cssi/SciSciGPT-SciSciNet huggingface dataset:
Prostaglandin E2 Stimulates a Ca2+-dependent K+ Channel in Human Erythrocytes and Alters Cell Volume and Filterability

Abstract To understand the mechanism by which human red blood cells (RBCs) contribute to hemostasis and thrombosis, we have examined the effects of metabolites released by activated platelets on intact RBCs. Prostaglandin E2 (PGE2), a signal molecule produced by activated platelets, was observed to lower the filterability of human erythrocytes by ~30% at 10−10 M. PGE2 also caused a reduction in mean cell volume of ~10%. The shrinkage of red cells after PGE2 treatment was confirmed by documenting a decrease in osmotic fragility and an increase in cell density following exposure to the hormone. Careful analysis, however, revealed that only ~15% of the erythrocytes responded to stimulation with PGE2. Examination of the cause of cell shrinkage showed that induction of a PGE2-stimulated K+ efflux pathway leading to rapid loss of cellular K+ was responsible. The PGE2-stimulated K+ loss was also observed to be Ca2+-dependent, suggesting the possible involvement of the Gardos channel. Gardos channel participation was supported by the observation that two Gardos channel inhibitors, charybdotoxin and clotrimazole, independently blocked the PGE2-stimulated K+ efflux. Further evidence for Gardos channel activation came from experiments aimed at characterizing the efflux pathway followed by the obligatory counterion. Thus, K+ efflux was readily stimulated even when NO−3 was substituted for Cl−, suggesting that neither KCl cotransport nor Na/K/2Cl cotransport plays a prominent role in the PGE2-induced cell shrinkage. Further, the anion transporter band 3 was implicated as the counterion efflux route, since DIDS inhibited the PGE2-stimulated cell volume change without blocking the change in membrane potential. Taken together, we propose that release of PGE2 by activated platelets constitutes part of a mechanism by which activated platelets may recruit adjacent erythrocytes to assist in clot formation.
Pricing games among interconnected microgrids

We consider a scenario with multiple independent microgrids close to each other in a region that are connected to each other and to the central grid (macrogrid). In each time slot, a given microgrid may produce more than, less than or as much power as it needs, and there is uncertainty on which of these events may occur. The microgrids with excess power, those with deficit power and the macrogrid trade power in an electricity market, in which each microgrid with excess power quotes a price for it and the microgrids with deficit power buy power from the microgrids who quote the lowest prices. This results in price competition among the microgrids with excess power, and this competition has several distinguishing features not normally present in price competition in traditional markets studied in economics. We analyze this price competition using the framework of game theory, explicitly compute a Nash Equilibrium and show its uniqueness.
A semi-Lagrangian double Fourier method for the shallow water equations on the sphere

We describe a numerical method, based on the semi-Lagrangian semi-implicit approach, for solving the shallow water equations (SWEs) in spherical coordinates. The most popular spatial discretization method used in global atmospheric models is currently the spectral transform method, which generates high-order numerical solutions and provides an elegant solution to the pole problems induced by a spherical coordinate system. However, the standard spherical harmonic spectral transform method requires associated Legendre transforms, which for problems with resolutions of current interest, have a computational complexity of O(N3), where N is the number of spatial subintervals in one dimension. Thus, the double Fourier spectral method, which uses trigonometric series, may be a viable alternative. The advantage of the double Fourier method is that fast Fourier transforms, which have a computational complexity of O(N2 log N), can be used in both the longitudinal and latitudinal directions. In this implementation, the SWEs are discretized in time by means of the three-time-level semi-Lagrangian semi-implicit method, which integrates along fluid trajectories and allows large time steps while maintaining stability. Numerical results for the standard SWEs test suite are presented to demonstrate the stability and accuracy of the method.
High-frequency spinal cord stimulation: An emerging treatment option for patients with chronic pain

Abstract Chronic pain is a complex syndrome estimated to affect over 100 million Americans. Pharmaceutical-based therapy, including the use of opioids, is widely accepted as a primary treatment strategy but is associated with addiction, overdose, and diversion risk. Spinal cord stimulation (SCS) is a well-established, device-based alternative for pain management. Though effective in treating leg pain, traditional SCS has been much less effective at achieving long-term back-pain relief. In addition, stimulation with traditional SCS often leads to tingling sensations and inadvertent postural-related shocks that many patients find unpleasant. A newly developed SCS system (Nevro Corp., Menlo Park, CA) shows promise in addressing these limitations. This new device is similar to traditional SCS systems but is able to stimulate at much higher frequencies, up to 10 kHz. Prospective clinical studies of high-frequency SCS (HF-SCS) suggest improved effectiveness in treating chronic low-back pain and other types of pain that often do not respond well to traditional SCS. In addition, HF-SCS appears capable of delivering pain relief without paresthesia, both simplifying the implant procedure and improving patient satisfaction. The system is currently undergoing study in a multicenter, randomized controlled clinical trial in the United States. If the results are positive, HF-SCS could represent an important advancement in the treatment of chronic pain.
SPECIFIC RECOGNITION OF A TRANSCRIPTIONAL ELEMENT WITHIN THE HUMAN H-RAS PROTOONCOGENE BY THE P53 TUMOR-SUPPRESSOR

Abstract. The nuclear phosphoprotein p53 is frequently inactivated in human cancer. Although it was previously classified as an oncoprotein, p53 has emerged as a tumor suppressor controlling cell cycle progression by regulating gene transcription. A major biochemical property of wild-type p53 is its ability to bind DNA in a sequence-specific manner. The human c-H-ras gene contains within its first intron sequences that partially match the p53 consensus binding site. We determined that these sequences represent a bona fide p53 element, since in vitro translated wild-type p53 recognized them with high affinity. Furthermore, wild-type p53 activated transcription from a reporter plasmid containing the c-H-ras element as an enhancer. These findings suggest that p53 regulates cellular growth by coordinate transcription of genes that suppress and promote cellular proliferation. Introduction The p53 gene encodes a sequence-specific transcription factor that induces cell cycle arrest or programmed cell death in response to DNA damage (1-6). In more than half of all human tumors p53 is inactivated by missense mutations (7-10). Such tumors become refractory to stimuli that would normally induce apoptosis or cell cycle arrest (11). The protein encoded by the p53 gene has been studied extensively. The N-terminus of p53 contains a transactivation domain (12,13), the C-terminus a tetramerization domain (14-17), and the central region a sequence-specific DNA binding domain (18-21). The latter domain is inactivated by point mutations in human tumors (7-10).
Extracting the distribution of laser damage precursors on fused silica surfaces for 351 nm, 3 ns laser pulses at high fluences (20-150 J/cm 2 )

Surface laser damage limits the lifetime of optics for systems guiding high fluence pulses, particularly damage in silica optics used for inertial confinement fusion-class lasers (nanosecond-scale high energy pulses at 355 nm/3.5 eV). The density of damage precursors at low fluence has been measured using large beams (1-3 cm); higher fluences cannot be measured easily since the high density of resulting damage initiation sites results in clustering. We developed automated experiments and analysis that allow us to damage test thousands of sites with small beams (10-30 µm), and automatically image the test sites to determine if laser damage occurred. We developed an analysis method that provides a rigorous connection between these small beam damage test results of damage probability versus laser pulse energy and the large beam damage results of damage precursor densities versus fluence. We find that for uncoated and coated fused silica samples, the distribution of precursors nearly flattens at very high fluences, up to 150 J/cm2, providing important constraints on the physical distribution and nature of these precursors.
Novel reflected light confocal profilometer

We present an instrument that uses a novel technique to render topographical maps of microscopic reflecting surfaces in which depth resolution can be an order of magnitude or more better than the lateral resolution of the confocal microscope. In a confocal scanning reflected-light microscope, the illumination light coming out of the objective is a cone of light with its axis parallel to the optical axis and focused into a diffraction-limited spot. If the specimen is smooth within the size of the spot, then the laws of reflection apply. When the reflecting surface is perpendicular to the optical axis, the reflected light is a cone that coincides with the illumination light. If the reflecting surface is not perpendicular to the optical axis, the axis of the reflected cone of light is at an angle with respect to the optical axis equal to twice the tilt angle of the surface and oriented in the direction of the surface tilt. Because of this tilt, a portion of the back focal plane (BFP) of the objective does not receive any of the reflected light, while in the diametrically opposite side, the aperture stop blocks part of the reflected light. For a given illumination profile, the distribution of light on the BFP is determined by the tilt and orientation angles of the reflecting surface and thus can be used to recover these angles for each pixel in the specimen. These angles are then used to render a topographical map of the reflecting surface.© (1997) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Porous Media Modeling of Two-Phase Micro-Channel Cooling of Electronic Chips With Non-Uniform Power Distribution

Compared to single phase heat transfer, two-phase micro-channel heat sinks utilize latent heat to reduce the needed flow rate and maintaining a rather uniform temperature close to the boiling temperature. The challenge in the application of cooling for electronic chips is the necessity of modeling a large number of micro channels using large number of meshes and extensive computation time. In the present study, a modified porous media method modeling of two phase flow in micro-channels is performed. Compared with conjugate CFD method, it saves computation effort and provides a more convenient means to perform optimization of channel geometry. The porous media simulation is applied to a real chip. The channels of high heat load will have higher qualities, larger flow resistances and lower flow rates. At a constant available pressure drop over the channels, the low heat load channels show much higher mass flow rates than needed. To avoid this flow mal-distribution, the channel widths on a chip are adjusted to ensure the exit qualities and mass flow rate of channels are more uniform. As a result, the total flow rate on the chip is drastically reduced, and the temperature gradient is also minimized. However, it only gives a relatively small reduction on the maximum surface temperature of chip.Copyright © 2013 by ASME
A technique for modelling p-n junction depletion capacitance of multiple doping regions in integrated circuits

Abstract The continuing advancements in integrated circuit technology have placed new burdons on the circuit design engineer, who must rely extensively upon computer simulation to correctly predict circuit behavior. One challenge is to develop better modelling techniques to more accurately deal with complex p-n junction structures often used in modern VLSI designs. This paper presents an easily implemented method for deriving parameters which accurately model the behavior of MOS VLSI structures containing complex p-n junction capacitance components. The methodology is applicable to both planar and laterally diffused junctions, whether formed by direct ion implantation or by diffusion from a finite or infinite source. The theories behind the equations used and results of the application of this new technique are discussed. A flow chart for a fitter program based on the new method is presented and described. The corresponding program written for the TI-59 scientific programmable calculator is available. Final model parameters are given and are shown to produce a numerical capacitance model which is accurate to within 2%.
Testing the National Software Reference Library

Abstract The National Software Reference Library (NSRL) is an essential data source for forensic investigators, providing in its Reference Data Set (RDS) a set of hash values of known software. However, the NSRL RDS has not previously been tested against a broad spectrum of real-world data. The current work did this using a corpus of 36 million files on 2337 drives from 21 countries. These experiments answered a number of important questions about the NSRL RDS, including what fraction of files it recognizes of different types. NSRL coverage by vendor/product was also tested, finding 51% of the vendor/product names in our corpus had no hash values at all in NSRL. It is shown that coverage or “recall” of the NSRL can be improved with additions from our corpus such as frequently-occurring files and files whose paths were found previously in NSRL with a different hash value. This provided 937,570 new hash values which should be uncontroversial additions to NSRL. Several additional tests investigated the accuracy of the NSRL data. Experiments testing the hash values saw no evidence of errors. Tests of file sizes showed them to be consistent except for a few cases. On the other hand, the product types assigned by NSRL can be disputed, and it failed to recognize any of a sample of virus-infected files. The file names provided by NSRL had numerous discrepancies with the file names found in the corpus, so the discrepancies were categorized; among other things, there were apparent spelling and punctuation errors. Some file names suggest that NSRL hash values were computed on deleted files, not a safe practice. The tests had the secondary benefit of helping identify occasional errors in the metadata obtained from drive imaging on deleted files in our corpus. This research has provided much data useful in improving NSRL and the forensic tools that depend upon it. It also provides a general methodology and software for testing hash sets against corpora.
Very low density lipoprotein subfractions in a subject with broad-β disease (type III hyperlipoproteinemia) and a subject with endogenous lipemia (type IV) chemical composition and electrophoretic mobility

1. 1. Three subfractions (sf 20–60, 60–100, 100–400) of very low density lipoproteins have been isolated from a subject with broad-β disease (Type III hyperlipoproteinemia) and a subject with endogenous (Type IV) lipemia by preparative ultracentrifugation through a saline density gradient. The subfractions and the entire very low density lipoproteins, isolated in a single, separate ultracentrifugation, have been examined by analytical ultracentrifugation, paper and agarose electrophoresis, and chemical analysis. Recovery in the three subfractions as compared with the entire very low density lipoproteins (by both chemical analysis and analytical ultracentrifugation) confirmed the validity of the subfractionation procedure. 2. 2. The subject with broad-β disease exhibited a large quantity of sf > 400 lipoproteins and a very low density lipoprotein distribution with a higher peak Sf value than his counterpart with endogenous lipemia. 3. 3. Electrophoresis revealed pre-β mobility for all subtractions in the subject with endogenous lipemia and sf 60–100 and 100–400 subfractions in the subject with broad-β disease; in the latter, β-mobility was confined to the Sf 20–60 very low density lipoprotein subclass. 4. 4. In both subjects comparison of chemical composition among subfractions revealed progressive increases in protein, phospholipid, and cholesterol content and a parallel decrease in triglyceride as sf rate decreased. 5. 5. Chemical composition of all very low density lipoprotein subfractions appeared to be normal in the subject with endogenous lipemia. His counterpart with broad-β disease revealed abnormal increases in cholesterol ester and reciprocal decreases in triglyceride in all subfractions.
A classification of organic redox reactions and writing balanced equations for them, with special attention to heteroatoms and heterocyclic compounds

Organic redox reactions are classified either as atom transfers (balanced by inspection) or as more complex transformations (balanced by change in oxidation number, ON, by change in DOX value, by electrochemical half-reaction, or by simultaneous linear algebraic equations). Examples presented include not only involvement of hydrogen or oxygen but also extensions to halogens, nitrogen, phosphorus, and sulfur. Complex reactions are subdivided into ones which proceed (a) without change in the number of carbon atoms per molecule, (b) with fragmentation of the carbon assemblage in the starting material, or (c) with condensation of two or more molecules of organic starting materials.
Greenhouse effect and coastal wetland policy: How Americans could abandon an area the size of Massachusetts at minimum cost

Climatologists generally expect an anthropogenic global warming that could raise sea level 30–150 cm in the next century and more thereafter. One of the impacts would be the loss of coastal wetlands. Although the inundation of adjacent dryland would enable new wetlands to form, much of this land is or will soon be developed. If developed areas are protected, wetlands will be squeezed between an advancing sea and the land being protected, which has already happened in China and the Netherlands, where people have built dikes for centuries. Unlike those countries, the United States has enough land to accommodate the landward migration of wetlands; but governments lack the funds to purchase all the coastal lowlands that might be inundated and the legal authority to prohibit their development. We propose a third approach: allowing property owners to use coastal lowlands today as they choose, but setting up a legal mechanism to ensure that the land is abandoned if and when sea level rises enough to inundate it. Although compensation may be required, this approach would cost less than 1% as much as purchasing the land, and would be (1) economically efficient by enabling real estate markets to incorporate expectations of future sea level rise; (2) constitutional by compensating property owners; and (3) politically feasible by pleasing people who care about the long-term fate of the coastal environment without disturbing people who either are unconcerned about the distant future or do not believe sea level will rise. This article demonstrates that it would be irrational to delay policy formulation until sea level rise projections are more precise. The cost will be small if we act now but great if we wait, and sea level is already rising along most coasts. The US government should develop a strategy in the next three years.
Mechanics of Living Cells Measured by Laser Tracking Microrheology

To establish laser-tracking microrheology (LTM) as a new technique for quantifying cytoskeletal mechanics, we measure viscoelastic moduli with wide bandwidth (5 decades) within living cells. With the first subcellular measurements of viscoelastic phase angles, LTM provides estimates of solid versus liquid behavior at different frequencies. In LTM, the viscoelastic shear moduli are inferred from the Brownian motion of particles embedded in the cytoskeletal network. Custom laser optoelectronics provide sub-nanometer and near-microsecond resolution of particle trajectories. The kidney epithelial cell line, COS7, has numerous spherical lipid-storage granules that are ideal probes for noninvasive LTM. Although most granules are percolating through perinuclear spaces, a subset of perinuclear granules is embedded in dense viscoelastic cytoplasm. Over all time scales embedded particles exhibit subdiffusive behavior and are not merely tethered by molecular motors. At low frequencies, lamellar regions (820 +/- 520 dyne/cm(2)) are more rigid than viscoelastic perinuclear regions (330 +/- 250 dyne/cm(2), p 10 s. Over a broad range of frequencies (0.1-30, 000 rad/s), LTM provides a unique ability to noninvasively quantify dynamic, local changes in cell viscoelasticity.
Mechanistic Study of Copper-Catalyzed Aerobic Oxidative Coupling of Arylboronic Esters and Methanol: Insights into an Organometallic Oxidase Reaction

Copper-catalyzed aerobic oxidative coupling of arylboronic acid derivatives and heteroatom nucleophiles is a highly useful method for the formation of aryl-heteroatom bonds. Mechanistic studies reveal that this reaction proceeds via an “oxidase”-style mechanism. Kinetic and spectroscopic studies establish that transmetalation of the aryl group from boron to CuII is the turnover-limiting step and reoxidation of the reduced catalyst by O2 is rapid. Further mechanistic analysis implicates the involvement of an aryl-copper(III) intermediate that undergoes facile C−O bond formation.
STEM Faculty Experiences with Students with Disabilities at a Land Grant Institution

Preparing faculty to meet the needs of the increasing number of students with disabilities is a critical need in higher education, particularly in the STEM (science, technology, engineering, and mathematics) fields. Quality preparation is an emerging problem as the number of higher education students with disabilities is on the rise. In this study, researchers used a qualitative methodology to examine STEM faculty members’ experiences with students with disabilities at a land grant institution in the southeastern United States. The study was conducted to answer the following questions: (a) What experiences, positive and negative, have STEM faculty members had working with students with disabilities?(b) How do STEM faculty members describe students with disabilities?, and (c) What resources do faculty members need to adequately serve students with disabilities? Five researchers conducted individual interviews with STEM faculty members. Interviews were transcribed and analyzed, with the following themes emerging from the data: Challenges, Support, Knowledge, Awareness/Visibility, and Formal versus Informal Accommodations. Implications from this study relate to the improvement of services for students with disabilities at higher education institutions and to the preparation of STEM faculty to accommodate their students.
Consistent EEG Focalities Detected in Subjects with Primary Generalized Epilepsies Monitored for Two Decades

Summary: Purpose: To describe the evolution of interictal findings in serial EEGs from patients with primary generalized epilepsy. Methods: A cohort of 89 subjects with various primary generalized epilepsies were reviewed. Thirty-one did not meet a priori criteria. Of the 58 patients analyzed, 12 had only absence seizures, 28 had absence seizures followed by one or more generalized tonic-clonic seizures, 9 had generalized tonicclonic seizures followed by absence and/or myoclonic seizures, and 9 had juvenile myoclonic epilepsy. Patients were followed for a mean of 16 years. An average of 39 EEGs were obtained on each patient. Results: Thirty-two patients (56%) had focal features present in up to 65% of the EEGs in each of the patients. Accepted focalities were only those that were consistent in lateralization, location and, often, morphology across the span of the study. Focal findings were most often temporal or frontal. Conclusions: Patients with typical primary generalized epilepsies show a high incidence of focal EEG features that cannot be explained on the basis of structural lesions, coincidental factors, or to artifacts of the selection criteria. Although the data do not allow a definitive explanation, possible mechanisms include associated focal cortical pathology such as microdysgenesis, and development over time of localized, self-sustaining hyperexcitability in low-threshold cortical structures subjected to repeated generalized spike-wave activity. Either hypothesis implies the participation and interaction of genetic, ontogenic, and environmental factors.
Impacts of baicalein analogs with modification of the 6th position of A ring on the activity toward NF-κB, AP-1 or CREB mediated transcription

The water extract of Scutellariae baicalensis Georgi (S. baicalensis) has potential anti-tumor and anti-inflammatory activities. A major flavonoid isolated from S. baicalensis, baicalein, was also found to have anti-tumor and anti-inflammatory activities. These biological activities could be due to their antioxidant action and/or effect on different signal transduction pathways. We investigated the effects of several baicalein analogs with a substitution of hydrogen of the hydroxyl group at the 6th position of A ring on three signal pathway mediated transcription (NF-kappaB, AP-1, and CREB) associated with inflammation and cancer growth. We found that the analogs with O-alkyl group of the different carbon chain length or O-benzyl activated NF-kappaB transcription without TNFalpha stimulation. Some of the analogs increased TNFalpha stimulated NF-kappaB transcription by two- to threefold. None of the analogs studied has major effect on AP-1 signal transduction with or without TPA stimulation. All of the analogs increased CREB transcription with forskolin stimulation up to twofold. However, they did not have a potent effect (less or about twofold activation) on intrinsic CREB signal transduction. The modification of baicalein at the 6th position of A ring was not correlated with change in these signal transduction pathways and cytotoxicity. Though, they are structural analogs, they are not functional analogs. Modification of baicalein at the 6th position could alter the specificity of action toward different cellular targets. Flavonoids could be chemophores in the development of drugs targeted at different signal transcriptional pathway.
The investment decision of a Multinational Firm under uncertain quantity restrictions

In this paper we analyze the allocative investment decisions of a Multinational Firm (MNF) when it faces uncertain quantity restrictions such as a voluntary export restraint or a quota imposed by the host government. The model with uncertain quantity restrictions is analyzed further by introducing additional uncertainties such as a foreign tax rate, transfer prices, foreign exchange rates and foreign demand. The MNF invests more in the host country due to uncertain quantity restrictions. The risk averse MNF invests more in the host country despite its uncertain tax rate if the transfer price is less than the expected marginal revenue loss due to the uncertain quantity restriction. The uncertain transfer price leads the MNF to invest more in the foreign country if the tax rates are dissimilar between the two countries. Foreign demand uncertainty and foreign exchange rates uncertainty have the same effects on capital allocation between the host country and home country. In particular, we derive the condition under which the direction of investment is unambiguous.
Cloning and characterization of a lysosomal phospholipase A2, 1-O-acylceramide synthase.

Recently, a novel enzyme, 1-O-acylceramide synthase (ACS), was purified and characterized from bovine brain. This enzyme has both calcium-independent phospholipase A2 and transacylase activities. The discovery of this enzyme led us to propose a new pathway for ceramide metabolism in which the sn-2-acyl group of either phosphatidylethanolamine or phosphatidylcholine is transferred to the 1-hydroxyl group of ceramide. In this study, the partial amino acid sequences from the purified enzyme revealed that the enzyme contains amino acid sequences identical to those of human lecithin:cholesterol acyltransferase-like lysophospholipase (LLPL). The coding sequences of the mouse, bovine, and human genes were obtained from the respective kidney cDNAs by PCR. The open reading frames of LLPL were cloned into pcDNA3 to generate carboxyl-terminally tagged proteins. The expression of mouse LLPL in COS-7 cells demonstrated that transfected cells had higher transacylase and phospholipase A2 activities than did non-transfected cells. Immunoprecipitation confirmed that LLPL had ACS activity. There were no significant lecithin:cholesterol acyltransferase and lysophospholipase activities in the mouse LLPL-transfected cells under either acidic or neutral conditions. Amino acid sequences from cDNAs of mouse, human, and bovine LLPLs demonstrated a signal peptide cleavage site, one lipase motif (AXSXG), and several N-linked glycosylation sites in each LLPL molecule. The replacement of serine with alanine in the lipase motif of mouse LLPL resulted in elimination of enzyme activity, indicating that the serine residue is part of the catalytic site. Deglycosylation of mouse, human, and bovine LLPLs yielded core proteins with a molecular mass of 42 kDa without change in enzyme activities. LLPL was post-translationally modified by signal peptide cleavage and N-linked glycosylation, and each mature LLPL had the same size core protein. Subcellular fractionation demonstrated that ACS activity co-localized withN-acetylglucosaminidase. Therefore, LLPL encodes a novel lysosomal enzyme, ACS.
Chronic Idiopathic Cough: A Discrete Clinical Entity?

Study objectives Despite the success of specialist cough clinics, there is increasing recognition of a subgroup of chronic coughers in whom a diagnosis cannot be made even after thorough, systematic investigation. We call this condition chronic idiopathic cough (CIC). The aim of this study is to compare the clinical characteristics of CIC patients with those of coughers in whom a diagnosis has been established (non-CIC) to see if there is a recognizable clinical pattern that distinguishes CIC from non-CIC. Design Retrospective analysis of the medical records of chronic cough patients. Setting The Royal Brompton Hospital Chronic Cough Clinic, London. Patients One hundred patients with chronic cough referred to the Royal Brompton Hospital Cough Clinic between October 2000 and February 2004. Results Seventy-one percent of all patients were female. Median age was 57 years (range, 19 to 81 years), with a median duration of symptoms of 48 months (range, 2 to 384 months). The primary diagnoses were CIC (42%), postnasal drip syndromes (22%), gastroesophageal reflux disease (16%), asthma (7%), and others (13%). In CIC patients, the median age at referral, age at onset of cough, and proportion of females did not differ significantly from non-CIC patients. CIC patients had a longer median duration of cough (72 months vs 24 months, p = 0.002), were more likely to report an upper respiratory tract infection (URTI) as the initial trigger of their cough (48% vs 24%, p = 0.0014), and had a significantly lower cough threshold in response to capsaicin (log concentration of capsaicin required to induce five or more coughs, - 0.009 vs 0.592, p = 0.032) than non-CIC patients. Conclusions Patients with CIC commonly describe a URTI that initiates their cough, which then lasts for many years, and they demonstrate an exquisitely sensitive cough reflex. We believe that CIC may be a distinct clinical entity with an as-yet unidentified underlying pathology.
Inhibition of lipoprotein lipase by an apoprotein of human very low density lipoprotein.

Summary The effects of two apolipoproteins isolated from human very low density lipoproteins (apoLp-Glu and apoLp-Ala) on lipoprotein lipase (LPL) activity have been studied. ApoLp-Glu markedly stimulated LPL as reported by others. ApoLp-Ala isolated by techniques previously described also activated LPL at low levels. However, with further purification by hydroxylapatite chromatography all activation by apoLp-Ala was eliminated with the removal of a small contaminant immunochemically identical to apoLp-Glu. ApoLp-Ala consistently inhibits LPL when present at levels above 2% of the substrate (w/w). This inhibition was not overcome by addition of phospholipid, apoLp-Glu, or more enzyme.
Functional Analysis of Phenylalanine Residues in the Active Site of Cytochrome P450 2C9

The two published crystal structures of cytochrome P450 2C9, complexed with (S)-warfarin or flurbiprofen, implicate a cluster of three active site phenylalanine residues (F100, F114, F476) in ligand binding. However, these three residues appear to interact differently with these two ligands based on the static crystal structures. To elucidate the importance of CYP2C9’s active site phenylalanines on substrate binding, orientation, and catalytic turnover, a series of leucine and tryptophan mutants were constructed and their interactions with (S)-warfarin and (S)-flurbiprofen examined. The F100→L mutation had minor effects on substrate binding and metabolism of each substrate. In contrast, the F114L and F476L mutants exhibited substantially reduced (S)-warfarin metabolism and altered hydroxy metabolite profiles but only modestly decreased nonsteroidal antiinflammatory drug (NSAID) turnover while maintaining product regioselectivity. The F114→W and F476→W mutations also had opposing effects on (S)-warfarin ve...
AVERAGE TIME GAPS IN CONGESTED FREEWAY FLOW

Characteristics of time gaps (that is, the time separation between the rear of the lead vehicle and the front of the following vehicle) in congested freeway flow provide an important link between microscopic and macroscopic traffic flow. Although individual time gaps are a microscopic phenomenon, average time gaps can easily be determined from commonly collected macroscopic traffic flow data. Data from San Diego freeways and the Queen Elizabeth Way in Ontario, Canada are analyzed to show that average time gaps in congested flow are essentially constant with respect to speed; that they vary considerably between lanes at a single location and, for the same lane, from site to site; that they display considerable scatter; and that at some sites there is a distinct increase in average time gaps in the median lane in the transition to congested flow but at others there is no change or a slight reduction. The variability of average time gaps is not easily explained, although differences in driver populations may partly explain differences among different sites. Hysteresis due to acceleration and deceleration does not appear to be an explanation for the high degree of scatter in average time gaps, since no positive correlation was found between speed changes and average time gaps.
Histological and immunological characteristics of, and the effect of immunosuppressive treatment on, xenograft vasculopathy.

: Like allografts, vascularized xenografts are susceptible to a process of chronic rejection. We have used the hamster-to-rat aortic transplant model to study characteristics of this phenomenon and to determine whether it could be controlled or prevented by immunosuppressive therapy. Golden Syrian hamster aortas were transplanted into untreated Lewis rats, athymic rats, and Lewis rats receiving cyclosporin (10 mg/kg), leflunomide (5, 10 or 15 mg/kg), or 10 mg/kg of both drugs. Grafts were harvested on days 2, 7, 14, 28 and 56. Grafts and recipient spleens were analysed using computerized morphometry, immunohistochemistry and immunofluorescence. Blood was taken on various days for the measurement of anti-hamster antibodies (flow cytometry) and of the leflunomide metabolite A77 127. In untreated rats, by day 56, transplanted aortas developed a cell-free media with a mature neointimal lesion consisting of actin-positive cells, CD4 T cells, and macrophages. There were large increases in anti-hamster immunoglobulin M (IgM) and IgG, collections of proliferating cell nuclear antigen (PCNA)-positive cells in splenic germinal centres, and IgM, C3 and C5a deposition in aortas. In athymic recipients, the media architecture was preserved, and the changes in the neointima and in anti-hamster IgM and IgG were markedly abrogated, but not prevented. In Lewis rats receiving leflunomide, absence of circulating or deposited IgM did not prevent neointimal formation by day 14. Combination treatment was the most effective at preventing neointimal formation and humoral changes. Leflunomide monotherapy was the least effective. There were no changes in peak concentrations of the main metabolite of leflunomide over 8 weeks. The hamster-to-rat aortic transplant model is suitable for the study of xenograft vasculopathy, the histological and serological changes of which are predominantly T-cell dependant. Combination treatment with 10 mg/kg of cyclosporin and 10 mg/kg of leflunomide was most effective in preventing xenograft vasculopathy.
Synthesis of CdSe/ZnS and CdTe/ZnS quantum dots: refined digestive ripening

We report synthesis of CdSe and CdTe quantum dots (QDs) from the bulk CdSe and CdTe material by evaporation/cocondensation using the solvated metal atom dispersion (SMAD) technique and refined digestive ripening. The outcomes of this new process are (1) the reduction of digestive ripening time by employing ligands (trioctylphosphine oxide (TOPO) and oleylamine (OA)) as capping agent as well as digestive ripening solvent, (2) ability to tune the photoluminescence (PL) from 410nm to 670 nm, (3) demonstrate the ability of SMAD synthesis technique for other semiconductors (CdTe), (4) direct comparison of CdSe QDs growth with CdTe QDs growth based on digestive ripening times, and (5) enhanced PL quantum yield (QY) of CdSe QDs and CdTe QDs upon covering with a ZnS shell. Further, the merit of this synthesis is the use of bulk CdSe and CdTe as the starting materials, which avoids usage of toxic organometallic compounds, eliminates the hot injection procedure, and size selective precipitation processes. It also allows the possibility of scale up. These QDs were characterized by UV-vis, photoluminescence (PL), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), and powder XRD.
Impact of permutation enforcement when minimizing total weighted tardiness in dynamic flowshops with uncertain processing times

This paper is motivated by the problem of meeting due dates in a flowshop production environment with jobs with different weights and uncertain processing times. Enforcement of a permutation schedule to varying degrees for dynamic flowshops is investigated with the goal of minimizing total weighted tardiness (TWT). The approaches studied are categorized as follows: (1) pure permutation scheduling (2) shift-based scheduling (3) pure dispatching (which leads to non-permutation sequences). A simulation-based experimental study was carried out to study the performance of the above methods with respect to minimizing TWT when new jobs arrive to the flowshop at every shift change. Results indicate significant gains in performance are possible when the permutation requirement is relaxed and shift-based scheduling is allowed. Shift-based scheduling yields competitive results with respect to the pure dispatching approach, even though dispatching has the advantage of a full relaxation of the permutation requirement.
Iron prochelator BSIH protects retinal pigment epithelial cells against cell death induced by hydrogen peroxide.

Dysregulation of localized iron homeostasis is implicated in several degenerative diseases, including Parkinson’s, Alzheimer’s, and age-related macular degeneration, wherein iron-mediated oxidative stress is hypothesized to contribute to cell death. Inhibiting toxic iron without altering normal metal-dependent processes presents significant challenges for standard small molecule chelating agents. We previously introduced BSIH (isonicotinic acid [2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzylidene]-hydrazide) prochelators that are converted by hydrogen peroxide into SIH (salicylaldehyde isonicotinoyl hydrazone) chelating agents that inhibit iron-catalyzed hydroxyl radical generation. Here, we show that BSIH protects a cultured cell model for retinal pigment epithelium against cell death induced by hydrogen peroxide. BSIH is more stable than SIH in cell culture medium and is more protective during long-term experiments. Repetitive exposure of cells to BSIH is nontoxic, whereas SIH and desferrioxamine induce cell death after repeated exposure. Combined, our results indicate that cell protection by BSIH involves iron sequestration that occurs only when the cells are stressed by hydrogen peroxide. These findings suggest that prochelators discriminate toxic iron from healthy iron and are promising candidates for neuro- and retinal protection.
Modulation of the Apoptotic Response: Potential for Improving the Outcome in Clinical Radiotherapy.

The most prevalent mechanism of cell kill by radiation is mitosis dependent and results from lethal DNA double-strand breaks and failure to maintain normal replication. Apoptosis is believed to represent a minor component of the clinical effects of radiation. Apoptosis is a preprogrammed death pathway that is constitutively expressed in many cells, albeit in an inactive form, regulated by antiapoptotic mechanisms. Data are presented to show that in irradiated cells the balance between proapoptotic and antiapoptotic signalling may determine the apoptotic outcome in vitro and in vivo. This balance can be modulated by pharmacological intervention to produce a more proapoptotic phenotype, increasing apoptotic cell kill by radiation. These studies establish the basic principles of signaling-based apoptosis therapy, designed to overcome the relative resistance to radiation-induced apoptosis and to improve the therapeutic ratio in the treatment of human tumors with fractionated radiation.
Telling Family Stories: The Family Building Projective Technique:

Talking about family issues can be very difficult for mentally ill clients in an adult partial hospitalization program (PHP). This article presents the Family Building Projective Technique (FBPT), which has been demonstrated to be an effective therapeutic tool that assists clients in discussing emotionally charged family issues in an education group setting. FBPT creates a non-threatening environment for PHP clients to bring up family issues that might otherwise go unaddressed. This technique situates the issues within the context of a story of a fictional family created by the clients. This context allows for the exploration of challenging family issues in a time limited session and provides an opportunity to increase understanding of the impact each person has in a family system.
Shadowing in Formative Evaluation Making Capacity Building Visible in a Professional Development School

Shadowing is a data collection method that involves following a person, as they carry out those everyday activities relevant to a research study. This article explores the use of shadowing in a formative evaluation of a professional development school (PDS). Specifically, this article discusses how shadowing was used to understand the role of a professor-in-residence (PIR) working with a PDS, and how this role facilitates capacity building at the school. After describing what shadowing is, its uses, and challenges, a brief overview of the PDS model and the role of a PIR, the authors describe their experiences with (1) developing and managing a relationship with the PIR and (2) how validity was established for the study. The article concludes with suggestions for integrating shadowing in formative evaluations.
Social organization as an expression of role behavior among Old World monkeys

Except for a few hours after birth, maternal status or maternal role behavior does not reduce the frequency of agonistic behaviors toward a subordinate mother. Although each species social adaptations can be understood only within the framework of its lifeway and ecology, there are phylogenetic adaptations which structure both signal systems and role behaviors. The expression of an individual's role behaviors is shaped by social context. Performance of certain behavioral roles may alter individual physiology, and in turn alter appearance and activity to enhance the behavior. A phylogenetic adaptation which restricts each social group to one functional adult male with respect to certain roles is widespread among Old World monkeys. Where social adaptation to a particular lifeway has dispersed these roles among several males, the adaptation is expressed as an alpha role, leader role, or central hierarchy. Supported by the Wenner-Gren Foundation for Anthropological Research Incorporated and NIH Grant FR-00165.
Resolution of chemical species in flow injection analysis by using self-modeling curve resolution

Abstract Mixtures can be resolved into their components by separation, spectrometric and kinetic (chemical) procedures, which have varying degrees of efficiency. Chemometric methods of data processing have proved useful for increasing resolution, especially in spectral and chromatographic procedures. This study shows that chemometric methods are also useful for kinetic flow-injection methods based on chemical reactions combined with multichannel spectral detection, where neither the reaction nor the detector provides adequate resolution. The problem of background absorbance of a sample in a flow-injection system with an ultraviolet/visible photodiode array detector is solved by applying a self-modeling curve resolution method. The example used is a mixture of methyl violet and phenolphthalein.
A Bacteriological Study of Stored, Sulphite Treated Peeled Potatoes

SUMMARY Peeled, sulphite treated potatoes were stored at 23° for 3 days or at 6° for 7 days in packs sealed with perforated or unperforated polythene or with Saran film. After storage, gas samples were withdrawn from the packs for analysis and viable counts made of micro organisms associated with the potatoes. There was a marked increase in the CO2 concentration and a corresponding decrease in O2 concentration in the unperforated packs; samples from these packs tended to have a lower bacterial count than samples from perforated packs. 180 bacterial isolates representing the spoilage flora were examined. At 23° the major groups of isolates were Gram negative bacteria attacking glucose fermentatively (Enterobacteriaceae) or oxidatively (fluorescent pseudomonads); isolates from storage at 6° were all pseudomonads most of which were fluorescent. Twentyeight % of the pseudomonads, but none of the fermentative isolates, were pectolytic.
Populating the whole landscape.

Every de Sitter vacuum can transition to every other de Sitter vacuum despite any obstacle, despite intervening anti--de Sitter sinks, despite not being connected by an instanton. Eternal inflation populates the whole landscape.