cssi/SciSciGPT-SciSciNet huggingface dataset:
Human pharmacokinetics of BL-P1654, compared with ampicillin.

BL-P1654 is a new ureido-penicillin which has significant activity against both pseudomonas and klebsiella. Its pharmacokinetics were evaluated in five studies in four healthy adult male volunteers after 1-g doses given as: 5- and 30-min intravenous infusions, a 30-min infusion 1 h after the oral administration of 1 g of probenecid, and an intramuscular injection. For comparison, volunteers also received a 30-min infusion of 1 g of ampicillin. Serum levels of the antibiotic were found to fit a two-compartment open model using a Burroughs-5500 computer. After a 30-min infusion, peak serum levels of BL-P1654 (72.8 mug/ml [standard deviation] +/- 5.9) were 50% greater than those of ampicillin (53.6 +/- 8.9). Six hours later, the relative difference was even greater (4.58 +/- 0.25 versus 0.35 +/- 0.09). At 75 min after the 1-g intramuscular injection of BL-P1654, peak serum levels averaged 28.4 +/- 10.3 mug/ml. The half-life of BL-P1654 (2.04 h) was significantly longer than for ampicillin (1.15 h), and the renal clearances of BL-P1654 and ampicillin were 79 versus 244 ml/min per 1.73 m(2), respectively. Probenecid produced no significant change in blood levels, volume of distribution, half-life, or renal clearance, indicating that there is no net tubular secretion of this antibiotic.
Inhibition of mitochondrial function in astrocytes: implications for neuroprotection

Much evidence suggests that astrocytes protect neurons against ischemic injury. Although astrocytes are more resistant to some insults than neurons, few studies offer insight into the real time changes of astrocytic protective functions with stress. Mitochondria are one of the primary targets of ischemic injury in astrocytes. We investigated the time course of changes in astrocytic ATP levels, plasma membrane potential, and glutamate uptake, a key protective function, induced by mitochondrial inhibition. Our results show that significant functional change precedes reduction in astrocytic viability with mitochondrial inhibition. Using the mitochondrial inhibitor fluorocitrate (FC, 0.25 mmol/L) that is preferentially taken by astrocytes we found that inhibition of astrocyte mitochondria increased vulnerability of co-cultured neurons to glutamate toxicity. In our studies, the rates of FC-induced astrocytic mitochondrial depolarization were accelerated in mixed astrocyte/neuron cultures. We hypothesized that the more rapid mitochondrial depolarization was promoted by an additional energetic demand imposed be the co-cultured neurons. To test this hypothesis, we exposed pure astrocytic cultures to 0.01-1 mmol/L aspartate as a metabolic load. Aspartate application accelerated the rates of FC-induced mitochondrial depolarization, and, at 1 mmol/L, induced astrocytic death, suggesting that strong energetic demands during ischemia can compromise astrocytic function and viability.
The biochemistry and functional morphology of the Entamoeba.

Article de synthese sur ce genre concernant l'organisation infracellulaire, le metabolisme et les aspects moleculaires des relations hote parasite
Acute urinary retention in females

Twenty-six hospitalized females were evaluated prospectively for acute urinary retention. They could be divided into three etiologic groups: 1) transient; 2) neuropathic; and 3) pelvic causes. An initial division into the first two categories could be obtained in 21 patients by the history, physical examination and urine cultures, sparing further unnecessary testing. The rest were evaluated by pelvic sonogram, and unexpected potentially life-threatening pathology was found in 4 patients. An algorithm for the evaluation and treatment of acute urinary retention in females is presented.
Solar Stellar Irradiance Comparison Experiment II (SOLSTICE II) for the NASA Earth Observing System's Solar Radiation and Climate Experiment mission

The SOLar STellar Irradiance Comparison Experiment II (SOLSTICE II) is a component the NASA Earth Observing System’s Solar Radiation and Climate Experiment mission. SOLSTICE II will use a pair of diffraction grating spectrometers to measure solar irradiance from 115 nm to 320 nm with a spectral resolution of 1 nm and a cadence of 6 hours, with an absolute accuracy of 5%, and with a relative accuracy of 0.5% per year. We will achieve an initial 5% absolute accuracy by calibrating the instrument’s radiometric sensitivity before launch using the Synchrotron Ultraviolet Radiation Facility at the National Institute for Standards and Technology in Gaithersburg, Md. Once the instrument is on-orbit, we will track changes in its sensitivity with irradiance measurements of an ensemble of bright, stable, main-sequence B-A stars. SOLSTICE II is an evolution of the SOLSTICE I instrument that is currently operating on the Upper Atmosphere Research Satellite. In this paper we review the basic SOLSTICE concept and describe the characteristics, operating modes, and anticipated performance of the SOLSTICE II instrument.
Are there charmed quarks in the nucleon

Abstract A simple relation between structure functions for deep inelastic leptoproduction off any nuclear target is presented to test for charmed quarks in the nucleon. In the case of SU(3) × SU(3) current symmetry, a similar relation for isoscalar nuclear targets is obtained. Existing CERN neutrino data are not accurate enough to draw any definite conclusions.
The modeling of batch and continuous emulsion polymerization reactors. Part I: Model formulation and sensitivity to parameters

A detailed model for the prediction of the behavior of batch or continuous emulsion polymerization reactors has been formulated, and an efficient numerical scheme for simulation developed. The model makes use of population balance equations and detailed mechanisms for chemical and physical rate processes. The numerical procedure chosen for its solution is orthogonal collocation on finite elements. In this paper, a few comparisons with experimental data are presented to demonstrate the model validity. Finally, a parametric sensitivity study is carried out to identify the most important kinetic and physical parameters. In the sequel, a comprehensive comparison of model predictions with a wide variety of experimental data will be presented.
Effect of spectral emissivity on single broadband MWIR image simulation: Part II

In preceding work, it was shown that the relative error in the predicted intensity of an individual pixel in any broadband MWIR image simulation that employs some form of band-average emissivity and/or average detector responsivity approximation in its models will be about equal to the fractional standard deviation of the MWIR emissivity of the corresponding material. This relationship between the error in simulated integrated image intensity and the variation in spectral emissivity over the MWIR band for a set of 27 commonly encountered scenery materials was shown to behave like a simple power curve, with the power inversely proportional to scene temperature. However, what is more important than the error in a single simulated image pixel is how a multi-pixel simulated image is effected. In this follow-on paper, the errors associated with band-average emissivity approximations are quantified with respect to errors in synthetic images. Comparisons of image contrast and image correlation using band-average emissivity and spectral emissivity are performed. The impact of band-average emissivity in a simple synthetic image on a perception experiment is presented as an example of an application-dependent effect.
Adolescent Screen Time and Rules to Limit Screen Time in the Home

Abstract Purpose To investigate associations between adolescent screen time behaviors, screen time rules, and presence of electronic media in the bedrooms of adolescents. Methods Parents and adolescents (N = 160 dyads) from the cities of Boston, Cincinnati, and San Diego were asked to complete a questionnaire which included questions related to demographics, screen time rules, availability of media devices, and screen time behavior. Separate multiple regression models were used for adolescent and parent reports to test correlates of adolescent television (TV) watching, video game play, and computer usage for entertainment. Results Data from adolescents indicated that rules for watching TV, computer usage, and total number of screen time rules were significantly correlated with time spent watching TV ( β = −.22, p β = −.18, p β = −.18, p β = .18 and .24, p β = .19, p Conclusion Having clear rules, setting limits on screen time, and not having screen-based media in the bedroom were associated with fewer hours of screen time for adolescents.
Intraventricular administration of MSH induces hyperalgesia in rats

In a completely crossed, double blind designed study, six rats received intraventricular injections of 0.1, 1.0 and 10 micrograms of alpha-MSH and a placebo. The rats were tested for response to painful thermal stimuli with the tail-flick test. All of the doses of alpha-MSH produced hyperalgesia during the first 20 min of testing. Only the 1.0 microgram dose of alpha-MSH produced hyperalgesia throughout the 80 min course of the experiment. This study, coupled with previous reports that MSH/ACTH fragments may attenuate morphine-induced analgesia, suggest that MSH can have opposite actions from those of the endorphins. It is possible that alpha-MSH and related peptides may be endogenous anti-opiates.
Wilson's disease: Changes in methionine metabolism and inflammation affect global DNA methylation in early liver disease

Hepatic methionine metabolism may play an essential role in regulating methylation status and liver injury in Wilson disease (WD) through the inhibition of S-adenosylhomocysteine hydrolase (SAHH) by copper (Cu) and the consequent accumulation of S-adenosylhomocysteine (SAH). We studied the transcript levels of selected genes related to liver injury, levels of SAHH, SAH, DNA methyltransferases genes (Dnmt1, Dnmt3a, Dnmt3b) and global DNA methylation in the tx-j mouse (tx-j), an animal model of WD. Findings were compared to those in control C3H mice, and in response to Cu chelation by penicillamine (PCA) and dietary supplementation of the methyl donor betaine to modulate inflammatory and methylation status. Transcript levels of selected genes related to endoplasmic reticulum stress, lipid synthesis, and fatty acid oxidation were down-regulated at baseline in tx-j mice, further down-regulated in response to PCA, and showed little to no response to betaine. Hepatic Sahh transcript and protein levels were reduced in tx-j mice with consequent increase of SAH levels. Hepatic Cu accumulation was associated with inflammation, as indicated by histopathology and elevated serum ALT and liver tumor necrosis factor alpha (Tnf-α) levels. Dnmt3b was down-regulated in tx-j mice together with global DNA hypomethylation. PCA treatment of tx-j mice reduced Tnf-α and ALT levels, betaine treatment increased S-adenosylmethionine and up-regulated Dnmt3b levels, and both treatments restored global DNA methylation levels. Conclusion: reduced hepatic Sahh expression was associated with increased liver SAH levels in the tx-j model of WD, with consequent global DNA hypomethylation. Increased global DNA methylation was achieved by reducing inflammation by Cu chelation or by providing methyl groups. We propose that increased SAH levels and inflammation affect widespread epigenetic regulation of gene expression in WD.
2DE identification of proteins exhibiting turnover and phosphorylation dynamics during sea urchin egg activation.

Abstract The animal egg is a unique quiescent cell, prepackaged with maternal mRNAs and proteins that have functions in early development. Rapid, transient signaling at fertilization alters egg physiology, resulting in Ca 2+ release from the endoplasmic reticulum (ER) and cytoplasmic alkalinization. These events trigger the zygote developmental program through initiation of DNA synthesis and entry into mitosis. Post-translational modifications of maternal proteins are responsible for the spatio-temporal regulation that orchestrates egg activation. We used functional proteomics to identify the candidate maternal proteins involved in egg activation and early development. As the first step of this analysis, we present the data on the baseline maternal proteome, in particular, on proteins exhibiting changes in abundance and in phosphorylation state upon egg activation. We identify 94 proteins that were stable, reproducibly displayed a shift in isoelectric point, or changed in relative abundance at specific times after activation. The identities of these proteins were determined by quadrupole time-of-flight tandem mass spectrometry. The set of the most dynamic proteins appear to be enriched in intermediary metabolism proteins, cytoskeletal proteins, gamete associated proteins and proteins that have Ca 2+ mediated activities.
Multidimensional Quantum Trajectory Dynamics in Imaginary Time with Approximate Quantum Potential

The quantum trajectory dynamics in imaginary time with the momentum-dependent quantum potential [J. Chem. Phys. 2010, 132, 014112], which can be used for calculations of low-lying energy eigenstate...
“Just” desserts: an interpretive analysis of sports nutrition marketing

Straddling the boundary between “junk” and not, sports nutrition is unique among processed foods. Between-meal snacks full of refined carbohydrates, sugar, sodium and even caffeine, qualities that render foods “bad” and off limits in other contexts, these products are consumed during the “work” of organized leisure, and increasingly as part of everyday life by non-athletes. Masquerading as healthy food, with ingredients, flavours and consumption patterns suggestive of children’s candy and adult desserts (Douglas, M. (1972). Deciphering a meal. Daedalus, 101(1), 61–81; James, A. (1998). Confections, concoctions, and conceptions. In H. Jenkins (Ed.), The children’s culture reader (pp. 394–405). New York: New York University Press.), their use is legitimized by science and the symbolic capital of successful athletes, whose physical capital is used to advertise them (Bourdieu, P. (1978). Sport and social class. Social Science Information, 17(6), 819–840. doi:10.1177/053901847801700603). Semiotic devices relat...
Mutagenesis of Rat Dopamine β‐Hydroxylase: Examination in Cell‐Free System

Dopamine β-hydroxylase (DBH; EC 1.14.17.1) exists as membrane-bound and soluble forms in neurosecretory vesicles. The features of DBH required for glycosylation and incorporation into membranes were studied in a cell-free system. Translation of full-length DBH with microsomal membranes generated two glycosylated products (GH and GL) depending on the magnesium concentration. Carboxyl-terminal, in contrast to amino-terminal, truncations gave translation products that were glycosylated by microsomal membranes. Site-directed mutants were generated with the second AUG codon and the region of a putative signal sequence cleavage site modified. Translation without membranes indicated that the second AUG is not used to initiate translation. The mutant with Glu 41 →Leu 41 and Ser 43 →Thr 43 yielded only the GH form with membranes, whereas mutation of Ser 43 →Ala 43 generated both GH and GL forms. Both glycosylated forms comigrated with the microsomal membranes on sucrose gradients. Endoglycosidase H digestion indicated that the differences between the GH and GL forms are not due to the sugar moiety. The results suggest a role for cleavage of a signal sequence in the formation of different forms of DBH. The possibility that these mutations change the secondary structure near the signal cleavage site, affecting processing, is discussed
Dependence of MOS Device Radiation-Sensitivity on Oxide Impurities

The role of various impurities in the thermally grown silicon dioxide films of metal-oxide-semiconductor (MOS) structures has been investigated. It has been determined that aluminum and sodium within such films strongly influence the radiation-sensitivity of the corresponding MOS devices. The results of the present investigation indicate that much of the radiation-induced positive space charge accumulated within the silicon dioxide films is directly related to the drift and accumulation of ions such as those of sodium. Ionizing radiation, as fran cobalt-60 gamna rays, liberates sodium ions, which are bonded by coulombic forces to non-bridging oxygens, and consequently, the sodium ions drift in the applied gate fields. The space charge due to the accumulation of sodium near the silicon dioxide-silicon interface then causes a perturbation in the surface properties of the silicon. The insight afforded by the above model provides a basis for the fabrication of surface-controlled devices less sensitive to radiation, as well as for the fabrication of radiation dosimeters where the converse in radiation sensitivity is desired. Utilizing appropriate dopants in the silicon dioxide films the desired radiation hardening and dosimetry objectives can be realized.
Highly ionized species and circumstellar shells in B8-A1 stars

The nature of the C IV and Si IV absorption seen in the spectra of apparently normal late-type B and early-type A stars located within 200 pc of the sun was investigated by examining a total of 93 archival IUE spectra of 41 stars. In three of these objects, variable or asymmetric C IV profiles indicate that the absorption features have a stellar origin. One star, HD 119921, showed shortward-shifted discrete C IV and Si IV absorption components similar to those observed in Be stars. All of the stars with detected C IV in their spectra had large values of v sin i. Four of the stars showing C IV and Si IV also showed sharp absorption features in Si II, with two of these stars displaying variable Si II features. These results strongly suggest that these stars are unidentified Be/Ae and shell stars.
A clonal derivative of tunicamycin-resistant Chinese hamster ovary cells with increased N-acetylglucosamine-phosphate transferase activity has altered asparagine-linked glycosylation.

A population of Chinese hamster ovary (CHO) cells resistant to the antibiotic tunicamycin (TM) had previously been isolated (Criscuolo, B.A., and Krag, S.S. (1982) J. Cell Biol. 94:586-591) by a stepwise selection procedure using progressive increments of TM added to the medium. TM inhibits asparagine-linked glycoprotein biosynthesis by blocking the transfer of N-acetylglucosamine-1-phosphate from the sugar nucleotide UDP-N-acetylglucosamine to the isoprenoid lipid carrier, dolichyl phosphate. Four clonal derivatives were isolated from the TM-resistant population in the presence of 27 micrograms TM/ml and were found to overproduce the N-acetylglucosamine-phosphate transferase activity to the same extent (approximately 15-fold compared to wild-type cells). One of these clones, 3E11, was greater than 550-fold more resistant to TM than wild-type cells. The resistance phenotype remained during at least 2.5 months of growth in the absence of TM. 3E11 cells exhibited chromosomal translocations, but no homogeneously staining regions (HSR) or double minute chromosomes. The N-acetylglucosamine-phosphate transferase activity in 3E11 cells was membrane-associated and was inhibited by TM. A 140,000-dalton membrane protein and at least four other membrane proteins were enriched in 3E11 cells. Mannosylphosphoryldolichol synthase and glucosylphosphoryldolichol synthase activities were not elevated in membranes prepared from 3E11 cells. Asparagine-linked glycosylation was altered such that 3E11 cells synthesized primarily a truncated oligosaccharide, Man5GlcNAc2, perhaps due to the reduced amount of mannosylphosphoryldolichol relative to wild-type cells.
In Vivo Multiphoton Microscopy of Deep Brain Tissue

Although fluorescence microscopy has proven to be one of the most powerful tools in biology, its application to the intact animal has been limited to imaging several hundred micrometers below the surface. The rest of the animal has eluded investigation at the microscopic level without excising tissue or performing extensive surgery. However, the ability to image with subcellular resolution in the intact animal enables a contextual setting that may be critical for understanding proper function. Clinical applications such as disease diagnosis and optical biopsy may benefit from minimally invasive in vivo approaches. Gradient index (GRIN) lenses with needle-like dimensions can transfer high-quality images many centimeters from the object plane. Here, we show that multiphoton microscopy through GRIN lenses enables minimally invasive, subcellular resolution several millimeters in the anesthetized, intact animal, and we present in vivo images of cortical layer V and hippocampus in the anesthetized Thy1-YFP line H mouse. Microangiographies from deep capillaries and blood vessels containing fluorescein-dextran and quantum dot-labeled serum in wild-type mouse brain are also demonstrated.
Piece for the End of Time: In Defence of Musical Ontology

Aaron Ridley has recently attacked the study of musical ontology-an apparently fertile area in the philosophy of music. I argue here that Ridley's arguments are unsound. There are genuinely puzzling ontological questions about music, many of which are closely related to questions of musical value. While it is true that musical ontology must be descriptive of pre-existing musical practices and that some debates, such as that over the creatability of musical works, have little consequence for questions of musical value, none of this implies that these debates themselves are without value.
FR900482 class of anti-tumor drugs cross-links oncoprotein HMG I/Y to DNA in vivo

Abstract Background: Overexpression of the high-mobility group, HMG I/Y, family of chromatin oncoproteins has been implicated as a clinical diagnostic marker for both neoplastic cellular transformation and increased metastatic potential of several human cancers. These minor groove DNA-binding oncoproteins are thus an attractive target for anti-tumor chemotherapy. FR900482 represents a new class of anti-tumor agents that bind to the minor groove of DNA and exhibit greatly reduced host toxicity compared to the structurally related mitomycin C class of anti-tumor drugs. We report covalent cross-linking of DNA to HMG I/Y by FR900482 in vivo which represents the first example of a covalent DNA–drug–protein cross-link with a minor groove-binding oncoprotein and a potential novel mechanism through which these compounds exert their anti-tumor activity. Results: Using a modified chromatin immunoprecipitation procedure, fragments of DNA that have been covalently cross-linked by FR900482 to HMG I/Y proteins in vivo were polymerase chain reaction-amplified, isolated and characterized. The nuclear samples from control cells were devoid of DNA fragments whereas the nuclear samples from cells treated with FR900482 contained DNA fragments which were cross-linked by the drug to the minor groove-binding HMG I/Y proteins in vivo. Additional control experiments established that the drug also cross-linked other non-oncogenic minor groove-binding proteins (HMG-1 and HMG-2) but did not cross-link major groove-binding proteins (Elf-1 and NFκB) in vivo. Our results are the first demonstration that FR900482 cross-links a number of minor groove-binding proteins in vivo and suggests that the cross-linking of the HMG I/Y oncoproteins may participate in the mode of efficacy as a chemotherapeutic agent. Conclusions: We have illustrated that the FR class of anti-tumor antibiotics, represented in this study by FR900482, is able to produce covalent cross-links between the HMG I/Y oncoproteins and DNA in vivo. The ability of this class of compounds to cross-link the HMG I/Y proteins in the minor groove of DNA represents the first demonstration of drug-induced cross-linking of a specific cancer-related protein to DNA in living cells. We have also demonstrated that FR900482 cross-links other minor groove-binding proteins (HMG-1 and HMG-2 in the present study) in vivo; however, since HMG I/Y is the only minor groove-binding oncoprotein presently known, it is possible that these non-histone chromatin proteins are among the important in vivo targets of this family of drugs. These compounds have already been assessed as representing a compelling clinical replacement for mitomycin C due to their greatly reduced host toxicity and superior DNA interstrand cross-linking efficacy. The capacity of FR900482 to cross-link the HMG I/Y oncoprotein with nuclear DNA in vivo potentially represents a significant elucidation of the anti-tumor efficacy of this family of anticancer agents.
Fusion-bonded mutilayered SOI for MEMS applications

3-stack and 4-stack, 6" dia. multilayered SOI have been fabricated using two different processes, and the bonding ability, thickness uniformity, and stress investigated. High-quality bonding was achieved with good thickness control, independent of the fabrication method used. The stress in the overall structure was controlled by the balance between the combined stress at the oxide silicon interfaces of the SOI buried oxide layers and that exerted by the oxide on the back surface of the handle wafer. An imbalance of 0.5 μm corresponded to a generated bow of about 12 μm. The etch rate of the buried oxide was enhanced along the bonding interface, particularly in the case of an oxide-oxide join, and was found to be strongly dependent on the bond annealing temperature.
How survey administration can affect response in electronic surveys

Electronic surveys have become one of the most popular methods of data collection in research. In order to obtain satisfactory results, good response rates are needed. We examine response rates to a survey administered in a face-to-face class-based setting collected using an electronic survey tool. The electronic survey was administered in four separate instances where each instance involved the survey administrator using either an active or passive administrative approach, and either offering or declining to offer extra credit. While no significant difference was found in actual responses to questions between the four groups, a significant difference was found in response rates between respondents who were offered extra credit and those who were not, and between surveys that were administered using active versus passive approaches. Other expected findings include higher responses in individual groups using the active approach and offering extra credit. An unexpected result occurred in the groups where no extra credit was offered: No significant difference was found between the active and passive administrations.
Evaluation of copper-64-labeled somatostatin agonists and antagonist in SSTr2-transfected cell lines that are positive and negative for p53: implications for cancer therapy.

Abstract Objectives Radiolabeled somatostatin analogs have become important agents for molecular imaging and targeted radiotherapy of somatostatin receptor-positive tumors. Here we determine the effect of the tumor suppressor protein, p53, on trafficking 64 Cu to tumor cell nuclei from DOTA vs. CB-TE2A-conjugated agonist Y3-TATE and the antagonist 64 Cu-CB-TE2A-sst2-ANT in cell lines that are positive or negative for p53. Methods Receptor binding, internalization, cyclic adenosine monophosphate (cAMP) and nuclear localization studies were performed with the somatostatin receptor subtype 2 (SSTr2) agonists, 64 Cu-CB-TE2A-Y3-TATE and 64 Cu-DOTA-Y3-TATE vs. antagonist, 64 Cu-CB-TE2A-sst2-ANT, in SSTr2-transfected p53 +/+ and −/− HCT116 colorectal carcinoma cells. Results The antagonist, 64 Cu-CB-TE2A-sst2-ANT, bound 8–9-fold more SSTr2 binding sites than did the 64 Cu-labeled agonists. 64 Cu-CB-TE2A-Y3-TATE was more efficiently internalized than 64 Cu-DOTA-Y3-TATE, while 64 Cu-CB-TE2A-sst2-ANT showed lower yet significant levels of internalization. CB-TE2A-Y3-TATE acted as a full agonist, inhibiting cAMP production, whereas CB-TE2A-sst2-ANT showed no inhibition of cAMP production. The 64 Cu from agonists 64 Cu-DOTA-Y3-TATE and 64 Cu-CB-TE2A-Y3-TATE showed greater nuclear localization at 24 h in p53 +/+ vs. −/− cells; however, there was no difference in the levels of 64 Cu from the antagonist based on p53 status. Surprisingly, the DOTA and CB-TE2A-conjugated agonists showed similar nuclear localization in the p53 +/+ and −/− cells, suggesting no difference in 64 Cu release from these chelators in the HCT116 cell lines. Conclusion Based on these in vitro data, the agonist 64 Cu-CB-TE2A-Y3-TATE demonstrates the most promise as an agent for targeted radiotherapy in p53 positive, SSTr2-positive tumors.
Incidence of amyotrophic lateral sclerosis in three counties in western Washington state

We conducted a population-based study of amyotrophic lateral sclerosis (ALS) in King, Pierce, and Snohomish counties in western Washington state. Between April 1, 1990 and March 31, 1995, neurologists diagnosed 235 patients with ALS, including 127 men (54%) and 108 women (46%). The incidence rate, age-adjusted to the 1990 total U.S. population, was higher for men at 2.1 per 100,000 per year (95% CI, 1.3 to 2.9) than for women at 1.9 (95% CI, 1.1, 2.7) and increased with age for both men and women. These incidence rates are consistent with other studies from northern latitudes.
Endoscopic treatment with multiple stents for post–liver-transplantation nonanastomotic biliary strictures

Background Over the past decade, ERCP has become the preferred method of treatment for biliary strictures in patients after orthotopic liver transplantation (OLT). Although data strongly support ERCP for treating anastomotic strictures, the little information available for the role of ERCP in the treatment of nonanastomotic strictures (NAS) has been unpromising. Objective We investigated the efficacy and safety of using balloon dilation and multiple biliary stents to treat NAS. Design A retrospective study. Setting A tertiary-care medical center. Patients Fifteen patients who were diagnosed with post-OLT NAS between January 2003 and June 2007. Interventions ERCP with balloon dilation and multiple stenting. Main Outcome Measurements Resolution, complication, and recurrence rates. Results Eleven of the 15 patients completed endoscopic treatment, of whom 9 had cholangiographic improvement, biochemical normalization, and cholestatic symptom relief (treatment success), and 1 required retransplantation (treatment failure). None of the 9 successfully treated patients experienced NAS recurrence in a mean follow-up of 17 months. Of the remaining 4 patients, 1 died of nonbiliary causes and 3 were still undergoing treatment with stents in place, of whom 2 have near-normalized total serum bilirubin and were cholestatic symptom free. Limitations A retrospective study, small sample size, single endoscopist. Conclusions Endoscopic treatment of NAS with balloon dilation and multiple stents appears to be safe and effective, and it may reduce the need for retransplantation because of NAS. Larger studies are still required to confirm its utility as a mainstay for treating NAS and to determine what factors are associated with endoscopic treatment success.
Current concepts in the pathophysiology of testicular undescent

At present, we believe that descent of the testes within the human is a complex event mediated by both hormonal and mechanical factors. We hypothesize that descent of the testes occurs as a result of the secretion of an androgen-independent factor from a normal testis (descendin). This paracrine factor is responsible for the rapid proliferation (outgrowth) of the ipsilateral gubernaculum. The development of the gubernaculum results in creating a dilated inguinal canal, the width of which matches the testicular width. Descent of the testes through the inguinal canal is an interplay between abdominal pressure, a patent processus vaginalis, and androgen-induced gubernacular regression. We hypothesize that androgens (under control of an intact hypothalamic pituitary axis) alter the viscoelastic properties of the gubernaculum, reducing the turgidity of the gubernaculum and allowing intra-abdominal pressure to push the testis into the scrotum. Cryptorchidism can therefore result when any one or more of the involved factors malfunction.
Activized Learning with Uniform Classification Noise

We prove that for any VC class, it is possible to transform any passive learning algorithm into an active learning algorithm with strong asymptotic improvements in label complexity for every nontrivial distribution satisfying a uniform classification noise condition. This generalizes a similar result proven by (Hanneke, 2009; 2012) for the realizable case, and is the first result establishing that such general improvement guarantees are possible in the presence of restricted types of classification noise.
Stability analysis of an approximate scheme for moving horizon estimation

We analyze the stability properties of an approximate algorithm for moving horizon estimation (MHE). The strategy provides instantaneous state estimates and is thus suitable for large-scale feedback control. In particular, we study the interplay between numerical approximation errors and the convergence of the estimator error. In addition, we establish connections between the numerical properties of the Hessian of the MHE problem and traditional observability definitions. We demonstrate the developments through a simulation case study.
Gallbladder cancer-associated thrombotic microangiopathy

Cancer-associated thrombotic microangiopathy (TMA) is a rare but serious condition seen in patients diagnosed with malignancy. Certain tumor characteristics highlight this entity, such as large tumor burden, adenocarcinoma histology with mucinous features and bone marrow infiltration. Although these tumors may originate from any site, the majority are of stomach, breast or prostate origin. The optimal therapy is unknown but there is evidence that immediate initiation of an effective antineoplastic regimen is important. However, it is difficult to differentiate cancer-associated TMA from primary thrombotic thrombocytopenic purpura in a timely manner. We present the first case of cancer-associated TMA in a patient secondary to a locally advanced gallbladder adenocarcinoma that lacked mucinous features and bone marrow involvement. The clinical presentation closely mimicked primary thrombocytopenic purpura and led to the ineffective use of plasma exchange. Nonetheless, the patient eventually received systemic chemotherapy and had a remarkable response by the resolution of her TMA.
Mycobacterial Bacilli Are Metabolically Active during Chronic Tuberculosis in Murine Lungs: Insights from Genome-Wide Transcriptional Profiling

Chronic tuberculosis represents a major health problem for one-third of the world's population today. A key question relevant to chronic tuberculosis is the physiological status of Mycobacterium tuberculosis during this important stage of infection. To examine the molecular bases of chronic tuberculosis and the role of host immunity in mycobacterial growth, we determined the mycobacterial transcriptional profiles during chronic and reactivation phases of murine tuberculosis using in vivo microarray analysis (IVMA). Following 28 days of aerosol infection, mycobacterial counts remained stable, although the bacilli were metabolically active with a 50% active transcriptome. The expression of genes involved in lipid and carbohydrate pathways was significantly enriched during the middle stage of chronic tuberculosis, suggesting a nutrient-rich microenvironment. A total of 137 genes were significantly regulated in mid-chronic tuberculosis (45 and 60 days) compared to an early stage (14 days) of infection. Additional sets of genes, including the virulence regulator virS, were up-regulated during the reactivation stage, indicating their possible roles in mycobacterial resurgence. Interestingly, a set of potential transcriptional regulators was significantly induced at the late stage of chronic tuberculosis. Bioinformatic analysis identified a large number of genes that could be regulated by one of the potential transcriptional regulators encoded by rv0348, including the sigF operon. Taken together, IVMA provided a better definition of the transcriptional machinery activated during chronic and reactivation stages of tuberculosis and identified a novel transcriptional regulator. A similar approach can be adopted to study key stages of intracellular pathogens.
Angiotensin II in the Evolution of Experimental Heart Failure

Although angiotensin II (Ang II) has been implicated in the pathophysiology of congestive heart failure, its temporal and regional changes during the development and progression of the disease are poorly defined. Our objective was to assess circulating, renal, cardiac, and vascular Ang II in a canine model of rapid ventricular pacing-induced heart failure that evolves from early left ventricular dysfunction to overt congestive heart failure. Ang II was measured by radioimmunoassay with low cross-reactivity to other angiotensins. Control, early left ventricular dysfunction, and overt congestive heart failure dogs were studied. Early left ventricular dysfunction was characterized by impaired cardiac function, cardiac enlargement, preserved renal perfusion pressure, maintained urinary sodium excretion, and normal plasma renin activity. Overt congestive heart failure was characterized by further impaired cardiac function and cardiac enlargement, reduced renal perfusion pressure, urinary sodium retention, and increased plasma renin activity and plasma Ang II. In early left ventricular dysfunction dogs, renal cortical, renal medullary, ventricular, and aortic Ang II were unchanged, and atrial Ang II was decreased. In overt congestive heart failure dogs, Ang II was increased in the kidney and heart compared with normal dogs and in all tissues compared with early left ventricular dysfunction dogs. The greatest increase in tissue Ang II occurred in the renal medulla. We conclude that early increases in local renal, myocardial, and vascular Ang II do not occur in this model of early left ventricular dysfunction and may even be suppressed. In contrast, increased myocardial and particularly renal Ang II in association with increased circulating Ang II are hallmarks of overt experimental congestive heart failure. These studies provide new insights into the temporal and regional alterations in Ang II during the progression of experimental congestive heart failure.
The historian's craft and economics

History refers both to the past and to the systematic study of the past. Attempts to make a case for history in economics generally emphasize the first definition. There are benefits from increased attention to the past. This paper argues that significant benefits can be gained from increased attention to the systematic study of the past, the historian's craft. The essence of the historian's craft is the critical evaluation of sources. Failure to critically evaluate sources has the potential to lead to erroneous conclusions, whether one is using historical documents or more recently created data.
The Glass Infrastructure: Using Common Sense to Create a Dynamic, Place-Based Social Information System

Most organizations have a wealth of knowledge about themselves available online, but little for a visitor to interact with on-site. At the MIT Media Lab, we have designed and deployed a novel intelligent signage system, the Glass Infrastructure (GI) that enables small groups of users to physically interact with this data and to discover the latent connections between people, projects, and ideas. The displays are built on an adaptive, unsupervised model of the organization developed using dimensionality reduction and common sense knowledge which automatically classifies and organizes the information. The GI is currently in daily use at the lab. We discuss the AI model’s development, the integration of AI into an HCI interface, and the use of the GI during the lab’s peak visitor periods. We show that the GI is used repeatedly by lab visitors and provides a window into the workings of the organization.
Serologic typing of Staphylococcus epidermidis biotype 4.

Three hundred sixty-five isolates of Staphylococcus epidermidis (coagulase-negative), obtained over a 12-month period from 10 selected wards at New York University Medical Center-Goldwater Memorial Hospital, Roosevelt Island, N.Y., were typed serologically by slide agglutination. The isolates were first biotyped by the BairdParker scheme and then subtyped as proteinase-positive or proteinase-negative so that the selection of strains for immunologic study was based on biochemical and enzymatic factors rather than on random choice. The biotyping scheme of Baird-Parker and the differentiation between proteolytic and nonproteolytic strains were of limited use in the identification of a particular strain, although these methods were helpful in initial categorization of isolates of S. epidermidis. Antisera to proteinase-positive and proteinase-negative S. epidermidis biotypes 1 and 4 were absorbed with different permutations of homologous and heterologous thermostable (TS) and thermolabile (TL) antigens, and four distinct TL and two distinct TS antigenic groups, representing five different serotype patterns (i.e., Al-2, B1-2, C-D1, C-D1-2, and El), were detected. The TL antigens also appeared to be more widespread and were shared more frequently by strains of S. epidermidis than were TS antigens, but the use of both TS and TL antigens provided a better serologic system than use of either TS or TL antigens alone.
Rapid Screening for Lupus Erythematosus Ceils Using Cytocentrifuge-prepared Buffy Coat Monolayers

A method for the rapid screening of the lupus erythematosus (LE) cell test using cytocentrifuge-prepared buffy coat monolayers is presented. Morphologic features of LE cells are well preserved, and technician screening time is decreased significantly.
Scenario Exploration for Sustainability of the Multimodal Intercity Transportation System

As concern for environmental impact of various sectors grows, new methodologies and tools are needed to explore scenarios representing the wide variety of possible future socioeconomic environments and technologies. Sustainability of the transportation system is of paramount importance, as it is a driver of economic growth and a non negligible sector in terms of emissions. This study focuses on the two main modes of transportation for longdistance travel in the continental United States: commercial air transportation and automobiles. A parametric simulation environment, the Transportation Sytem-of-Systems simulator, has been developed and is used to assess the multimodal response of travelers to changes in prices and the impact on fuel use. The multimodal approach provides insight into potential mode shifts and tradeoffs in the transportation System-of-Systems. In high fuel price scenarios, both mode shifts and overall demand reduction occur. The introduction of more fuel efficient aircraft and automobiles is accelerated, which helps to maintain mobility while limiting CO2 emissions. With more fuel efficient vehicles, the effects of higher fuel prices is attenuated. Fuel price increase may be implemented separately on each mode at different times, and in most cases result in a decrease in CO2 emissions. The decrease in CO2 emissions resulting from increases in fuel price is limited (up to 2%) compared to the gain obtained through new technologies (of the order of 30%). Due to the multi-objective nature of this problem, multi-attribute decision making is used to identify the best scenario. High fuel price scenarios perform better if emphasis is on emissions reduction, but are penalized when mobility is weighted more strongly.
Pathology and Molecular Biology of the Pituitary Region

Tumors of the pituitary gland and sellar region represent approximately 10–15 % of all brain tumors. Numerous types of tumors may involve the sellar region, reflecting its complex anatomy. Table 4.1 lists the most frequent tumors arising in the pituitary and sellar region. By far the most common of these are pituitary adenomas, benign epithelial tumors derived from cells of the adenohypophysis. In fact, pituitary adenomas represent the third most common primary intracranial tumor in neurosurgical practice, outnumbered only by gliomas and meningiomas. Pituitary adenomas predominantly affect women between the third and sixth decades, but no age group is spared. Adenomas are uncommon in the pediatric population, and most tumors of childhood are clinically functioning adenomas that are thought to be more aggressive. Rates for pituitary tumors in the United States are slightly higher among African Americans than Caucasians. Incidental adenomas can be found in nearly 10 % of autopsied patients.
Psychosocial Development Factors Associated with Occupational and Vocational Identity Between Infancy and Adolescence

The identification with an occupation is a challenge most adolescents face in their transition into adulthood. Psychosocial development theory suggests that adolescents’ identification with an occupation develops across the lifespan, making youth work roles, choices, and behaviors products of their integrated psychosocial development experiences. This review examines the existing occupational and vocational identity literature to identify the associations with factors relevant to psychosocial development between infancy and adolescence, and integrates them to provide a more comprehensive understanding of how adolescents identify with an occupation. The review reveals that the factors important to healthy psychosocial development in each of Erikson’s five pre-adult stages largely were predictive of occupational identity status in adolescence. Disagreement was present in the literature, with most of it centered on the role of complex outer and environmental factors. The review highlights gaps in the literature and prioritizes areas for future research based largely on a return to Erikson’s intention of treating occupational identity as developmental. The review adds to the current debates and knowledge of youth development and of how adolescents identify with an occupation by providing an integration of the existing empirical evidence not just at the point of adolescence, but also across the entire pre-adult lifespan.
A High Temperature Passive GaN-HEMT Mixer for Downhole Communications

Abstract Declining reserves of easily accessible natural resources have motivated the oil and gas industry to drill deeper. Temperatures in these hostile wells can exceed 210 °C. Cooling and conven...
Information fusion-based meta-classification predictive modeling for ETF performance

This study is aimed at determining the future share net inflows and outflows of Exchange Traded Funds (ETFs). The relationship between net flows is closely related to investor perception of the future and past performance of mutual funds. The net flows for Exchange Traded Funds are expected to be less related to overall fund performance, but rather based on the characteristics of the fund that make it attractive to an individual investor. In order to explore the relationship between investor's perception of ETFs and subsequent net flows, this study is designed to shed light on the multifaceted linkages between fund characteristics and net flows. A meta-classification predictive modeling approach is designed for the use of large data sets. Then its implementation and results are discussed. A thorough selection of fifteen attributes from each fund, which are the most likely contributors to fund inflows and outflows, is deployed in the analyses. The large data set calls for the use of a robust systematic approach to identifying the attributes of the funds that best predict future inflows and outflows of the fund. The predictive performance of the proposed decision analytic methodology was assessed via the 10-fold cross validation, which yielded very promising results.