with skip connections is trained as the generator that learns to remove the aliasing artifacts by projecting onto the image manifold. The LSGAN learns the texture details, while the $\ell _{1}/\ell _{2}$ cost suppresses high-frequency noise. A discriminator network, which is a multilayer convolutional neural network (CNN), plays the role of a perceptual cost that is then jointly trained based on high-quality MR images to score the quality of retrieved images. In the operational phase, an initial aliased estimate (e.g., simply obtained by zero-filling) is propagated into the trained generator to output the desired reconstruction. This demands a very low computational overhead. Extensive evaluations are performed on a large contrast-enhanced MR dataset of pediatric patients. Images rated by expert radiologists corroborate that GANCS retrieves higher quality images with improved fine texture details compared with conventional Wavelet-based and dictionary-learning-based CS schemes as well as with deep-learning-based schemes using pixel-wise training. In addition, it offers reconstruction times of under a few milliseconds, which are two orders of magnitude faster than the current state-of-the-art CS-MRI schemes.
PEA-15 C-Terminal Tail Allosterically Modulates Death-Effector Domain Conformation and Facilitates Protein–Protein Interactions

Phosphoprotein enriched in astrocytes, 15 kDa (PEA-15) exerts its regulatory roles on several critical cellular pathways through protein–protein interactions depending on its phosphorylation states. It can either inhibit the extracellular signal-regulated kinase (ERK) activities when it is dephosphorylated or block the assembly of death-inducing signaling complex (DISC) and the subsequent activation of apoptotic initiator, caspase-8, when it is phosphorylated. Due to the important roles of PEA-15 in regulating these pathways that lead to opposite cellular outcomes (cell proliferation vs. cell death), we proposed a phosphostasis (phosphorylation homeostasis) model, in which the phosphorylation states of the protein are vigorously controlled and regulated to maintain a delicate balance. The phosphostasis gives rise to the protective cellular functions of PEA-15 to preserve optimum cellular conditions. In this article, using advanced multidimensional nuclear magnetic resonance (NMR) techniques combined with a novel chemical shift (CS)-Rosetta algorithm for de novo protein structural determination, we report a novel conformation of PEA-15 death-effector domain (DED) upon interacting with ERK2. This new conformation is modulated by the irregularly structured C-terminal tail when it first recognizes and binds to ERK2 at the d-peptide recruitment site (DRS) in an allosteric manner, and is facilitated by the rearrangement of the surface electrostatic and hydrogen-bonding interactions on the DED. In this ERK2-bound conformation, three of the six helices (α2, α3, and α4) comprising the DED reorient substantially in comparison to the free-form structure, exposing key residues on the other three helices that directly interact with ERK2 at the DEF-docking site (docking site for ERK, FxF) and the activation loop. Additionally, we provide evidence that the phosphorylation of the C-terminal tail leads to a distinct conformation of DED, allowing efficient interactions with Fas-associated death domain (FADD) protein at the DISC. Our results substantiate the allosteric regulatory roles of the C-terminal tail in modulating DED conformation and facilitating protein–protein interactions of PEA-15.
Pilot Assisted Adaptive Thresholding for Sneak-Path Mitigation in Resistive Memories With Failed Selection Devices

Resistive random-access memory (ReRAM) with the crossbar structure is one promising candidate to be used as a next generation non-volatile memory device. In a crossbar ReRAM, in which a memristor is positioned on each row-column intersection, the sneak-path problem is one of the main challenges for a reliable readout. The sneak-path problem can be solved with additional selection devices. When some selection devices fail short, the sneak-path problem re-occurs. The re-occurred sneak-path problem is addressed in this paper. The re-occurred sneak-path event can be described combinatorially and its adverse effect can be modeled as a parallel interference. Based on a simple pilot construction, we probabilistically characterize the inter-cell dependency of the re-occurred sneak-path events. Utilizing this dependency, we propose adaptive thresholding schemes for resistive memory readout using side information provided by pilot cells. This estimation theoretic approach effectively reduces the bit-error rate while maintaining low redundancy overhead and low complexity.
Futuristic Methods for Treatment of HIV in the Nervous System

While many pathogens can seed the central nervous system (CNS) and cause severe morbidity and mortality, HIV presents a unique challenge. HIV is known to cross into the CNS early on in infection, and long-term infection leads to neurocognitive impairment. Antiretrovirals (ARVs) have decreased the complications related to HIV, and extended the lifespan for those living with the virus; however, they haven’t lowered the overall prevalence of neurocognitive disorders. One theory is due to compartmentalization of the virus in the CNS, leading to low level viremia and inflammation. ARVs have variable penetrance into the brain, which may explain the compartmentalization. Many new techniques are being used to tackle this problem such as nanotechnology. Nanotechnology offers a means of modifying existing ARVs and increasing their CNS penetration as well as sustaining CNS concentrations by conjugating them with liposomes, or ligands that can bind to receptors on the surface of the blood-brain barrier. Further, techniques such as machine learning can help in understanding the pathogenesis of cognitive disorders by using computer algorithms to sort through hundreds of variables and determine pathological HIV genes or proteins that can be used to develop medications in the future. While these applications are still in the early-stages, they offer hope in tackling a longstanding problem.
On the mechanism of predominant urea formation from thermal degradation of CO2-loaded aqueous ethylenediamine

This study attempts to explain the well-known experimental observation that 1,3-bis(2-aminoethyl)urea (urea) is preferentially formed over the other major product, 2-imidazolidone (IZD), from thermal degradation of aqueous ethylenediamine (EDA) during the CO2 capture process. This is in direct contrast to the case of monoethanolamine (MEA), preferentially forming oxazolidinone (OZD), rather than urea, which undergoes further reactions leading to more stable products. Given their similar molecular structures, the different preferred degradation pathways of EDA and MEA impose an intriguing question regarding the underlying mechanism responsible for the distinct difference. Thermal degradation of both EDA and MEA tends to proceed mainly via formation of an isocyanate intermediate that may further undergo either cyclization to IZD (or OZD) or a reaction with EDA (or MEA) forming urea. For the EDA case, our first-principles simulations clearly demonstrate that the urea formation reaction is kinetically more, but thermodynamically less, favorable than the cyclization reaction; the opposite is true for the MEA case. Our further analysis shows that EDA–isocyanate is less prone to cyclization than MEA–isocyanate, which in turn allows for more facile urea formation. The reconfiguration dynamics of isocyanate is found to be governed by the dynamic nature of the interaction between its terminal group and surrounding solvent molecules. Our work highlights the importance of kinetic effects associated with the local structure and dynamics of solvent molecules around the intermediates that may significantly alter the degradation process of amine solvents.
MiR-125b protects against ethanol-induced apoptosis in neural crest cells and mouse embryos by targeting Bak 1 and PUMA

MicroRNAs are a class of small noncoding RNAs that have been implicated in regulation of a broad range of cellular and physiologic processes, including apoptosis. The objective of this study is to elucidate the roles of miR-125b in modulating ethanol-induced apoptosis in neural crest cells (NCCs) and mouse embryos. We found that treatment with ethanol resulted in a significant decrease in miR-125b expression in NCCs and in mouse embryos. We also validated that Bcl-2 antagonist killer 1 (Bak1) and p53-upregulated modulator of apoptosis (PUMA) are the direct targets of miR-125b in NCCs. In addition, over-expression of miR-125b significantly reduced ethanol-induced increase in Bak1 and PUMA protein expression, caspase-3 activation, and apoptosis in NCCs, indicating that miR-125b can modulate ethanol-induced apoptosis by the regulation of Bcl-2 and p53 pathways. Furthermore, microinjection of miR-125b mimic resulted in a significant increase in miR-125b expression and a decrease in the protein expression of Bak1 and PUMA in ethanol-exposed mouse embryos. Up-regulation of miR-125b also significantly reduced ethanol-induced caspase-3 activation and diminished ethanol-induced growth retardation in mouse embryos. This is the first demonstration that miR-125b can prevent ethanol-induced apoptosis and that microinjection of miRNA mimic can prevent ethanol-induced embryotoxicity.
The numbers game of soybean breeding in the United States

Abstract: Soybean [Glycine max (L.) Merr.] represents one of the most essential crops to the world’s economy and food security due to its unique seed composition. Public soybean breeding programs in the United States played an important role in developing the genetic basis of American soybean and discovering many economically important traits. After the passage of the Plant Variety Protection Act (PVP) in 1970 and the authorization to patent living matter in 1980, private companies have dominated the market share of commercial soybean varieties and public breeding programs shifted the efforts towards basic and applied research and education of the next generation of plant breeders. The short history of soybean breeding combined with a very narrow genetic basis derived from few ancestors can only make us reflect on all the innovations yet to be unveiled and the multiple possibilities to explore the unique traits that the golden miracle bean offers.
Rethinking Overhead as a Measure of Effectiveness

How should the effectiveness of a not-for-profit organization be measured? An outcome-based model – for example, one that looks at how well an organization performs its mission – would be a good choice. However, outcome-based metrics are rarely available. Or, if available, they are not generally standardized metrics that provide comparison to other similarly based organizations or industries. Therefore, donors and stakeholders have traditionally looked to “overhead ratios” – the percentage of an organization’s budget spent on non-program-related activities. The smaller this ratio (the less spent on overhead), the more an organization spends on program services – the actual performance of its mission. Fairly or not, under this model, the organization that spends more on non-program costs is viewed as less effective than a similar organization that spends less on overhead. While the overhead percentage metric has been employed by stakeholders and donors for decades, the question of whether it yields a meaningful measurement of an organization’s effectiveness is being reconsidered.
Virtual student-transplant patient interactions empower patients and enhance student transplantation knowledge.

Abstract Introduction There is variation in exposure to transplantation in undergraduate medical education. We created a program pairing medical students with transplant patients for semi-structured, virtual encounters and studied the impact on both students and patients using qualitative content analysis. Methods Fifty medical students were paired with transplant recipients and donors for non-medical virtual encounters. Separate focus groups were conducted, deidentified, and analyzed using a constant comparative method. Results Three themes related to the student experience emerged: transplant-related relationships, a deeper understanding of the patient's journey to transplant, and alterations of their personal view of organ donation and transplantation. Three themes emerged from the patient's experiences: the benefits of conversations, the patient as a teacher, and spreading the message of organ donation and transplantation. Conclusions This novel program demonstrates that virtual student-patient interactions are a useful approach to engage patients and a unique way to teach medical students about transplantation and donation.
Darlington, Cyril Dean

Darlington, Cyril Dean (1903–1981) British cytologist who worked on the formation of the sex cells. Keywords: genetics; cytology; chromosome; culture; evolution
Specific membranous structures associated with the replication of group A arboviruses.

Abstract Intracytoplasmic membranous structures of a unique type were associated with the replication of three group A arboviruses: Semliki Forest virus (SFV), Sindbis virus, or Western equine encephalomyelitis virus. The structures, referred to as type 1 cytopathic vacuoles (CPV-1), were membrane-limited and characteristically lined by regular membranous spherules measuring 50 nm in diameter. The membranous spherules typically contained a fine central density, but were neither virus cores nor virions. Detection of CPV-1 by electron microscopy at 3 to 6 hr postinfection coincided with the time of rapid virus growth and preceded the accumulation of virus nucleocapsids. A range of 20 to 100 CPV-1 profiles were counted per 100 ultrathin cell sections at 6 to 9 hr postinfection when viruses were grown in chick embryo, baby hamster kidney, or mouse L cells. Maximum counts remained in the same range even when the multiplicity of infection was varied over 100-fold. Inhibition of cellular ribonucleic acid (RNA) and protein synthesis by actinomycin D during SFV infection did not decrease the counts of CPV-1; however, biogenesis of CPV-1 was decreased when viral replication was limited by inhibitors of viral RNA synthesis (guanidine) or of viral protein synthesis (cycloheximide). On the basis of present and earlier findings, we concluded that formation of CPV-1 must result from a virus-specified modification of pre-existing host cell macromolecules.
Secure Grid Computing with Trusted Resources and Internet Datamining

Internet-based Grid computing is emerging as one of the most promising technologies that may change the world. Dr. Hwang and his research team at the University of Southern California (USC) are working on self-defense tools to protect Grid resources from cyber attacks or malicious intrusions, automatically. This project builds an automated intrusion response and trust management system to facilitate authentication, authorization, and security binding in using metacomputing Grids or peer-to-peer web services. The trusted GridSec infrastructure supports Internet traffic datamining, encrypted tunneling, optimized resource allocations, network flood control and anomaly detection, etc. The USC team is developing a NetShield library to protect Grid resources. This new security system adjusts itself dynamically with changing threat patterns and network traffic conditions. This project promotes the acceptance of Grid computing through international collaborations with the research groups in INRIA, France, Chinese Academy of Sciences, and Melbourne University. The fortified Grid infrastructure will benefit securitysensitive allocations in digital government, electronic commerce, anti-terrorism activities, and cyberspace crime control. The broader impacts of this ITR project are far reaching in an era of growing demand of Internet, Web and Grid services.
Neurodegenerative disorders and ischemic brain diseases.

Degeneration and death of neurons is the fundamental process responsible for the clinical manifestations of many different neurological disorders of aging, incuding Alzheimer's disease, Parkinson's disease and stroke. The death of neurons in such disorders involves apoptotic biochemical cascades involving upstream effectors (Par-4, p53 and pro-apoptotic Bcl-2 family members), mitochondrial alterations and caspase activation. Both genetic and environmental factors, and the aging process itself, contribute to intiation of such neuronal apoptosis. For example, mutations in the amyloid precursor protein and presenilin genes can cause Alzheimer's disease, while head injury is a risk factor for both Alzheimer's and Parkinson's diseases. At the cellular level, neuronal apoptosis in neurodegenerative disorders may be triggered by oxidative stress, metabolic compromise and disruption of calcium homeostasis. Neuroprotective (anti-apoptotic) signaling pathways involving neurotrophic factors, cytokines and “conditioning responses” can counteract the effects of aging and genetic predisposition in experimental models of neurodegenerative disorders. A better understanding of the molecular underpinnings of neuronal death is leading directly to novel preventative and therapeutic approaches to neurodegenerative disorders.
The Benefits of Cooperative Learning Arrangements in Second Language Instruction

Abstract This paper identifies some of the advantages that cooperative learning arrangements offer in second language and bilingual instruction. There are six main benefits (two linguistic, two curricular and two social): (1) increased frequency and variety of second language practice through different types of interaction; (2) possibility for development or use of the first language in ways that support cognitive development and increased second language skills; (3) opportunities to integrate language with content instruction; (4) inclusion of a greater variety of curricular materials to stimulate language use as well as concept learning; (5) freedom for language teachers to master new professional skills, particularly those emphasizing communication; and (6) opportunities for students to act as resources for each other and, thus, assume a more active role in learning. Pertinent empirical findings from various settings of linguistic diversity are presented and theoretical foundations summarized to show t...
The Molecular Biology of HPV-Related Head and Neck Cancer

Human papillomaviruses (HPVs) are epitheliotropic, non-enveloped, circular deoxyribonucleic acid (DNA) viruses of ~7,900 base pairs. There are over 100 distinct subtypes of HPVs that infect squamous epithelia and cause both benign and cancerous lesions [1, 2]. Benign lesions caused by HPV include both mucosal and epithelial warts.
Effect of parasympathetic nerve stimulation on the uterine vascular bed.

Abstract Direct stimulation of the pelvic parasympathetic nerves of 4 nonpregnant and 20 gravid ewes between 51 and 136 days' gestation caused no change in uterine vascular conductance. Similarly, surgical and pharmacologic pelvic parasympatholysis caused minimal or nonsignificant changes in uterine conductance and uterine blood flow. These results suggest that parasympathetic uterine vascular innervation is absent in the ewe.
Disruption of Myxoviruses with Tween 20 and Isolation of Biologically Active Hemagglutinin and Neuraminidase Subunits

Myxoviruses were disrupted with Tween 20 at high p H, and the major surface antigens were separated in biologically active form. The neuraminidase had a sedimentation coefficient of 10.8 S , and the hemagglutinin had a sedimentation coefficient of 8.1 S . Electron microscopic examination of negatively stained preparations revealed structures identical in size and morphology to the neuraminidase and hemagglutinin subunits described by others. Inhibition of neuraminidase activity by antibody to the hemagglutinin which occurred with intact viruses (probably for “steric” reasons) did not occur after the viruses were disrupted with Tween 20. Serological assays for neuraminidase were possible in the presence of the mild surfactant, whereas serological assays for hemagglutinin were possible after removal of the reagent. Disruption of myxoviruses with Tween 20 therefore provides a method for the independent study of these antigens during antigenic drift. Images