cssi/SciSciGPT-SciSciNet huggingface dataset:
Eukaryotic-like signaling and gene regulation in a prokaryote that undergoes multicellular development

How cell–cell signaling coordinates cell movement, gene expression, and differentiation during the development of multicellular organisms is a fundamental question. At the molecular level, the answer is complex, even in the simplest cases. Myxococcus xanthus is one of the simplest organisms that undergo development to produce a multicellular structure of uniform size and shape. Cells of this bacterium sense nutrient limitation and alter their gliding movements to produce mounds (Fig. 1). Within these nascent fruiting bodies, cells differentiate into spores. Driving this developmental process is a program of gene expression that is temporally and spatially regulated by intracellular and extracellular signals. Are the typical prokaryotic signaling and gene regulatory mechanisms sufficient for multicellular development of M. xanthus ? Previous work has indicated that eukaryotic-like mechanisms play a role. The work of Jelsbak et al . (1) in this issue of PNAS extends this observation by describing a group of 12 M. xanthus genes that seem to encode enhancer-binding proteins (EBPs) with a forkhead-associated (FHA) domain. The authors show that the FHA domain of one of the EBPs is required for normal development. Because FHA domains interact with phosphothreonine residues, the results suggest a crucial link to eukaryotic-like Ser/Thr protein kinases (STPKs), which are abundant in M. xanthus . Fig. 1. Cartoon depicting starved M . xanthus cells forming a mound, then a fruiting body, which would contain ≈105 spores. Bacterial EBPs derive their name from the fact that they activate transcription by σ54-RNA polymerase (σ54-RNAP) in much the same way some EBPs activate transcription in eukaryotes. σ54-RNAP requires interaction with an EBP to form the transcriptionally competent open promoter complex. Bacterial EBPs bind to DNA enhancer elements typically located 70–150 bp upstream of the transcription start site (reviewed in ref. 2). Bending of DNA allows …
Giant Cell Astrocytoma of the Retina: A Tumor of Possible Mueller Cell Origin

A 5-month-old boy presented with a right retrolental mass and glaucoma. Both B-scan ultrasonography and CAT scanning failed to disclose any evidence of intralesional calcification, the absence of which is unusual for retinoblastoma. An aqueous lactic dehydrogenase (LDH) determination disclosed elevated levels of this enzyme, which were six times that detected in the blood. Pathologic examination of the enucleated globe revealed rubeotic glaucoma, and a massively necrotic retinal tumor that had filled the vitreous cavity. A small focus of viable tumor in the posterior pole of the lesion displayed a population of rounded astrocytic giant cells, with abundant eosinophilic cytoplasm and eccentrically placed vesicular nuclei possessing prominent nucleoli. The cytoplasm of these tumors cells contained a moderate number of PTAH-positive fibrils, and these were identified positively as glial in nature by immunoperoxidase reaction for the presence of glial fibrillary acidic protein (GFAP). Mueller cells in a portion of surviving retina also stained positively for GFAP. Electron microscopic studies performed on a rim of surviving tumor cells abutting the subretinal space demonstrated features consistent with a Mueller cell origin, namely, abundant profiles of smooth and rough-surfaced endoplasmic reticulum and elaborate villous processes, the latter being typically produced by Mueller cells as they project beyond the external limiting membrane of the retina.
Geology of Mexico: Celebrating the Centenary of the Geological Society of Mexico.S. A. Alaniz-Alvarez and A. F. Nieto-Samaniego, Editors. Geological Society of America, Special Paper 422, 465 Pp. Boulder, Colorado. 2007. ISBN 13-978-0-8137-2422-5. Price: members $73; non-members $105.

The Geological Society of America (GSA) has previously published several special papers on diverse topics concerning the geology of Mexico. These have all been important contributions and are a valuable resource to those interested in the geology of Mexico. This new volume comprises a selection of 16 papers that were previously published in Spanish in three special volumes of the Boletin de la Sociedad Geologica Mexicana to commemorate the first centenary of the Geological Society of Mexico. This English version of the centenary volumes is divided in three main sections: Review of Selected Geological Provinces of Mexico (chapters 1–6), Major Faults (chapters 7–12), and Ore Deposits (chapters 13–16). In chapter 1, Ferrari et al. provide a summary of the current knowledge of the Sierra Madre Occidental, describing the stratigraphy and structures that have affected this large silicic province. A summary of previous geophysical, geochemical, and petrological studies, and a discussion on the proposed models for the origin of this province are also presented. The stratigraphy and structures of the Mesa Central are the focus of a paper by Nieto-Samaniego et al. Mineral deposits in this area, such as epithermal veins, skarns, IOCG, and VMS, are briefly covered in this chapter. The Cenozoic tectonic and magmatic evolution of southwestern Mexico is covered …
Silencing in Classroom Interaction: Producing and Relating Social Spaces

Researchers have studied silencing practices in a number of ways, including focusing on turn taking and temporal dynamics, documenting specific interactional strategies, and analyzing the types of discourses expelled from a given context. The article forwards an alternate approach, arguing that silencing is an interactional achievement that involves producing, dividing, and relating social spaces such that participants are positioned as more or less privileged or silenced. In the production of social space for silencing, I argue that 2 key processes are active: narrating social "scenes" through talk and producing embodied spaces. The production of social space in the service of silencing is traced diachronically (as a joint, dialogic accomplishment over time) and synchronically (as the articulation of multiple social spaces in a single moment). The argument is developed from an analysis of a segment of interaction concerning women's rights within a high school history classroom, in which a girl is silence...
Development and validation of a serum total testosterone liquid chromatography–tandem mass spectrometry (LC–MS/MS) assay calibrated to NIST SRM 971

Abstract Background At our institution, serum testosterone in adult males is measured by immunoassay while female and pediatric specimens are sent to a reference laboratory for liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis due to low concentrations. As this is of significant cost, a testosterone LC–MS/MS assay was developed in-house. Methods A 5500 QTRAP® using electrospray ionization and a Shimadzu Prominence with a C18 column were used. Gradient elution with formic acid, water and methanol:acetonitrile at 0.5 ml/min had a 7-min run-time. A liquid–liquid extraction with hexane:ethyl acetate was carried out on 200 μl of serum. Multiple reaction monitoring was employed. Results Sample preparation took ~ 80 min for 21 samples. Six calibrators were used (0–1263 ng/dl; concentration assigned by NIST SRM 971) with 3 quality controls (9, 168 and 532 ng/dl). The limits of detection and quantitation were 1 and 2 ng/dl respectively. Extraction recovery was ~ 90% and ion suppression ~ 5%. Within-run and total precision studies yielded Conclusions An accurate and sensitive LC–MS/MS assay for total testosterone was developed. Bringing this assay in-house reduces turnaround time for clinicians and patients and saves our institution funds.
Structure and properties of a tetranuclear iron(III) cage complex. A model for hemerythrin

The reaction of glutaric acid with LFe 2 Cl 6 (L=1,4-bis(1,4,7-triaza-1--cyclononyl)butane) in the presence of base and KPF 6 affords the novel tetranuclear cage complex [LFe 2 O(C 5 H 6 O 4 )] 2 (PF 6 ) 4 (2). Complex 2 forms dichroic (orange and green) crystals in the triclinic space group P1, with the following unit cell parameters: a=11.141 (2) A, b=11.2344 (14) A, c=17.278 (2) A, α=72.648 (9) o , γ=70.702 (10) o , V=1913.5 (4) A 3 , and Z=1.
Cation‐exchange resins for removal of alkali metal cations from oligonucleotide samples for fast atom bombardment mass spectrometry

Cation-exchange resins are useful matrix additives for the positive and negative ion FAB-MS determination of nucleotides. Several factors including the amount and type of matrix, the amount and type of the resin, the molecular weight of the nucleotide, and the salt content of the nucleotide sample are investigated. For positive ions, the most abundant [M+H] + ions are obtained with 1 μL of DTT/DTE with 75-100 resin beads in the H + form is used. For negative ions, the most abundant [M-H] - ions are produced from 1 μL TEA and 75-100 resin beads in the NH 4 + form. In several cases, the use of cation-exchange resins give superiors results compared to those obtained with other matrix additives
Bit Wear, Horseback Riding and the Botai Site in Kazakstan

Abstract Bit wear is the damage that occurs on the occlusal surfaces of the second premolar teeth when a horse chews the bit. Bit wear can provide evidence of horseback riding and/or horse draught from teeth found in archaeological sites. This article revises our earlier definition of bit wear and describes wear on an expanded study collection of modern bitted and feral horses (72 individuals). An experiment is described in which previously unbitted horses were ridden with organic bits to simulate the wear made by pre-metallic bits. Because the evaluation of bit wear depends partially on the age of the horse, a crown-height/age curve for horse lower second premolars is presented. Finally, horse premolars from the archaeological site of Botai in Kazakstan are evaluated using the new definition of bit wear and are found to provide evidence for horseback riding in northern Kazakstan between 3400 and 2700 BC .
Stratigraphy and depositional environments of Baltimore Canyon Trough

The Baltimore Canyon Trough, lying offshore from the United States Middle Atlantic States, contains a thickness of at least 14 km of marine and nonmarine sedimentary rocks. One deep offshore stratigraphic test (COST B-2 well), several wells on the coastal plain, 18 shallow core holes (Deep Sea Drilling Project, Atlantic Slope Project, and Atlantic Margin Coring Project) on the continental shelf and slope, and scattered oceanographic cores and dredgings provide rich foraminiferal assemblages from which the geologic age and depositional environments have been determined. The oldest sedimentary rocks penetrated are Upper Jurassic terrigenous sandstone and shale, which are interspersed with shallow-marine limestone. Lower Cretaceous rocks, where penetrated, are also chiefly t rrigenous sandstone and shale, but Upper Cretaceous rocks are progressively more marine. Paleogene strata reflect even deeper marine conditions (bathyal carbonate deposits in the B-2 well). In the Neogene, terrigenous clastic deposits replaced the Paleogene carbonate sequences throughout the trough. Deposition began with thick (> 800 m) deltaic beds in the Miocene and Pliocene and culminated in sandy and, in many places, nonfossiliferous strata of the Pleistocene shelf. Surprisingly thick (> 300 m) silty and sandy clay composes the Pleistocene section on the continental slope. These stratigraphic and paleoecologic relations are graphically illustrated in eight geologic cross sections parallel with and perpendicular to the axis of the trough.
Developing the contents of institutional fact books

Fact books can differ in the information they contain and the manner in which it is presented, but there are useful strategies for developing the contents of a general purpose fact book for individual colleges and universities.
Advances in the Management of Superficial Bladder Cancer

Given its high tendency to recur, coupled with an ever-present possibility to progress to potentially life-threatening muscle-invasive disease, superficial bladder cancer remains a challenging clinical problem. Optimal management begins with early detection and accurate risk assessment through careful attention to clinical features, aided by an emerging array of urinary markers and molecular characterizations. Prevention of recurrence requires the sequential application of tools to completely remove all visible disease, avert reimplantation during surgical resection, ablate microscopic foci, and prevent the emergence of new primary tumors amidst a field of carcinogen-exposed urothelium. Previously standard adjunctive intravesical chemo- and immunotherapies are enjoying new vitality as optimization strategies, new drugs, and rational drug combinations provide the potential for improved efficacy with reduced toxicity. New technological advances such as fluorescence-aided cystoscopy, microwave chemothermotherapy, and electromotive chemotherapeutic drug delivery offer further hope for better outcomes even for disease previously refractory to conservative measures. Yet despite these advances, aggressive surgical management involving bladder removal continues to be an indispensable life-saving maneuver that must be considered in all high-risk cases that fail to promptly respond to other measures.
Influence of alumina impurities on microstructure of LSM–CeO2 composites

Abstract A two-phase model composite of LSM–CeO 2 was developed to simulate triple phase boundaries of SOFC and to study the impact of alumina impurities on the microstructure. Interfaces between cerium oxide and 10 at.% strontium-doped lanthanum manganite (LSM) were characterized using X-ray diffraction, atomic-force microscopy, focused ion beam milling, field-emission scanning electron microscopy, X-ray energy dispersive spectroscopy and transmission electron microscopy. LSM, which is synthesized by conventional mechanical milling, is found to be doped with alumina from the grinding balls. When LSM powder is mixed with CeO 2 and sintered at 1400 °C for 4 h, manganese aluminate spinel, MnAl 2 O 4 and Mn 2 AlO 4 , forms at LSM/LSM, LSM/CeO 2 and CeO 2 /CeO 2 boundaries. The influence of (Mn,Al) 3 O 4 phase on the mechanical integrity and performance of the cells is discussed.
Methacrylate as an Embedding Medium for Woody Tissues

Methacrylate can be readily infiltrated into woody tissues. After infiltration, the tissue is transferred to a polymerizing mixture of 95:5 butyl methacrylate to methyl methacrylate by volume. For each 100 ml of polymerizing mixture, 2 grams of Luperco CDB catalyst are added. The hardness of the matrix may be increased by increasing the proportion of methyl methacrylate. Polymerization is accomplished by 2 days in a 50° C oven or 2 days in a small ultraviolet radiation chamber (42° C), the latter being the technique of choice. The blocks can be sectioned readily at 6 μ to more than 30 μ. Sectioning is facilitated by keeping the block wet with a 1:1 glycerol-alcohol solution. Best preparations are obtained when the matrix is removed after sectioning; however, staining in safranin O-fast green FCF may be-accomplished through the matrix. The technique is very rapid, convenient to use, and has produced excellent preparations from several species of woody plants.
Contents of polyamines in selected foods

Abstract Dietary polyamines, putrescine, spermidine and spermine, participate in many biochemical processes, mainly in cell proliferation and differentiation. Polyamines were determined as N-benzamides by micellar electrokinetic capillary chromatography in 153 samples of 21 foods, mostly culinary processed. Very low putrescine contents were observed in processed meats, pork liver and kidney, while the highest mean contents exceeded 55 mg kg−1 in stewed green pea, grapefruit and fresh green pepper. Higher spermine than spermidine contents were typical for foods of animal origin, while the opposite was observed in plant products. Mean spermidine contents, exceeding 20 mg kg−1, were found in dry soybean, stewed green pea, yellow pea puree and roasted chicken breast. Roasted chicken breast, stewed pork kidney, roasted pork liver and roasted pork neck had mean spermine contents above the same level. Polyamine content varies widely within individual food items, what makes application of the results by dietitians rather difficult.
On Identifying the Processes Underlying Schizophrenic Speech Disorder

Speech of people with schizophrenia is often difficult to follow. There is evidence that neuropsychological deficits associated with schizophrenia explain some of the variance in speech disorder, but its nature and causes overall are not well understood. This study rated speech samples from 60 schizophrenic outpatients for thought disorder, conceptual disorganization, linguistic structural breakdown, and communication failure. A battery of neuropsychological tests potentially relevant to coherent speech production was administered, and associations between these variables and the speech measures were assessed. Consistent with previous research, the measure of functional effect, communication failure, was more highly associated with neuropsychological test performance than were the measures of putative cause: thought disorder, conceptual disorganization, or linguistic structural breakdown. Performance on tests of attention, immediate memory, working memory, organizational sequencing, and conceptual sequencing all were significantly related to the frequency of communication failures in the speech. In hierarchical regression, attention, working memory, and conceptual sequencing each contributed significantly and together explained 29% of the variance. Some other potential contributors to test in future research include auditory attention, internal source memory, emotional disturbances, and social cognitive deficits.
Scheduling job shops with uncertainties

Effective management of production uncertainties is becoming critical in the era of "time-based competition". The consideration of uncertainties, however, is difficult because of the combinatorial nature of the problem as well as the probabilistic nature of uncertain factors. This paper presents a novel approach for job-shop scheduling considering major uncertain characteristics, e.g., machine breakdowns and uncertain processing times. A separable problem formulation that balances modeling accuracy and solution time is presented with the objective to minimize expected part tardiness penalty. A solution methodology based on a combined Lagrangian relaxation, stochastic dynamic programming and "ordinal optimization" is developed. Initial numerical results supported by simulation demonstrate that the schedules generated have low expected penalties, a highly desirable property for achieving product delivery with short lead times.
3-Deoxyfructose concentrations are increased in human plasma and urine in diabetes.

3-Deoxyglucosone (3-DG) is a reactive dicarbonyl sugar thought to be a key intermediate in the nonenzymatic polymerization and browning of proteins by glucose. 3-DG may be formed in vivo from fructose, fructose 3-phosphate, or Amadori adducts to protein, such as NE-fructoselysine (FL), all of which are known to be elevated in body fluids or tissues in diabetes. Modification of proteins by 3-DG formed in vivo is thought to be limited by enzymatic reduction of 3-DG to less reactive species, such as 3-deoxyfructose (3-DF). In this study, we have measured 3-DF, as a metabolic fingerprint of 3-DG, in plasma and urine from a group of diabetic patients and control subjects. Plasma and urinary 3-DF concentrations were significantly increased in the diabetic compared with the control population (0.853 ± 0.189 vs. 0.494 ± 0.072 μM, P < 0.001, and 69.9 ± 44.2 vs. 38.7 ± 16.1 nmol/mg creatinine, P < 0.001, respectively). Plasma and urinary 3-DF concentrations correlated strongly with one another, with HbA1c ( P < 0.005 in all cases), and with urinary FL ( P < 0.02 and P = 0.005, respectively). The overall increase in 3-DF concentrations in plasma and urine in diabetes and their correlation with other indexes of glycemic control suggest that increased amounts of 3-DG are formed in the body during hyperglycemia in diabetes and then metabolized to 3-DF. These observations are consistent with a role for increased formation of the dicarbonyl sugar 3-DG in the accelerated browning of tissue proteins in diabetes.
Sweeping Minimum Perimeter Enclosing Parallelograms: Optimal Crumb Cleanup

We examine the problem of pushing all the points of a planar region into one point using parallel sweeps of an innite line, minimizing the sum of the lengths of the sweep vectors. We characterize the optimal 2-sweeps of triangles, and provide a linear-time algorithm for convex polygons.
The effect of peritrich ciliates on the production of Acartia hudsonica in Long Island Sound

We studied the effects of attached peritrich ciliates on the fitness of natural populations of Acartia hudsonica (Pinhey) in Stony Brook Harbor, Long Island Sound. Ciliate infection occurred during late spring, and ciliate load (No. ind.-‘) was not related to copepod age, stage, or body size. Simulated in situ experiments conducted throughout the period of abundance of A. hudsonica showed that egg production rate (No. d-l) was positively correlated to ambient water temperature, but negatively correlated to ciliate load. Salinity and the concentration of total or >8-10 pm Chl a were not significant in explaining the variation in egg production rate. Egg hatching success (O/o) was not influenced by the infection status (presence or absence) of the female. Infected nauplii had lower survival rates (d-l) compared to uninfected nauplii, but their developmental rates (molts d -I) were not significantly different. Significantly slower average sinking rates were found for infected adults compared to uninfected adults. Slower sinking rates for infected copepods may have been due to an increase in surface area which increased drag. Infected adults with slower sinking rates may be more susceptible to predation. Our findings show that peritrich ciliates can play a role in the seasonal decline and future recruitment of A. hudsonica.
Electron Transfer and Adsorption of Myoglobin on Self-Assembled Surfactant Films: An Electrochemical Tapping-Mode AFM Study

We have studied myoglobin (Mb) on graphite basal plane and on self-assembled didodecyldi- methylammonium bromide (DDAB) mono- and multilayers with in situ tapping-mode AFM, cyclic voltammetry, and differential capacitance measurements. On graphite, Mb molecules adsorb and aggregate into chainlike features. The aggregation indicates an attractive interaction between the adsorbed molecules. In contrast, the molecules are randomly distributed on the DDAB layers. The adsorption on DDAB changes drastically the domains and defects in the DDAB layers due to a strong Mb-DDAB interaction. On both the bare and the DDAB-coated electrodes, the protein undergoes a fast electron-transfer reaction involving Fe 3+ + 1e - T Fe 2+ in the heme group. The structure of the DDAB film is potential dependent. At low potentials, the film is in a solidlike phase. When the potential is raised to 0 V, the film transforms into a liquidlike phase via a first- order phase transition. The liquidlike phase may be responsible for the fast diffusion of Mb through the DDAB layers.
Orientation bandwidths of spatial mechanisms measured by masking

Orientation tuning curves were measured at 10 spatial frequencies ranging from 0.5 to 11.3 cycles per degree (cpd) using a masking paradigm. The stimuli were spatially localized test patterns of 1.0 octave bandwidth superimposed upon cosine grating masks. By using a model that corrects for the nonlinearity inherent in the masking process, we obtain the half-amplitude half-bandwidths (θ1/2) of Cartesian-separable receptive fields that may underlie orientation selectivity. Additional experiments show that the data are not compatible with separability in polar coordinates (spatial frequency and orientation). The orientation half-bandwidths have been found to decrease somewhat with increasing spatial frequency, going from about 30° at 0.5 cpd to 15° at 11.3 cpd, for both sustained and transient forms of temporal modulation. Similar bandwidths are obtained from data where the test is oriented along 45°. These bandwidth estimates are shown to be consistent with subthreshold summation data as well as physiological data from monkey striate cortex.
Numerical Analysis of Rotationally Symmetric Shells under Transient Loadings

This report involves the development of procedures for determining the dynamic response of rotationally symmetric open ended thin shells of revolution under time dependent distributed impulsive and thermal loadings. The solution is restricted to thermal loadings which are small in the circumferential direction but which may vary in any manner in the meridional direction of the shell. Inertia forces are considered in a direction normal to the middle surface and in a direction along the meridians of the shell. Time dependent boundary conditions may be prescribed at each of the two edges of the shell. The field equations are derived in the form of eight first-order partial differential equations with respect to the meridional direction of the shell. The solution for each Fourier harmonic is obtained by employing finite difference representations for all time and spatial derivatives. The complete system of equations is solved implicitly for the first time increment, whereas explicit relations are used for the meridional and transverse displacements for the second and succeeding time increments. The developed equations have been programmed in FORTRAN IV language for solution by computer. Solutions obtained with this program for typical shells and loadings are found to be stable and in agreement for a range of values of the space and time increments. It is concluded that the finite difference methods employed here constitute a most expeditious procedure for obtaining reliable and accurate values of the response histories of rotationally symmetric shells of revolution under transient loadings.
Transporters involved in source to sink partitioning of amino acids and ureides: opportunities for crop improvement

In most plant species, amino acids are the predominant chemical forms in which nitrogen is transported. However, in nodulated tropical or subtropical legumes, ureides are the main nitrogen transport compounds. This review describes the partitioning of amino acids and ureides within the plant, and follows their movement from the location of synthesis (source) to the sites of usage (sink). Xylem and phloem connect source and sink organs and serve as routes for long-distance transport of the organic nitrogen. Loading and unloading of these transport pathways might require movement of amino acids and ureides across cell membranes, a task that is mediated by membrane proteins (i.e. transporters) functioning as export or import systems. The current knowledge on amino acid and ureide transporters involved in long-distance transport of nitrogen is provided and their importance for source and sink physiology discussed. The review concludes by exploring possibilities for genetic manipulation of organic nitrogen transporter activities to confer increases in crop productivity.
Estrogens and Glucocorticoids Have Opposing Effects on the Amount and Latent Activity of Complement Proteins in the Rat Uterus

The mammalian uterus faces unique immunological challenges. It must nurture and protect the semiallogenic fetus from attack by the maternal immune system while guarding against infection by pathogens that compromise fetal and maternal health. Complement has recently been implicated in the etiology of pregnancy loss, but its regulation by steroid hormones and its role in host defense in the uterus are not clearly defined. Here we use biochemical, functional, and physiological assays to elucidate the regulation of complement proteins in the rat uterus. We demonstrate that estrogens (17 beta-estradiol) and glucocorticoids (dexamethasone) have major, but opposing, effects on the amount and latent activity of complement effectors in the uterus. Treatment with 17 beta-estradiol induced vasodilation and an increase in vascular permeability, which resulted in extravasation of plasma and complement into the uterus, rather than de novo complement biosynthesis. In vitro assays revealed that 17 beta-estradiol induced a potent bactericidal activity in uterine luminal fluid and that the antibacterial component was complement. These proinflammatory and immunomodulatory effects were evident within 4 h of treatment and were blocked by coadministration of dexamethasone. We also found that estrogen effects on the vasculature were mediated in part by activation of the contact system and bradykinin B1 receptors. These results indicate that complement plays a central role in innate immunity in the female reproductive tract and suggest that estrogens or glucocorticoids might be used therapeutically to enhance or inhibit complement-dependent processes in the uterus.
Contract-based system-level composition of analog circuits

Efficient system-level design is increasingly relying on hierarchical design-space exploration, as well as compositional methods, to shorten time-to-market, leverage design re-use, and achieve optimal performances. However, in analog electronic systems, circuit behaviors are so tightly dependent on their interface conditions that accurate system performance estimations based on characterizations of individual stand-alone circuits is a hard task. Since there is no general solution to this problem, analog system integration has traditionally used ad-hoc solutions heavily dependent on designers' experience. In this paper, we build upon the analog platform-based design methodology by exploiting contracts to enforce correct-by-construction system-level composition. Contracts intuitively capture the thought process of a designer, who aims at guaranteeing circuit performance only under specific assumptions (e.g. loading and dynamic range) on the interface properties. Our approach allows automatic detection and composition of compatible components in a given library. We apply our methodology to an ultra-wide band receiver front-end to show that contracts allow pre-designed IP components to be smoothly integrated and design decisions to be reliably made at a higher abstraction level, both key factors to improve designer productivity.
Calcineurin Regulates Myocardial Function during Acute Endotoxemia

Rationale: Cyclosporin A (CsA) is known to preserve cardiac contractile function during endotoxemia, but the mechanism is unclear. Increased nitric oxide (NO) production and altered mitochondrial function are implicated as mechanisms contributing to sepsis-induced cardiac dysfunction, and CsA has the capacity to reduce NO production and inhibit mitochondrial dysfunction relating to the mitochondrial permeability transition (MPT). Objectives: We hypothesized that CsA would protect against endotoxin-mediated cardiac contractile dysfunction by attenuating NO production and preserving mitochondrial function. Methods: Left ventricular function was measured continuously over 4 h in cats assigned as follows: control animals (n = 7); LPS alone (3 mg/kg, n = 8); and CsA (6 mg/kg, n = 7), a calcineurin inhibitor that blocks the MPT, or tacrolimus (FK506, 0.1 mg/kg, n = 7), a calcineurin inhibitor lacking MPT activity, followed in 30 min by LPS. Myocardial tissue was then analyzed for NO synthase-2 expression, tissue nitration, protein carbonylation, and mitochondrial morphology and function. Measurements and Main Results: LPS treatment resulted in impaired left ventricular contractility, altered mitochondrial morphology and function, and increased protein nitration. As hypothesized, CsA pretreatment normalized cardiac performance and mitochondrial respiration and reduced myocardial protein nitration. Unexpectedly, FK506 pretreatment had similar effects, normalizing both cardiac and mitochondrial parameters. However, CsA and FK506 pretreatments markedly increased protein carbonylation in the myocardium despite elevated manganese superoxide dismutase activity during endotoxemia. Conclusions: Our data indicate that calcineurin is a critical regulator of mitochondrial respiration, tissue nitration, protein carbonylation, and contractile function in the heart during acute endotoxemia.
Behavioral Assessment and Treatment Overview

The behavioral assessment allows practitioners to gather information about weight history, previous weight loss attempts, environmental circumstances and social support, and any comorbid psychiatric disturbances that may complicate the course of weight loss treatment. Techniques for completing the assessment, however, may vary. In some instances, the clinician may conduct an intake interview with obesity identified as the presenting problem. In other circumstances, a provider may decide to broach the topic of weight loss after working with a patient for several weeks, months or even years. In both situations it is helpful to approach a discussion of weight in a supportive, nonjudgmental manner. In the former situation, it can be beneficial to initiate the assessment with a discussion of neutral, demographic information such as marital status, current living situation, and occupation. This conversational tone can help establish rapport and may help the patient feel more at ease when disclosing information about this sensitive issue. It also can be helpful to orient the patient at the onset to the structure of the session, indicating that treatment recommendations will be reviewed at the close of the evaluation. Patients should be thanked for completing the self-report questionnaires, if used, and the interviewer should use this written information to guide the assessment. Although it is important to keep the patient on task and gather pertinent information, it is also worthwhile to allow patients the opportunity to freely discuss the impact their overweight status has had on their lives. Assessment tools such as the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) can provide detailed information about this.
Amanita bisporigera-Induced Hepatic Failure: A Fatal Case of Mushroom Ingestion

Wild mushroom poisoning from the genus Amanita is a medical emergency, with Amanita phalloides being the most common offender. Patients may complain of nausea, vomiting, diarrhea and/or abdominal pain. If not aggressively treated, fulminant hepatic failure may develop within several days of ingestion. In this case report, a patient poisoned with Amanita bisporigera is described, along with the typical clinical presentation, patient outcomes, and treatment options for dealing with an Amanita mushroom poisoning.
Maximum magnitude earthquakes induced by fluid injection

Analysis of numerous case histories of earthquake sequences induced by fluid injection at depth reveals that the maximum magnitude appears to be limited according to the total volume of fluid injected. Similarly, the maximum seismic moment seems to have an upper bound proportional to the total volume of injected fluid. Activities involving fluid injection include (1) hydraulic fracturing of shale formations or coal seams to extract gas and oil, (2) disposal of wastewater from these gas and oil activities by injection into deep aquifers, and (3) the development of enhanced geothermal systems by injecting water into hot, low-permeability rock. Of these three operations, wastewater disposal is observed to be associated with the largest earthquakes, with maximum magnitudes sometimes exceeding 5. To estimate the maximum earthquake that could be induced by a given fluid injection project, the rock mass is assumed to be fully saturated, brittle, to respond to injection with a sequence of earthquakes localized to the region weakened by the pore pressure increase of the injection operation and to have a Gutenberg-Richter magnitude distribution with a b value of 1. If these assumptions correctly describe the circumstances of the largest earthquake, then the maximum seismic moment is limited to the volume of injected liquid times the modulus of rigidity. Observations from the available case histories of earthquakes induced by fluid injection are consistent with this bound on seismic moment. In view of the uncertainties in this analysis, however, this should not be regarded as an absolute physical limit.
Cathepsin L occupies a vacuolar compartment and is a protein maturase within the endo/exocytic system of Toxoplasma gondii

Regulated exocytosis allows the timely delivery of proteins and other macromolecules precisely when they are needed to fulfil their functions. The intracellular parasite Toxoplasma gondii has one of the most extensive regulated exocytic systems among all unicellular organisms, yet the basis of protein trafficking and proteolytic modification in this system is poorly understood. We demonstrate that a parasite cathepsin protease, TgCPL, occupies a newly recognized vacuolar compartment (VAC) that undergoes dynamic fragmentation during T. gondii replication. We also provide evidence that within the VAC or late endosome this protease mediates the proteolytic maturation of proproteins targeted to micronemes, regulated secretory organelles that deliver adhesive proteins to the parasite surface during cell invasion. Our findings suggest that processing of microneme precursors occurs within intermediate endocytic compartments within the exocytic system, indicating an extensive convergence of the endocytic and exocytic pathways in this human parasite.
Associations of Fc gamma receptor (FcgR2a, FcgR3a and FcgR2c) genotype with outcome in metastatic renal cell carcinoma (mRCC) patients receiving high dose interleukin 2 (HD-IL2)

HD-IL2 was given to patients with mRCC in a prospective trial (ClinicalTrials.gov ID: NCT00554515) that demonstrated an overall response rate of 25%. To identify predictors of response, we genotyped patients for single nucleotide polymorphisms (SNPs) in FcgR genes: FcgR2a, FcgR3a, and FcgR2c. These FcgRs are variably expressed on immune cells, and bind to the IgG portion of antibodies, triggering activation. FcgR2a [SNP = histidine/arginine (H/R); expressed on neutrophils, monocytes-macrophages and antigen-presenting cells (APCs)] and FcgR3a [SNP = valine/phenylalanine (V/F); expressed on NK cells and some APCs] impact patient response to immunotherapy [mainly monoclonal antibody-based (mAb) therapies] in several malignancies, as both FcgR2a-H and FcgR3a-V have higher antibody binding affinity than FcgR2a-R or FcgR3a-F, respectively. FcgR2c, also expressed on NK cells, has a SNP that regulates its expression [C nucleotide = expression; T nucleotide = non-expression (C/T)]. About 20-40% of individuals express FcgR2c; little is known about the role of FcgR2c expression in cytokine-based immunotherapy. We found associations of FcgR genotypes with patient response to HD-IL2. Dual combination analyses of FcgR3a with FcgR2a genotypes revealed significantly improved %Tumor Shrinkage in patients with either FcgR3a-VV and/or FcgR2a-HH (n=34) as compared to those patients genotyped as FcgR3a-VF or FF with FcgR2a-HR or RR (n=70) (p=0.047). For analyses including both FcgR3a and FcgR2c genotypes, significantly improved OS was seen in those with ≥2 alleles of either FcgR3a-V and/or FcgR2c-C (n=27) vs. those with < 2 alleles of either FcgR3a-V and/or FcgR2c-C (n=79) (p=0.013). We further considered combinations that included the genotypes of all 3 genes; we identified 42 patients with “favorable” genotypes and 64 with “unfavorable”. We saw significant improvement in the %Tumor shrinkage (p = 0.033) and a trend for improvement in OS (p = 0.071) in the “favorable genotype” group. As reported previously by others, some cancer patients make endogenous anti-tumor Ab. The association of these “favorable” FcgR genotypes with outcome suggests there may be a beneficial interaction of “favorable” FcR genotypes with endogenous anti-tumor Ab. Favorable FcgRs may support the induction of in vivo antibody-dependent cell-mediated cytotoxicity (ADCC) or antibody-dependent cellular phagocytosis (ADCP). In addition, ADCP by APC with a favorable pattern of FcgRs, may be playing a role in enhancing induction of effective adaptive immunity, via augmented antigen presentation. Further analyses are needed to validate these exploratory findings and clarify the mechanisms by which these favorable FcgR genotypes are associated with improved outcome in these patients with mRCC treated with HD-IL2.
Investing in Security Price Informativeness: The Role of IPO Underpricing

I develop a theory in which firms enhance the information content of their future stock prices by using underwriters to direct underpriced IPO allocations to information-producing investors. Sufficiently large allocations and the promise of future, profitable IPO participation provide incentives for investors to produce information after the IPO. Increasing underpricing strengthens these incentives, resulting in a more informative post-IPO price and higher firm value. Firms' desires for more informative post-IPO pricing lead to new rationales for IPO underpricing and the intermediating role of underwriters. Empirical tests support the theory's novel implications.
Jumpstarting the Judicial Externship Experience: Building Upon Common Themes for Student Success in the Classroom and in the Judge's Chambers

Judicial externships provide a unique opportunity for students to experience the inner workings of a judge’s chambers. Because students’ experiences vary from one judicial placement to another, teaching the classroom component of this externship can be a challenge. By focusing on common themes shared by the students, regardless of their specific court placements, faculty can create a more cohesive and relevant classroom setting.This article proposes four common themes for faculty to focus on in the classroom: judicial ethics, judicial research and writing, judicial decision-making, and professionalism. Students will be faced with potential ethical issues as soon as they arrive at their judicial placements. We need to make sure students are prepared to identify potential ethical issues and know how to proceed. Many students select the judicial externship because they want to improve their research and writing skills, and want to learn how judges make decisions. We can help prepare students for the type of writing that is expected of them in a judicial chambers and how to understand the judicial decision-making process. Finally, we cannot forget to teach the importance of professionalism in the judicial externship and how it can impact the student’s experience, this semester and beyond.Through these themes and suggested methods of teaching, faculty can effectively complement their students’ courtroom experiences with skills learned in the classroom.
Comparison of Immunochemical (Enzyme-Linked Immunosorbent Assay) and Immunohistochemical Methods for the Detection of Central Nervous System Tissue in Meat Products

Three methods are widely used in the United States to detect the presence of central nervous system (CNS) tissue in meat products: the fluorescent enzyme-linked immunosorbent assay (F-ELISA), developed in this laboratory, the colorimetric Ridascreen Risk Material 10/5 ELISA (R-ELISA), and the U.S. Department of Agriculture, Food Safety and Inspection Service immunohistochemical (IHC) procedure. These assays are based on the immunological detection of glial fibrillary acidic protein (GFAP), a neural antigen largely restricted to the CNS. The objective of the current study was to compare the sensitivity and repeatability of these tests for detecting the presence of neural tissue in meat. Ground beef spiked with 0.05 to 0.5% of bovine brain, spinal cord (SC), or dorsal root ganglia, as well as advanced meat recovery samples, were evaluated by each of the three GFAP detection procedures. Interassay coefficients of variation for the F-ELISA GFAP standards were 7 to 25%, and intra-assay variation due to samplin...
Massive gas gangrene secondary to occult colon carcinoma

Gas gangrene is a rare but often fatal soft-tissue infection. Because it is uncommon and the classic symptom of crepitus does not appear until the infection is advanced, prompt diagnosis requires a high index of suspicion. We present a case report of a middle-aged man who presented with acute onset lower-extremity pain that was initially thought to be due to deep vein thrombosis. After undergoing workup for pulmonary embolism, he was found to have massive gas gangrene of the lower extremity secondary to an occult colon adenocarcinoma and died within hours of presentation from multisystem organ failure.
Experimental and Computational Studies of Gravity-Driven Dense Granular Flows

The current paper focusses on the characterization of gravity-driven dry granular flows in cylindrical tubes. With a motive of using dense particulate media as heat transfer fluids (HTF), the study was primarily focused to address the characteristics of flow regimes with a packing fraction of ∼60%. Experiments were conducted to understand the effects of different flow parameters, including: tube radius, tube inclination, tube length and exit diameter. These studies were conducted on two types of spherical particles — glass and ceramic — with mean diameters of 150 μm and 300 μm respectively. The experimental data was correlated with the semi-empirical equation based on Beverloo’s law. In addition, the same flow configuration was studied through three-dimensional computer simulations by implementing the Discrete Element Method for the Lagrangian modelling of particles. A soft-particle formulation was used with Hertz-Mindilin contact models to resolve the interaction forces between particles. The simulation results were used to examine the velocity, shear rate and packing fraction profiles to study the detailed flow dynamics. Curve-fits were developed for the mean velocity profiles which could be used in developing hydrodynamic analogies for granular flows. The current work thus identifies the basic features of gravity driven dense granular flows that could form a basis for defining their rheology.Copyright © 2015 by ASME
Androgen-dependent regulation of human angiotensinogen expression in KAP-hAGT transgenic mice.

We previously reported a novel transgenic model expressing human angiotensinogen from the kidney androgen-regulated protein promoter, and demonstrated sexually dimorphic expression. Herein, we inve...