cssi/SciSciGPT-SciSciNet huggingface dataset:
An Engineered Synthetic Pathway for Discovering Nonnatural Nonribosomal Peptides in Escherichia coli.

Peptides that are synthesized independently of the ribosome in plants, fungi, and bacteria can have clinically relevant anticancer, antihemochromatosis, and antiviral activities, among many other. Despite their natural origin, discovering new natural products is challenging, and there is a need to expand the chemical diversity that is accessible. In this work, we created a novel, compressed synthetic pathway for the heterologous expression and diversification of nonribosomal peptides (NRPs) based on homologs of siderophore pathways from Escherichia coli and Vibrio cholerae To enhance the likelihood of successful molecule production, we established a selective pressure via the iron-chelating properties of siderophores. By supplementing cells containing our synthetic pathway with different precursors that are incorporated into the pathway independently of NRP enzymes, we generated over 20 predesigned, novel, and structurally diverse NRPs. This engineering approach, where phylogenetically related genes from different organisms are integrated and supplemented with novel precursors, should enable heterologous expression and molecular diversification of NRPs.IMPORTANCE Nonribosomal peptides (NRPs) constitute a source of bioactive molecules with potential therapeutic applications. However, discovering novel NRPs by rational engineering of biosynthetic pathways remains challenging. Here, we show that a synthetic compressed pathway in which we replaced biosynthetic genes with their ancestral homologs and orthologs enabled successful heterologous NRP expression. Polyamines added exogenously were incorporated into nascent NRPs, and molecular production was pressured by growing the host under conditions that make such NRPs beneficial for survival. This multilayered approach resulted in the assembly of over 20 distinct and novel molecules. We envision this strategy being used to enable the production of NRPs from heterologous pathways.
Genetic variants associated with physical performance and anthropometry in old age: a genome-wide association study in the ilSIRENTE cohort.

Unraveling the complexity of aging is crucial for understanding its mechanisms and its role as a risk factor for most chronic conditions. Advancements marked by genome-wide association studies (GWASs) have sparked interest in gene cataloguing in the context of aging and age-related conditions. Here, we used GWAS to explore whether single nucleotide polymorphisms (SNPs) were associated with functional and anthropometric parameters in a cohort of old community-dwellers enrolled in the ilSIRENTE study. Analyses were carried out in men and women aged 80+ years enrolled in the ilSIRENTE study (n = 286) and replicated in the inCHIANTI study (n = 1055). Genotyping was accomplished on Infinium Human610-QUAD version 1. In the ilSIRENTE population, genetic variants in ZNF295 and C2CD2 (rs928874 and rs1788355) on chromosome 21q22.3, were significantly associated with the 4-meter gait speed (rs928874, p = 5.61 × 10−8; rs1788355, p = 5.73 × 10−8). This association was not replicated in the inCHIANTI population. Our findings suggest that specific SNPs may be associated with a key measure of physical performance in older adults. GWASs using larger samples are needed to confirm these preliminary results to enhance our comprehension of complex age-associated phenomena.
Development of a novel fluorescent activity assay for lecithin:cholesterol acyltransferase.

Background Lecithin:cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies cholesterol. Recombinant human LCAT (rhLCAT) is now being developed as an enzyme replacement therapy for familial LCAT deficiency and as a possible treatment for acute coronary syndrome. The current 'gold standard' assay for LCAT activity involves the use of radioisotopes, thus making it difficult for routine clinical use. Methods We have developed a novel and more convenient LCAT activity assay using fluorescence-labelled cholesterol (BODIPY-cholesterol), which is incorporated into proteoliposomes as a substrate instead of radiolabelled cholesterol. Results The apparent Km and Vmax were 31.5 µmol/L and 55.8 nmol/h/nmoL, rhLCAT, respectively, for the 3H-cholesterol method and 103.1 µmol/L and 13.4 nmol/h/nmol rhLCAT, respectively, for the BODIPY-cholesterol method. Although the two assays differed in their absolute units of LCAT activity, there was a good correlation between the two test assays ( r = 0.849, P < 1.6 × 10-7, y = 0.1378x + 1.106). The BODIPY-cholesterol assay had an intra-assay CV of 13.7%, which was superior to the intra-assay CV of 20.8% for the radioisotopic assay. The proteoliposome substrate made with BODIPY-cholesterol was stable to storage for at least 10 months. The reference range ( n = 20) for the fluorescent LCAT activity assay was 4.6-24.1 U/mL/h in healthy subjects. Conclusions In summary, a novel fluorescent LCAT activity assay that utilizes BODIPY-cholesterol as a substrate is described that yields comparable results to the radioisotopic method.
A Critical Review of the Current State of IPSE Technology

Abstract : In the past ten years there has been a great deal of interest in the concept of an Integrated Project Support Environment (IPSE) as a complete, unifying framework of services supporting most (or all) phases of software development and maintenance. In this paper we evaluate the current state of research work in this area, suggest some reasons for the relative lack of success, and make proposals for ensuring measured progress in the future.
Effect of pretreatment distress on daily fatigue after chemotherapy for breast cancer

9090 Background: Fatigue is one of the most frequently reported and aversive side effects of cancer chemotherapy. Prospective research has found that cancer patients’ levels of emotional distress p...
Is Routine Continuous EEG for Traumatic Brain Injury Beneficial

Severe traumatic brain injury (TBI) is associated with increased risk for early clinical and subclinical seizures. The use of continuous electroencephalography (cEEG) monitoring after TBI allows for identification and treatment of seizures that may otherwise occur undetected. Benefits of "routine" cEEG after TBI remain controversial. We examined the rate of subclinical seizures identified by cEEG in TBI patients admitted to a Level I trauma center. We analyzed a cohort of trauma patients with moderate to severe TBI (head Abbreviated Injury Score ≥3) who received cEEG within seven days of admission between October 2011 and May 2015. Demographics, clinical data, injury severity, and costs were recorded. Clinical characteristics were compared between those with and without seizures as identified by cEEG. A total of 106 TBI patients with moderate to severe TBI received a cEEG during the study period. Most were male (74%) with a mean age of 55 years. Subclinical seizures were identified by cEEG in only 3.8 per cent of patients. Ninety-three per cent were on antiseizure prophylaxis at the time of cEEG. Patients who had subclinical seizures were significantly older than their counterparts (80 vs 54 years, P = 0.03) with a higher mean head Abbreviated Injury Score (5.0 vs 4.0, P = 0.01). Mortality and intensive care unit stay were similar in both groups. Of all TBI patients who were monitored with cEEG, seizures were identified in only 3.8 per cent. Seizures were more likely to occur in older patients with severe head injury. Given the high cost of routine cEEG and the low incidence of subclinical seizures, we recommend cEEG monitoring only when clinically indicated.
Acculturation in Context: The Relationship Between Acculturation and Socioenvironmental Factors With Level of and Change in Cognition in Older Latinos

Objectives Latinos are 1.5 times as likely to develop Alzheimer's dementia as non-Latino Whites. This health disparity may arise from multiple influences with culturally relevant factors receiving increasing attention. Models of acculturation stress the importance of considering acculturation-related factors within the context of socioenvironmental factors to better capture the Latino experience in the United States. Methods We measured 10 acculturation and contextually-related variables in 199 Latinos (age 69.7 years) without dementia participating in Rush Alzheimer's Disease Center studies. We tested the relationship between these variables via Principal Component Analysis (PCA), then investigated how resulting components associated with level of and longitudinal change in global and domain-specific cognition using separate linear mixed-effects models adjusted for relevant confounders and their interactions with time. Results The PCA revealed a 3-factor unrotated solution (variance explained ~70%). Factor 1, representing acculturation-related aspects of nativity, language- and social-based acculturation, was positively associated with level, but not change, in global cognition, semantic memory, and perceptual speed. Factor 2, representing contextually-related socioenvironmental experiences of discrimination, social isolation, and social networks, was negatively associated with level of global cognition, episodic and working memory, and faster longitudinal decline in visuospatial ability. Factor 3 (familism only) did not associate with level or change in any cognitive outcome. Discussion Acculturation- and contextually-related factors differentiated from each other and differentially contributed to cognition and cognitive decline in older Latinos. Providers should query acculturation and lived experiences when evaluating cognition in older Latinos.
False Data Injection Attack Against Power System Small-Signal Stability.

Small-Signal Stability (SSS) is crucial for the control of power grids. However, False Data Injection (FDI) attacks against SSS can impact the grid stability, hence, the security of SSS needs to be studied. This paper proposes a formal method of synthesizing FDI attack vectors (i.e., a set of measurements to be altered) that can destabilize power systems. We formulate an FDI attack as an optimization problem using AC power flow, SSS model, and stability constraints. The attacker capability is modeled as the accessibility to a limited set of measurements. The solution of the proposed FDI attack model provides a destabilizing attack vector if exists. We implement the proposed mechanism and evaluate its performance by conducting several case studies using the WSCC 3-machine 9-bus system. The case study results showed that the possibility of random FDIs (i.e., with no knowledge of the power system) in launching a destabilizing attack is too low to be successful. However, an intelligent attacker can leverage the grid knowledge to make the system unstable, even with limited access to the measurements.
Firearm licenses associated with elevated pediatric blood lead levels in Massachusetts.

Abstract Objective To determine the association between firearm-related lead exposure and pediatric blood lead levels. Methods Using data available through the Massachusetts Departments of Public Health and Criminal Justice Information Services, we examined the association between active class A firearm licenses in a community with the prevalence of elevated blood lead levels in children aged 0–4. Correlational and hierarchical multiple regression analyses were conducted with potential confounders and other exposures such as lead paint, lead in water, presence of firing ranges, and social, economic, and occupational variables. Results Data from 351 Massachusetts sub-counties were examined. Sub-counties with higher rates of firearm licensure also report higher rates of lead exposure among children. Children in the highest quartile communities were 2.16 times more likely to have elevated BLLs when compared to their peers in the lower quartiles. A one standard deviation change in firearm licensure percentage was found to reflect a 0.96% increase in elevated pediatric blood lead levels. Regression analyses demonstrated that the inclusion of firearm licensure significantly improved the prediction of pediatric BLL. Models were adjusted for percent of a population employed in construction, agriculture, forestry, fishing, hunting, and mining, income distribution, and potential lead paint exposure, which were found to be the primary predictors of elevated pediatric blood lead levels. Discussion Firearm use and ownership remains one of the least researched areas in the public health sphere. While the risks of childhood lead exposure are widely understood, including the mechanisms of firearm-related lead exposure and tracking, to date no research has extensively examined it in children and on the community level. Our findings indicate a dire need for continued research on the risks associated with firearm use, ownership, and lead exposure.
Non-destructive quality monitoring of 3D printed tissue scaffolds via dielectric impedance spectroscopy and supervised machine learning

Abstract Majority of methods currently used for quality assessment of tissue engineered medical products (TEMPs) are offline and destructive in nature, which is one of the factors impeding the scale up and translation of these technologies. In this study, we investigate quality assessment of TEMP via dielectric impedance spectroscopy (DIS) and supervised machine learning (ML) as a non-destructive alternative that requires minimal human intervention. 3D printed, NaOH-treated polycaprolactone (PCL) scaffolds seeded with human adipose-derived stem cells (hASC), NIH 3T3, MG63, and human chondrocyte cells were assessed via DIS over 4 days of in vitro culture. The results showed that the cell type and duration in culture had a significant effect on the delta permittivity (Δe, an important DIS metric. Five supervised ML algorithms – K Nearest Neighbors (KNN), Logistic Regression, Random Forest Classifiers, Support Vector Machines, and artificial neural network – were then used to analyze the comprehensive structured permittivity datasets to determine their ability to discern between different cell types and culture durations. The KNN algorithm demonstrated the best accuracy (99%). The outcomes of this study demonstrate the approach of using DIS and supervised ML in conjunction for assessment of TEMPs in an automated manufacturing system.
TGFβR Inhibition Represses TGF-β1 Initiated Keratin-7 Expression in Human Salivary Gland Progenitor Cells

Towards the goal of engineering an implantable salivary gland for the treatment of xerostomia, we culture primary human salivary gland stem/progenitor cells (hS/PCs) in hyaluronic acid (HA)-based hydrogels containing a covalently conjugate integrin-binding peptide (RGDSP). We characterize how RGDSP affects hS/PC phenotype and discover the presence of cells expressing both amylase and keratin-7 (K7) in our 3D cultures. Typically, amylase is expressed by acinar cells, and K7 is found in ducts. After assaying an array of transforming growth factor-{beta} (TGF-{beta}) superfamily members, we find increased expression of TGF-{beta}1 and growth/differentiation factor-15 (GDF-15) in RGDSP cultures. However, 2D model studies confirm that only TGF-{beta}1 is required to induce K7 expression in hS/PCs. We then demonstrate that with pharmacological inhibition of TGF-{beta} signaling, K7 expression is repressed while amylase expression is maintained in RGDSP cultures. Thus, TGF-{beta} signaling regulates K7 expression in hS/PCs, and modulation of TGF-{beta} signaling is essential for the regeneration of salivary gland function.
The impact of Diaphorina citri vectored Candidatus Liberibacter asiaticus on citrus metabolism.

'Candidatus' Liberibacter asiaticus is associated with the devastating citrus disease Huanglongbing. It is transmitted by grafting infected material to healthy plants and by the feeding of the Asian citrus psyllid (Diaphorina citri). Previously, we demonstrated that a metabolomics approach using proton-Nuclear Magnetic Resonance spectroscopy discriminates healthy from diseased plants via grafting. The present work assessed the capability of this technology in discriminating healthy and diseased plants when the bacterium is vectored by psyllids. One-year old greenhouse-grown 'Lisbon' lemon trees were exposed to either carrier psyllids (Exposed, n = 10), or psyllids that were free of Liberibacter asiaticus (Control, n = 6). Leaf metabolites were tracked for 1 year and disease diagnosis was made using quantitative polymerase chain reaction. Overall, 31 water-soluble metabolites were quantified in leaves, including 4 sugars and 12 amino acids. Analysis via non-metric multidimensional scaling and principal components analysis revealed significant differences between the leaf metabolome of Control vs. infected trees beginning at 8 weeks post-exposure, including alterations in glucose and quinic acid concentrations. These findings provide a longitudinal overview of the metabolic effects of HLB during the early phases of disease, and confirm previous experimental work demonstrating that infection elicits changes in the leaf metabolome that enables discrimination between healthy and infected plants. Here we demonstrate that the mode of inoculation (i.e. graft- vs. psyllid-) results in a similar pathology.
Fibroblast growth factor receptor signaling in kidney and lower urinary tract development

Fibroblast growth factor receptors (FGFRs) and FGF ligands are highly expressed in the developing kidney and lower urinary tract. Several classic studies showed many effects of exogenous FGF ligands on embryonic renal tissues in vitro and in vivo. Another older landmark publication showed that mice with a dominant negative Fgfr fragment had severe renal dysplasia. Together, these studies revealed the importance of FGFR signaling in kidney and lower urinary tract development. With the advent of modern gene targeting techniques, including conditional knockout approaches, several publications have revealed critical roles for FGFR signaling in many lineages of the kidney and lower urinary tract at different stages of development. FGFR signaling has been shown to be critical for early metanephric mesenchymal patterning, Wolffian duct patterning including induction of the ureteric bud, ureteric bud branching morphogenesis, nephron progenitor survival and nephrogenesis, and bladder mesenchyme patterning. FGFRs pattern these tissues by interacting with many other growth factor signaling pathways. Moreover, the many genetic Fgfr and Fgf animal models have structural defects mimicking numerous congenital anomalies of the kidney and urinary tract seen in humans. Finally, many studies have shown how FGFR signaling is critical for kidney and lower urinary tract patterning in humans.
Memory design and exploration for low power, embedded systems

In this paper, we describe a procedure for memory design and exploration for low power embedded systems. Our procedure tries to reduce the power consumption due to memory traffic by (i) applying memory optimizing transformations such as loop transformations, (ii) storing frequently accessed variables in a register file and an on-chip cache, and (iii) reducing the conflict misses by appropriate choice of cache size and data placement in off chip memory. We then choose a cache configuration (cache size, line size) that satisfies the system requirements of area, number of cycles and energy. We include energy in the performance metrics, since for different cache configurations, the variation in energy is quite different from the variation in the number of cycles. Our memory exploration procedure considers only a selected set of candidate points, thereby reducing the search time significantly.
Adaptively-tunable RF photonic filters

The emergence of silicon photonics has enabled potential implementations of RF photonic filters with the size, weight, and power requirements of radio systems with small form factors. This paper presents a fourth-order elliptic digital filter designed in the optical domain with all-pass filter (APF) unit cells. A monitor-based adaptive tuning algorithm is proposed to calibrate the optical filter response with high accuracy and provide rapid filter reconfiguration.
Kinetic Mechanism of the Histone Acetyltransferase GCN5 from Yeast

The transcriptional coactivator GCN5 from yeast (yGCN5) is a histone acetyltransferase that is essential for activation of target genes. GCN5 is a member of a large family of histone acetyltransferases that are conserved between yeast and humans. To understand the molecular mechanisms of histone/protein acetylation, a detailed kinetic analysis was performed. Bi-substrate kinetic analysis using acetyl-coenzyme A (AcCoA) and an H3 histone synthetic peptide indicated that both substrates must bind to form a ternary complex before catalysis. Product inhibition studies revealed that the product CoA was a competitive inhibitor versus AcCoA. Desulfo-CoA, a dead-end inhibitor, also demonstrated simple competitive inhibition versus AcCoA. Acetylated (Lys14Ac) H3 peptide displayed noncompetitive inhibition against both H3 peptide and AcCoA. These results support a sequential ternary complex (ordered Bi-Bi) kinetic mechanism, where AcCoA binds first, followed by H3 histone. Acetylated (Lys14Ac) H3 product is released first, and CoA is the last product to leave. Also, two methods were developed to measure the binding affinities of AcCoA/CoA for GCN5. Employing the fluorescent CoA analog etheno-CoA (epsilonCoA, 1-N(6)-etheno-CoA), a K(d) for epsilonCoA of 5.1 +/- 1.1 microm was determined by fluorescence anisotropy. This value was similar to the K(d) value of 8.5 +/- 2.6 microm for AcCoA obtained using equilibrium dialysis and to the K(i) (inhibition constant) of 6.7 microm for CoA obtained from steady-state kinetic assays. Together, these data suggest that the acetyl moiety of AcCoA contributes little to the binding energy.
Radiation damage studies of multi-guard ring p-type bulk diodes☆

Abstract Several diodes with different multi-guard ring structures were fabricated from 10 kΩ cm p-type bulk material. Studies on the performance of such devices are presented here. They include the measurement of the leakage current, breakdown voltage and charge collection efficiency before and after 2×10 14 p/cm 2 irradiation with 63.3 MeV kinetic protons.
Using a simple game to introduce accounting students to certain internal control concepts

Abstract Lack of experience with real accounting systems can hinder the understanding of internal control concepts in accounting information systems (AIS) courses. Experiential learning, in which game playing or simulations are used, is one way of overcoming this deficiency. This paper presents a simple inexpensive and effective game which can be used to introduce AIS students to the concepts of documentation and segregation of duties. Using the game can stimulate class participation and achieve greater understanding of these fundamental internal control concepts.
Large conductance calcium-activated potassium channels affect both spontaneous firing and intracellular calcium concentration in cerebellar Purkinje neurons

We investigated the contribution of large conductance calcium-activated potassium (BK) channels to spontaneous activity of cerebellar Purkinje neurons in mice and rats. In Purkinje neurons which fire tonically, block of BK channels increased the firing rate and caused the neurons to fire irregularly. In Purkinje neurons which exhibited a trimodal pattern of activity, present primarily in mature animals, block of BK channels had little effect on firing rate or regularity but shortened the single cycle duration of the trimodal pattern. The contribution of BK channels to the action potential waveform was also examined. BK channels contributed a brief afterhyperpolarization (AHP) of approximately 3 mV which followed each action potential, but made little contribution to action potential repolarization. The amplitude of the BK-dependent AHP did not change with age although there was an increase in the total AHP. The difference in the contribution of BK channels to the firing rate among the two populations of Purkinje neurons was the consequence of the decrease in the fractional contribution of BK channels to the AHP. We also found that block of BK channels increases intracellular calcium concentration during spontaneous firing. Thus, although BK channels do not affect action potential repolarization, they nevertheless control calcium entry with each action potential by contributing to the AHP.
Glomus Jugulare Tumors

The first report of a glomus jugulare tumor is attributed to Rosenwasser (1945) with his publication, “Carotid Body Tumor of the Middle Ear and Mastoid.” The true nature of the neoplasm was recognized by the pathologist Otani, but Rosenwasser suggested its origin from the glomus jugularis (sic), recently rediscovered by Guild (1941). Lubbers (1937) was actually the first to describe the presence of a carotid-body-like tumor in the middle ear, but he erroneously attributed it to metastasis from a contralateral carotid body tumor. Bartels (1949) reviewed the slides of this case and confirmed the identical appearance of the 2 tumors. Kohlmeier (1948), independently and unaware of Guild’s publication, correctly recognized the true nature of these middle ear neoplasms. Zak (1954) introduced the term Otani’s tumor. He recognized in 1945 that “endothelial” and other tumors of the petrous bone were in reality of glomic origin.
Glycogen Biogenesis in Rat 1 Fibroblasts Expressing Rabbit Muscle Glycogenin

Glycogenin, a self-glucosylating protein involved in the initiation of glycogen biosynthesis, varies in intracellular concentration from barely detectable in liver to a high level in muscle. The effect of increasing the glycogenin level on glycogen synthesis was studied in rat 1 fibroblasts stably overexpressing rabbit muscle glycogenin. In the presence of glucose, all of the expressed glycogenin was attached to polysaccharide and the free protein could only be detected by western blot analysis after incubation of cells in a glucose-depleted medium or treatment of the cell extract with alpha-amylase. In control cells, increased extracellular glucose concentrations promoted translocation of glycogen synthase from the soluble to the pellet fraction with an increase in the associated glycogen. Overexpression of glycogenin did not affect total intracellular glycogen and glycogen synthase levels at any concentration of glucose but significantly reduced glucose-induced accumulation of insoluble glycogen and translocation of glycogen synthase. Immunofluorescence analysis revealed a diffuse cytoplasmic distribution of glycogenin expressed in rat 1 cells. In rat 1 cells incubated with glucose, discrete deposits of glycogen were detected by staining with HIO4/Schiff but this was eliminated by overexpressing glycogenin. Analysis of [14C]glucose- or [35S]methionine-labeled extracts from glycogenin-expressing cells by continuous polyacrylamide gel electrophoresis and by two-dimensional gel electrophoresis revealed a continuum of glycogenin-containing species from low molecular mass to sizes significantly greater than 400 kDa. We conclude that (a) overexpression of glycogenin does not enhance glycogen synthesis but causes production of more, smaller, glycogen molecules with a concomitant change in their intracellular localization; (b) glycogenin and elevated glucose have opposing effects on the distribution of glycogenin and glycogen synthase in rat 1 cells; and (c) the biogenesis of glycogen in rat 1 cells occurs without the accumulation of any major intermediate form.
Assessing the value of information in organizations: A challenge for the 1980s

Abstract In an effort to confront the key issue of where the information society is leading us, this essay begins where most discussions leave off: if advanced industrial societies are dedicating increasingly greater resources to the use of information services and technologies, what is the value of information in organizational and governmental processes? To assess the value of information: information technology, information/library science, information resource management, value/burden, organizational theory, and the economic theory of information. Based on this overview, we propose a conceptual framework which is sensitive to the major objectives and assumptions of previous approaches, but which also attempts to expand the criteria for the assessment of information value.
Electrocardiographic Left Ventricular Hypertrophy as a Predictor for Nonsignificant Coronary Artery Disease in Patients With Non-ST-Segment Elevation Myocardial Infarction:

Left ventricular hypertrophy (LVH) can lead to subendocardial ischemia by altering the coronary blood flow and its transmural myocardial distribution in the setting of increased oxygen demand. We hypothesized that electrocardiographic LVH predicts nonsignificant coronary artery disease (CAD) in patients with non-ST-segment elevation myocardial infarction (NSTEMI). We performed a retrospective analysis of 406 consecutive patients with NSTEMI who underwent coronary angiography. The LVH was diagnosed using Sokolow-Lyon and Cornell voltage criteria. Nonsignificant CAD was defined as stenosis less than 50% in the left main and 70% in any other coronary arteries. Of the 406 patients, 100 (25%) patients had electrocardiographic LVH and 99 (24%) patients had nonsignificant CAD. Patients with electrocardiographic LVH had a higher prevalence of nonsignificant CAD (32% vs 22%, P = .04) and a lower rate of in-hospital revascularization (45% vs 69%, P < .001) than those without LVH. On multivariate analysis, electrocardiographic LVH was an independent predictor of nonsignificant CAD (odds ratio 1.94; 95% confidence interval 1.12-3.35; P = .02). In conclusion, electrocardiographic LVH is an independent predictor of nonsignificant CAD and associated with a lower rate of in-hospital revascularization in patients with NSTEMI.
Performance of Two Strains of Rainbow Trout Reared at Four Densities with Supplemental Oxygen

Abstract Wild and domesticated strains of rainbow trout (Oncorhynchus mykiss) were reared in triplicate groups at four fish densities in two separate studies. Fish weight gain, survival, length increase, length variability, feed conversion (weight fed/weight gain), dorsal fin condition, fish health, and water quality were monitored during each 4-month test. Dissolved oxygen was supplemented to maintain afternoon effluent oxygen levels at 6–7 ppm (61–71% saturation). Survival decreased with increasing density for both strains: wild strain survival was reduced because of cannibalism, and domesticated strain survival was reduced because of mechanical failures that reduced dissolved oxygen. Weight gain and total length increased with increasing densities for the wild strain, but the opposite occurred for the domesticated strain. Length coefficient of variation (SD/mean) increased directly with increasing fish density. Feed conversions of both strains were adversely affected by increased densities, but dorsal ...
The House Un-American Activities Committee and Its Opponents: A Study in Congressional Dissonance

THE POWER AND autonomy of its committees have long been accepted as central factors in the functioning of Congress. Yet little research has been directed at exploring the relationships between committees and their parent chambers. This is particularly true of the most important situation-that in which a significant group in the parent chamber is dissatisfied with the actions of a committee and seeks to force a change in its behavior. The questions of the kinds of sanctions available, who applies them, and with what consequences have deep implications for an understanding of committee behavior. The House Committee on Un-American Activities has been at the center of a storm of controversy since its inception thirty years ago. Throughout its history the Committee has faced sharp criticism in the House, thus presenting us with a clear example of dissonance between the expectations of a group of House members and the behavior of a committee. The study of this conflict can lead to much useful information about the legislative process and is the object of this work. The alternatives open to members of the House in attempting to force the Un-American Activities Committee to conform to their expectations are varied, and many have been tried through the years. When Representatives F. Edward Hebert (D-La.) and John Rankin (D-Miss.) left the Committee in 1949 it was widely believed that they were denied reappointment or induced to resign by Speaker Rayburn because of their behavior on the Committee.' It has also been rumored that Representative Francis Wal-
The dynamics of make or buy decisions

Abstract Make or buy decisions are strategically important for business firms, particularly when production and marketing of components involves specialized technology and assets. Recent theories of make or buy decisions compare the cost of administering transactions inside a firm and across markets. In this paper, we extend these theories to a dynamic market in which profit from the use of specialized assets declines over time due to entry and substitution of technology. Using optimal control theory, we investigate the patterns of vertical integration under different parametric conditions. We also prevent empirical evidence from time series and cross-sectional data that lend support to the analytical results from the model.
Toll-like receptor 7–induced naive human B-cell differentiation and immunoglobulin production

Background Toll-like receptors contribute to the establishment of adaptive immune responses. Objective The reported studies were conducted to examine the effects of the Toll-like receptor (TLR)–7 ligand, resiquimod, on human naive B-cell differentiation. Methods Naive human B cells were cultured with resiquimod in the presence or absence of IL-2 and IL-10. Secreted IgM and IgG were measured by ELISA, and IL-6, IL-10, and IFN-α were measured by a multiplex protein array. Cell proliferation was assessed by measuring [ 3 H]thymidine uptake. mRNA for activation-induced cytidine deaminase and I γ1 -C μ circle transcripts was measured by means of RT-PCR. Results Resiquimod induced the production of IgM and, to a lesser extent, IgG by naive human B cells in association with the secretion of IL-6 and IL-10, and a weak proliferative response. IL-2 and IL-10 synergized with resiquimod in markedly augmenting resiquimod-induced IgM and IgG production and proliferation. Resiquimod also stimulated production of IgG by B cells isolated from the blood of a patient with the X-linked hyper-IgM syndrome, with a greater response when these cells were costimulated with IL-2 and IL-10. The stimulated naive B cells from healthy volunteers displayed molecular evidence of immunoglobulin class-switch recombination—namely the appearance of activation-induced cytidine deaminase and I γ1 -C μ circle transcripts. Conclusion Perturbation of TLR-7 on naive human B cells can lead to the induction of immunoglobulin class switch and IgG production in the absence of B-cell receptor cross-linking and CD40-CD40L interaction. The results are relevant to vaccine development and mechanisms by which microbial infection may lead to autoimmunity.
Variation in retinal degeneration phenotype inherited at the prcd locus

Progressive rod-cone degeneration (prcd) is a recessively inherited visual cell disease. Neither the genetic abnormality nor the corresponding biochemical defect have yet been identified. Unique abnormalities of visual cell structure, function and renewal, however, characterize the disease phenotype and act as a marker for the prcd gene. The disease was first described in miniature poodle dogs (MP) but broadly similar retinal degenerations have been recognized, clinically, in other breeds. Crossbreeding experiments with prcd-affected MP and retinal degenerate English (ECS) and American (ACS) cocker spaniels now demonstrate that all the progeny are affected with a retinal degeneration indistinguishable from prcd in the MP. This indicates that the gene mutation in each breed is at the same (prcd) locus. In purebred prcd-affected ECS (prcd-ECS), however, the disease phenotype consistently differs from that in prcd-MP in its rate of progression and in the topographical distribution of disease within the retina. Ultrastructural variation in disease expression are also recognizable between the two phenotypes. These differences in disease phenotype may be ascribable to different genetic backgrounds in the two breeds, reflecting the effect of modifying genes, or may indicate separate, allelic, mutations at the same locus.
Spatial direct numerical simulation of boundary-layer transition mechanisms: Validation of PSE theory

A study of instabilities in incompressible boundary-layer flow on a flat plate is conducted by spatial direct numerical simulation (DNS) of the Navier-Stokes equations. Here, the DNS results are used to evaluate critically the results obtained using parabolized stability equations (PSE) theory and to study mechanisms associated with breakdown from laminar to turbulent flow. Three test cases are considered: two-dimensional Tollmien-Schlichting wave propagation, subharmonic instability breakdown, and oblique-wave breakdown. The instability modes predicted by PSE theory are in good quantitative agreement with the DNS results, except a small discrepancy is evident in the mean-flow distortion component of the two-dimensional test problem. This discrepancy is attributed to far-field boundary-condition differences. Both DNS and PSE theory results show several modal discrepancies when compared with the experiments of subharmonic breakdown. Computations that allow for a small adverse pressure gradient in the basic flow and a variation of the disturbance frequency result in better agreement with the experiments.
Symptom-based controller therapy: A new paradigm for asthma management

Appropriate management of persistent asthma, according to US and international guidelines, requires daily use of controller medications, most generally, inhaled corticosteroids (ICS). This approach, although effective and well established, imposes burdens of treatment and side effects onto asthma patients. A growing body of evidence suggests that patients with persistent asthma need not be managed with daily ICS, but rather can use them on an intermittent basis, occasioned by the occurrence of symptoms sufficient to warrant treatment with a rescue inhaler. Large, randomized, controlled studies, over a range of asthma severity, and in a range of ages from pediatrics to adults, suggest that, in well-selected patients, a symptom-based approach to administering controller therapy may produce equivalent outcomes, while reducing exposure to ICS. The concept of providing anti-inflammatory treatment to the patient, at the time inflammation is developing, is termed ‘temporal personalization’. The evidence to date suggests that symptom-based controller therapy is broadly useful in selected asthma patients, and is a management approach that could be incorporated into US and international guidelines for asthma.
The Conformational Plasticity of Protein Kinases

Protein kinases operate in a large number of distinct signaling pathways, where the tight regulation of their catalytic activity is crucial to the development and maintenance of eukaryotic organisms. The catalytic domains of different kinases adopt strikingly similar structures when they are active. By contrast, crystal structures of inactive kinases have revealed a remarkable plasticity in the kinase domain that allows the adoption of distinct conformations in response to interactions with specific regulatory domains or proteins.
Pulse field-sweep EPR of copper proteins

Abstract P ulse f ield-sweep EPR (PFSEPR) is developed as a low-power, microwave pulse technique to resolve hyperfine structure underlying inhomogeneously broadened EPR lines. PFSEPR arises from transfer of saturation due to spin state mixing from forbidden Δm I ≠ 0 EPR transitions. We report its first use to resolve large copper hyperfine couplings which are unresolved by standard X-band EPR. As applied to copper, PFSEPR has better sensitivity than ENDOR with comparable spectral resolution. The details of energy levels and state mixing which account for PFSEPR transitions in these copper systems are developed here. PFSEPR transitions from stellacyanin provide hyperfine and quadrupole couplings in good agreement with those predicted by various EPR simulations and determined by ENDOR. Copper couplings from the Cu A signal of cytochrome- c oxidase are comparable to previously published estimates, but PFSEPR suggests underlying state mixing of copper levels.
Elliptic integral solutions to a class of space flight optimization problems

This paper is initially concerned with the minimum-time, exoatmospheric flight of a rocket with constant thrust acceleration magnitude, as in the cases of nuclear and solar electric propulsion. Gravitational acceleration is assumed to be a constant scalar multiple of the radius vector, plus a correction term which is a given function of time. The solution to the state equations is obtained in terms of elliptic integrals. A method is presented for the solution of the two-point boundary-condition problem associated with orbital transfer. At most, the latter method requires iteration upon final time, angle of injection, and two other parameters which are bounded. An example problem is provided which involves a rocket with very low thrust and a spiraling trajectory of many revolutions, but an altitude change of only several hundred miles above the earth. Finally, the original elliptic integral solution is extended to a larger class of low and intermediate thrust problems with constant thrust magnitude, mass decreasing with time, and an inverse square gravitational force.
Three Dimensional Modeling of Unfired Ceramics During Lamination

A finished ceramic component with complex geometries such as micro-channels requires a high degree of dimensional accuracy. This accuracy depends upon precise control of the unfired ceramic body before sintering. One method for creating precise micro-channel geometries is the fugitive phase approach. In this approach, a sacrificial material, the fugitive phase, is used to form channels or voids in the unfired ceramic body. The fugitive phase is removed or sacrificed during the subsequent sintering. For this paper, the authors examine the lamination step of the fugitive phase approach computationally. The lamination step is where the unfired ceramic and fugitive phase pieces are layered and pressed together to remove voids before sintering. The compression of the unfired ceramic during pressing causes pressure gradients, viscoelastic deformation, displacement of the fugitive phase pieces, and rebounding. Three dimensional modeling is used to capture out of plane movement or bending of the long fugitive phase pieces that are used to form long micro-channels. For this research, the unfired ceramic phase consists of tape cast mullite and the fugitive phase is paper. This work primarily examines viscoelastic material models of the unfired ceramic phase for a range of temperatures. The filling of voids, movement of the fugitive phases, pressure gradients, and the rebounding that occurs when the unfired ceramic body is removed from the die press are also noted. The information obtained from computational simulations is used to help direct concurrent experimental investigations.© 2014 ASME
Preparation of polysomes and radioactively labeled RNA from adult Drosophila melanogaster

Abstract In order to study gene regulation during insect oogenesis, methods were developed for the preparation and analysis of undegraded polysomes from abdomens of adult females of Drosophila melanogaster . Polysomes are contaminated (25%) with material which appears to band isopycnically in sucrose gradients at a density of 1.14 g/cc after treatment with sodium deoxycholate and EDTA. A method for obtaining radioactive polysomal RNA by feeding adult flies on ( 32 P)-containing food is also described. Over 96% of the 26S rRNA fractionated by chromatography on poly(uridylic acid)-Sepharose is heat-labile; less than 6% of the poly(adenylic acid)-containing RNA is heat labile, suggesting minimal contamination with 26S rRNA. These methods should provide a basis for studying the role of mRNA metabolism in the regulation of gene expression during oogenesis.
Temperature-dependent resetting of the molecular circadian oscillator in Drosophila

Circadian clocks responsible for daily time keeping in a wide range of organisms synchronize to daily temperature cycles via pathways that remain poorly understood. To address this problem from the perspective of the molecular oscillator, we monitored temperature-dependent resetting of four of its core components in the fruitfly Drosophila melanogaster: the transcripts and proteins for the clock genes period (per) and timeless (tim). The molecular circadian cycle in adult heads exhibited parallel responses to temperature-mediated resetting at the levels of per transcript, tim transcript and TIM protein. Early phase adjustment specific to per transcript rhythms was explained by clock-independent temperature-driven transcription of per. The cold-induced expression of Drosophila per contrasts with the previously reported heat-induced regulation of mammalian Period 2. An altered and more readily re-entrainable temperature-synchronized circadian oscillator that featured temperature-driven per transcript rhythms and phase-shifted TIM and PER protein rhythms was found for flies of the 'Tim 4' genotype, which lacked daily tim transcript oscillations but maintained post-transcriptional temperature entrainment of tim expression. The accelerated molecular and behavioural temperature entrainment observed for Tim 4 flies indicates that clock-controlled tim expression constrains the rate of temperature cycle-mediated circadian resetting.
Effect of random potential fluctuations on electron transport in n -type InSb

A number of previous investigators have concluded that the low-temperature transport properties of n-type InSb can only be understood by assuming the existence of an impurity band which is separated from the conduction band by a finite binding energy. However, we show that the experimental results are fully consistent with a one-band interpretation as long as the effects of potential fluctuations due to random inhomogeneities in the impurity concentration are considered. Single-site electron mobilities are compared with a large body of experimental data from the literature covering the temperature range 1.3 to 80 K. Experiment and theory are found to agree well as long as the magnitude of the fluctuations \ensuremath{\gamma} is small compared to the thermal energy of the electrons ${E}_{0}$. However, when \ensuremath{\gamma}\ensuremath{\gg}${E}_{0}$ in compensated samples at low temperatures, the experimental mobilities fall far below the results of the single-site theory (which ignores the fluctuations). This behavior is consistent with that observed for one-band conduction in other semiconductors. Also considered are effects of the potential fluctuations in the alternative case where an impurity band is assumed to be present.