cssi/SciSciGPT-SciSciNet huggingface dataset:
Film Coating Theory and Practice

Recent theory and developments relating to the formation and modification of synthetic polymeric films are discussed in relation to the pharmaceutical uses of such films in dosage form development. Fundamental mechanical and physicochemical properties of films as affected by plasticization, solvent effects, polymer chemistry, film additives, and other factors are considered in relation to film dissolution, permeability, and diffusion properties.
Nonlinear inferential control

Abstract Due to unmeasured distrubances and nonlinearities typical for chemical processes the performance of state reconstruction schemes based on linearized system is often unsatisfactory. Unmeasured disturbances yield biased state estimates because generally only proportional feedback is used in the estimators. Set point changes or large disturbances make linear estimators invalid for most chemical processes. Static and dynamic nonlinear estimation schemes are derived in this paper when persistent or slowly varying disturbances (nonstationary noise) affect the system. Because an analytical solution for general nonlinear systems is impossible, approximate methods are suggested to reduce the computational effort necessary for evaluating the estimate. The method is applied to two CSTR's in series where concentration estimates are obtained from temperature measurements. The results are significantly better than those obtained by linear estimation techniques. A convenient measurement selection criterion is also derived which aims at minimizing the sensitivity of the estimate to unmeasured disturbances.
Persistence, diagnostic specificity and genetic liability for context-processing deficits in schizophrenia

Context-processing deficits have been shown in schizophrenia during first-episode, medication-naive status, that persist after short-term antipsychotic treatment and also in first-degree relatives of individuals with schizophrenia. To confirm longer term persistence of deficits, we examined schizophrenia patients (n=63) during first-episode, medication-naive status through to one-year follow-up, compared to healthy control (n=83) and non-schizophrenia psychosis comparison (n=47) groups, as well as unaffected first-degree relatives of individuals with schizophrenia (n=31). Context-processing ability was assessed by performance on the AX-CPT (Continuous Performance Test) at baseline, 8 weeks, 6 months, and 1 year (relatives only at baseline). Reaction time, error rates and signal detection indices (d'-context) of context processing were analyzed. Linear discriminant analyses (LDA) on early timepoints (baseline, 8 weeks) were conducted to predict confirmatory diagnosis (schizophrenia vs. psychosis control) at 6 months. Schizophrenia patients showed evidence of impaired context-processing relative to both the healthy and psychosis comparator groups at baseline and continued through to 1 year. While context-processing impairments persisted in schizophrenia patients through one year, the impairments in psychosis controls, which were more modest at baseline, remitted at follow-up. First-degree relatives showed deficits that were intermediate between the schizophrenia and healthy control groups. LDA showed 67% classification rates for distinguishing schizophrenia from non-schizophrenia psychosis. The persistence, diagnostic specificity and association with genetic liability give support for context processing impairments serving as a cognitive endophenotype for schizophrenia and evaluation of context processing could contribute to diagnostic assessments.
Hypomyelinated mutant mice: description of jpmsd and comparison with jp and qk on their present genetic backgrounds.

Summary Hypomyelinated mutant mice are valuable natural animal systems for analysis of CNS myelin development, chemistry and diseases. One mutant, jp msd , has never received thorough morphological description. We here describe the detailed morphology of jp msd , compare it with well-studied jp and qk on their present genetic backgrounds, and discuss the genetic histories of all 3 mutants. Region for region, jp msd has twice as much myelin as jp, but 1/2-1/5 as much as qk. Both jp and jp msd have scarce oligodendrocytes, rare nodes of Ranvier, clustering of myelin segments, abnormal lipid-filled cells, frequent degenerating cells, and rare distored myelin profiles. In contrast, qk has abnormally numerous oligodendrocytes, frequent nodes of Ranvier, no obvious myelin clustering, no lipid-filled cells, rare degenerating cells, and frequent abnormal or distorted myelin profiles. jp and jp msd are quantitatively different, but qualitatively similar. Since its origin, the jp msd disease has inadvertently been ameliorated by transferring the mutation to a different background. Persistent differences in the remainder of the genome might account for all remaining apparent differences between jp and jp msd . In contrast, qk is totally dissimilar in morphology and presumably in pathophysiology.
Residential rurality and oral health disparities: influences of contextual and individual factors.

The purposes of the study were (a) to identify disparities between urban and rural adults in oral health and (b) to examine contextual (i.e., external environment and access to dental care) and individual (i.e., predisposing, enabling, and lifestyle behavioral) factors associated with oral health problems in a community population. Study data were derived from a two-stage, telephone-mailed survey conducted in 2006. The subjects were 2,591 adults aged 18 years and older. Cochran-Mantel-Haenszel statistics for categorical variables were applied to explore conditional independence between both health access and individual factors and oral health problems after controlling for the urban or rural residence. Logistic regression was used to investigate the simultaneous associations of contextual and individual factors in both rural and urban areas. Approximately one quarter (24.1%) of the study population reported oral health problems. Participants residing in rural areas reported more oral health disparities. Oral health problems were significantly associated with delaying dental care. These problems also were more common among those who were less educated, were African American, skipped breakfast every day, and currently smoked. The study findings suggest that oral health disparities persist for people in rural areas, and improving oral health status is strongly related to better access to oral health care and improved lifestyles in both rural and urban areas.
Furan-induced dose-response relationships for liver cytotoxicity, cell proliferation, and tumorigenicity (furan-induced liver tumorigenicity)

Rodent studies of furan are associated with liver cell necrosis, release of liver-associated enzymes, increased hepatocyte proliferation, and hepatocarcinogenesis. For carcinogens whose proposed mode of action is cytolethality, it is hypothesized that the dose-response curve for tumor development would parallel the dose-response curve for cell death with compensatory proliferation in the target organ. To prospectively test this hypothesis, female B6C3F(1) mice were exposed to furan at carcinogenic doses and lower for 3 weeks or 2 years. At 3 weeks and in the 2-year study, there were dose-dependent and significant increases in hepatic cytotoxicity at 1.0, 2.0, 4.0, and 8.0mg furan/kg. For cell proliferation as measured by 5-bromo-2'-deoxyuridine (BrdU) labeling index (LI), there was a statistically significant trend with increasing dose levels of furan and increased LI at 8.0mg/kg. There was an increased incidence of foci of altered hepatocytes, hepatocellular adenomas, and adenomas or carcinomas at 4.0 and 8.0mg/kg and carcinomas at 8.0mg/kg. The multiplicity of microscopic tumors was increased and latency was decreased in mice exposed to 8.0mg/kg. Prevalence of hepatic nodules at necropsy was increased in mice exposed to 4.0 and 8.0mg/kg. Data demonstrate an association among furan-induced hepatic cytotoxicity, compensatory cell replication, and liver tumor formation in mice; at high doses >or=4.0mg/kg, furan induced hepatotoxicity, compensatory cell replication and tumorigenesis in a dose-related manner, while furan did not produce tumors at cytotoxic doses of 1.0 and 2.0mg/kg.
Immunology: Fixing the odds against tuberculosis

A study that defines the interactions between three immunity-regulating molecules — type 1 interferon, interleukin-1 and prostaglandin E2 — will help to explain the variable outcomes of tuberculosis infections. See Letter p.99 Tuberculosis is re-emerging as a major threat to public health following the spread of multi-drug-resistant Mycobacterium tuberculosis and complications caused by the HIV epidemic. And there is still no globally effective vaccine. Now a collaboration between laboratories across the United States and in Brazil, China and India has developed an immunotherapeutic approach that targets innate immunity in a mouse tuberculosis model through the manipulation of the cytokines interferon (present in excess in active tuberculosis) and interleukin-1 (thought to have protective effects). Katrin Mayer-Barber and colleagues show that these cytokines are functionally linked through the eicosanoids. This work serves as a proof of concept for treatments directed at the host eicosanoid network, and suggests feasible alternatives to conventional chemotherapy.
Pseudomonas aeruginosa Infection and Humoral Antibody Response of Patients with Cystic Fibrosis

Study of the humoral antibody response of patients with cystic fibrosis to the heat-stable O (and possibly K) antigens of Pseudomonas aeruginosa revealed that these antibodies in significant titers do not lead to eradication of the microorganism from the respiratory tract. In three out of six patients, antibodies directed against the strains isolated from both sputum and the lungs at autopsy were present in elevated titers. The antibody response to P. aeruginosa is strikingly affected by the condition of the host and differs in patients with cystic fibrosis or with one or another kind of malignancy. Pseudomonas aeruginosa infection of man serves as an unusually impressive example of a disease illustrating the important role of the host. The spectrum of clinical entities ranges from serious and even fatal infection complicated by bacteremia in patients with underlying diseases, such as severe burns, leukemia, and immunodeficiencies, to persistent, but localized infection of the respiratory tract in subjects with cystic fibrosis. The documentation of the immune response to this pathogen may contribute to the elucidation of the diagnosis of, and immunity against, this infection or colonization and is the subject of this brief
Portal Hypertensive Polyposis: A Consequence of Esophageal Variceal Ligation?

A 59-year-old man with history of nonalcoholic steatohepatitis (NASH) cirrhosis and portal hypertension with previous esophageal variceal ligation presented with 2 days of melena and fatigue. He was taking 20 mg of propranolol 3 times per day. Hemoglobin was 7 g/dL and platelets were 59,000/L. Esophagogogastroduodenostomy (EGD) performed 1 year earlier revealed large distal esophageal varices requiring ligation with 5 bands and gastritis located in the antrum. EGD during this admission revealed small distal esophageal varices, as well as 3 large polyps and many small polyps in the distal body and antrum (Figures 1 and 2). The large polyps were resected via hot snare polypectomy (Figure 3). Two hemoclips were applied to 1 polypectomy site and argon plasma coagulation ablation was performed for the base of the largest polyp. Histopathologic examination of the polyps revealed hyperplastic-like gastric polyps with marked foveolar hyperplasia with cystic dilations, edematous and fibrotic stroma, a prominent capillary proliferation in the lamina propria, and scattered telangiectactic vessels, consistent with portal hypertensive polyposis (PHP).
Relaxation times in chemostat culture

This paper establishes theoretical estimates for the relaxation time to steady state in chemostat cultures. For the simplest case with Monod kinetics two characteristic times τ1, τ2 arise. The quantity τ1 is significant at low dilution rates while τ2 dominates at dilution rates near washout. The deterioration in the stability characteristics of the chemostat system near washout can be delayed through the use of increased substrate concentrations in the reservoir medium.
NAD(P)H Oxidase: Marker of the Dedifferentiated Neointimal Smooth Muscle Cell?

In recent years, there has been intense interest in vascular NAD(P)H oxidases and their role in vascular injury and atherosclerosis. Balloon injury has been shown to cause large increases in O2– stemming from NAD(P)H oxidases,1 while other studies have shown that hypercholesterolemia and atherosclerosis can induce vascular expression of NADPH oxidase.2 3 4 This induction has been implicated in cell phenotype change and proliferation, and a similar process can be inferred to occur during vascular grafting.5 Two key studies have demonstrated that overexpression of NAD(P)H oxidase in cells leads to transformation to a proliferative phenotype,6 7 and various redox mechanisms transducing this transformation in injury have been elucidated.8 On the contrary, other reports have shown that deletion of 2 essential components of phagocyte NAD(P)H oxidase fail to inhibit lesion formation in apoE–/– mice.9 10 However, it remains to be determined whether those components and NAD(P)H oxidase do play a role under conditions in which the renin-angiotensin system is activated.11 12 In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology , West et al13 present exciting findings suggesting a role for NAD(P)H oxidase–expressing cells in intimal hyperplasia after venous bypass. The authors performed elegant immunohistochemical analyses in an attempt to carefully determine the source and state of differentiation of cells in the subintimal space. They found that cells that strongly express p22 phox (an essential NADPH oxidase component) do not express smoothelin, a marker for highly differentiated smooth muscle cells.14 Their intriguing results show that whereas most cells in the neointima are positive for α-actin, desmin, and smoothelin (all markers for smooth muscle cells) and yet weakly positive for p22 phox , those that strongly express p22 phox do not express desmin or smoothelin. These data suggest that there …
Joining Statistics with NLP for Text Categorization

Automatic news categorization systems have produced high accuracy, consistency, and flexibility using some natural language processing techniques. These knowledge-based categorization methods are more powerful and accurate than statistical techniques. However, the phrasal pre-processing and pattern matching methods that seem to work for categorization have the disadvantage of requiring a fair amount of knowledge-encoding by human beings. In addition, they work much better at certain tasks, such as identifying major events in texts, than at others, such as determining what sort of business or product is involved in a news event.Statistical methods for categorization, on the other hand, are easy to implement and require little or no human customization. But they don't offer any of the benefits of natural language processing, such as the ability to identify relationships and enforce linguistic constraints.Our approach has been to use statistics in the knowledge acquisition component of a linguistic pattern-based categorization system, using statistical methods, for example, to associate words with industries and identify phrases that information about businesses or products. Instead of replacing knowledge-based methods with statistics, statistical training replaces knowledge engineering. This has resulted in high accuracy, shorter customization time, and good prospects for the application of the statistical methods to problems in lexical acquisition.
Superconductivity in a strongly interacting two-dimensional electron liquid: Gap structure.

Both the ac conductivity and the local dynamic spin response function of the commensurate flux phase of the [ital t]-[ital J] model in two dimensions are computed near half filling. This purported anyonic superconductor shows two different zero-temperature gaps in these quantities, which correspond to the gap for quasiparticle charge excitations and quasiparticle spin excitations, respectively. In both instances, the gap exists over the entire Fermi surface. The ac conductivity also shows the expected Drude [delta]-function peak with a weight that scales with the hole concentration and with an optical mass given by 2.95 in units of the band mass, (2[ital t])[sup [minus]1]. This value agrees with that obtained from exact cluster calculations on the [ital t]-[ital J] model.
Analysis of seven-year moderate resolution imaging spectroradiometer vegetation water indices for drought and fire activity assessment over Georgia of the United States

Using a seven-year history of the satellite measurements and meteorology data over Georgia, USA, this study investigated the capability of a series of satellite-derived vegetation water indices for drought monitoring, as well as the connection between fire occurrence and drought conditions. The vegetation water indices are normalized calculations between MODIS near infrared band 2 and shortwave infrared bands 5, 6, 7, and the difference between bands 6 and 7, denoted by NDWI2,5, NDWI2,6, NDWI2,7 and NMDI, respectively. Results show that the drought conditions indicated by NMDI, NDWI2,6 and NDWI2,7 agree well with what have been identified by meteorology data. NMDI, however, has demonstrated more dependable results regarding seasonal moisture variations, as well as stronger responses to drought conditions than NDWI2,6, and NDWI2,7. The annual fire number exhibits high correspondence to drought conditions. Drought intensity also influenced fire extent and the most widespread fires occurred during the driest years. Analysis reveals that NMDI can be used as an effective indicator for fire risk monitoring. It is expected that this research will greatly benefit many applications, such as monitoring drought and detecting fire danger potential.
Analysis of whistler mode sidebands of magnetospheric triggered emissions

Very low frequency (VLF) magnetospheric wave injection experiments performed at Siple Station, Antarctica and the High Frequency Active Auroral Research Program (HAARP) in Gakona, Alaska show that magnetospherically amplified waves are often accompanied by bandwidth spreading and also discrete sidebands resulting from the nonlinear interactions with energetic electrons. Analysis of the sidebands provides access to several key parameters of the nonlinear interaction. While the amplitude of sidebands from the Siple Station experiment have been previously analyzed, the relative phase of the sidebands has received very little attention due in part to the high cost of digital spectral analysis in the 1970s and 1980s. Using recently digitized data from the Siple Station experiment, we analyze the sidebands of signals injected in Antarctica and received at the magnetic conjugate point in Lake Mistissini, Canada after ducted propagation and amplification. The data were originally recorded on magnetic tape in 1986. The sidebands are analyzed to determine the type of modulation with which they are generated. Some past work has suggested that the sidebands result from amplitude modulation that occurs during the saturation and associated amplitude oscillation of the main emission. At the same time, certain theories have suggested that sidebands should be generated by phase modulation of the nonlinear cyclotron current. It is shown that certain sideband events exhibit phase modulation of the main carrier. The results are interpreted in terms of theoretical formulations of a phase-space hole resulting from electron phase trapping in an inhomogeneous magnetized plasma. Under these formulations, the modulation results from oscillation of phase trapped electrons about the stable phase point.
The convulsive patterns provoked by indoklon, metrazol and electroshock: some depth electrographic observations in human patients.

Abstract The convulsive patterns provoked by the inhalation of hexafluorodiethyl ether (Indoklon), the intravenous injection of pentylenetetrazol (Metrazol), and the administration of electroshock have been recorded by means of multielectrode leads implanted into the brains of five psychotic patients (unmedicated) preceding frontal lobotomy. The patterns observed in these tracings, which were free from muscular contamination, during the prodromal, tonic and clonic phases of the seizure and the postictal period have been described and correlated with the accompanying clinical phenomena. Evidence has been found suggesting that: (1) Indoklon and Metrazol during the prodromal phase, and both these agents plus electroshock during the seizure proper act on the human brain through a common operating mechanism; (2) regardless of how it is initiated and controlled, the convulsive discharge develops with some degree of independence in the various parts of the brain, and (3) the predominance and longer persistence in the frontal areas of the slow disturbance following electrically induced seizures are related to the structural and functional organization of the brain rather than to a local action of the convulsant.
An options-based solution to the sequential auction problem

The sequential auction problem is commonplace in open, electronic marketplaces such as eBay. This is the problem where a buyer has no dominant strategy in bidding across multiple auctions when the buyer would have a simple, truth-revealing strategy if there was but a single auction event. Our model allows for multiple, distinct goods and market dynamics with buyers and sellers that arrive over time. Sellers each bring a single unit of a good to the market while buyers can have values on bundles of goods. We model each individual auction as a second-price (Vickrey) auction and propose an options-based, proxied solution to provide price and winner-determination coordination across auctions. While still allowing for temporally uncoordinated market participation, this options-based approach solves the sequential auction problem and provides truthful bidding as a weakly dominant strategy for buyers. An empirical study suggests that this coordination can enable a significant efficiency and revenue improvement over the current eBay market design, and highlights the effect on performance of complex buyer valuations (buyers with substitutes and complements valuations) and varying the market liquidity.
Time-Reversal Processing and Autofocus of Targets Behind Complex Wall

Through-the-wall radar imaging (TWRI) beyond a single wall is a growing area of study [1]. Some previous work was done to mitigate wall effects under little or no knowledge of the wall [2]-[4]. However, past TWRI work has primarily been focused on imaging behind uniform dielectric walls. In this paper, we seek to leverage such effort for complex cinderblock walls commonly used in modern building construction. For walls formed by periodic blocks, much worse frequency-dependent distortion is expected as electromagnetic propagation through wall structures gives rise to Floquet modes. The work in [5] began dealing with this problem for far-field radar scan. In this paper, we focus on integrating electromagnetic propagation models (of the complex wall) with near zone imaging techniques to improve focusing of interior targets.
Spatial mapping of the internal and external electromagnetic fields of negative index metamaterials.

We perform an experimental study of the phase and amplitude of microwaves interacting with and scattered by two-dimensional negative index metamaterials. The measurements are performed in a parallel plate waveguide apparatus at X-band frequencies (8–12 GHz), thus constraining the electromagnetic fields to two dimensions. A detection antenna is fixed to one of the plates, while a second plate with a fixed source antenna or waveguide is translated relative to the first plate. The detection antenna is inserted into, but not protruding below, the stationary plate so that fields internal to the metamaterial samples can be mapped. From the measured mappings of the electric field, the interplay between the microstructure of the metamaterial lattice and the macroscopic averaged response is revealed. For example, the mapped phase fronts within a metamaterial having a negative refractive index are consistent with a macroscopic phase—in accordance with the effective medium predictions—which travels in a direction opposite to the direction of propagation. The field maps are in excellent agreement with finite element numerical simulations performed assuming homogeneous metamaterial structures.
Cell Immobilization with Polyurethane Foam for Retaining Trichoderma reesei Cells During Foam Fractionation for Cellulase Collection

In situ affinity foam fractionation is a potential powerful tool for continuous, selective removal of products from bioprocesses. When evaluating its applicability to cellulase production by Trichoderma reesei fermentation, we encountered the difficulty of significant removal of fungal mycelia along with the cellulase. To solve this problem, cell immobilization using cut pieces of hydrophilic polyurethane (PU) foam was evaluated. Five commercial PU foams with different pore sizes and porosities were tested. Two were found to support good cell growth, cellulase production, and cell loading (about 0.6 g dry cells per g PU). The PU-immobilized mycelia were successfully retained in the foaming process.
Regulation of E-cadherin

Numerous studies suggest that loss of E-cadherin is necessary to induce Epithelial–mesenchymal transition (EMT) and metastasis. Snail is a major contributor to EMTs. The Snail family of zinc-finger transcription factors interact with the E-cadherin promoter to repress transcription during EMT. The present article reviews the regulation of E-cadherin and discusses recent novel insights into the molecular basis in the process of EMT.
Scheduling analysis of the Micro Channel Architecture for multimedia applications

In recent years, fixed priority real-time scheduling has made significant advances. These advances have been applied primarily to CPU scheduling. While CPU scheduling is an important aspect of real-time designs, other shared system resources require the same attention in order for a system to transfer real-time traffic. This paper addresses one such resource, the system bus, and presents a methodology for analyzing bus structures, specifically buses carrying continuous media (CM), using fixed priority scheduling. A scheduling bus model for the Micro Channel Architecture which incorporates the non-ideal, real-world bus features is presented. A continuous media (CM) task set is used to explore design issues. These issues include the following: priority level assignment on the bus, the effect of task period transformation, the use of multi-level scheduling, and the effort of limited priority levels on the bus. In addition formulations are made for setting bus parameters such as tenure time and DRAM refresh periods to optimize continuous media scheduling. >
Preliminary evidence of health care provider support for naloxone prescription as overdose fatality prevention strategy in New York City.

Preliminary research suggests that naloxone (Narcan), a short-acting opiate antagonist, could be provided by prescription or distribution to heroin users to reduce the likelihood of fatality from overdose. We conducted a random postal survey of 1.100 prescription-authorized health care providers in New York City to determine willingness to prescribe naloxone to patients at risk of an opiate overdose. Among 363 nurse practitioners, physicians, and physician assistants responding, 33,4% would consider prescribing naloxone, and 29.4% were unsure. This preliminary study suggests that a substantial number of New York City health care providers would prescribe naloxone for opiate overdose prevention.
Percentile Ranking and Citation Impact of a Large Cohort of National Heart, Lung, and Blood Institute–Funded Cardiovascular R01 Grants

Rationale:Funding decisions for cardiovascular R01 grant applications at the National Heart, Lung, and Blood Institute (NHLBI) largely hinge on percentile rankings. It is not known whether this approach enables the highest impact science. Objective:Our aim was to conduct an observational analysis of percentile rankings and bibliometric outcomes for a contemporary set of funded NHLBI cardiovascular R01 grants. Methods and Results:We identified 1492 investigator-initiated de novo R01 grant applications that were funded between 2001 and 2008 and followed their progress for linked publications and citations to those publications. Our coprimary end points were citations received per million dollars of funding, citations obtained <2 years of publication, and 2-year citations for each grant’s maximally cited paper. In 7654 grant-years of funding that generated $3004 million of total National Institutes of Health awards, the portfolio yielded 16 793 publications that appeared between 2001 and 2012 (median per gra...
A model for staff training in the psychiatric hospital treatment of adolescents.

Abstract In hospital settings which emphasize the importance of therapeutic relationships in the treatment process, ward staff often function as central adult models with whom the adolescent patients can gradually identify. The need for training programs to aid staff to develop requisite feelings of competence and confidence is widely recognized. This paper offers a model for a group training approach for ward staff who work with hospitalized adolescents. The techniques include a style of thinking, recognition of personal attitudes and personal anxiety, the uses of didactic information, and group leadership.
Enhancing Learning Outcomes: The Effects of Instructional Technology, Learning Styles, Instructional Methods, and Student Behavior:

The delivery of marketing education seems to be rapidly shifting toward pedagogy rich in experiential learning and strongly supported with educational technology. This study integrates and extends previous research efforts and investigates the simultaneous effects of multiple influences of technology and nontechnology factors on learning outcomes. Responses were obtained across a marketing curriculum with technology-accustomed students. The findings suggest that the use of preferred instructional methods will enhance each of the three different measures of learning outcomes, while encouraging supportive class behaviors can increase self report performance and course grade. Regardless of the dependent outcome measure, only one of the five instructional technology variables proved significant, suggesting that in contrast to previous studies that examined technology in isolation, when analyzed relative to other learning factors, technology’s influence is secondary. Implications are discussed with practical s...
Imaging P-glycoprotein transport activity at the human blood-brain barrier with positron emission tomography.

Background Numerous knockout mouse studies have revealed that P-glycoprotein (P-gp) significantly limits drug distribution across the mouse blood-brain barrier (BBB). To determine the importance of P-gp at the human BBB, we developed a state-of-the-art, noninvasive, quantitative imaging technique to measure P-gp activity by use of carbon 11-labeled verapamil as the P-gp substrate and cyclosporine (INN, ciclosporin) as the P-gp inhibitor. Methods In brief, 11C-verapamil (approximately 0.2 mCi/kg) was administered to healthy volunteers (n = 12 [6 women and 6 men]) as an intravenous infusion over a period of approximately 1 minute before and after at least a 1-hour infusion of cyclosporine (2.5 mg · kg−1 · h−1). Arterial blood samples and brain positron emission tomography images were obtained at frequent intervals for 45 minutes. Both blood and plasma radioactivity contents were determined in each verapamil sample. The content of verapamil and its metabolites in the 20- and 45-minute plasma samples was determined by a rapid solid-phase extraction method. The brain uptake of 11C-radioactivity (brain area under the curve [AUCbrain]/blood area under the curve [AUCblood]) was determined in the presence and absence of cyclosporine. Results The AUCbrain/AUCblood ratio of 11C-radioactivity was increased by 88% ± 20% (1.02 ± 0.18 versus 0.55 ± 0.10, P < .001) in the presence of cyclosporine (mean blood concentration, 2.8 ± 0.4 μmol/L) without affecting 11C-verapamil metabolism or plasma protein binding. The corresponding increases for the brain white and gray matter were 84% ± 13% and 84% ± 18%, respectively. Conclusions This is the first time that P-gp activity at the human BBB has been measured. The modest inhibition of human BBB P-gp by cyclosporine has implications for P-gp-based drug interactions at the human BBB. Our method for imaging P-gp activity can be used to identify multidrug-resistant tumors or to determine the contribution of P-gp polymorphism, inhibition, or induction to interindividual variability in drug response. Clinical Pharmacology & Therapeutics (2005) 77, 503–514; doi: 10.1016/j.clpt.2005.01.022
Alternative sources of gametes : reality or science fiction?

Although great progress has been made in both the investigation and treatment of infertility, a considerable number of patients still fail to conceive. Spermatogenic failure and/or oocyte ageing appear to be responsible for a large proportion of cases. The use of donor gametes may bring legal, ethical and even social problems of acceptance that can discourage infertile couples from the donor route. Fortunately, emerging reproductive technologies and preliminary results from animal experiments provide some hope for alternative sources of gametes through which these infertile patients can finally conceive their own genetic child. In conjunction with intracytoplasmic sperm injection (ICSI), fertilization of human oocytes with immature sperm precursors, e.g. spermatids and even secondary spermatocytes, has resulted in healthy babies. Pregnancies have also resulted from the use of spermatids derived from in-vitro spermatogenesis. In the mouse, even primary spermatocytes appear able to participate in normal embryogenesis. In view of the possibility for transplantation and even xenotransplantation of spermatogonia to a host testis in animals, a similar use of human male stem cells might provide an attractive source for the treatment of males with arrested spermatogenesis, as well as male cancer patients. Transplantation of somatic cell nuclei and their haploidization within oocytes may prove to be a practical way of eradicating age-related aneuploidy and so constitute an innovative source of healthy oocytes. Most importantly, however, the safety of the procedures described here needs to be proven before their application to the human arena. Finally, we discuss the implications of cytoplasmic quality and of genetic imprinting in the context of these manipulations.
Reformulated REA Ethanol Assay Evaluated

In 1984, Abbott Laboratories introduced a radiative energy attenuation (REA) assay for the determination of ethanol on the TDX analyzer. The author's laboratory evaluated this method and compared its results with those obtained by a commonly used gas-liquid chromatographic (GLC) technique and the Du Pont aca. The REA method was found to be accurate, reproducible, and easy to use (1). Recently, Abbott reformulated the ethanol assay by replacing the iodonitrotetrazolium violet (INT) dye with thiazolyl blue (3-[4,5-dimethyl thiazol-2yl]-2,5-diphenyl tetrazolium bromide). The reason for this reformulation, according to the manufacturer, was to eliminate the probe wash protocol recommended after every run with the original REA ethanol assay. This wash, which used a 10% tetraethylammonium hydroxide solution, was necessary to remove small amounts of dye retained in the probe following the use of the INT-based assay. The introduction of the thiazolyl blue (MTT) notwithstanding, the Abbott REA ethanol assay using the linked enzymecatalytic reactions of alcohol dehydrogenase (EC 1.1.1.1) and diaphorase (EC 1.6.4.3, dihydrolipoamide reductase (NAD +)] is identical to the original assay. The reduced MTT yields a purple color with an absorbance peak at 565 nm which overlaps the excitation and emission spectrum of fluorescein (a fluorescent indicator added to the reaction having an excitation peak at 485 nm and an emission peak at 525 nm). The fluorescence intensity decreases logarithmically with increasing concentrations of reduced MTT making the concentration of ethanol proportional to the degree of inner filter effect on the fluorophore. The new REA formulation for determining ethanol was evaluated and its results compared with those obtained by GLC and an ethanol-specific enzymatic method performed on the Du Pont aca. Ethanol concentrations obtained by the MTT reagent system were also compared directly to results obtained by the original REA ethanol assay. The sample collection protocols and the analytical procedures used in this evaluation were identical to those used in the previous evaluation (1). Correlations between the various methods were determined by least-squares linear regression analysis of the experimentally obtained values using NWA Statpak | (Northwest Analytical, Inc.) on an Apple Macintosh TM computer (Apple Computer, Inc.).
Penicillin is the drug of choice to treat all stages of syphilis despite a paucity of clinical trials data for the treatment of some stages, pregnant women and HIV-infected people

Commentary on : Clement ME, Okeke NL, Hicks CB. Treatment of syphilis: a systematic review. JAMA 2014;312:1905–17.[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Syphilis rates are increasing particularly in men, many of whom are HIV co-infected. In some areas, syphilis continues to affect women leading to high rates of congenital infections. Non-treponemal serological tests are still the mainstay of staging and assessing response to therapy. These tests are, at best, an indirect marker of disease activity. In some cases, changes in non-treponemal titres may reflect factors other than syphilis infection.1 In the pre-antibiotic era, people with early syphilis, whose non-treponemal antibody tests failed to revert to negative (ie, remained ‘serofast’), had a worse long-term prognosis. This systematic review examines the evidence supporting penicillin and non-penicillin-based regimens for the treatment of: (1) the different stages of syphilis; (2) pregnant women and (3) HIV-infected people. The … [1]: {openurl}?query=rft.jtitle%253DJAMA%26rft.volume%253D312%26rft.spage%253D1905%26rft_id%253Dinfo%253Adoi%252F10.1001%252Fjama.2014.13259%26rft_id%253Dinfo%253Apmid%252F25387188%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1001/jama.2014.13259&link_type=DOI [3]: /lookup/external-ref?access_num=25387188&link_type=MED&atom=%2Febmed%2F20%2F2%2F63.atom [4]: /lookup/external-ref?access_num=000344532600020&link_type=ISI
MPEG4 performance-driven avatar via robust facial motion tracking

In this paper, an MPEG4 real-time performance-driven avatar is proposed. The facial motion parameters, namely head rotation angles and translation distances as well as a set of action unit weights, are estimated from live video on a per-frame basis using a two-step robust facial motion tracking algorithm. The estimated parameters are then converted into MPEG4 facial animation parameter (FAP) values by solving an overdetermined constrained linear least-squares optimization problem. These FAP values can be used to drive an MPEG4-compliant face model to generate on-the-fly realistic facial animation that resembles the facial actions of the performer in the video. Such a real-time performance-driven avatar has important applications in a broad range of areas including very low bit rate video communication, movie and game industries as well as human-computer intelligent interaction.
Minimal-order realizations for continuous-time two-power input-output maps

This paper considers two-power input-output maps which are continuous-time, impulsive, and time-invariant. Realizability, by a very general class of nonlinear differential systems, is characterized simply in terms of the symmetric Volterra transfer function. The characterization leads directly to a family of minimal-order realizations having the (feedforward) structure described by Crouch [6]. Members of the family have states which are related by quadratic homeomorphisms. An especially simple member of the family serves as a canonical form. The development is self-contained and unlike Crouch's requires only elementary mathematical tools.
Rac1 Is a Critical Mediator of Endothelium-Derived Neurotrophic Activity

The therapeutic potential of neurotrophic factors has been hampered by their inability to achieve adequate tissue penetration. Brain blood vessels, however, could be an alternative target for neurosalvage therapies by virtue of their close proximity to neurons. Here we show that hemizygous deletion of Rac1 in mouse endothelial cells (ECs) attenuates brain injury and edema after focal cerebral ischemia. Microarray analysis of Rac1(+/-) ECs revealed enrichment of stress response genes, basement membrane components, and neurotrophic factors that could affect neuronal survival. Consistent with these expression profiles, endothelial Rac1 hemizygosity enhanced antioxidative and endothelial barrier capacities and potentiated paracrine neuroprotective activities through the up-regulation of the neurotrophic factor, artemin. Endothelial Rac1, therefore, could be an important therapeutic target for promoting endothelial barrier integrity and neurotrophic activity.
Predicting Times to Corrosion from Field and Laboratory Chloride Data

Corrosion of steel in concrete is one of the major causes of the premature failure of steel reinforced concrete. In marine and deicing salt environments the ingress of chloride is the primary cause for the breakdown of passivity and the onset of severe corrosion. In this paper, we show how to develop effective diffusion coefficients for chloride ingress based on chloride profiles from several marine structures. Predictions of the times to reach chloride levels associated with initiation of severe corrosion are made. Chloride profiles using effective diffusion coefficients determined in other studies are given for bridge decks and parking structures. There are significant benefits of increased concrete cover and the use of corrosion inhibitors in increasing the time to corrosion. Finally, comparisons of Standard Test Method for Electrical Indication of Concrete's Ability to Resist Chloride Ion Penetration (ASTM C 1202) coulomb values with effective diffusion coefficients, determined from field and laboratory studies, indicate that effective diffusion coefficients for low permeability concretes can be estimated using simple modifications of this test method. Thus, we demonstrate that knowledge of the chloride profile is useful to assess the future performance of existing structures that are not undergoing active corrosion, and in predicting the time to corrosion initiation of new structures.
Eastern Boundary Ventilation and the Structure of the Thermocline

Abstract The effect of relaxing the zero geostrophic zonal flow condition at the eastern boundary on the structure of the ventilated thermocline is described. It is argued that the effect of dissipation can allow a vertical exchange of mass between layers at the eastern boundary. A model is studied analytically that assumes such an interchange while continuing to forbid a net eastward mass flux at each latitude. The consequences of the relaxation of this condition are striking. Each active layer in the ventilated thermocline can now have a non-zero thickness on the eastern wall. As a result, each such layer has a stagnant shadow zone near the eastern boundary. Each shadow zone extends across the gyre at low latitudes. Hence the isopycnal surfaces, while shallow, remain at finite depth as the equator is approached. The shadow zones are nested, i.e., the shadow zone of the deepest layer is laterally most extensive and the zone shrinks eastward and southward with decreasing depth. The vertical recirculation ...
Spirometric Norms in Healthy Adults of Ahmednagar District of Maharashtra

Context: Pulmonary function test (PFT) is an invaluable tool for assessment of lung function and is also the investigation of choice for overall assessment of respiratory function. Though its application in diagnosis and management of respiratory diseases is not yet routine in our country but predictive normal values are essential for meaningful clinical interpretation of these tests. Aims: To obtain reference values for various lung functions and develop suitable predictive equations. Methods and Material: Non-smoking healthy adult subjects attending the OPD/Indoor patients, hospital staff and medical students at Vikhe Patil Hospital, Ahmednagar underwent spirometric evaluation of various lung functions on a autospirometer. Three such efforts were made for each recording and best was selected based on standardisation of spirometry study based on ATS/ERS task force series. Statistical Analysis: Data was analysed as mean and standard deviation. Highly significant parameters were used as predictor variables and regression equations were formulated using multiple regression technique. Results: In both males and females age and height showed consistently high correlation with various pulmonary function parameters. Increase in age by one year resulted in 0.017 L decline in FVC whereas increase in height by a centimeter improved FVC by 0.063 L. Conclusion: Lung function is known to vary with ethnicity. Therefore, it is important to establish normative values relevant to the ethnic characteristics of local populations. Further studies of lung function in different communities may contribute to the understanding of the relative roles of genetic constitution and exogenous influence on lung function development.
FLIGHT OF FASCINATION

John J. Videler Oxford University Press (2005) 258 pp. ISBN 0-19-856603-4 £55.00 ![Figure][1] Birds are spontaneously intriguing to humans - witness the economics of the industry associated with bird watching and backyard feeders - and birds are often the subjects
Effects of Serum Factors upon Myelin Organization in Organotypic Cultures of Nervous Tissue

Recent studies (1-3) have shown that when myelinated, organotypic cultures of central nervous system (CNS) tissue are exposed to heated (complement-inactivated) anti-whole CNS antiserum from rabbits with acute experimental allergic encephalomyelitis (EAE), myelin sheaths are not destroyed, but oligodendroglia are stimulated to produce profuse, aberrant arrays of their processes and the periodicity of myelin sheaths acquires a unique morphology. The same serum in the presence of complement demyelinates the tissue within the first few hours of exposure (4, 5). In addition, there appears to be a specific effect of EAE serum on CNS elements. These changes are associated with the binding of antibody to the myelin sheaths (6). To test whether similar abnormalities could be induced in the peripheral nervous system (PNS), the present study involved cultures of PNS and CNS tissue exposed to heated and unheated serum from rabbits with experimental allergic neuritis (EAN), induced by challenge with PNS tissues in complete Freund’s adjuvant (CFA).