cssi/SciSciGPT-SciSciNet huggingface dataset:
Comparative Evaluation of Disodium Edetate and Diethylenetriaminepentaacetic Acid as Iron Chelators to Prevent Metal -Catalyzed Destabilization of a Therapeutic Monoclonal Antibody

Understanding the effect of metal chelators with respect to their ability to inhibit metal catalyzed degradation in biologic products is a critical component for solution formulation development. Two metal chelators, disodium edetate (Na2EDTA) and diethylenetriaminepen- taacetic acid (DTPA), were evaluated for their ability to stabilize IgG2 mAb in solution formulations spiked with various levels of iron. Real-time stability attributes such as oxidation, soluble aggregate formation, deamidation and fragmentation demonstrated that DTPA was equivalent to Na2EDTA with respect to inhibiting iron-induced degradation over the range of iron concentrations studied. When sufficient chelator was present to stoichiometrically complex trace iron contamination, both Na2EDTA and DTPA exhibited the capacity to reduce protein degradation. However, sub-stoichiometric ratios of both chelators were unable to inhibit the degradation induced by free iron ions, which were found to bind weakly to the mAb. This bound iron did not measurably alter the secondary or the tertiary structure of the mAb, but appeared to decrease its intrinsic thermodynamic stability, probably by causing subtle perturbations in the tertiary structure. These destabilization effects were not observed when the chelators were present at stoichiometric ratios highlighting the feasibility of using DTPA as an alternate trace metal chelator to Na2EDTA in biologic protein formulations. 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4239-4250, 2010
Hormonal regulation of guanosine triphosphate cyclohydrolase activity and biopterin levels in the rat adrenal cortex.

The regulation of GTP-cyclohydrolase (GTPCH) activity and tetrahydrobiopterin (BH4) levels in the adrenal cortex were studied in intact and hypophysectomized rats. Treatment with a single dose of reserpine (5 mg/kg) or insulin-induced hypoglycemia (4 h) elevated adrenocortical BH4 3-fold by 10 h; BH4 levels remained elevated after 24 h and returned to control levels by 48–72 h. GTP-CH was significantly increased 24 h after hypoglycemic shock, and the increased enzyme activity preceded the changes in BH4 levels after reserpine treatment. Two and a half hours of stress by immobilization also increased GTP-CH activity and BH4 levels in the adrenal cortex. The activities of sepiapterin reductase and dihydrofolate reductase, putative enzymes in the biosynthetic pathway from GTP to BH4, were not increased by reserpine. Both reserpine and insulin increased the apparent maximum velocity for GTP, with no increase in the affinity of the enzyme for its substrate, further suggesting that the experimental treatments i...
A comparison of pragmatic accommodation of nonnative and native speakers in written English

: The analysis of 10 edited essays written by freshman native and nonnative speakers of English who are novice, non proficient writers of English indicates that both groups produce approximately the same number and kinds of sentence level deviations from standard written English. At this level the nonnative speakers appear no more ‘foreign’ than do the native speakers. At the discourse level, the nonnative students produce fewer faulty structures, and produce more coherent essays with clearer illocutionary guides for the reader. This analysis indicates that nonnative speakers in a college writing class can certainly profit from instruction focused on developing discourse level strategies that structure coherence overtly and provide obvious illocutionary guides for the reader.
Regional Distribution of the GABAA/Benzodiazepine Receptor (α Subunit) mRNA in Rat Brain

A human cDNA clone containing the 5' coding region of the GABAA/benzodiazepine receptor alpha subunit was used to quantify and visualize receptor mRNA in various regions of the rat brain. Using a [32P]CTP-labelled antisense RNA probe (860 bases) prepared from the alpha subunit cDNA, multiple mRNA species were detected in Northern blots using total and poly A rat brain RNA. In all brain regions, mRNAs of 4.4 and 4.8 kb were observed, and an additional mRNA of 3.0 kb was detected in the cerebellum and hippocampus. The level of GABAA/benzodiazepine receptor mRNA was highest in the cerebellum followed by the thalamus = frontal cortex = hippocampus = parietal cortex = hypothalamus much greater than pons = striatum = medulla. In situ hybridization revealed high levels of alpha subunit mRNA in cerebellar gray matter, olfactory bulb, thalamus, hippocampus/dentate gyrus, and the arcuate nucleus of the hypothalamus. These data suggest the presence of multiple GABAA/benzodiazepine receptor alpha subunit mRNAs in rat brain and demonstrate the feasibility of studying the expression of genes encoding the GABAA/benzodiazepine receptor after pharmacological and/or environmental manipulation.
Characterizing the effects of the PLL jitter due to substrate noise in discrete-time delta-sigma modulators

This paper investigates the impact of clock jitter induced by substrate noise on the performance of the oversampling /spl Delta//spl Sigma/ modulators. First, a new stochastic model for substrate noise is proposed. This model is then utilized to study the clock jitter in clock generators incorporating phase-locked loops (PLLs). Next, the effect of the clock jitter on the performance of the /spl Delta//spl Sigma/ modulator is studied. It will be shown that substrate noise degrades the signal-to-noise ratio of the /spl Delta//spl Sigma/ modulator while the noise shaping does not have any effect on clock jitter induced by substrate noise. To verify the analysis experimentally, a circuit consisting of a second-order /spl Delta//spl Sigma/ modulator, a charge-pump PLL, and forty multistage digital tapered inverters driving 1-pF capacitors is designed in a 0.25-/spl mu/m standard CMOS process. Several experiments on the designed circuit demonstrate the high accuracy of the proposed analytical models.
Dual Enrollment as a Liminal Space.

This chapter addresses some of the tensions inherent to dual enrollment and relates them to larger challenges in higher education.
Pyoderma Vegetans of the Penis

Pyoderma vegetans is a rare benign skin disease characterized by chronic vegetative pustular plaques. We report a case of pyoderma vegetans of the penile foreskin successfully treated with circumcision. To our knowledge this is the first reported case of pyoderma vegetans of the penis. CASE REPORT A 42-year-old HIV positive man with a history of recurrent, acyclovir resistant herpes simplex virus infection of the penis presented with painful weeping pustular lesions of the foreskin that had been increasing in size for several months. The patient denied fever, chills, voiding complaints or penile trauma. Physical examination demonstrated raised, tender, circumferential, exudative plaques producing copious amounts of serous fluid (fig. 1). The remainder of the phallus was normal. Scrotal, testicular and rectal examinations were unremarkable. Circumcision was performed (fig. 2). Pathological evaluation revealed benign skin with epithelial hyperplasia and extensive dermal inflammation with neutrophils, lymphocytes and eosinophils consistent with pyoderma vegetans. Bacterial, viral and fungal cultures were negative. Physical examination 4 months later showed no residual lesions.
From Communication to Collaboration: Simulating the Emergence of Inter-organizational Collaboration Network

Inter-organizational networks often have multiple dimensions, each one denoting a type of relationship. In this research, we studied how one dimension of the network, a collaboration network, emerges from organizations' interaction on another dimension--the communication network. We modeled the emergence of collaboration as an event-based multi-agent team formation process that incorporates the structure of the underlying communication network, the diffusion of project information, and network-based influence. As a case study, we used an agent-based simulation to study the collaboration among humanitarian organizations. We also analyzed how changes to the communication network among humanitarian organizations affect their collaboration network. The experiment results suggest that different strategies to promote communication may have positive or negative impacts on the future collaboration network.
Get screened: a pragmatic randomized controlled trial to increase mammography and colorectal cancer screening in a large, safety net practice.

Most randomized controlled trials of interventions designed to promote cancer screening, particularly those targeting poor and minority patients, enroll selected patients. Relatively little is known about the benefits of these interventions among unselected patients. "Get Screened" is an American Cancer Society-sponsored randomized controlled trial designed to promote mammography and colorectal cancer screening in a primary care practice serving low-income patients. Eligible patients who are past due for mammography or colorectal cancer screening are entered into a tracking registry and randomly assigned to early or delayed intervention. This 6-month intervention is multimodal, involving patient prompts, clinician prompts, and outreach. At the time of the patient visit, eligible patients receive a low-literacy patient education tool. At the same time, clinicians receive a prompt to remind them to order the test and, when appropriate, a tool designed to simplify colorectal cancer screening decision-making. Patient outreach consists of personalized letters, automated telephone reminders, assistance with scheduling, and linkage of uninsured patients to the local National Breast and Cervical Cancer Early Detection program. Interventions are repeated for patients who fail to respond to early interventions. We will compare rates of screening between randomized groups, as well as planned secondary analyses of minority patients and uninsured patients. Data from the pilot phase show that this multimodal intervention triples rates of cancer screening (adjusted odds ratio 3.63; 95% CI 2.35 - 5.61). This study protocol is designed to assess a multimodal approach to promotion of breast and colorectal cancer screening among underserved patients. We hypothesize that a multimodal approach will significantly improve cancer screening rates. The trial was registered at Clinical Trials.gov NCT00818857
Function of polyphenol oxidase in higher plants

Recent evidence has supported the folllowing views: 1. Polyphenol oxidase (PPO) is a plastidic enzyme that is unclear-coded, but is inactive until incorporated into the plastid. 2. In healthy green tissues PPO exists in a latent form on the thylakoid membrane and is not involved in synthesis of phenolic compounds. In leucoplasts, proplastids, or amyloplasts PPO is often present in a latent form in rudimentary thylakoids. 3. PPO normally functions as a phenol oxidase in vivo only in sencent or damaged cells. 4. In the functional chloroplast, PPO may be involved in some aspect of oxygen chemistry – pherhaps mediation of pseudocyclic photophosphorylation.
Incidence of aortic root dilatation in pectus excavatum and its association with Marfan syndrome.

Objective To investigate the incidence of aortic root dilatation in pectus excavatum. Design Retrospective medical record review and echocardiographic reanalysis. Setting Morgan Stanley Children's Hospital of New York–Presbyterian. Participants Surgical candidates with pectus excavatum (n = 37) and age-matched controls (n = 44) referred for an echocardiogram from 1994 to 2002. Interventions Two-dimensional and color Doppler transthoracic echocardiograms. Outcome Measures The aortic annulus and root were measured and z scores were calculated and compared. Medical records were reviewed for genetic evaluation. Results Patients with pectus excavatum and age-matched controls were reanalyzed. There was no difference in age, weight, height, or body surface area between patients and controls. There were no differences in the mean aortic annulus diameter, mean aortic annulus z score, or mean aortic root measurements. However, the aortic root z score was significantly higher in the pectus excavatum group compared with the controls: 0.9 (SD, 1.06) vs 0.0 (SD, 1.25) ( P = .001). There were more patients with an aortic root z score of 2 or greater in the pectus excavatum group (9 of 37 patients) than in the control group (0 of 43 controls), with a calculated odds ratio of 29.7 (95% confidence interval, 1.10-1.59). Genetic evaluation was performed in 5 patients with a pectus excavatum and dilated aortic root; 2 of them received diagnoses of Marfan syndrome. Conclusions Aortic root dilatation is more common in patients with pectus excavatum than in a control population. Echocardiographic screening may be useful in the identification of aortic root dilatation in patients with isolated pectus excavatum.
Evolution of cortical metabolic abnormalities and their clinical correlates in Sturge-Weber syndrome.

Abstract Background The natural course of Sturge-Weber syndrome (SWS) is poorly understood, although neurological symptoms are often progressive. Aims To track longitudinal changes in brain glucose metabolism measured with positron emission tomography (PET) and their relation to clinical changes during the early course of SWS. Methods Fourteen children (age 3 months to 3.9 years at enrollment) with SWS and unilateral leptomeningeal angioma underwent two consecutive glucose metabolism PET scans with a mean follow-up time of 1.2 years. Longitudinal changes of the extent of cortical glucose hypometabolism on the angioma side were measured and correlated with age, clinical seizure frequency and hemiparesis. Results An increase in the size of the hypometabolic cortex was seen in 6 children, coinciding with an age-related increase in cortical glucose metabolism measured in unaffected contralateral cortex. These 6 patients were younger both at the initial (mean age 0.75 vs. 2.8 years; p Conclusions In SWS, detrimental metabolic changes occur before 3 years of age coinciding with a sharp increase of developmentally regulated cerebral metabolic demand. Progressive hypometabolism is associated with high seizure frequency in these children. However, metabolic abnormalities may remain limited or even partially recover later in some children with well-controlled seizures. Metabolic recovery accompanied by neurological improvement suggests a window for therapeutic intervention in children with unilateral SWS.
Logistic regression when binary predictor variables are highly correlated

Standard logistic regression can produce estimates having large mean square error when predictor variables are multicollinear. Ridge regression and principal components regression can reduce the impact of multicollinearity in ordinary least squares regression. Generalizations of these, applicable in the logistic regression framework, are alternatives to standard logistic regression. It is shown that estimates obtained via ridge and principal components logistic regression can have smaller mean square error than estimates obtained through standard logistic regression. Recommendations for choosing among standard, ridge and principal components logistic regression are developed. Published in 2001 by John Wiley & Sons, Ltd.
Growing Evidence for Human Health Benefits of Boron

Growing evidence from a variety of experimental models shows that boron is a bioactive and beneficial (perhaps essential) element for humans. Reported beneficial actions of boron include arthritis ...
Differential effects of shared attention on perception of heading and 3-D object motion.

When a person moves in a straight line through a stationary environment, the images of object surfaces move in a radial pattern away from a single point. This point, known as thefocus of expansion (FOE), corresponds to the person’s direction of motion. People judge their heading from image motion quite well in this situation. They perform most accurately when they can see the region around the FOE, which contains the most useful information for this task. Furthermore, a large moving object in the scene has no effect on observer heading judgments unless it obscures the FOE. Therefore, observers may obtain the most accurate heading judgments by focusing their attention on the region around the FOE. However, in many situations (e.g., driving), the observer must pay attention to other moving objects in the scene (e.g., cars and pedestrians) to avoid collisions. These objects may be located far from the FOE in the visual field. We tested whether people can accurately judge their heading and the three-dimensional (3-D) motion of objects while paying attention to one or the other task. The results show that differential allocation of attention affects people’s ability to judge 3-D object motion much more than it affects their ability to judge heading. This suggests that heading judgments are computed globally, whereas judgments about object motion may require more focused attention.
Kringle‐kringle interactions in multimer kringle structures

The crystal structure of a monoclinic form of human plasminogen kringle 4 (PGK4) has been solved by molecular replacement using the orthorthombic structure as a model and it has been refined by restrained least-squares methods to an R factor of 16.4% at 2.25 A resolution. The X-PLOR structure of kringle 2 of tissue plasminogen activator (t-PAK2) has been refined further using PROFFT (R = 14.5% at 2.38 A resolution). The PGK4 structure has 2 and t-PAK2 has 3 independent molecules in the asymmetric unit. There are 5 different noncrystallographic symmetry "dimers" in PGK4. Three make extensive kringle-kringle interactions related by noncrystallographic 2(1) screw axes without blocking the lysine binding site. Such associations may occur in multikringle structures such as prothrombin, hepatocyte growth factor, plasminogen (PG), and apolipoprotein [a]. The t-PAK2 structure also has noncrystallographic screw symmetry (3(1)) and mimics fibrin binding mode by having lysine of one molecule interacting electrostatically with the lysine binding site of another kringle. This ligand-like binding interaction may be important in kringle-kringle interactions involving non-lysine binding kringles with lysine or pseudo-lysine binding sites. Electrostatic intermolecular interactions involving the lysine binding site are also found in the crystal structures of PGK1 and orthorhombic PGK4. Anions associate with the cationic centers of these and t-PAK2 that appear to be more than occasional components of lysine binding site regions.
SAGE: self-tuning approximation for graphics engines

Approximate computing, where computation accuracy is traded off for better performance or higher data throughput, is one solution that can help data processing keep pace with the current and growing overabundance of information. For particular domains such as multimedia and learning algorithms, approximation is commonly used today. We consider automation to be essential to provide transparent approximation and we show that larger benefits can be achieved by constructing the approximation techniques to fit the underlying hardware. Our target platform is the GPU because of its high performance capabilities and difficult programming challenges that can be alleviated with proper automation. Our approach, SAGE, combines a static compiler that automatically generates a set of CUDA kernels with varying levels of approximation with a run-time system that iteratively selects among the available kernels to achieve speedup while adhering to a target output quality set by the user. The SAGE compiler employs three optimization techniques to generate approximate kernels that exploit the GPU microarchitecture: selective discarding of atomic operations, data packing, and thread fusion. Across a set of machine learning and image processing kernels, SAGE's approximation yields an average of 2.5× speedup with less than 10% quality loss compared to the accurate execution on a NVIDIA GTX 560 GPU.
MMSE-optimal training sequences for spectrally-efficient Multi-User MIMO-OFDM systems

This paper proposes a new family of optimal training sequences in terms of minimizing the mean-square channel estimation error for spectrally-efficient Multi-User MIMO-OFDM systems with an arbitrary number of transmit antennas and an arbitrary number of training symbols. It addresses uplink transmission scenarios where the users overlap in time and frequency and are separated using spatial processing at the base station. In particular, optimal training sequences can be obtained easily from standard signal constellations such as QPSK with desired low PAPR, making it appealing for practical use.
Autoimmunity, immunoglobulin adsorption and dilated cardiomyopathy: has the time come for randomized clinical trials?

Over the past 10 to 15 years there has been increasing evidence suggesting that abnormalities in cellular and humoral immunity may contribute to the overall pathogenesis of dilated cardiomyopathy. Circulating autoantibodies to a variety of cardiac antigens including G-protein–linked receptors (
5th workshop on system-level virtualization for high performance computing (HPCVirt 2011)

The emergence of virtualization enabled hardware, such as the latest generation AMD and Intel processors, has raised significant interest in High Performance Computing (HPC) community. In particular, system-level virtualization provides an opportunity to advance the design and development of operating systems, programming environments, administration practices, and resource management tools. This leads to some potential research topics for HPC, such as failure tolerance, system management, and solution for application porting to new HPC platforms. The workshop on System-level Virtualization for HPC (HPCVirt 2011) is intended to be a forum for the exchange of ideas and experiences on the use of virtualization technologies for HPC, the challenges and opportunities offered by the development of system-level virtualization solutions themselves, as well as case studies in the application of system-level virtualization in HPC.
DD79: Vom Wert des Versprechens (Dezember 2008)

In Aktienkursen steckt oft viel Hoffnung, manchmal gar Glaube oder ganz heise Luft – zu anderen Zeiten Misstrauen oder tiefe Depression. Das Reale bedeutet fast nichts. Es ist fast schon von gestern. Es kommt nicht darauf an, was ist. Der Wert eines Etwas bemisst sich danach, was man sich von ihm verspricht. Und so konnten wir nebenbei auch gleich forsch fragen: „Was verspricht man sich von Ihnen?“
eNOS Function and Dysfunction in the Penis

Endothelial nitric oxide (NO) synthase (eNOS) has an indispensable role in the erectile response. In the penis, eNOS activity and endothelial NO bioavailability are regulated by multiple post-translational molecular mechanisms, such as eNOS phosphorylation, eNOS interaction with regulatory proteins and contractile pathways, and actions of reactive oxygen species (ROS). These mechanisms regulate eNOS-mediated responses under physiologic circumstances and provide various mechanisms whereby endothelial NO availability may be altered in states of vasculogenic erectile dysfunction (ED). In view of the recent advances in the field of eNOS function in the penis and its role in penile erection, the emphasis in this review is placed on the mechanisms regulating eNOS activity and its interaction with the RhoA/Rho-kinase pathway in the physiology of penile erection and the pathophysiology of ED.
Identification of the intestinal Na-phosphate cotransporter

Na-dependent phosphate uptake in intestinal brush-border membrane vesicles was sensitive to arginine group-specific reagents in a substrate-sensitive manner. Four different arginine group-specific reagents were tested. All four reagents irreversibly inhibited Na-dependent phosphate uptake with the concentration for 50% inhibition, K0.5, varying between 150 and 40 microM. Maximum inhibition approached 80%. Addition of substrates during exposure to these reagents resulted in protection of Na-phosphate cotransport only in the presence of Na and phosphate. Na-phosphate cotransporter labeling at or near the phosphate site was accomplished using a pretreatment step with phenylglyoxal and substrates followed by a fluorescent phenylglyoxal-labeling step. Fluorescein isothiocyanate-phenylglyoxal (FITC-PG) specifically labeled a 130-kDa polypeptide on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) in a substrate-sensitive manner, consistent with its effect on Na-phosphate cotransport. n-Acetylimidazole (NAI) inhibited Na-phosphate cotransport in a Na+- but not K+ -sensitive manner. NAI or fluorescein n-acetylimidazole (FNAI) inhibited Na-dependent phosphate uptake with a K0.5 for inhibition of 38 microM. Maximum inhibition of Na-phosphate cotransport was 75%. On SDS-PAGE, FNAI labeled five polypeptide bands in a Na-sensitive manner including the 130-kDa polypeptide band labeled by FITC-PG. Of these five bands only the 130-kDa polypeptide lost substrate protectability against FITC-PG inhibition of Na-phosphate cotransport and FITC-PG labeling on prior exposure to NAI in the absence of Na+. On this basis the 130-kDa polypeptide is tentatively identified as the intestinal Na-phosphate cotransporter and this polypeptide band contains both the Na substrate site and the phosphate substrate site.
Numerical simulation of CO2 huff-n-puff in complex fracture networks of unconventional liquid reservoirs

Abstract Horizontal drilling and hydraulic fracturing produce Unconventional Liquid Reservoirs (ULRs) economically. One of the characteristics of the ULRs is high production declining rate, and thus enhanced oil recovery techniques such as Huff-n-Puff will ensue. In addition, the existence of complex fracture network has been proven by both field and simulation work. This study investigated the potential of CO 2 huff-n-puff in ULRs with complex fracture networks. Two fracture characterization techniques for complex fracture network such as fractal-based, and microseismic-based were applied to reduce uncertainties of fracture networks and thus improve the accuracy of simulation input. In order to study complex CO 2 recovery mechanism, lab-measured data was upscaled to the field-scale, and then used for evaluating production performance of a simple fracture network. Detailed sensitivity analysis showed that diffusion in the field scale is negligible compared with other recovery mechanisms such as oil swelling, gas expansion, viscosity reduction, etc. The following comparison between dual continuum and the explicit fracture modeling approaches highlights the importance of heterogeneity due to the explicit fractures. Dual continuum models yields less accurate pressure behavior than explicit discrete fracture models even though production behavior could be history matched.
The Long Time Structure of the Rotor Wake in Ground Effect

The form of the rotor wake in the presence of a ground has been investigated using a vortex model of the rotor wake. Both hover and forward ight have been considered and the presence of the ground is modelled using the method of images. A lifting-line theory is used to model the rotor blade and a time-stepping vortex method has been used to obtain the evolution of tip-vortex. A numerical scheme has been designed to compute up to a hundred rotor revolutions. Our results show that periodicity is obtained after about thirty rotor revolutions near the blade as well as near the ground although this value depends to some extent on the advance ratio. Unsteadiness near the tail rotor has been studied by computing the deviation of the downwash and y-velocities from the mean at a hypothetical tail rotor and on its advancing and retreating sides.
A Question of Faith: Religious Bias and Coercion Undermine Military Leadership and Trust

Using French and Raven's (1959) bases of social power, leadership is defined in terms of a dependency between leader and follower. The authors show how referrent and expert power are critical to the ascientific construct of leadership in predicting the extent to which trust can be created within organizational relationships. Using popular press reports of religious bias within military organizations, the authors illustrate how using one's religious values as a proxy for organizational values not only create a divisive organizational climate, but are counter to the mandates set forth by the US Constitution. The authors introduce the Oath of Equal Character as a potential remedy to the pervasive religiousity noted in government organizations across the US Armed Forces and advocate how the appropriate creation and judicious use of referrent power is chiefly responsible for the emergence of trusting relationships in military organizations.
Library research and government funding—A less than ardent romance

Federal funding for library research, although disguised in the 1960s and 1970s as science information research, nevertheless allowed both research libraries and library education programs to study the phenomena under which acquisitions and operational decisions could be made intelligently and cost effectively. This has now been almost completely eliminated, and it has been replaced by mathematical and sociological studies undertaken by individuals with neither a background nor interest in libraries, and by the funding of examinations that determine only how libraries might serve a larger national priority in which they play at best an incidental part.
Protection of alveolar macrophages from hyperoxia by gamma-glutamyl transpeptidase

Exposure to hyperoxia causes loss of alveolar macrophage cell function. Toxicity was measured as suppression of the respiratory burst stimulated by phorbol myristate acetate subsequent to exposure (43.5% depression by 2-h exposure to 5 atm absolute O2 vs. controls). The presence of extracellular glutathione significantly protected these cells (7% loss). gamma-Glutamyl transpeptidase, a membrane enzyme with its active site directed outward, was necessary for use of extracellular glutathione. This was demonstrated using the gamma-glutamyl transpeptidase inhibitor, serine-borate complex, which significantly blocked both protection of cells by extracellular glutathione and extracellular glutathione-dependent synthesis of glutathione. The principal use of glutathione in antioxidant defense is as a substrate for glutathione peroxidase. The apparent Km for glutathione of glutathione peroxidase of rat alveolar macrophages was determined to be 2 mM; however, rat alveolar macrophages have approximately 1.3 mM intracellular glutathione, which is insufficient for maximal enzymatic activity. During hyperoxic exposure, this deficit would probably be more significant. Thus the ability of extracellular glutathione along with gamma-glutamyl transpeptidase activity to provide amino acids for de novo glutathione synthesis appears to be a potentially important component of antioxidant defense.
Parametric Oscillations in Semiconductor Lasers

Externally induced optical parametric interactions within a laser cavity can induce diverse behavior depending upon the nature of the interaction and the oscillation conditions of the laser cavity. We have been particularly interested in the possibility of utilizing such interactions for the generation of short optical pulses from semiconductor lasers. Parametric interactions become simpler to implement as the round trip cavity time is decreased, thus increasing the modulation frequency required. This is in contrast to gain switching and other conventional microwave injection tech niques,which become more difficult as the frequency is increased [1]. Consequently, parametric interactions should be advantageous when the oscillation frequency is greater than a few tens of gigahertz.
Lung cancer: Low-dose CT screening — determining the right interval

Annual thoracic CT screening is currently recommended for individuals deemed to be at high risk of developing lung cancer; however, Patz and co-workers now raise the very important question of choosing the optimal interval between screening exams, in order to balance the potential benefits and harms associated with each round of CT. Herein, we present important considerations for determining such intervals.
Structure-Function Relationships of Micrococcus lysodeikticus Membranes: A Bacterial Membrane Model System

In the course of his studies on the antibacterial and bacteriolytic properties of various tissues and secretions, Fleming (1922) noticed the complete lysis of some of the colonies of a yellow-pigmented organism growing in the vicinity of the mucus. Fleming (1922) isolated the micrococcus species and gave the name lysozyme to the lytic substance. Glynn (1968) records the history of the origin of the name given to this lysozyme-sensitive organism as follows: “The name Micrococcus lysodeikticus for the yellow bacteria we owe to Sir Almroth Wright who would never use a simple word in English or even Latin if he could invent a more complicated one in Greek.” The species designation for this gram-positive organism is indeed a hybrid epithet meaning “lysis indicator” (lysodeikticus). Fleming never described the organism in the traditional style of the bacteriologist, probably because he was deliberately searching for natural antibiotics and was much more interested in bacterial lysis and the antibacterial properties of lysozyme and later penicillin. As a result the use of lysodeikticus as a species of Micrococcus has had a spotty history and, after having been mentioned transiently in Bergy’s Manual of Determinative Bacteriology, it is no longer recorded in this August catalog. The high susceptibility to lysis by lysozymes from various tissues and secretions reported by Fleming (1922) was undoubtedly the principal feature of this bacterium to attract attention and has probably resulted in the persistence of its name. The general morphological, biochemical, and physiological properties of this organism certainly lump it with other micrococci and related Sarcina species. Micrococcus luteus is widely used as the officially described species.
Paraneoplastic Cerebellar Degeneration (PCD) Syndrome in Diffuse Large B-cell Lymphoma (DLBCL): expanding the spectrum of malignancies associated with cerebellar degeneration (P5.260)

Background: Case reports have previously described the association of Hodgkin’s Lymphoma, thymoma, lung and breast cancer, ovarian and testicular tumors, melanoma, renal cell carcinoma, follicular lymphoma and adenocarcinoma of stomach with PCD but DLBCL, a subtype of NHL, presenting with PCD is particularly rare, to our knowledge having been described only twice previously in patients with primary gastric lymphoma. Clinical Case: 66yo right-handed woman with history of controlled hypertension presented with right upper limb incoordination and intention tremor in August’14, progressing to involve right lower extremity and then the contralateral body and “head jerks” over next 3-4 months. Symptoms were always worse on right hemibody. Patient had marked instability in posture and a wide-base unsteady gait, requiring a walker. She reported progressive growth of multiple masses on the scalp, largest being on the forehead, associated with pressure headaches. Denied changes in vision, urinary incontinence or seizures. Patient underwent extensive neurological work-up as an outpatient without cause for ataxia. In February’15, the masses on head continued to grow and the patient was noted to have a new enlarging painless right cervical lymphadenopathy. She underwent an excisional biopsy leading to the diagnosis of DLBCL. On examination she had marked dystaxia, dysmetria, dysdiadochokinesia worse on right hemibody, mild dysarthria and resting tremor of head. Cerebellum was normal on imaging and CSF was negative for malignancy. PCD panel was negative for anti- hu, anti zic4, anti-gad65, anti-ri, anti-ma1 and anti-ma2, anti-cv2, anti-yo and anti-amphiphysin antibodies. Over the course she has received 5 cycles of R-Chop, 1 cycle R-Epoch, and 4 cycles of HD MTX with significant improvement in her cerebellar symptoms. Discussion: We will further discuss the patient’s imaging, other diagnostic studies, response to treatment and need for thorough evaluation of patients for underlying malignancy in similar presentation. Disclosure: Dr. Saini has nothing to disclose. Dr. Weisz has nothing to disclose. Dr. Hoffman has nothing to disclose.
Amulet: An Energy-Efficient, Multi-Application Wearable Platform

Wearable technology enables a range of exciting new applications in health, commerce, and beyond. For many important applications, wearables must have battery life measured in weeks or months, not hours and days as in most current devices. Our vision of wearable platforms aims for long battery life but with the flexibility and security to support multiple applications. To achieve long battery life with a workload comprising apps from multiple developers, these platforms must have robust mechanisms for app isolation and developer tools for optimizing resource usage.We introduce the Amulet Platform for constrained wearable devices, which includes an ultra-low-power hardware architecture and a companion software framework, including a highly efficient event-driven programming model, low-power operating system, and developer tools for profiling ultra-low-power applications at compile time. We present the design and evaluation of our prototype Amulet hardware and software, and show how the framework enables developers to write energy-efficient applications. Our prototype has battery lifetime lasting weeks or even months, depending on the application, and our interactive resource-profiling tool predicts battery lifetime within 6-10% of the measured lifetime.
Small RNAs and Regulation of Gene Expression in Entamoeba histolytica

Entamoeba histolytica harbors a variety of small RNA populations as well as homologues of proteins of the RNA interference (RNAi) pathway, suggesting the presence of a functional RNAi pathway in this unicellular eukaryote. Additionally, several attempts in adapting RNAi-based gene-silencing techniques in E. histolytica were successful, proving that a functional RNAi pathway is indeed present in this protozoan parasite. The most abundant small RNA population has a 5′-polyphosphate structure indicating a Dicer-independent biogenesis pathway. Bioinformatic and functional analyses of small RNAs highlights a role in gene silencing, which contributes to strain-specific gene expression patterns. However, whether the small RNAs have regulatory roles contributing to gene expression changes during tissue invasion or developmental changes is not known. Furthermore, the exact mechanism by which the small RNAs mediate gene expression regulation is also not known. In this chapter we give an overview on the known elements of the Entamoeba RNAi pathway, the characteristics of the small RNA populations, and summarize the insights we have gained from studying gene expression regulation by small RNAs.
Hepatic atrophy following preoperative chemotherapy predicts hepatic insufficiency after resection of colorectal liver metastases

Background & Aims For patients with colorectal liver metastases (CLM) undergoing major hepatectomy, extensive preoperative chemotherapy has been associated with increased morbidity and mortality. The impact of extensive chemotherapy on total liver volume (TLV) change is unclear. The aims of the current study were twofold: (1) to determine the change of TLV following preoperative chemotherapy in patients undergoing resection for CLM and (2) to investigate the correlations among TLV change, postoperative hepatic insufficiency (PHI), and death from liver failure. Methods Clinicopathological features of patients with CLM who underwent preoperative chemotherapy and curative resection were reviewed (2008–2015). TLV change (degree of atrophy) was defined as the percentage difference of TLV (estimated by manual volumetry)/standardized liver volume (SLV) ratio: ([Pre-chemotherapy TLV]−[Post-chemotherapy TLV])×100÷SLV (%). Receiver operating characteristic (ROC) analysis was performed to decide the accurate cut-off value of degree of atrophy to predict PHI. The Cox proportional hazard model was performed to identify the predictors of severe degree of atrophy and PHI. Results The study cohort consisted of 459 patients, of which 154 patients (34%) underwent extensive preoperative chemotherapy (≥7 cycles). ROC analysis identified the degree of atrophy ≥10% as an accurate cut-off to predict PHI, which was significantly correlated with ≥7 cycles of preoperative chemotherapy. Four factors independently predicted PHI: standardized future liver remnant ≤30% (odds ratio [OR] 4.03, p =0.019), high aspartate aminotransferase-to-platelet ratio index (OR 5.27, p =0.028), degree of atrophy ≥10% (OR 43.5, p p =0.005). Degree of atrophy ≥10% was associated with increased mortality from liver failure (0% [0/374] vs. 15% [13/85], p Conclusion Extensive preoperative chemotherapy induced significant atrophic change of TLV. Degree of atrophy ≥10% is an independent predictor of PHI and death in patients with CLM undergoing preoperative chemotherapy and resection. Lay summary Extensive preoperative chemotherapy for patients with colorectal liver metastases (CLM) could induce hepatic atrophy. A higher degree of atrophy is an independent predictor of postoperative hepatic insufficiency and death in patients with CLM undergoing preoperative chemotherapy and resection.
Co-targeting the HER and IGF/insulin receptor axis in breast cancer, with triple targeting with endocrine therapy for hormone-sensitive disease

Interactions between HER2, estrogen receptor (ER), and insulin-like growth factor I receptor (IGF1R) are implicated in resistance to monotherapies targeting these receptors. We have previously shown in pre-clinical studies synergistic anti-tumor effects for co-targeting each pairwise combination of HER2, IGF1R, and ER. Strikingly, synergy for HER2/IGF1R targeting occurred not only in a HER2+ model, but also in a HER2-normal model. The purpose of the current study was therefore to determine the generalizability of synergistic anti-tumor effects of co-targeting HER2/IGF1R, the anti-tumor activity of triple-targeting HER2/IGF1R/ER in hormone-dependent cell lines, and the effect of using the multi-targeting drugs neratinib (pan-HER) and BMS-754807 (dual IGF1R/insulin receptor). Proliferation and apoptosis assays were performed in a large panel of cell lines representing varying receptor expression levels. Mechanistic effects were studied using phospho-protein immunoblotting. Analyses of drug interaction effects were performed using linear mixed-effects regression models. Enhanced anti-proliferative effects of HER/IGF-insulin co-targeting were seen in most, though not all, cell lines, including HER2-normal lines. For ER+ lines, triple targeting with inclusion of anti-estrogen generally resulted in the greatest anti-tumor effects. Double or triple targeting generally resulted in marked increases in apoptosis in the sensitive lines. Mechanistic studies demonstrated that the synergy between drugs was correlated with maximal inhibition of Akt and ERK pathway signaling. Dual HER/IGF-insulin targeting, and triple targeting with inclusion of anti-estrogen drugs, shows striking anti-tumor activity across breast cancer types, and drugs with broader receptor specificity may be more effective than single receptor selective drugs, particularly for ER− cells.
Concordance Between Clinical Practice and Published Evidence: Findings From Virginia Commonwealth University School of Dentistry

Abstract Objectives To evaluate the concordance between clinical practice and published evidence by dental faculty and graduating students of the Virginia Commonwealth University School of Dentistry. Methods A questionnaire previously developed by the National Dental Practice-Based Research Network with 12 clinical scenarios was administered to VCU faculty and graduating students. Responses were scored as either consistent or inconsistent with published evidence and then analyzed for differences between dental faculty, graduating students, and the national results. Results There were 43 dental faculty members with at least half-time student contact who responded to the survey. Faculty concordance ranged from 33% to 100%, and general practice faculty had the highest concordance (82%). Eighty-five of the graduating class of 98 responded to the survey, and student concordance ranged from 18% to 92% and averaged 67%. General practice faculty had higher concordance with published evidence than recently graduated dental students. Conclusions Graduating students and dental faculty demonstrated higher concordance with evidence-based practice than practitioners in the National Dental Practice-Based Research Network. General practice dental faculty demonstrated adequate concordance, but students demonstrated only a medium-level concordance. Practitioners involved in teaching dental students are better able to keep up with evolving evidence and are better able to demonstrate evidence-based practice.
CONTROL ASPECTS AND BUSINESS CONSIDERATIONS

This chapter discusses the control aspects and business considerations. The control mechanism is an audit program. The audit control program is a many-faceted program. If performed properly, it would involve individuals at various levels throughout the organization ranging from the computer installation technician up to and including the corporate internal auditor. The use of a comprehensive audit checklist for each of the areas of the DP security program provides a test of the control mechanism that is in place or point out lack of control, as the case might be. The properly developed audit control checklist would be usable at any level in the organization. DP security is a business of protecting the DP environment within reasonable cost limitations. As a business, DP security would involve risk/management decisions—decisions that are predicated on what is there to protect; decisions that would weigh asset value and loss probability against additional cost to protect.