cssi/SciSciGPT-SciSciNet huggingface dataset:
Ligand-Dependent Conformations and Dynamics of the Serotonin 5-HT2A Receptor Determine Its Activation and Membrane-Driven Oligomerization Properties

From computational simulations of a serotonin 2A receptor (5-HT2AR) model complexed with pharmacologically and structurally diverse ligands we identify different conformational states and dynamics adopted by the receptor bound to the full agonist 5-HT, the partial agonist LSD, and the inverse agonist Ketanserin. The results from the unbiased all-atom molecular dynamics (MD) simulations show that the three ligands affect differently the known GPCR activation elements including the toggle switch at W6.48, the changes in the ionic lock between E6.30 and R3.50 of the DRY motif in TM3, and the dynamics of the NPxxY motif in TM7. The computational results uncover a sequence of steps connecting these experimentally-identified elements of GPCR activation. The differences among the properties of the receptor molecule interacting with the ligands correlate with their distinct pharmacological properties. Combining these results with quantitative analysis of membrane deformation obtained with our new method (Mondal et al, Biophysical Journal 2011), we show that distinct conformational rearrangements produced by the three ligands also elicit different responses in the surrounding membrane. The differential reorganization of the receptor environment is reflected in (i)-the involvement of cholesterol in the activation of the 5-HT2AR, and (ii)-different extents and patterns of membrane deformations. These findings are discussed in the context of their likely functional consequences and a predicted mechanism of ligand-specific GPCR oligomerization.
Controlled opioid withdrawal evaluation during 72 h dose omission in buprenorphine-maintained patients

Abstract Buprenorphine's clinical utility as an opioid dependence pharmacotherapy may be enhanced with less-than-daily dosing. This study assessed opioid withdrawal after an acute 72 h dose omission in buprenorphine-maintained patients (8 mg/day s.1.). Eight outpatients required to remain free of opioids, cocaine and benzodiazepines completed four double-blind, double-dummy, Latin-square ordered conditions. Test conditions of 8 or 16 mg s.l. buprenorphine were followed by 2 days of placebo dosing. Control conditions were buprenorphine maintenance (8 mg/day), to provide a reference for evaluation of placebo test days and naloxone administration (10 mg/70 kg i.m.) during 8 mg buprenorphine maintenance to assess withdrawal measure sensitivity. Subjective measures and pupil diameter were significantly influenced only by naloxone. The lack of subjective symptoms and physiological signs of opioid withdrawal during 72 h of acute dose omission supports the feasibility of less-than-daily dosing at buprenorphine doses of 8 mg/day in patients who have demonstrated an ability to remain drug-free for an extended period.
Analysis of the dynamic behavior of flooded porous electrodes.

Steady state and transient analysis of flooded isothermal porous electrodes without bulk flow of electrolyte
Secured Transactions: An Integrated Classroom Approach Using Financial Statements and Acronyms

Students struggle with the subject of secured transactions under the Uniform Commercial Code. In this article, the author presents a method that uses balance-sheet information to help students visualize the difference between secured and unsecured creditors. The balance sheet is also used in the Uniform Commercial Code process, in which one must classify the collateral to know the procedural steps to follow to become a secured creditor. The balance-sheet approach helps students identify inventories, real property (land), intangible assets, accounts receivable, and so forth. The students use acronyms to organize the steps necessary for becoming a secured creditor. The acronym CAPP helps students understand that one must classify the collateral, attach the security interest, perfect it, and obtain priority.
Bilateral acute carpal tunnel syndrome and hyperthyroidism: a case report

A 26-year-old man acutely developed bilateral sensory symptoms of carpal tunnel syndrome (CTS). Neurophysiological investigations confirmed the diagnosis of CTS with findings suggesting conduction block of sensory fibers. Endocrinological studies revealed a hyperthyroidism. He was treated with methimazole and propranolol with improvement of thyroid function. The neurophysiological and clinical follow-up revealed a progressive improvement of CTS. The echography performed at wrist bilaterally failed to show any rough compressive factors in the carpal tunnel. The clinical, neurophysiological and endocrinological evolution suggest a relationship between hyperthyroidism and acute bilateral CTS.
Sketching Cross Sections with a Portable Microcomputer: ABSTRACT

Computer applications have been carried to the field long ago by geophysicists and their "dog houses." The advent of inexpensive battery-powered microcomputers promises to allow the field geologist to participate in this application. The field geologist may record data directly onto a computer-readable medium and calculate statistics or plot a cross section. A program for routine plotting of cross sections in the field has been developed and field-tested. The program proved to be useful to 30 computer-illiterate geologists on a 6-week mapping project in New Mexico. The program allows the user to control vertical exaggeration and displays the correct apparent dip along the chosen line of section. Cubic-spline interpolation is used to plot both topography and folded bedding planes. The program executes in Pascal on an Apple IIc in a few seconds. End_of_Article - Last_Page 273------------
Software-codec-based full motion video conferencing on the PC using visual pattern image sequence coding

This paper presents a real time full motion video conferencing system based on the Visual Pattern Image Sequence Coding (VPISC) software codec. The prototype system hardware is comprised of two personal computers, two camcorders, two frame grabbers, and an ethernet connection. The prototype system software has a simple structure. It runs under the Disk Operating System, and includes a user interface, a video I/O interface, an event driven network interface, and a free running or frame synchronous video codec that also acts as the controller for the video and network interfaces. Two video coders have been tested in this system. Simple implementations of Visual Pattern Image Coding and VPISC have both proven to support full motion video conferencing with good visual quality. Future work will concentrate on expanding this prototype to support the motion compensated version of VPISC, as well as encompassing point-to-point modem I/O and multiple network protocols. The application will be ported to multiple hardware platforms and operating systems. The motivation for developing this prototype system is to demonstrate the practicality of software based real time video codecs. Furthermore, software video codecs are not only cheaper, but are more flexible system solutions because they enable different computer platforms to exchange encoded video information without requiring on-board protocol compatible video codex hardware. Software based solutions enable true low cost video conferencing that fits the `open systems' model of interoperability that is so important for building portable hardware and software applications.
Enhanced production of isoamyl acetate from beet molasses with addition of fusel oil by Williopsis saturnus var. saturnus

Abstract Fusel oil which contains high level of amyl alcohols (approximately 45–55%) is a by-product obtained from the distillation of alcohol made by fermentation of molasses. Williopsis saturnus is a yeast which is able to convert isoamyl alcohol into isoamyl acetate. The aim of this study was to increase the formation of isoamyl acetate by the addition of fusel oil at the ratios of 1%, 2% and 3% (v/v) to molasses based fermentation medium using W. saturnus . It was found out that bioconversion of added fusel oil into isoamyl acetate was possible and an addition of 1% fusel oil led to an increase in isoamyl acetate concentration from 118 to 354 mg/L.
Improving Hormonal Therapy for Breast Cancer

: Since Beatson's observation of breast cancer regression after oophorectomy one hundred years ago (1), therapies directed toward the estrogen-estrogen receptor (ER) endocrine axis have become a cornerstone of breast cancer treatment. Surgical ablative techniques, such as oophorectomy, adrenalectomy, and hypophysectomy have been largely replaced by pharmacological approaches that inhibit estrogen-dependent breast cancer growth, either by reducing estrogen synthesis (LHRH agonists, aromatase inhibitors, and progestins), by blocking ER function (tamoxifen) or by interfering with the cellular response to ER activation (androgens). Indeed, one could argue that hormone therapy for breast cancer represents one of the most successful areas of logical drug design in cancer treatment. Recent drug developments have led to improved side-effect profiles for hormonal agents. In addition, the remarkable organ-selective agonist/antagonist properties of tamoxifen-related compounds are the basis for an effort to develop hormone replacement therapies that combine breast cancer treatment/prevention with reduced osteoporosis and heart disease risk. While the ER axis will remain a primary focus for the further development of hormonal therapies (Table 1), the value of ER as a therapeutic target will always be limited by the primary or acquired estrogen insensitivity that nearly all breast cancers ultimately display. Current hopes for circumventing this problem lie in the vast therapeutic potential afforded by recent molecular insights into growth regulatory pathways. Logical choices for novel therapeutic targets for “estrogen insensitive” breast cancer includes alternative nuclear hormone receptors, growth factor receptors, and signal transduction molecules in “ER-independent” growth-regulatory pathways. Inhibitors of pathophysiological processes intrinsic to tumor progression, such as angiogenesis, invasion, and metastasis are also promising noncytotoxic alternatives in breast cancer therapy (Table 2). Studies of growth regulators in breast cancer are also likely to lead to new tumor markers to accurately guide choices from the increasing array of therapeutic options available.
Prey selection by the Lake Superior fish community

Abstract Mysis diluviana is an important prey item to the Lake Superior fish community as found through a recent diet study. We further evaluated this by relating the quantity of prey found in fish diets to the quantity of prey available to fish, providing insight into feeding behavior and prey preferences. We describe the seasonal prey selection of major fish species collected across 18 stations in Lake Superior in spring, summer, and fall of 2005. Of the major nearshore fish species, bloater ( Coregonus hoyi ), rainbow smelt ( Osmerus mordax ), and lake whitefish ( Coregonus clupeaformis ) consumed Mysis , and strongly selected Mysis over other prey items each season. However, lake whitefish also selected Bythotrephes in the fall when Bythotrephes were numerous. Cisco ( Coregonus artedi ), a major nearshore and offshore species, fed largely on calanoid copepods, and selected calanoid copepods (spring) and Bythotrephes (summer and fall). Cisco also targeted prey similarly across bathymetric depths. Other major offshore fish species such as kiyi ( Coregonus kiyi ) and deepwater sculpin ( Myoxocephalus thompsoni ) fed largely on Mysis , with kiyi targeting Mysis exclusively while deepwater sculpin did not prefer any single prey organism. The major offshore predator siscowet lake trout ( Salvelinus namaycush siscowet ) consumed deepwater sculpin and coregonines, but selected deepwater sculpin and Mysis each season, with juveniles having a higher selection for Mysis than adults. Our results suggest that Mysis is not only a commonly consumed prey item, but a highly preferred prey item for pelagic, benthic, and piscivorous fishes in nearshore and offshore waters of Lake Superior.
3D Patchy Reconnection in Solar Coronal Mass Ejections

Summary form only given. Coronal mass ejections (CME's), sudden eruptions of coronal plasma and magnetic field into the interplanetary medium, are one of the most dynamic phenomena in the solar corona. These CME's are an important driver of space weather both through their interaction with the Earth's magnetosphere and through the magnetic reconnection and flaring which is driven in the solar corona in their wake. We will present simulations of the eruption of these CME's, and the formation of coronal current sheets behind them. We will focus on the dynamics of reconnection in these post-CME current sheets, in particular studying the effect of multiple patches of localized reconnection. We impose this reconnection in an MHD simulation by enhancing the resistivity in small regions for a short time, thus allowing a finite amount of flux to reconnect. This forms a pair of 3D reconnected flux tubes piercing the current sheet. These tubes then retract from the reconnection region, pushing their way through the surrounding magnetic field. We will discuss how this model relates to in situ WIND observations of the reconnection structure of CME's, to the efficiency of heating in solar flares, and to the generation of descending post-eruption voids seen in the high corona by TRACE and LASCO
Major hepatic resection for hepatocellular carcinoma with or without portal vein embolization: Perioperative outcome and survival

Background Preoperative portal vein embolization (PVE) is performed to minimize perioperative risks of major hepatic resection for hepatocellular carcinoma (HCC), but its effects on tumor growth are ill defined. Perioperative outcome and survival after major hepatic resection for HCC, with and without PVE, were investigated. Methods Patients that underwent major hepatic resection (≥3 segments) for HCC between January 1998 and May 2007 were analyzed retrospectively. Preoperative PVE was performed when the remnant liver volume was predicted to be insufficient. Results A total of 54 patients underwent major hepatic resection for HCC: 21 patients with PVE before resection (PVE group) and 33 patients without PVE (non-PVE group). PVE and non-PVE groups had similar rates of fibrosis or cirrhosis, hepatitis C virus, hepatitis B virus, American Joint Committee on Cancer stage, preoperative transarterial chemoembolization, overall postoperative complications, and positive margin (P = nonsignificant for all rates). There were no perioperative deaths in the PVE group and 6 (18%) deaths in the non-PVE group (P = .038). Median follow-up was 21 months. Excluding perioperative deaths, overall survival rates at 1, 3, and 5 years were 94%, 82%, and 72%, respectively, in the PVE group and 93%, 63%, and 54%, respectively, in the non-PVE group (P = .35). Similarly, disease-free survival (DFS) rates were not significantly different between the groups, with 1-, 3-, and 5-year DFS rates of 84%, 56%, and 56%, respectively, in the PVE group and 66%, 49%, and 49%, respectively, in the non-PVE group (P = .38). Conclusion PVE before major hepatic resection for HCC is associated with improved perioperative outcome. Excluding perioperative mortality, overall survival and DFS rates were similar between patients with and without preoperative PVE.
Delayed chronic endothelial damage after brief global forebrain ischemia in the rat

We have previously shown that 10- and 12.5-min (but not 7-min) of global ischemia induces secondary brain damage, including incomplete infarcts in striatum and hippocampal CA.1 sector associated with endothelial degeneration and microvascular thrombosis over 4–10 weeks. 1–3 12.5-min ischemia also induces cerebral amyloid b-peptide (Ab) deposition at 8–10 weeks, concentrated in the basal cortex. Peri-vascular neuronal shrinkage degeneration coincides with evident Ab deposition.2, 3 The present study investigated endothelial degeneration in cortex in an effort to understand the relationship to brain Ab deposition.
Involvement of the Helix-Loop-Helix Protein Id-1 in the Glucocorticoid Regulation of Tight Junctions in Mammary Epithelial Cells

Abstract Mammary epithelial cell-cell junctions undergo morphological and structural differentiation during pregnancy and lactation, but little is known about the transcriptional regulators that are involved in this process. In Con8 mammary epithelial tumor cells, we have previously documented that the synthetic glucocorticoid, dexamethasone, induces the reorganization of the tight junction and adherens junction and stimulates the monolayer transepithelial electrical resistance (TER), a reliable in vitro measurement of tight junction sealing. Western blots demonstrated that dexamethasone treatment rapidly and strongly stimulated the level of the Id-1 protein, which is a serum-inducible helix-loop-helix transcriptional repressor. The steroid induction of Id-1 was robust by 4 h of treatment and maintained over a 24-h period. Isopropyl-1-thio-β-d-galactopyranoside-inducible expression of exogenous Id-1 in Con8 cells was shown to strongly facilitate the dexamethasone induction of TER in the absence of serum without altering the dexamethasone-dependent reorganization of ZO-1, β-catenin, or F-actin. Ectopic overexpression of Id-1 in the SCp2 nontumorigenic mammary epithelial cells, which does not undergo complete dexamethasone-dependent tight junction reorganization, enhanced the dexamethasone-induced ZO-1 tight junction localization and stimulated the monolayer TER. Moreover, antisense reduction of Id-1 protein in SCp2 cells prevented the apical junction reorganization and dexamethasone-stimulated TER. Our results implicate Id-1 as acting as a critical regulator of mammary epithelial cell-cell interactions at an early step in the glucocorticoid-dependent signaling pathway that controls tight junction integrity.
The impact of increased disclosure requirements and the standardization of accounting practices on earnings management through the reserve for income taxes

We examine whether the regulatory changes required by the Sarbanes–Oxley Act of 2002 (SOX) and Financial Accounting Standards Board Interpretation No. (FIN) 48 reduced the propensity for earnings management through the reserve for income taxes. Given prior evidence that firms use this reserve to manage earnings to beat the consensus analyst forecast, the regulatory changes implemented by both SOX and FIN 48 allow us to study the effects of accounting regulation on earnings management. We find that neither SOX nor FIN 48 reduced earnings management through the reserve for income taxes. Thus, in contrast to research that examines whether SOX affected nontax, accrual-based earnings management, our results suggest managers continue to take advantage of their discretion over the accounting for income taxes to beat the consensus analyst forecast in both the post-SOX and post-FIN 48 periods.
The proteins and glycoproteins of insect cells in culture

Abstract Cell surface proteins, glycoproteins, and glycopeptides from insect cells in culture were studied using Sephadex gel filtration and sodium dodecyl sulphate polacrylamide gel electrophoresis. Various qualitative and quantitative differences were observed, the most important being the absence of both the LETS (large external transforming sensitive) protein and a major molecular weight class of glycopeptides in all four cell lines. The implications of the data are discussed with reference to the adhesive properties of insect cell lines.
Selected complications in neuro-oncology patients

Objectives : To identify the causes of and discuss nursing management of those complications that are unique to the brain tumor patient population. Data Sources : Published articles and books related to neurological and nonneurological complications in the neuro-oncology patient. Conclusions : Seizures, cerebral edema, thromboembolism, and endocrine dysfunction are several complications experienced by the neuro-oncology patient. These complications can be caused by the tumor or treatment of this disease. Implications for nursing practice : Care of the neuro-oncology patient is complex. Knowledge of the potential complications that patients may experience and how to manage these problems serves to enhance their quality of life.
Sensitivity to apomorphine in the guinea pig as a function of age and body weight

Male albino guinea pigs aged 4–10 weeks were challenged with 0.1, 0.2, and 0.4 mg/kg apomorphine. Mean stereotypy scores rose significantly as a function of age. Stereotypy scores were better correlated with age than with body weight, suggesting that CNS maturation, rather than weight-related factors, was responsible. Although age and body weight were correlated, there was enough variability to make body weight an unreliable indicator of age.
On neural network design — Part I: Using the MVQ algorithm

In this two-part study we present a new design methodology for neural classifiers. The design procedure utilizes a multiclass vector quantization (MVQ) algorithm for information extraction from the training set. The extracted information suffices to specify the hidden layer in a canonical neural network architecture. The extracted information also leads to the specification of neuron inhibition rules and subsequently the design of the hidden layer-to-output map. In Part I of the study we focus attention on the MVQ algorithm and how it is used to extract information from a training set. The extracted information is referred to as thecodebook. The codebook is used to directly specify the hidden layer. This specification can take the form of a perceptron layer, a radial basis layer, or a heterogeneous layer involving a mixture of neuron types. These and otherh-layer specifications are determined directly from the same extracted information. The MVQ codebook also suffices to scale the activation function of each neuron. In Part II we consider the nonsimplistic hidden layer-to-output map design. We note that the MVQ algorithm, as it extracts information, decomposes the design set into disjoint neighborhoods. For each neighborhood we identify subsets of the hidden layer neurons, which are significant sensors for the neighborhood. For each such subset we construct an output map. Inhibition rules are established to ensure that the proper output map is activated. In benchmark simulations the overall design exhibits excellent performance, to the extent that we are hard pressed to identify bounds on performance, if any.
Tumor inhibitors. LXIV. isolation and structural elucidation of novel bufadienolides, the cytotoxic principles of Bersama abyssinica

Abstract The isolation and structural elucidation of six new cytotoxic bufadienolides from Bersama abyssinica are reported. Bersaldegenin 1,3,5-orthoacetate (1), 16β-hydroxy-bersaldegenin 1,3,5-orthoacetate (10), bersamagenin 1,3,5-orthoacetate (18), and 16β-hydroxybersamagenin 1,3,5-orthoacetate (19) appear to be the first recognized naturally occurring orthoacetates. Interrelations of bersaldegenin 3-acetate (5) with 1 and of 16β-hydroxybersaldegenin 3-acetate (15) with 10 are described. The bersaldegenin derivatives 1 and 10 were interrelated with the corresponding bersamagenin derivatives 18 and 19 via the common reduction products 24 and 25. A novel intramolecular facilitation of equilibration of bersaldegenin 1,3,5-orthoacetate (1) and bersaldegenin 1-acetate (2) is described, and a plausible rationalization which involves participation of the aldehyde group is presented. The parallelism between cytotoxic activity and inhibition of transport ATPase among the foregoing and other bufadienolides is noted, and a speculative rationalization is discussed.
Development of an in-fiber whitelight interferometric distance sensor for small distance measurement

The development of an in-fiber whitelight interferometric distance sensor based on the mode coupling effect of a Long Period Fiber Grating (LPFG) for absolute distance measurement has been investigated. Unlike the Fabry-Perot interferometric distance sensor that uses a regular single mode fiber as the sensor probe, the LPFG-based distance sensor employs a single mode fiber whose cladding region is coated with a reflective film and having a LPFG located at a distance from the cleaved fiber end. The LPFG serves as a beam splitter that separates the light into a core mode and a cladding mode and recombines the two light waves to generate interference, from which the absolute distance can be deducted. Because the optical path difference of the LPFG-based interferometric distance sensor is contributed by both the free-space cavity distance and the distance between the LPFG and the fiber end, it does not impose a limit on the minimum measurable distance. In this paper, the experimental setup for mechanically inducing LPFG in the optical fiber is first described. It is demonstrated that the transmission characteristics of the LPFG can be easily controlled by adjusting the grating period and the applied pressure. The implementation and data analysis of an LPFG-based whitelight interferometric distance sensor are then discussed in detail. Experimental results verified that the distance sensor is capable of measuring small distances that can not be measured by a Fabry-Perot interferometric distance sensor.
Exact solution for (2+1)-dimensional critical collapse

We find an exact solution in closed form for the critical collapse of a scalar field with a cosmological constant in 2+1 dimensions. This solution agrees with the numerical simulations done by Pretorius and Choputik of this system.
A Blade Loss Response Spectrum for Flexible Rotor Systems

A shock spectrum procedure is developed to estimate the peak displacement response of linear flexible rotor-bearing systems sugjected to a step change in unbalance (i.e., a blade loss). A progressive and a retrograde response spectrum are established. These blade loss response spectra are expressed in a unique non-dimensional form and are functions of the modal damping ratio and the ratio of rotor spin speed to modal damped whirl speed. Modal decomposition using complex modes is utilized to make use of the unique feature of the spectra for the calculation of the peak blade loss displacement response of the rotor system. The procedure is applied to three example systems using several modal superposition strategies. The results of each are compared to true peak displacement obtained by a separate transient response program.
The Effect of Catalysts on the Deflagration Limits of Ammonium Perchlorate

Abstract The effect of KMnO4, Fe2 3, CuO and copper chromite on the pressure limits of combustion of ammonium perchlorate was investigated. The lower pressure limit in all cases increased with small additions of each catalyst and then decreased at higher concentrations of catalyst. An upper pressure limit was observed in the deflagration of samples with high concentrations of KMnO4. It was further observed that the effect of catalysts depends strongly on the way they are distributed as well as their concentration. The catalysis were found to be much more effective at a smaller particle size.
Too quiet to hear a whisper

Add some noise, and many dynamic systems respond to weak signals more strongly. Some sort of threshold process was thought to be necessary for this effect, but a new model removes the restriction.
BCL-2 Translation Is Mediated via Internal Ribosome Entry during Cell Stress

The cellular response to stress involves a rapid inhibition of cap-dependent translation via multiple mechanisms, yet some translation persists. This residual translation may include proteins critical to the cellular stress response. BCL-2 is a key inhibitor of intrinsic apoptotic signaling. Its primary transcript contains a 1.45-kb 5′-untranslated region (UTR) including 10 upstream AUGs that may restrict translation initiation via cap-dependent ribosome scanning. Thus, we hypothesized that this 5′-UTR may contain an internal ribosome entry site (IRES) that facilitates BCL-2 translation, particularly during cell stress. Here we show that the BCL-2 5′-UTR demonstrated IRES activity both when translated in vitro and also when m7G-capped and polyadenylated mRNA was transiently transfected into 293T cells. The activity of this IRES in unstressed cells was ∼6% the strength of the hepatitis C virus IRES but was induced 3–6-fold in a dose-dependent manner following short term treatment with either etoposide or sodium arsenite. Thus, the IRES-mediated translation of BCL-2 may enable the cell to replenish levels of this critical protein during cell stress, when cap-dependent translation is repressed, thereby maintaining the balance between pro- and anti-apoptotic BCL-2 family members in the cell and preventing unwarranted induction of apoptosis.
Phase separation in dividing two-phase flows

Abstract Phase separation in dividing T- and Y-junctions was investigated experimentally and analytically in this study. New air/water phase separation data are presented for three horizontal test sections (a T-junction, a 45° Y-junction and a 135° Y-junction). Emphasis was placed on low extraction rates through the side branch. A phenomenological model was developed which was based on the idea of dividing streamlines in which centrifugal and interfacial drag forces were assumed to be dominant. Comparisons between model predictions and the available data, corresponding to different flow regimes, pressures, fluid properties, inlet flow rates and qualities and extraction rates, showed good agreement thus supporting the assumptions inherent in the model.
Spot cryoablation: a cool new way to achieve pulmonary vein isolation.

1 s P p p r n m M r c r Presently, the most advocated approach for catheter abation of paroxysmal atrial fibrillation (PAF) involves elecrically isolating the pulmonary veins (either individually or n pairs of ipsilateral veins) by placing circumferential raiofrequency lesions in the left atrial antrum surrounding he veins. Using this strategy, most investigators have consisently reported long-term arrhythmia-free rates of 70%. here is some debate regarding whether electrical isolation is ither necessary or sufficient for clinical success. However, here is a large amount of evidence suggesting that recurrence f PAF is associated with recovery of pulmonary vein (PV) onduction, and therefore clinical outcome without electrical solation cannot be better than the same strategy with isolation. hus, PV isolation represents, at the minimum, a very clear nd-point for catheter ablation of PAF. Techniques for achieving pulmonary vein isolation are eing continually refined, but nonetheless, failed isolation ontinues to limit the efficacy of this procedure. In some ases, it may not be possible to achieve transmural radiorequency (RF) linear lesions because of difficult catheter anipulation or increased atrial wall thickness. When ideal ontact is not possible, RF applications may indeed create nough intramural edema to prevent transmural atrial leions from being created by subsequent applications. In this ituation, new RF applications can be placed more proximal o the initial line in the PV antral region to achieve PV solation. However, moving further away from the PV can ake electrical isolation more difficult to be obtained, as the trial wall gets thicker at the PV antral area. Alternatively, dditional RF ablations can be delivered distally, inside the V, where a thinner wall typically is found. The concern ith these strategies is that the risk of esophageal thermal amage or PV stenosis may outweigh their potential benefit. herefore, in this difficult situation it is reasonable not to roceed with any further RF ablations even with the possiility of a less favorable outcome if PV isolation is not btained. In this issue of Heart Rhythm, Kenigsberg et al ropose that cryoablation delivered deep inside the pulmoary vein is safe and effective in achieving bidirectional
Asthma in the elderly.

In children and young adults, asthma often presents many of the following features: atopy is common; airflow obstruction is fully reversible; differential diagnoses are few (except in the very young); and concomitant illnesses are uncommon. Although asthma in the elderly (meaning, for the purposes of this discussion, age 65 years and older) may share all of these characteristics, exceptions become increasingly common with advancing age. In older persons, the prevalence of allergic asthma (as defined by skin test sensitivity) is relatively small; fixed airflow obstruction may be present during clinical remissions of asthma; the differential diagnosis of new-onset wheezing is broad; and comorbid disease, especially coronary artery disease, often complicates both diagnosis and therapy. Even the definition of asthma becomes somewhat obscured in an older population: persons with chronic bronchitis and emphysema who exhibit episodic dyspnea and wheezing and a reversible component to their airflow obstruction ch...
Corporate preparedness for pandemic influenza: a survey of pharmaceutical and biotechnology companies in Montgomery County, Maryland.

The authors surveyed biotechnology and pharmaceutical companies in Montgomery County, Maryland, to determine the industry's level of preparedness for an influenza pandemic. Four out of 5 companies had no plans in place, indicating a need for public health officials to aid these businesses in developing preparedness plans.
Oxidation Chemistry of Axially Protected Mo2 and W2 Quadruply Bonded Compounds

Reported is a facile, high-yielding one-pot synthesis of the quadruply bonded ditungsten (II,II) compound W2(dpa)4 (1) (dpa = 2,2′-dipyridylamide), which was obtained from W(CO)6 at high temperature in naphthalene. A similar reaction in 1,2-dichlorobenzene furnished a ditungsten (III, III) species as the major product that was crystallized as [W2(dpa)3Cl2][BPh4] (3). The [W2(dpa)3Cl2]+ cation is better prepared by oxidation of 1 with SO2Cl2. Compound 1 was characterized by X-ray crystallography and cyclic-voltammetry, and is compared with its earlier reported molybdenum analogue, Mo2(dpa)4 (2). One-electron oxidation products of 1 and 2, [W2(dpa)4][BPh4] (1BPh4) and [Mo2(dpa)4][BPh4] (2BPh4), respectively, have also been synthesized. The crystallographically determined metal−metal distances of 2.23 A and 2.14 A in 1BPh4 and 2BPh4, respectively, are in agreement with metal−metal bond orders of 3.5. Unlike most previously reported Mo25+ and W25+ compounds, the primary coordination spheres around the M2-unit...
Dissolution of Sodium Salicylate from Tablet Matrices Prepared by Wet Granulation and Direct Compression

A quantitative evaluation of dissolution of active ingredients from tablets is discussed. An investigation of filler-binder, lubricant, disintegrating agent, and hardness on the dissolution rate of sodium salicylate from tablet bases was studied by means of a 4 × 3 × 2 × 2 factorial experiment and analysis of variance. The utilization of a filler, spray-dried lactose, which required no preliminary granulation, gave significantly faster release rates than granulations prepared with acacia mucilage, starch paste, or ethylcellulose. The presence of a disintegrating agent notably affected the dissolution rate of the active ingredient, especially where wet granulation was employed. The release of sodium salicylate from several bases was a result of the interaction of many variables and was not dependent solely upon the effect of an individual component.
Near constancy of the pressure dependence of T c across families of organic and fullerene superconductors

Pressure strongly depresses the superconducting transition temperature ${\mathit{T}}_{\mathit{c}}$ of both the doped fullerenes and the \ensuremath{\beta}-ET[(BEDT-TTF${)}_{\mathit{nX}\mathit{m}}$, (BEDT-TTF)=bis(ethylenedithio)tetrathiofulvalene)] organic superconductors. An outstanding puzzle in these materials is the weak variation ${\mathit{dT}}_{\mathit{c}}$/dP across families of compounds with large variations in ${\mathit{T}}_{\mathit{c}}$. This property has been used to argue against phonon-induced pairing. However, closer examination of the volume dependence of ${\mathit{T}}_{\mathit{c}}$ reveals that the weak variation of ${\mathit{dT}}_{\mathit{c}}$/dP is consistent with moderate (but not weak) electron-phonon coupling. \textcopyright{} 1996 The American Physical Society.
Bioartificial Lung Engineering

End-stage lung disease is a major health care challenge. Lung transplantation remains the definitive treatment, yet rejection and donor organ shortage limit its broader clinical impact. Engineering bioartificial lung grafts from patient-derived cells could theoretically lead to alternative treatment strategies. Although many challenges on the way to clinical application remain, important early milestones toward translation have been met. Key endodermal progenitors can be derived from patients and expanded in vitro. Advanced culture conditions facilitate the formation of three-dimensional functional tissues from lineage-committed cells. Bioartificial grafts that provide gas exchange have been generated and transplanted into animal models. Looking ahead, current challenges in bioartificial lung engineering include creation of ideal scaffold materials, differentiation and expansion of lung-specific cell populations and full maturation of engineered constructs to provide graft longevity after implantation in vivo. A multidisciplinary collaborative effort will not only bring us closer to the ultimate goal of engineering patient-derived lung grafts, but also generate a series of clinically valuable translational milestones such as airway grafts and disease models. This review summarizes achievements to date, current challenges and ongoing research in bioartificial lung engineering.
Risk Reduction Therapies for Patients with Coronary Artery Disease: A Call for Increased Implementation

Recent decades have witnessed significant advances in the use of interventional procedures and medical therapies for relief of symptoms associated with obstructive coronary artery disease (CAD). At the same time, however, little progress has been made in understanding and implementing preventive therapy and risk reduction. Our traditional focus on treatment of severe coronary obstruction has addressed only part of the problem. We now need to adopt a more comprehensive approach aimed at the entire spectrum of atherosclerotic disease. Numerous clinical trials have demonstrated that risk-reduction strategies can produce marked decreases in the incidence of cardiovascular events as well as in total mortality. Despite this strong body of evidence, risk-reduction therapies continue to be underutilized. Comprehensive changes in healthcare delivery systems are needed to ensure that risk-reduction strategies become a routine part of care for patients with cardiovascular disease.
Ultra low on-resistance Super 3D MOSFET under 300 V breakdown voltage

For the range of under 300 V breakdown voltage, we have already proposed a new structural power MOSFET that we call Super 3D MOSFET. At 70 V breakdown voltage, the simulated total specific on-resistance was 19 mohm.mm/sup 2/, and below the R/sub on/ Si limit. In this work, we present the structural design for the breakdown voltage, taking the electric field concentration into consideration at its 3-dimensional corner. Furthermore, we present the experimental results for an actual prototype fabrication. The on-resistance and breakdown voltage are respectively 27 mohm.mm/sup 2/ and 49 V. This on-resistance is reduced drastically in comparison with the conventional trench-gated MOSFET.
Analysis of Flexible Pavement Response and Performance Using Isotropic and Anisotropic Material Properties

Several research studies have shown that unbound pavement layers exhibit anisotropic properties. Anisotropy is caused by the preferred orientation of the aggregate, to which both the shape characteristics of the aggregate and the compaction force itself contribute. The result is that unbound pavement layers have higher stiffness in the vertical direction than in the horizontal direction. The efficacy of using anisotropic properties to represent unbound layers is demonstrated by comparing pavement surface deflection measurements under wheel loads to finite element predictions based on models that incorporate isotropic and anisotropic properties for the unbound base and subbase layers. The surface deflections in the flexible pavements of the AASHO road test were selected for this comparison because the AASHO road test is such a widely used database and because of the tight control of traffic, pavement cross sections, and material quality at the road test. The paper also analyzes the influence of characterizing pavement layers as isotropic and anisotropic on the predictions of fatigue and permanent deformation performance of flexible pavements using the recently developed National Cooperative Highway Research Program 1-37A models. The results show that the anisotropic behavior of pavement layers explains part of the shift and calibration factors used to relate laboratory measurements to field performance.
How many radiologists will be needed in the years 2000 and 2010? Projections based on estimates of future supply and demand.

Predicting the appropriate number of diagnostic radiologists needed in the United States for the next decade is an important but difficult task. Previous attempts have been characterized by incomplete data, conflicting results, and ultimately, as the future revealed itself, erroneous conclusions [1-3]. Nonetheless, with major changes expected in health care, estimation of physician workforce needs is perhaps more critical than ever before. In this study, both the future supply of diagnostic radiologists and the demand for diagnostic radiology services in the United States were analyzed. Projected supply of diagnostic radiologists was calculated by using data about the number presently in practice, the current number of radiology residents, and the rate at which diagnostic radiologists leave the profession through either retirement or death. Demand for radiologic services in the future was evaluated by estimating effects of possible changes in population and demography, health care reform, technology, univ...
OPTIMAL AGE-DEPENDENT PREVENTIVE MAINTENANCE POLICIES WITH IMPERFECT MAINTENANCE

This paper proposes three age-dependent preventive maintenance models with imperfect repair and/or imperfect preventive maintenance (pm). In these models imperfect repair is treated in a way that after repair the lifetime of a unit will decrease to a fraction of its immediately previous one and its repair time will increase to a multiple of immediately previous one. In this paper, the expected maintenance cost rate and asymptotic average availability are derived with a consideration that the maintenance and repair times are not negligible. The optimum maintenance policies are then determined for the three imperfect maintenance models respectively. A class of related optimization problems is also discussed. Finally, a numerical example is presented to illustrate the results.
Overexpression of neurotrophin 4 in skin enhances myelinated sensory endings but does not influence sensory neuron number

The growth factors neurotrophin 4 (NT4) and brain-derived neurotrophic factor (BDNF) are expressed in the developing skin, activate the trkB tyrosine kinase receptor, and influence the development and survival of specific types of sensory afferents. Whether each factor is capable of regulating the same or overlapping populations of cutaneous afferents during development is unknown. A previous study of mice overexpressing BDNF in the developing skin (BDNF-OE mice) revealed that these animals exhibited increased hair follicle innervation, Meissner corpuscle size, and Merkel cell number in glabrous skin, although no change in the total number of sensory neurons was observed. To determine if NT4 affects cutaneous innervation in a manner similar to BDNF, transgenic mice overexpressing NT4 in skin, under the control of the keratin 14 gene promoter, were examined. Similar to BDNF-OE mice, NT4-OE mice had increased innervation to the skin but no increase in sensory neuron number in either the dorsal root ganglion or trigeminal ganglion. NT4 overexpression also enhanced hair follicle innervation and the size and density of innervation to Meissner corpuscles. Unlike BDNF overexpression, NT4 overexpression did not alter the number of Merkel cells in the glabrous skin, but it did enhance the number of myelinated axons in nerves projecting to skin. Thus, the same pattern of BDNF and NT4 overexpression within the skin produces phenotypes that are both similar and distinctive.
Mechanical Behavior of Textile Composite Materials Using a Hybrid Finite Element Approach

A novel analytical solution is presented to describe the mechanical behavior and failure of textile reinforced composites. This solution is constructed from two parts. First a geometrical model, based on a processing science approach coupled with graphical rendering, is utilized to quantify the spatial characteristics of the fabric preform inside the composite. A 3-D iterative hybrid finite element analysis is then used, utilizing data acquired from the geometrical model, to predict the stress-strain behavior of the composite. Inelastic behavior is modeled using an expanded Hahn and Tsai model and maximum stress criterion is used to predict initial failure. Damage progression is predicted based on a stiffness reduction approach. AS4 carbon/epoxy plain weave composite laminates, with a range of fiber volume fractions, have been tested. A 3-D woven E-glass/poly-vinyl-ester (PVE) angle interlock composite was also tested. Analytical results are compared with results from this experiment as well as other analytical models and experimental data in the literature. Theoretical model predictions are in agreement with most experimental data.
Risk management in gathering economies

Abstract This article extends the literature on the interplay of environmental risk and welfare into the setting of coastal fisheries gathering. It reviews the sources of covariate and idiosyncratic production risk creating income shocks to gatherers and discusses the institutions that best mediate shocks across different settings. We rely upon a principal-agent framework between larva-gathering agents employed by boat-owning principals who supply seed to shrimp farms. Two datasets from a Central American fishery are used to test the hypotheses concerning contractual performance across environments. Which contract provides the highest mean income (and variation) depends upon the underlying production catch data. In the farm production records dataset with strong catch trends, a simplified relative payments contract would perform better in reducing income risk in locations of stronger covariate shocks, but at the price of significantly lower mean earnings for gatherers. In areas of idiosyncratic shocks, su...
Deep genome-wide measurement of meiotic gene conversion using tetrad analysis in Arabidopsis thaliana.

Gene conversion, the non-reciprocal exchange of genetic information, is one of the potential products of meiotic recombination. It can shape genome structure by acting on repetitive DNA elements, influence allele frequencies at the population level, and is known to be implicated in human disease. But gene conversion is hard to detect directly except in organisms, like fungi, that group their gametes following meiosis. We have developed a novel visual assay that enables us to detect gene conversion events directly in the gametes of the flowering plant Arabidopsis thaliana. Using this assay we measured gene conversion events across the genome of more than one million meioses and determined that the genome-wide average frequency is 3.5×10−4 conversions per locus per meiosis. We also detected significant locus-to-locus variation in conversion frequency but no intra-locus variation. Significantly, we found one locus on the short arm of chromosome 4 that experienced 3-fold to 6-fold more gene conversions than the other loci tested. Finally, we demonstrated that we could modulate conversion frequency by varying experimental conditions.