cssi/SciSciGPT-SciSciNet huggingface dataset:
Survival of Lactobacillus bulgaricus During Freezing and Freeze-Drying After Growth in the Presence of Calcium

Two morphologically distinct isolates of L. bulgaricus 1243 (designated F and O), were examined for stability during freezing and freeze-diying following growth in a nutrient broth medium supplemented with varying concentrations of calcium. While cellular morphology did not influence survival during −20°C frozen storage, calcium prevented freezing death in both isolates. Maximum survival occurred at calcium concentrations ranging between 5.4 × 10−3 and 6.7 × 10−3M. Calcium supplemented L. bulgaricus 1243-F displayed a five-fold decline in viable count (3.2 × 108 to 6.1 × 107) due to −20°C freezing, compared with cells propagated in broth without calcium, which declined 200-fold (1.7 × 108 to 6.3 × 105). Mg++ and Mn++ salts failed to exert protective effects. Calcium was ineffective in preventing freeze-injury, since cells displayed decreased acid production in milk following −20°C storage.
Chelating Ligands Tethered to Carbon Nanotubes

Carbon nanotubes offer an inert platform on which various species may be supported. A range of applications have been addressed using this approach. Anchoring sites on the nanotubes are usually groups introduced via an oxidative procedure. These groups provide convenient reactive functionality that can be accessed in a variety of ways. In this case, carboxyl functionality have been utilized to attach, through a linker, a good coordinating ligands, 1-10-phenanthroline. In the first instance, 1,10-phenanthroline was converted to the 5 ,6-epoxide by treatment with hypochlorite. The epoxide was opened in sulfuric acid to generate the 5 -hydroxy compound. This, in turn, was treated with ethylene oxide in the presence of a base to provide the alkoxylated compound. The alcohol terminus, as the alkoxide, was used to couple the nanotubes by displacement of tosyl anion from the methylol ester. The carboxyl groups at the nanotubes surface were reduced to the corresponding alcohol and treated with p-toluenesulfonyl chloride in the presence of pyridine to generate the tosylate used for coupling. In a second approach the carboxyl groups were converted to the corresponding acid chloride which was treated with alkoxylated phenanthroline to achieve coupling via an ester linkage.
Composition range of binary amorphous alloys

We have studied a number of binary metal-metal and metalloid alloy systems made by a single vapor-quench method under very consistent conditions. In each case, amorphous alloys are found in one continuous composition range (${x}_{\mathrm{min}\mathrm{\ensuremath{\le}}\mathrm{x}\mathrm{\ensuremath{\le}}{x}_{\mathrm{max})}}$ regardless of the number of eutectic points in the equilibrium phase diagrams. It is found that the atomic size difference is the single most important factor in the quantitative determination of the composition range.
Homogeneity of large-field color matches in congenital red-green color deficients

Rayleigh matches obtained from red–green color deficients with conventional methods show large individual differences within diagnostic categories. Similar matches obtained from the same observers with a large-field substitution method show much less variability and suggest that the differences observed among simple anomals, extreme anomals, and dichromats with conventional methods are probably not solely due to the visual pigments contained in the cones. A theory that attributes these differences to the relative number of abnormal cones present in the observer’s retina is described.
Antinociception produced by electrical stimulation of vagal afferents : independence of cervical and subdiaphragmatic branches

Abstract Expt. 1 showed that electrical stimulation of either the main dorsal or ventral branch of the subdiaphrrgmatic vagus could produce inhibition of the nociceptive tail-flick reflex in lightly anesthetized rats. The antinociception produced by electrical stimulation of the dorsal subdiaphragmatic vagus was eliminated by resection of the right cervical vagus, but relatively unaffected by resection of the left cervical vagus. The opposite effects for cervical vagal resection were obtained with electrical stimulation of the ventral branch of the subdiaphragmatic vagus. These results indicate that the antinociceptive effects of subdiaphragmatic vagal stimulation are mediated via uncrossed afferents traveling in the cervical vagus to activate an inhibitory spinopetal system. These findings are consistent with the established anatomy of vagal afferents. Expt. 2 showed that degeneration of the dorsal subdiaphragmatic vagus did not alter the threshold intensity of right cervical vagal stimulation necessary to produce inhibition of the tail-flick reflex. These results demonstrate that the antinociceptive effects of cervical vagal stimulation are primarily due to activation of the cardiopulmonary component of the nerve, rather than the subdiaphragmatic component. The second experiment also demonstratedthat the subdiaphragmatic branch of the vagus can be selectively degenerated with ricin while leaving the cervical branch intact, even though the cell bodies of both sets of afferents are located within the nodose ganglion. These data are discussed in terms of vagal afferents and their role in the modulation of nociceptive transmission.
Ethanol and Cocaine Intake by Rats Selectively Bred for Oral Opioid Acceptance

Lines which accept or reject the potent opioid etonitazene, and a randomly bred control line, were assessed for the specificity of selective breeding. Drug-naive subjects from generation 8 were offered a continuous choice between water and 10% ethanol for 20 days. There was no difference between the accepting and rejecting lines in preference for one fluid, or in amount of ethanol consumed. The same rats were then given a choice between water and increasing concentrations (0.08-0.64 mg/ml) of cocaine, 7 days at each concentration. There were no differences among the lines in preference for the drug, but the rejecting line drank more of the cocaine solution than the accepting line. Finally, these rats were subjected to the regimen used in choosing rats for selective breeding, 4 days of a water-etonitazene choice. In their preference for etonitazene the order of the lines was as expected: accepting > control > rejecting. In addition, the accepting line drank more of the etonitazene solution than the other two lines. These data suggest that selection has been rather specific and not for a generalized tendency to become intoxicated.
iScore: Measuring the Interestingness of Articles in a Limited User Environment

Search engines, such as Google, assign scores to news articles based on their relevancy to a query. However, not all relevant articles for the query may be interesting to a user. For example, if the article is old or yields little new information, the article would be uninteresting. Relevancy scores do not take into account what makes an article interesting, which would vary from user to user. Although methods such as collaborative filtering have been shown to be effective in recommendation systems, in a limited user environment there are not enough users that would make collaborative filtering effective. We present a general framework for defining and measuring the "interestingness" of articles, incorporating user-feedback. We show 21% improvement over traditional IR methods
Sub-wavelength plasmonic modes in a conductor-gap-dielectric system with a nanoscale gap

We study guided modes in a conductor-gap-dielectric (CGD) system that includes a low-index dielectric gap layer of deep sub-wavelength thickness sandwiched between a conductor and a high-index dielectric cladding. Analysis of the dispersion equation for CGD modes provides an analytical estimation for the cut-off thickness of the gap layer. This guided mode is unusual because it exists when the gap thickness is less than the cutoff thickness. In the direction normal to the interfaces, the modal electric field is tightly confined within the gap. Sub-wavelength lateral mode confinement is readily provided by a spatial variation of the gap-layer thickness: the modal field localizes at the narrowest gap. Various lateral confinement schemes are proposed and verified by numerical simulations. Possible applications of CGD modes include surface-plasmon nano-lasers (SPASERs) and sensors. If these plasmonic waveguides are scaled for operation at far infrared rather than telecomm wavelengths, then the propagation losses are dramatically reduced, thereby enabling the construction of practical chip-scale plasmonic integrated circuits or PLICs.
Constrained Monte Carlo and the method of control variates

A constrained Monte Carlo problem arises when one computes an expectation in the presence of a priori computable constraints on the expectations of quantities that are correlated with the estimand. This paper discusses different applications settings in which such constrained Monte Carlo computations arise, and establishes a close connection with the method of control variates when the constraints are of equality form.
Dietary Supplementation of Two Varying Sources of n-3 Fatty Acids and Subsequent Effects on Fresh, Cooled, and Frozen Seminal Characteristics of Stallions

Abstract The use of cooled and frozen semen offers many advantages to breeders. However, many stallions produce spermatozoa that are unable to endure the stresses associated with these preservation processes. Improving the quality and viability of equine spermatozoa via appropriate dietary alterations may render spermatozoa from these stallions commercially viable for preservation. One way to improve sperm quality may be through increasing dietary intake of PUFA, specifically docosahexaenoic acid (22:3n-3), to enhance the plasma membrane of the sperm cell. To evaluate this possibility, along with analyzing varying supplemental sources of n-3 fatty acids that are high in docosahexaenoic acid, stallions were placed into 1 of 2 treatment groups and fed either an algae- and flaxseed-based or a fish-based dietary supplement. Semen was collected every 2 wk for 112 d, 28 d before and 84 d during PUFA supplementation. Spermatozoa motion characteristics and membrane integrity and morphology of fresh, cooled, and stored (24 and 48 h), and frozen and thawed semen samples were analyzed. When spermatozoa obtained from stallions in each treatment were compared, no overall improvements were found ( P > 0.05) in motility, percentage of membrane-intact spermatozoa, and percentage of morphologically normal spermatozoa regardless of supplementation or source of supplementation.
The abortifacient effects of a newly developed vaginal silastic device impregnated with an 0.5% concentration of 15(s)-15-methyl-prostaglandin F2α methyl ester in the first trimester

Abstract Abortion was successfully induced in 15 of 20 patients from the 6th to the 12th week of gestation by intravaginal insertion of a newly developed silastic device containing an 0.5% concentration of 15(S)-15-methyl-prostaglandin F2α methyl ester. The mean abortion time for the 15 successful abortions was 11.33 hours, and multiparous patients aborted in a significantly faster mean time 7.33 hours, as compared to nulliparous patients, mean time 15.90 hours. The five patients who failed to abort with the prostaglandin all developed uterine activity and experienced cervical changes in conjunction with the prostaglandin administration. Abortion was achieved in these 5 patients by suction aspiration without the need for mechanical dilatation of the cervix or anesthesia. Fourteen patients in the study were premedicated with antiemetic and antidiarrheal drugs and 4 of the 14 experienced gastro-intestinal side effects. Six patients were not premedicated and all 6 developed gastro-intestinal side effects related to the prostaglandin administration. This technique of abortion induction was well tolerated and had good patient acceptance. Induction of abortion during the first trimester by intravaginal administration of a silastic device containing 15-ME-PGF2α could offer a valid alternative to the surgical interruption of pregnancy. The prostaglandin silastic device could also be employed along with surgical techniques to provide for a gradual softening and dilatation of the cervix thus eliminating the need for mechanical cervical dilatation with its potential of cervical damage leading to cervical incompetence and prematurity.
Julius Nyerere (1922 – 1999), an African Philosopher, Re-envisions Teacher Education to Escape Colonialism

Before the introduction of the Western system of education into Africa (18th century), the aim of indigenous education was to preserve the cultural heritage of the family, the clan, and the larger groups. Indigenous education was meant for every member of the society because it was believed that every member of society had a role to play in educating the child, thus the proverb “It takes a village to raise a child.” This paper addresses the philosophy of self-reliance as advocated by Julius Nyerere (1922 – 1999) when he became president of Tanzania in 1962. Nyerere was highly critical of the social, political, economic and cultural value system imposed on his country during the period of colonization, and he worked relentlessly to go back to the traditional African values. He believed that the Africans should decolonize their mind in order to accept themselves as Africans. He believed that the education system introduced by the British in 1900, when they colonized Tanzania, did not address the needs of the Tanzanian people, therefore Nyerere advocated for education that he believed was more culturally relevant. Nyerere’s philosophy of education has had a great impact on many African countries. This paper explores his educational philosophy of self-reliance and the impact of African Socialism on the African education system today. Furthermore, the paper critically discusses the reasons for the downfall of Nyerere while reemphasizing the power that educational ideas hold for transforming societies.
Teaching Ethics in a "What's in It for Me?" World

Increasingly, students have trouble in determining what is and is not ethical for personal or professional behavior. However, public safety and corporate competence depend on this distinction. Even substituting substandard materials to meet deadlines or operating outside their area of expertise cause no qualms for many engineering student. Extrinsic incentive or punishment is ineffective so the change must come from intrinsic motivational factors. While some programs have the luxury of an entire semester-length required course in ethics, others must attempt to include these critical concepts within the content of an already crowded curriculum. The author describes an approach used within the context of a technical / engineering management course to discuss some basic, representative ethical theories which provide a background for discussion. Without basic theoretical knowledge, case study fails to make an impression beyond arguing that unethical actions represent victimless crimes and supports the prevailing attitude that if no one I know is hurt, then it’s a good decision. The authors present a summary of the ethical theories used in the class, some activities, cases and questions that are included in the course module to emphasize the concepts and to drive home the point that “professional” behavior goes beyond networking to get the next promotion.
Detuning of the NSLS UV RF cavity to compensate for 1 Ampere of stored beam

A mechanically driven loop tuner in addition to water temperature variation is used to compensate for the reactive detuning of the 52.8-MHz RF accelerating cavity at a 1-A circulating current. This combination avoids the higher-order resonances that occur with a single mechanical tune. Injection to the 1-A level was achieved without causing vacuum activity. This may be a consequence of the titanium coating eliminating the multipactoring or the changes in the inner loop area configuration. The increased range of the water system in conjunction with the larger shorted loop size allows for greater tuning flexibility. >
The effect of free water in a maize canopy on microwave emission at 1.4 GHz

Free water in a maize canopy has the net effect of decreasing the brightness temperature at 1.4 GHz (wavelength of 21 cm). It appears that only one form of free water, dew, causes this decrease in brightness temperature. It is not clear how the other form of free water, intercepted precipitation, effects the brightness temperature. This effect occurs at both polarizations, but vertically polarized brightness is affected more than horizontally polarized brightness. We observed a decrease in the horizontally polarized and vertically polarized brightness temperature of a maize canopy of 2 and 4 K, respectively, when intercepted precipitation and dew were present. Since free water in the canopy has been observed to increase the brightness temperature of wheat and grass at 1.4 GHz, we hypothesize that the effect of free water on terrestrial microwave emission depends on the physical dimensions of vegetation canopy components (such as stems, leaves, and fruit) relative to the wavelength of observation. Free water on vegetation will increase terrestrial microwave emission when vegetation canopy components are electrically small, and decrease terrestrial microwave emission when the sizes of some vegetation canopy components are comparable to the observing wavelength and hence scattering in the canopy is significant, as in the case of maize. The electrical size of vegetation components therefore determines the relative enhancement of emission and scattering by free water in the canopy. The most widely used model of microwave emission does not account for the effect of free water on vegetation. Bias introduced by the presence of free water could be a significant source of error in retrieved soil moisture from future 1.4 GHz satellite radiometers.
Hereditary hyperferritinemia-cataract syndrome in two large multigenerational American families.

Purpose Hereditary hyperferritinemia cataract syndrome (HHCS), an autosomal-dominant disorder characterized by hyperferritinemia and bilateral cataracts, is caused by mutations in the iron-responsive element of the ferritin light chain ( FTL ) gene. The purpose of this study is to describe the genotypic and phenotypic manifestations of HHCS observed in 2 large sets of unrelated American families. Methods Forty-five patients were recruited from 2 unrelated families. Each underwent ophthalmological and general physical evaluation as well as laboratory testing of serum ferritin, iron, transferrin saturation, and total iron binding capacity. Serum DNA was evaluated for mutations by DNA amplification and sequencing of the FTL gene. Results Numerous cortical and nuclear white opacities in a stellate pattern occurred in 22 affected individuals and were the only clinical manifestation of HHCS. Of the 22, 16 (73%) demonstrated >1.00 D of astigmatism. Genetic analysis revealed mutation G32A in Pedigree 1 and mutation G32T in Pedigree 2, both heterozygous and located in the iron-responsive element of the ferritin light chain mRNA. Serum ferritin levels of affected subjects ranged from 555 to 2,453 μg/L (normal range, 24–336 μg/L male, 11–307 μg/L female), with greater ferritin levels and more severe cataracts associated with mutation G32A. Conclusions Most clinical and genetic findings from these families are consistent with previous reports of HHCS. Astigmatism, previously not associated with HHCS, was present in the majority. Ferritin levels and age of cataract surgery varied among subjects with both FTL gene mutations, suggesting that phenotypic variability is modulated by other genetic or environmental factors.
Transparent Symmetric Active/Active Replication for Service-Level High Availability

As service-oriented architectures become more important in parallel and distributed computing systems, individual service instance reliability as well as appropriate service redundancy becomes an essential necessity in order to increase overall system availability. This paper focuses on providing redundancy strategies using service-level replication techniques. Based on previous research using symmetric active/active replication, this paper proposes a transparent symmetric active/active replication approach that allows for more reuse of code between individual service-level replication implementations by using a virtual communication layer. Service- and client-side interceptors are utilized in order to provide total transparency. Clients and servers are unaware of the replication infrastructure as it provides all necessary mechanisms internally.
Elevated depressive symptoms and incident stroke in Hispanic, African-American, and White older Americans

Although depressive symptoms have been linked to stroke, most research has been in relatively ethnically homogeneous, predominantly white, samples. Using the United States based Health and Retirement Study, we compared the relationships between elevated depressive symptoms and incident first stroke for Hispanic, black, or white/other participants (N = 18,648) and estimated the corresponding Population Attributable Fractions. The prevalence of elevated depressive symptoms was higher in blacks (27%) and Hispanics (33%) than whites/others (18%). Elevated depressive symptoms prospectively predicted stroke risk in the whites/other group (HR = 1.53; 95% CI: 1.36–1.73) and among blacks (HR = 1.31; 95% CI: 1.05–1.65). The HR was similar but only marginally statistically significant among Hispanics (HR = 1.33; 95% CI: 0.92–1.91). The Population Attributable Fraction, indicating the percent of first strokes that would be prevented if the incident stroke rate in those with elevated depressive symptoms was the same as the rate for those without depressive symptoms, was 8.3% for whites/others, 7.8% for blacks, and 10.3% for Hispanics.
Molt regulation in green and red color morphs of the crab Carcinus maenas: gene expression of molt-inhibiting hormone signaling components

There was an error published in J. Exp. Biol. 217 , pp. [796-808][1]. In Fig. 3, the letters and numbers indicating which means were significantly different are missing from panel A. The correct figure is printed below. ![Fig. 3.][2] Fig. 3. Effects of eyestalk ablation (ESA) on hemolymph
Optical Space-Time Division Multiple Access

This work presents an approach to multiple access for free-space laser communication (lasercom) called space-time division multiple access, which aggregates traffic from multiple users at the network edge. The objective is to share resources to lower the cost, size, weight, and power consumption per user, thereby making lasercom feasible for users that require only moderate average information rates. This concept relies on fast, agile electronic beam steering, which was implemented in this investigation using liquid crystal optical phased arrays. We designed and built an experimental terminal incorporating a bidirectional communication aperture that was shared among the users, and two independently operated acquisition and tracking apertures. Using two remote user terminals, experiments were conducted to measure access node performance for a variety of operating conditions traceable to anticipated applications. The transmit and receive directions of the downlink and uplink communications channels were rapidly hopped between the two users, and data were exchanged between the access node and a user while the optical channel dwelled on the latter. Results showed that the measured information throughput efficiency correlated well with model predictions and was high enough to realize the expected advantages in applications with many users. Throughput efficiencies, defined as the actual data throughput as a percentage of the throughput without multiple access, exceeded 85% for dwell times of 100 ms and greater. This translates into an average information rate of 400 Mb/s for as many as 20 simultaneous users. Current optical phased arrays are capable of providing fast transitions between remote users, with values measured in the range 10-18 ms. The use of persistent tracking links was a key factor in achieving fast transitions, and it was found that motion of the remote terminals had no significant impact on performance.
The Perceived Acceptance Scale: Development and Validation

The Perceived Acceptance Scale (PAS), a new instrument designed to assess perceptions of acceptance within specific categories of relationships, is described. Acceptance is defined as relationship-specific and relatively stable cognitive appraisals that others care for and value us and that their concern is not contingent upon our holding particular attitudes or acting differently from how we typically act. We hypothesized that acceptance would predict relationship quality and mediate the association between perceptions of social support and emotional adjustment. Development of the PAS proceeded in two steps: (1) construct definition and initial scale construction; and (2) scale development and assessment of reliability and validity evidence. The PAS provides separate scores that reflect acceptance from one's mother, father, family in general and friends. These scores are internally consistent and exhibit test-retest reliability. Each PAS score showed discriminant and convergent validity in correlational ...
Analytical model for permanent magnet motors with surface mounted magnets

This paper presents an analytical method of modeling permanent magnet motors. The model is dependent only on geometrical and materials data making it suitable for insertion into design programs, avoiding long finite element analysis. Modeling is based on the calculation of the air gap field density waveform at every time instant. The model allows the rated performance calculation but also such effects as cogging torque, ripple torque, back-EMF form prediction, some of which are neglected in commonly used analytical models.
Disparity between ionic mediators of volume regulation and apoptosis in N1E 115 mouse neuroblastoma cells

Abstract Cellular volume loss or shrinkage is a ubiquitous feature of apoptosis and thus may contribute to this form of degeneration. Chloride (Cl−) and potassium (K+) efflux has been shown to participate in volume regulation and several recent reports have implicated K+ efflux in apoptotic neuronal death. Here pharmacological inhibitors of various K+ and Cl− channels and transporters were used to decipher the relationship between cellular volume regulation and apoptosis. Following exposure to a hypotonic media, cells swell but over time gradually recover, returning to their original cell volume in a process known as regulatory volume decrease (RVD). RVD in N1E 115 neuroblastoma cells was monitored using time-lapse videomicroscopy, cell size and DNA degradation were followed using flow cytometry and fragmented apoptotic nuclei were visualized using Hoechst staining. RVD was blocked by high K+, TEA and 4-AP (K+ channel blockers), DIDS and niflumic acid but not SITS (Cl− channel blockers), ethacrynic acid (Cl− pump blocker), bumetanide (Na+/K+/Cl− cotransporter blocker) and furosemide (K+/Cl− cotransport blocker). In contrast, only DIDS and SITS (blockers of the Cl−/HCO3 exchanger) inhibited apoptosis, suggesting that a common mechanistic link between RVD and apoptosis is the Cl−/HCO3 exchanger. Thus, this study does not support the notion that K+ channels are universal anti-apoptotic targets. Instead, the Cl−/HCO3 exchanger may prove to be a viable target of therapeutic intervention for treating pathological apoptosis and neurodegeneration.
Potential Role of a Novel Transcriptional Coactivator PELP1 in Histone H1 Displacement in Cancer Cells

The estrogen receptor plays an important role in breast cancer progression. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), also called modulator of nongenomic activity of estrogen receptor (MNAR), a novel coactivator of estrogen receptor, modulates estrogen receptor transactivation functions. The mechanisms by which PELP1 modulates estrogen receptor genomic functions is not known. Here, using biochemical and scanning confocal microscopic analysis, we have demonstrated nuclear localization and functional implications of PELP1. Subnuclear fractionation showed PELP1 association with chromatin and nuclear matrix fractions. Ligand stimulation promoted recruitment of PELP1 to 17β-estradiol responsive promoters, its colocalization with acetylated H3, and increased PELP1-associated histone acetyltransferase enzymatic activity. Far Western analysis revealed that PELP1 interacts with histone 1 and 3, with more preference toward histone 1. Using deletion analysis, we have identified the PELP1 COOH-terminal region as the histone 1 binding site. The PELP1 mutant lacking histone 1-binding domain acts as a dominant-negative and blocks estrogen receptor α-mediated transcription. Chromatin immunoprecipitation analysis showed a cyclic association and dissociation of PELP1 with the promoter, with recruitment of histone 1 and PELP1 occurring in opposite phases. PELP1 overexpression increased the micrococcal nuclease sensitivity of estrogen response element-containing nucleosomes. Our results provide novel insights about the transcription regulation of PELP1 and suggest that PELP1 participates in chromatin remodeling activity via displacement of histone 1 in cancer cells.
The relationship of large fire occurrence with drought and fire danger indices in the western USA, 1984-2008: the role of temporal scale

The relationship between large fire occurrence and drought has important implications for fire prediction under current and future climates. This study's primary objective was to evaluate correlations between drought and fire-danger-rating indices representing short- and long-term drought, to determine which had the strongest relationships with large fire occurrence at the scale of the western United States during the years 1984-2008. We combined 4-8-km gridded drought and fire-danger-rating indices with information on fires greater than 404.7 ha (1000 acres). To account for differences in indices across climate and vegetation assemblages, indices were converted to percentile conditions for each pixel. Correlations between area burned and short-term indices Energy Release Component and monthly precipitation percentile were strong (R2 = 0.92 and 0.89), as were correlations between number of fires and these indices (R2 = 0.94 and 0.93). As the period of time tabulated by indices lengthened, correlations with fire occurrence weakened: Palmer Drought Severity Index and 24-month Standardised Precipitation Index percentile showed weak correlations with area burned (R2 = 0.25 and -0.01) and number of large fires (R2 = 0.3 and 0.01). These results indicate associations between short-term indices and moisture content of dead fuels, the primary carriers of surface fire.
High-Throughput Screening (HTS) and Hit Validation to Identify Small Molecule Inhibitors with Activity against NS3/4A proteases from Multiple Hepatitis C Virus Genotypes

Development of drug-resistant mutations has been a major problem with all currently developed Hepatitis C Virus (HCV) NS3/4A inhibitors, including the two FDA approved drugs, significantly reducing the efficacy of these inhibitors. The high incidence of drug-resistance mutations and the limited utility of these inhibitors against only genotype 1 highlight the need for novel, broad-spectrum HCV therapies. Here we used high-throughput screening (HTS) to identify low molecular weight inhibitors against NS3/4A from multiple genotypes. A total of 40,967 compounds from four structurally diverse molecular libraries were screened by HTS using fluorescence-based enzymatic assays, followed by an orthogonal binding analysis using surface plasmon resonance (SPR) to eliminate false positives. A novel small molecule compound was identified with an IC50 value of 2.2 µM against the NS3/4A from genotype 1b. Mode of inhibition analysis subsequently confirmed this compound to be a competitive inhibitor with respect to the substrate, indicating direct binding to the protease active site, rather than to the allosteric binding pocket that was discovered to be the binding site of a few recently discovered small molecule inhibitors. This newly discovered inhibitor also showed promising inhibitory activity against the NS3/4As from three other HCV genotypes, as well as five common drug-resistant mutants of genotype 1b NS3/4A. The inhibitor was selective for NS3 from multiple HCV genotypes over two human serine proteases, and a whole cell lysate assay confirmed inhibitory activity in the cellular environment. This compound provides a lead for further development of potentially broader spectrum inhibitors.
Issues in the Design of a Flexible Distributed Architecture for Supporting Persistence and Interoperability in Collaborative Virtual Environments

CAVERN, the CAVE Research Network, is an alliance of industrial and research institutions equipped with CAVE-based virtual reality hardware and high-performance computing resources, interconnected by high-speed networks, to support collaboration in design, education, engineering, and scientific visualization.CAVERNsoft is the collaborative software backbone for CAVERN. CAVERNsoft uses distributed data stores to manage the wide range of data volumes (from a few bytes to several terabytes) that are typically needed for sustaining collaborative virtual environments. Multiple networking interfaces support customizable, latency, data consistency, and scalability that are needed to support a broad spectrum of networking requirements. These diverse database and networking requirements are characteristics typically unexhibited by previous desktop multimedia systems but are common in real-time immersive virtual reality applications.
Novels behind glass: The fragments and small opportunities of Cranford

The return of the Crystal Palace to the display window suggests the dexterity with which commodity culture turns objects into marketable goods. The Palace, with its origins in the technology of the window, may seem an object particularly susceptible to exchange; more difficult to imagine is the reduction and exchange of the home, conventionally considered a haven from exchange, the one realm not defined by the cash-nexus. Although the Exhibition did display objects intended for the home within its walls, viewers regularly distinguished the perception of objects on display in Hyde Park from that of domestic goods. Responding in Thackerayan fashion to the Exhibition of 1862, George Eliot invoked Ecclesiastes to contrast public display with domestic privacy: “‘this also is vanity,’ compared with a quiet life of home love.” Even today, when technologies of display have been extended from the shop-window to enclosed shopping malls and mail-order catalogues, display windows reduced and posted through the mail, and when the commodification of domestic material culture has become a banal fact of daily life, the common sight of an uninhabited domestic interior beyond the window of a furniture store remains odd and unsettling. In these still interiors, painterly images of nature morte , the absence of human life exaggerates the funereal weightiness of the furniture itself. Benjamin's comment on the “soulless luxuriance of the furnishings” in late-nineteenth-century interiors remains poignant: “The bourgeois interior of the 1860's to the 1890's, with its gigantic sideboards distended with carvings, the sunless corners where palms stand, the balcony embattled behind its balustrade, and the long corridors with their singing gas flames, fittingly houses only the corpse.
A randomized prospective assessment of recombinant leukocyte A human interferon with or without aspirin in advanced renal adenocarcinoma.

We performed a prospective, controlled trial of recombinant leukocyte A interferon (IFN-alpha 2A) with or without aspirin (ASA) in 176 patients with assessable advanced renal cell cancer in light of a 34% response rate (10 of 29 patients) from the two-agent regimen in an earlier nonrandomized trial. This encouraging result was substantially higher than the 15% response rate typically achieved with IFN therapy alone. Eighty-seven patients received IFN-alpha 2A 20 x 10(6) U/m2 intramuscularly three times a week, and 89 received the same IFN therapy with ASA 600 mg orally four times each day. Each group was balanced as to relevant prognostic discriminants. Response rates were 8% for the group receiving ASA in addition to IFN, and 13% for the group receiving IFN alone (P = .30). The median times to progression were 1.9 months for the group receiving IFN with ASA and 2.7 months for the group receiving IFN alone (log-rank P = .36). The median survival durations were 8.8 months for the IFN and ASA group and 8.0 months for the IFN-only group (log-rank P = .60). These figures are also inferior to those typically reported from other studies. Our findings reemphasize the crucial role of randomized trials, admittedly cumbersome and time-consuming, to determine accurately the value of apparently promising therapies. Although some patients may derive benefit from IFN therapy, our findings raise disturbing questions regarding the potential IFN-alpha 2A according to the dose and schedule used in this trial to have any substantive impact on the ultimate outcome of disseminated renal cell cancer.
Nonlinear quenching rates in SrI 2 and CsI scintillator hosts

Using 0.5 ps pulses of 5.9 eV light to excite electron-hole concentrations varied up to 2x10 20 e-h/cm 3 corresponding to energy deposition within electron tracks, we measure dipole-dipole quenching rate constants K 2 in SrI 2 and CsI. We previously reported determination of K 2 directly from the time dependence of quenched STE luminescence in CsI. The nonlinear quenching rate decreases rapidly within a few tens of picoseconds as the host excitation density drops below the Forster threshold. In the present work, we measure the dependence of integrated light yield on excitation density in the activated scintillators SrI 2 :Eu 2+ and CsI:Tl + . The “z-scan” method of yield vs. irradiance is applicable to a wider range of materials, e.g. when the quenching population is not the main light-emitting population. Furthermore, because of using an integrating sphere and photomultiplier for light detection, the signal-to-noise is substantially better than the time-resolved method using a streak camera. As a result, both 2 nd and 3 rd orders of quenching (dipole-dipole and Auger) can be distinguished. Detailed comparison of SrI 2 and CsI is of fundamental importance to help understand why SrI 2 achieves substantially better proportionality than CsI in scintillator applications. The laser measurements, in contrast to scintillation, allow evaluating the rate constants of nonlinear quenching in a population which has small enough spatial gradient to suppress the effect of carrier diffusion.
Site-Specific Detection and Management of Nematodes

Nematode distribution varies significantly throughout a field and is highly correlated to soil texture and other edaphic factors. Field-wide application results in nematicides being applied to areas without nematodes and the application of sub-effective levels in areas with high nematode densities. Efforts to use grid maps as a guide to site-specific application have proven to be too expensive to be cost effective. Recently, the availability of GPS –GIS has allowed the use of soil electrical conductivity systems to rapidly and inexpensively develop cost effective soil texture maps. These maps are used to project where nematodes are likely to occur within a field. Variable-rate application systems for granular and fumigant nematicides have been developed and tied via software to soil texture maps providing a mechanism for the effective delivery of nematicides in a site-specific , variable-rate manner in individual fields. Efforts in South Carolina, Georgia, and Arkansas are further developing this system and refining our knowledge of how soil texture and other edaphic factors affect the distribution of cotton nematodes .
Intravenous Carbohydrate Tolerance Tests on Swine

SummaryThe form of the carbohydrate tolerance curve obtained after the administration of glucose to normal growing pigs by the intravenous route, apparently closely parallels the type of curve procured when the test is made on normal human subjects.
The occurrence of pelecypods in early Paleozoic epeiric-sea environments, Late Ordovician of the Cincinnati, Ohio area

Within the Upper Ordovician section exposed in the Cincinnati, Ohio region, pelecypods are important elements in a number of facies representing a variety of epeiric-sea environments. The fine-clastic, offshore-shelf facies of Edenian through early Richmondian age in the area support pelecypod assemblages dominated by endobyssate and semi-infaunal filter-feeding taxa. Locally within these strata, infaunal deposit-feeding pelecypods are abundant. Shallow-water Maysvillian skeletal-carbonate facies are dominated by articulate brachiopods and trepostomes, with pelecypods being minor elements of these faunas. Overlying Richmondian skeletal carbonates document the movement of increasing numbers of byssate filter-feeding pelecypods into these trepostome-thicket environments. The Richmondian biotas include a diverse assemblage of both endobyssate and epibyssate pelecypod taxa. These pelecypod assemblages represent largely endemic taxa restricted to the eastern portions of Laurentia, marginal to the Taconic landmass and the Queenston deltaic complex. Reconstructions of the life habits of these pelecypods demonstrate the dominance of the endobyssate mode of life in Ordovician pelecypod faunas. The presence of large numbers of filter-feeding pelecypods in both mud and skeletalfacies in the Late Ordovician section exposed in the Cincinnati area suggests that these mollusks had become established in offshore as well as inshore shelf environments at this time. These first intrusions by filter-feeding pelecypods into offshore cratonic-shelf environments were truncated by the Late Ordovician extinction event, which had a devastating effect on the important endobyssate ambonychiid and modiomorphid pelecypod taxa. These pelecypod faunas in the Cincinnati area suggest that filter-feeding pelecypods were far more abundant and widespread in Ordovician epeiric-sea environments than previously published literature has indicated.
Association of Epstein–Barr Virus with Leiomyosarcomas in Young People with AIDS

Background Children with the acquired immunodeficiency syndrome (AIDS) have an unusually high incidence of smooth-muscle tumors (leiomyomas and leiomyosarcomas) in addition to malignant lymphomas. We tested the hypothesis that the smooth-muscle tumors in these children are associated with the Epstein–Barr virus (EBV). Methods Tissue specimens of five leiomyosarcomas and two leiomyomas from five children and one young man with AIDS were studied for evidence of the human immunodeficiency virus (HIV) and EBV by in situ hybridization and quantitative polymerase chain reaction (PCR). Comparison specimens included samples of leiomyosarcoma and leiomyoma from HIV-negative children. EBV clonality of leiomyosarcomas was determined by Southern blot analysis with oligonucleotide probes for EBV terminal-repeat fragments. Tumor specimens were tested by immunoperoxidase staining for infiltration by B lymphocytes and expression of the EBV receptor. Serologic testing for EBV was performed. Results In situ hybridization s...
Flame-retardant contamination of firefighter personal protective clothing – A potential health risk for firefighters

ABSTRACTThere is a high incidence of cardiovascular disease and certain cancers in firefighters that may be related to their occupational exposure to hazardous substances. Exposure may result from contaminated personal protective gear, as well as from direct exposure at fire scenes. This study characterized flame-retardant contamination on firefighter personal protective clothing to assess exposure of firefighters to these chemicals. Samples from used and unused firefighter protective clothing, including gloves, hoods and a coat wristlet, were extracted with methylene chloride and analyzed by EPA method 8270D Specific Ion Method (SIM) for polybrominated diphenyl ethers (PBDEs). Until recently PBDEs were some of the most common flame-retardant chemicals used in the US. Fifteen of the seventeen PBDEs for which analysis was performed were found on at least one clothing swatch. Every clothing sample, including an unused hood and all three layers of an unused glove, held a detectable concentration of at least ...
The immature and the mature myocardium. Responses to multidose crystalloid cardioplegia.

This study was designed to determine whether multidose St. Thomas’ Hospital cardioplegic solution is as effective for preservation of the immature myocardium during ischemia as it is for the mature myocardium. An isolated working heart model was used. Sets of six hearts from immature (3 to 4 weeks, 500 gm) and mature (24 weeks, 2 kg) rabbits were subjected to 60, 90, or 120 minutes of ischemia. Myocardial protection consisted of infusion of cardioplegic solution every 30 minutes at 4° C in a dose of 10 ml/kg of animal weight and maintenance of hypothermia at 10° C by immersion in a cold saline bath. The percent recovery of preischemic aortic flow was lower in the immature than the mature hearts after 90 minutes (60.3% ± 7.4% versus 101.8% ± 4.3%) and after 120 minutes (57.4% ± 10.6% versus 91.1% ± 13.6%) of ischemia (results expressed as mean value ± standard error of the mean, p
Chronic fatigue syndrome: a diagnostic challenge for the laboratory.

OBJECTIVE: To review the literature and current research about the causes of chronic fatigue syndrome (CFS). DATA SOURCES: Recent research articles about CFS and data gathered by the author. STUDY SELECTION: Performed by the author. DATA EXTRACTION: Performed by the author. DATA SYNTHESIS: Chronic fatigue syndrome (CFS) is a disease of pain, excessive fatigue after minor exertion, cognitive difficulties, and other symptoms-all occurring in cycles. While its etiology is unclear, CFS is associated with abnormal results of immune system tests. There is no specific marker for the illness. Treatment is symptomatic, and the long-term outlook for recovery is good. CONCLUSION: A rational, symptomatic approach to treating CFS patients can be made using the model developed at the author's institution. Research into the causes of CFS must continue.
Ischemic Heart Disease A Major Obstacle to Becoming Old

Four classes of etiologic agents that cause human illness have been discovered. Sometimes members of two or more classes of agents cooperate to cause illness. Knowledge of etiology is necessary if a disease is to be eradicated. The leading causes of death in the United States have changed dramatically in the last century. Infection has been replaced by chronic illnesses of obscure etiology. Ischemic heart disease is the leading cause of death in middle age and is the major obstacle to becoming old. There are numerous similarities between animals deficient in copper and people with ischemic heart disease. The most important of these similarities are glucose intolerance, hypercholesterolemia, abnormal electrocardiogram, hyperuricemia, and hypertension, as these characteristics are predictive of risk of ischemic heart disease. No other nutritional insult has produced these characteristics in experiments with animals; men fed diets low in copper have been found to have increased cholesterol, decreased glucose tolerance, and abnormal electrocardiograms. The process that results in ischemic heart disease is remarkably similar to that of copper deficiency. Links have been found between copper metabolism and several hypotheses on the origin of ischemic heart disease. Several aspects of the lipid hypothesis can be interpreted in terms of copper metabolism. More features of the etiology, pathogenesis, and pathophysiology of ischemic heart disease can be explained in terms of copper deficiency than can be explained by any other environmental insult.