cssi/SciSciGPT-SciSciNet huggingface dataset:
Synthesis and Analysis of Ultrafast Waveform Generation using Coherent Raman Sidebands

We combine four coherent Raman sidebands generated inside diamond with an OPA-generated beam to create an ultrashort pulse. By using frequency-resolved optical gating (FROG) and interferometric techniques, we characterize the resultant pulse.
Development of novel oocyte activation approaches using Zn2+ chelators in pigs.

Abstract Artificial oocyte activation is an essential step in somatic cell nuclear transfer (SCNT) and can enhance viability of embryos as a form of assisted reproductive technology (ART) in clinics. Most artificial activation methods have been developed to increase cytosolic calcium (Ca2+) level in oocytes. Interestingly, recent studies have demonstrated that mammalian oocytes can be activated using N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), a Zn2+ chelator. Although effective, TPEN is also known to induce apoptosis and shows poor selectivity between free Zn2+ and protein-bound Zn2+. The aim of this study was to identify different Zn2+ chelators that can activate pig oocytes. Among five Zn2+ chelators examined, 1,10-phenanthroline (Phen), and tris(2-pyridylmethyl)amine (TPA) successfully activated pig oocytes. The level of available Zn2+ was reduced without any increase in Ca2+ in oocytes incubated with Phen or TPA, indicating that the oocyte activation occurred independently of Ca2+ signal. When various concentrations (100–500 μM) and incubation durations (10–120 min) of Phen and TPA were used to activate pig oocytes, 500 μM for 60 min and 100 μM for 60 min of Phen and TPA treatments, respectively, were found to be most effective in supporting embryo development. The frequency of blastocyst formation after the treatments was higher than 40% at day 7. When oocytes were incubated with TPEN, Phen, or TPA under their optimal treatment conditions, there was no significant difference in the frequencies of day 7 blastocyst formation among the three treatments. However, day 5 blastocyst formation was observed from the Phen- and TPA-treated oocytes, whereas no blastocyst was formed at day 5 in the TPEN-treated oocytes. The average total cell number in day 7 blastocysts was higher in the Phen treatment group than in the TPEN treatment (P
Aeroacoustics of Rounded Forward-Facing Steps: Far-Field Behavior

Measurements and predictions of far-field sound radiated by rounded forward-facing steps immersed in an incompressible turbulent boundary were performed. Four different corner rounding radii equal ...
Proposal and justification of a treatment protocol for extraoral photobiomodulation therapy for the prevention of oral mucositis (Conference Presentation)

Background and Objective: Intraoral photobiomodulation therapy (PBMT) is effective at preventing oral mucositis (OM). Extraoral PBMT is a novel approach with distinct advantages over intraoral PBMT, but no evidence-based treatment protocol has been proposed. The goal of this contribution was to develop a practical and effective treatment protocol for extraoral PBMT to prevent OM. Methods: Extraoral PBMT was modeled using Monte Carlo simulations with parameters established in intraoral PBMT: 50 mW/cm2 (1 minute treatment time), at either 660 nm, used in superficial PBMT, or 850 nm, used in deeper PBMT. The effective therapeutic dose of ~ 2.0 J/cm2 was assumed to be identical for intraoral and extraoral PBMT. The results prompted a review of the literature regarding PBMT parameters for deep tissue treatment, as well as the mechanism of PBMT. Summary: Per our Monte Carlo simulations, the treatment parameters established for intraoral PBMT are not appropriate for extraoral delivery. Visible light (660 nm) showed poor penetration, producing an insufficient dose at the oral mucosa. The infrared light (850 nm) penetrated deeper. However, at 50 mW/cm2 and 1 minute treatment time, the dose was still less than targeted 2 J/cm2. Therefore, based on the optical properties of tissues, anatomy of the target population, and established protocols for deeper PBMT, we propose a wavelength of 850 nm, at 399 mW/cm2, and exposure time of 1-11 minutes, depending on the treatment site, to achieve the therapeutic dose of ~2 J/cm2 at the depth of the oral mucosa for preventing OM using extraoral PBMT.
Glucocorticoids mediate stress induction of the alarmin HMGB1 and reduction of the microglia checkpoint receptor CD200R1 in limbic brain structures

Exposure to stressors primes neuroinflammatory responses to subsequent immune challenges and stress-induced glucocorticoids (GCs) play a mediating role in this phenomenon of neuroinflammatory priming. Recent evidence also suggests that the alarmin high-mobility group box-1 (HMGB1) and the microglial checkpoint receptor CD200R1 serve as proximal mechanisms of stress-induced neuroinflammatory priming. However, it is unclear whether stress-induced GCs play a causal role in these proximal mechanisms of neuroinflammatory priming; this forms the focus of the present investigation. Here, we found that exposure to a severe acute stressor (inescapable tailshock) induced HMGB1 and reduced CD200R1 expression in limbic brain regions and pharmacological blockade of GC signaling (RU486) mitigated these effects of stress. To confirm these effects of RU486, adrenalectomy (ADX) with basal corticosterone (CORT) replacement was used to block the stress-induced increase in GCs as well as effects on HMGB1 and CD200R1. As with RU486, ADX mitigated the effects of stress on HMGB1 and CD200R1. Subsequently, exogenous CORT was administered to determine whether GCs are sufficient to recapitulate the effects of stress. Indeed, exogenous CORT induced expression of HMGB1 and reduced expression of CD200R1. In addition, exposure of primary microglia to CORT also recapitulated the effects of stress on CD200R1 suggesting that CORT acts directly on microglia to reduce expression of CD200R1. Taken together, these findings suggest that GCs mediate the effects of stress on these proximal mechanisms of neuroinflammatory priming.
Salicylate toxicity from ingestion of an oil of wintergreen containing insecticide.

To the Editor,Oil of wintergreen is well-recognized as a source of salicylate exposure and may be found in many creams, ointments, and essential oils [1]. However, methyl salicylate toxicity from t...
Analysis of Sebaceous Neoplasms for DNA Mismatch Repair Proteins in Muir-Torre Syndrome

Muir-Torre syndrome is a rare genodermatosis inherited most frequently in an autosomal dominant fashion. Current criteria for its diagnosis include at least one sebaceous tumor and an underlying visceral malignancy. Muir-Torre syndrome is strongly associated with a germline mutation in DNA mismatch repair genes. We report two patients with a history of colorectal carcinoma who presented with sebaceous neoplasms on the face and trunk. Immunohistochemical staining of the sebaceous neoplasms demonstrated absence of mismatch repair proteins MSH2 and MSH6. Genetic studies confirmed deletions in the MSH2 gene, and a diagnosis of Lynch syndrome was made. Immunohistochemical staining for mismatch repair genes MLH1, MSH2, MSH6 and PMS2 may aid in the diagnosis of Muir-Torre syndrome in cases where there is high suspicion. Genetic testing is an important final step in the confirmation of Muir-Torre syndrome.
Isolation and Characterization of Acidocalcisomes from Trypanosomatids

Acidocalcisomes are membrane-bounded, electron-dense, acidic organelles, rich in calcium and polyphosphate. These organelles were first described in trypanosomatids and later found from bacteria to human cells. Some of the functions of the acidocalcisome are the storage of cations and phosphorus, participation in pyrophosphate (PPi) and polyphosphate (polyP) metabolism, calcium signaling, maintenance of intracellular pH homeostasis, autophagy, and osmoregulation. Isolation of acidocalcisomes is an important technique for understanding their composition and function. Here, we provide detailed subcellular fractionation protocols using iodixanol gradient centrifugations to isolate high-quality acidocalcisomes from Trypanosoma brucei, which are subsequently validated by electron microscopy, and enzymatic and immunoblot assays with organellar markers.
The responsiveness and minimally important difference for the Accidental Bowel Leakage Evaluation questionnaire.

We describe the responsiveness and minimally important difference (MID) of the Accidental Bowel Leakage Evaluation (ABLE) questionnaire. Women with bowel leakage completed ABLE, Patient Global Impression of Improvement, Colo-Rectal Anal Distress Inventory, and Vaizey questionnaires pretreatment and again at 24 weeks post-treatment. Change scores were correlated between questionnaires. Student’s t tests compared ABLE change scores for improved versus not improved based on other measures. The MID was determined by anchor- and distribution-based approaches. In 266 women, the mean age was 63.75 (SD = 11.14) and 79% were white. Mean baseline ABLE scores were 2.32 ± 0.56 (possible range 1–5) with a reduction of 0.62 (SD = 0.79) by 24 weeks. ABLE change scores correlated with related measures change scores (r = 0.24 to 0.53) and differed between women who improved and did not improve (all p < 0.001). Standardized response means for participants who improved were large ranging from −0.89 to −1.12. Distribution-based methods suggest a MID of −0.19 based on the criterion of one SEM and −0.28 based on half a standard deviation. Anchor-based MIDs ranged from −0.10 to −0.45. We recommend a MID of −0.20. The ABLE questionnaire is responsive to change, with a suggested MID of −0.20.
ASA Statement on Statistical Significance and p-Values

In February 2014, George Cobb, Professor Emeritus of Mathematics and Statistics at Mount Holyoke College, posed these questions to an ASA discussion forum:
On the irrationality of rational design of an HIV vaccine in light of protein intrinsic disorder

The lack of progress in finding an efficient vaccine for a human immunodeficiency virus (HIV) is daunting. In fact, this search has spanned nearly four decades without much success. There are several objective reasons for such a failure, which include the highly glycosylated nature of HIV-1, the presence of neotopes, and high mutation rates. This article argues that the presence of highly flexible and intrinsically disordered regions in both human anti-HIV-1 antibodies and the major HIV-1immunogen, its surface glycoprotein gp120, represent one of the major causes for the lack of success in utilization of structure-based reverse vaccinology.
Mechanisms Supporting the Use of Beta-Blockers for the Management of Breast Cancer Bone Metastasis

The skeleton is heavily innervated by sympathetic nerves and represents a common site for breast cancer metastases, the latter being the main cause of morbidity and mortality in breast cancer patients. Progression and recurrence of breast cancer, as well as decreased overall survival in breast cancer patients, are associated with chronic stress, a condition known to stimulate sympathetic nerve outflow. Preclinical studies have demonstrated that sympathetic stimulation of β-adrenergic receptors in osteoblasts increases bone vascular density, adhesion of metastatic cancer cells to blood vessels, and their colonization of the bone microenvironment, whereas β-blockade prevented these events in mice with high endogenous sympathetic activity. These findings in preclinical models, along with clinical data from breast cancer patients receiving β-blockers, support the pathophysiological role of excess sympathetic nervous system activity in the formation of bone metastases, and the potential of commonly used, safe, and low-cost β-blockers as adjuvant therapy to improve the prognosis of bone metastases.
Evaluating the Aromatherapy Recommendation for Pain in the Holistic Nurses' Pain Relief Tools for Patients and Self-Care:

Purpose of Study: The purpose of the study was to evaluate the usefulness of the aromatherapy (AT) recommendation in the American Holistic Nurses Association's (AHNA’s) Holistic Nurses' Pain Relief...
Robustness and Generalization to Nearest Categories

Adversarial robustness has emerged as a desirable property for neural networks. Prior work shows that robust networks perform well in some out-of-distribution generalization tasks, such as transfer learning and outlier detection. We uncover a different kind of out-of-distribution generalization property of such networks, and find that they also do well in a task that we call nearest category generalization (NCG) - given an out-of-distribution input, they tend to predict the same label as that of the closest training example. We empirically show that this happens even when the out-of-distribution inputs lie outside the robustness radius of the training data, which suggests that these networks may generalize better along unseen directions on the natural image manifold than arbitrary unseen directions. We examine how performance changes when we change the robustness regions during training. We then design experiments to investigate the connection between out-of-distribution detection and nearest category generalization. Taken together, our work provides evidence that robust neural networks may resemble nearest neighbor classifiers in their behavior on out-of-distribution data. The code is available at this https URL
LSD degrades hippocampal spatial representations and suppresses hippocampal-visual cortical interactions.

Summary Lysergic acid diethylamide (LSD) produces hallucinations, which are perceptions uncoupled from the external environment. How LSD alters neuronal activities in vivo that underlie abnormal perceptions is unknown. Here, we show that when rats run along a familiar track, hippocampal place cells under LSD reduce their firing rates, their directionality, and their interaction with visual cortical neurons. However, both hippocampal and visual cortical neurons temporarily increase firing rates during head-twitching, a behavioral signature of a hallucination-like state in rodents. When rats are immobile on the track, LSD enhances cortical firing synchrony in a state similar to the wakefulness-to-sleep transition, during which the hippocampal-cortical interaction remains dampened while hippocampal awake reactivation is maintained. Our results suggest that LSD suppresses hippocampal-cortical interactions during active behavior and during immobility, leading to internal hippocampal representations that are degraded and isolated from external sensory input. These effects may contribute to LSD-produced abnormal perceptions.
Forging ahead or falling behind: the state of public participation in a ‘people-centred’ ASEAN

The Association of Southeast Asian Nations (ASEAN) has historically relied upon state-centred approaches to governance. However, there have been a number of instances where ASEAN has sought to shif...
Physico-Chemical Properties of Soils: A Symposium: Clay Minerals

Modern concepts of the structure, composition, and origin of clay minerals and current procedures for their identification are reviewed.
5th International Workshop on Embedded/Distributed HPC Systems and Applications (EHPC 2000)

The International Workshop on Embedded/Distributed HPC Systems and Applications (EHPC) is a forum for the presentation and discussion of approaches, research findings, and experiences in the applications of High Performance Computing (HPC) technology for embedded/distributed systems. Of interest are both the development of relevant technology (e.g.: hardware, middleware, tools) as well as the embedded HPC applications built using such technology.
On the location of 1-anilino-8-naphthalene-sulfonate in lipid model systems

Abstract The electron density distribution across the magnesium stearate bimolecular leaflet is calculated from the relative intensities of discrete X-ray diffraction patterns from magnesium stearate multilayers. The generalized Patterson function P′(χ) calculated for a system with 3 unit cells. The autocorrelation function P0(χ) is determined from P′(χ). The electron density distribution μ(χ) is calculated by a deconvolution of P0(χ) through a recursion process. Diffraction is recorded also from magnesium stearate multilayers with large numbers of unit cells. Phase angles are determined from μ(χ) and by swelling experiments. Electron density distributions ρ(χ) are calculated by Fourier syntheses. 1-Anilino-8-naphthalene-sulfonate (ANS) is incorporated into this system and the effects on its structure are discussed. X-ray diffraction data from lecithin/cardiolipin dispersions are presented. These diffracted intensities are a continuous function of the diffraction angle; they can be considered to arise from randomly oriented single bimolecular leaflets. The generalized Patterson function P′(χ) is calculated and it is shown that in this case P′(χ) is identical to the autocorrelation function P0(χ). μ(χ) is calculated by a deconvolution of P0(χ). ANS in different concentrations is incorporated in the lecithin/cardiolipin bimolecular leaflet and the resulting perturbation of its structure is discussed.
Biological control adoption in western U.S. orchard systems: Results from grower surveys

Abstract As part of a USDA Specialty Crop Research Initiative project to enhance biological control (BC) in western U.S. orchard systems, we surveyed walnut growers in California and pear growers in Oregon and Washington about their pest management decision-making and use of BC practices. Seventy-six percent of pear growers and 54% of walnut growers reported using one or more BC practices. BC users were more likely to minimize factors that harm natural enemies than enhance natural enemy habitats or release commercially produced natural enemies. Walnut growers with more education and orchard experience, as well as larger and more diversified operations, were more likely to use BC practices. Walnut and pear growers with some certified organic acreage, who considered environmental impacts when making pest management decisions, and who used selected pest management practices (pheromone mating disruption and degree-day calculations for codling moth control) were more likely to use BC practices. BC users relied more heavily on industry publications and university-based sources of pest management information, compared with non-users. The perceived benefits of BC adoption included reduced reliance on pesticides, reduced production costs, environmental protection, protection of beneficial insects, and improved worker safety and human health. The perceived barriers to BC adoption included lack of knowledge, questionable effectiveness, high cost, and lack of recommendation by pest management consultants. Our research not only contributes to the literature on the adoption of sustainable agricultural practices, but also can inform future BC research and outreach by offering insight into who uses BC practices and assessment of perceived adoption benefits and barriers.
Anomalous Hall Effect and Magnetotransport Effects in the Organic Superconductor (TMTSF)$_{2}$ ClO$_{4}$ [and Discussion]

The organic conductor (TMTSF)$\_{2}$ ClO$\_{4}$ exhibits unusual magnetotransport effects below 30 K. The resistivity and thermopower have large, anisotropic changes in a magnetic field, whereas the thermal conductivity is hardly affected. At lower temperature (T $\leq $ 5 K) a magnetic field applied along the c$^{\ast}$ direction causes a phase transition from a metallic, non-magnetic state to a semimetallic, magnetic state. This orbitally induced transition appears to be unique in nature. Above the threshold field for this transition steps in the Hall resistance are observed, suggestive of the quantum Hall effect. In this paper we review the magnetotransport experiment in these materials and discuss the possible origins of the unusual phenomena observed.
Induction of heat shock proteins in Chinese hamster ovary cells and development of thermotolerance by intermediate concentrations of puromycin

During 4 hr after puromycin (PUR: 20 micrograms/ml) treatment, the synthesis of three major heat shock protein families (HSPs: Mr = 110,000, 87,000, and 70,000) was enhanced 1.5-fold relative to that of untreated cells, as studied by one-dimensional gel electrophoresis. The increase of unique HSPs, if studied with two-dimensional gels, would probably be much greater. In parallel, thermotolerance was observed at 10(-3) isosurvival as a thermotolerance ratio (TTR) of either 2 or greater than 5 after heating at either 45.5 degrees C or 43 degrees C, respectively. However, thermotolerance was induced by only intermediate concentrations (3-30 micrograms/ml) of puromycin that inhibited protein synthesis by 15-80%; a high concentration of PUR (100 micrograms/ml) that inhibited protein synthesis by 95% did not induce either HSPs or thermotolerance. Also, thermotolerance was never induced by any concentration (0.01-10 micrograms/ml) of cycloheximide that inhibited protein synthesis by 5-94%. Furthermore, after PUR (20 micrograms/ml) treatment, the addition of cycloheximide (CHM: 10 micrograms/ml), at a concentration that reduces protein synthesis by 94%, inhibited both thermotolerance and synthesis of HSP families. Thus, thermotolerance induced by intermediate concentrations of PUR correlated with an increase in newly synthesized HSP families. This thermotolerance phenomenon was compared with another phenomenon termed heat resistance and observed when cells were heated at 43 degrees C in the presence of CHM or PUR immediately after a 2-hr pretreatment with CHM or PUR. Heat protection increased with inhibition of synthesis of both total protein and HSP families. Moreover, this heat protection decayed rapidly as the interval between pretreatment and heating increased to 1-2 hr, and did not have any obvious relationship to the synthesis of HSP families. Therefore, there are two distinctly different pathways for developing thermal resistance. The first is thermotolerance after intermediate concentrations of PUR treatment, and it requires incubation after treatment and apparently the synthesis of HSP families. The second is resistance to heat after CHM or PUR treatment immediately before and during heating at 43 degrees C, and it apparently does not require synthesis of HSP families. This second pathway not requiring the synthesis of HSP families also was observed by the increase in thermotolerance at 45.5 degrees C caused by heating at 43 degrees C after cells were incubated for 2-4 hr following pretreatment with an intermediate concentration of PUR.
Plasma Lipids of Dogs During and After Chronic Ethanol Administration.

SummaryThe response of plasma lipids to daily administration of ethanol (4 g kg body weight) for 12 weeks and following the cessation of ethanol administration was investigated in dogs. Chronic administration of ethanol resulted in marked and sustained increases in plasma concentrations of triglycerides, lipid phosphorus and total cholesterol, and in a decrease of plasma unesterified fatty acids. There was a slight increase in plasma volume. Upon discontinuing administration of ethanol the plasma lipids returned to baseline levels.
In the hippocampus in vivo, nitric oxide does not appear to function as an endogenous antiepileptic agent.

Using a reverberatory epilepiform discharge of hippocampal-parahippocampal circuits termed “maximal dentate activation”, this study investigated whether the local release of nitric oxide within these circuits functions as an antiepileptic agent. Two nitric oxide synthase inhibitors (l-nitro-arginine methyl ester and 7-nitro-indazole) and a guanylate cyclase inhibitor (methylene blue) were tested, and none had a significant effect on the time to onset or duration of maximal dentate activation. A membrane-permeable analogue of cyclic guanosine monophosphate (cGMP), 8-bromo-cGMP, caused an increase in the time to onset and a decrease in the duration of maximal dentate activation. The number of neurons expressing NADPH diaphorase activity (a marker for nitric oxide synthase) was also examined after repeated elicitation of maximal dentate activation. After 18 seizures there was a significant, but transient, decrease in the number of hilar/subgranular neurons that were NADPH diaphorase-positive. The decrease was only seen at 1 h after the last seizure. There was no induction of NADPH diaphorase activity. These results are not consistent with the hypothesis that, in hippocampal-parahippocampal circuits in vivo, nitric oxide is released in response to neuronal activity and then acts to terminate the neuronal activity.
Case studies of Z-module reasoning: Proving benchmark theorems from ring theory

A new method, called Z-module reasoning, was formulated for proving and discovering theorems from ring theory. In a case study, the ZMR system designed to implement this method was used to prove the benchmark x3 ring theorem from associative ring theory. The system proved the theorem quite efficiently. The system was then used to prove the x4 ring theorem from associative ring theory. Again, a proof was produced easily. These proofs, together with the successes in proving other difficult theorems from ring theory suggest that the Z-module reasoning method is useful for solving a class of problems relying on equality reasoning. This paper illustrates the Z-module reasoning method, and analyzes the computer proof of the x3 ring theorem.
Focal sweep videography with deformable optics

A number of cameras have been introduced that sweep the focal plane using mechanical motion. However, mechanical motion makes video capture impractical and is unsuitable for long focal length cameras. In this paper, we present a focal sweep telephoto camera that uses a variable focus lens to sweep the focal plane. Our camera requires no mechanical motion and is capable of sweeping the focal plane periodically at high speeds. We use our prototype camera to capture EDOF videos at 20fps, and demonstrate space-time refocusing for scenes with a wide depth range. In addition, we capture periodic focal stacks, and show how they can be used for several interesting applications such as video refocusing and trajectory estimation of moving objects.
Intricacies of cardiac damage in coxsackievirus B3 infection: Implications for therapy

Heart disease is the leading cause of death in humans, and myocarditis is one predominant cause of heart failure in young adults. Patients affected with myocarditis can develop dilated cardiomyopathy (DCM), a common reason for heart transplantation, which to date is the only viable option for combatting DCM. Myocarditis/DCM patients show antibodies to coxsackievirus B (CVB)3 and cardiac antigens, suggesting a role for CVB-mediated autoimmunity in the disease pathogenesis; however, a direct causal link remains to be determined clinically. Experimentally, myocarditis can be induced in susceptible strains of mice using the human isolates of CVB3, and the disease pathogenesis of postinfectious myocarditis resembles that of human disease, making the observations made in animals relevant to humans. In this review, we discuss the complex nature of CVB3-induced myocarditis as it relates to the damage caused by both the virus and the host's response to infection. Based on recent data we obtained in the mouse model of CVB3 infection, we provide evidence to suggest that CVB3 infection accompanies the generation of cardiac myosin-specific CD4 T cells that can transfer the disease to naive recipients. The therapeutic implications of these observations are also discussed.
Inhalation of Francisella novicida ΔmglA causes replicative infection that elicits innate and adaptive responses but is not protective against invasive pneumonic tularemia

Abstract Francisella tularensis causes the zoonosis tularemia in humans, and inhaled F. tularensis ssp. novicida induces lethal murine tularemia. Transcription of virulence factors in F. novicida is regulated by macrophage growth locus A ( mglA ), a global regulator required for bacterial replication in macrophages in vitro. We examined the infectivity and immunogenicity of attenuated F. novicida Δ mglA in the lung in vivo. Aerosolized Δ mglA caused replicative pulmonary infection that peaked at 7 days and was cleared thereafter, without clinical evidence of disease. In contrast, inhalation of wild type F. novicida resulted in more rapid bacterial replication and dissemination leading to death within 96 h. Early containment of Δ mglA infection was partially dependent on myeloid differentiation factor 88 and interferon-γ but did not require B or T cells. However, lymphocytes were necessary for subsequent bacterial clearance. Infection with Δ mglA elicited specific IgG1-predominant antibodies and variable interferon-γ recall responses to wild type F. novicida . Inoculation of mice with aerosolized Δ mglA afforded no protection against a subsequent low-dose aerosol challenge with wild type F. novicida . These findings establish that inhalation of F. novicida Δ mglA results in replicative infection that elicits innate and adaptive immune responses but not protective immunity against invasive pneumonic tularemia.
Consumer inputs to public policy programs

Consumer advocates and federal agency administrators suggest that consumer interests need greater emphasis in public programs. However, both groups often fail to specify how and where consumers can have input on public policy. Contributions by consumers must be available in the early stages of the program planning process. The challenge to consumers is to take an active role in the programming activities of federal agencies. In addition, federal agencies must implement procedures for consumers to effectively participate in public policy formulation.
A Comparison of the Microbiological Profile of Poults from Young Versus Old Turkey Breeder Hens

Abstract This study was performed to determine whether poults from young turkey breeder hens (YHP, 15 wk of lay) and whether poult bacterial profiles change over the life of a breeder hen flock. Within two hatcheries, YHP had higher numbers of coliforms present in intestines than OHP (p ≤ 0.05). Isolated incidences of significantly different bacteria counts by hen age existed in poults from a third hatchery for all bacteria groups examined. However, within each hatchery, there were more differences due to farm than due to breeder hen age. Seasonal variation had as much influence as hen age when evaluating poult bacterial profiles. It was concluded that factors such as individual farm management, poult environment, biosecurity and traffic control, breeder flock bacterial profiles, and weekly conditions in the hatchery probably have a greater effect on poult bacterial profile than age of breeder hen.
Penicillin — ein kolloider Elektrolyt

1. Es wird auf die Aehnlichkeit von Penicillin und Seifen vom kolloidchemischen Standpunkt aus hingewiesen, und es werden Grunde fur seine Klassifizierung als kolloider Elektrolyt gegeben. 2. Die Ergebnisse rein chemischer und physikalischer Forschung bezuglich der chemischen Formel fur Penicillin werden kurz besprochen. 3. Es wird auf Ergebnisse medizinischer Forschung, wie die antibiotische Aktivitat von Penicillin erhoht werden kann, und wie es wirkt, hingewiesen. 4. Die kolloidchemischen Eigenschaften von Penicillin-Solen, wie Oberflachenspannung, elektrische Ladung, Ionenaustausch und Adsorption werden eingehend besprochen. 5. Es wird, unter Hinweis auf die erhohte Wirksamkeit von Streptomycin in Anwesenheit kapillaraktiver Chemikalien, auf die Bedeutung der Kolloidchemie fur das Gebiet der Antibiotica hingewiesen.
Encapsulation of Rhodanese and Organic Thiosulfonates by Mouse Erythrocytes

Abstract Encapsulation of Rhodanese and Organic Thiosulfonates by Mouse Erythrocytes. Petrikovics, I., Mcguinn W. D., Cannon, E. P., Pei, L., and Wav, J. L., (1994) Fundam. Appl Toxicol. 23, 70-75. A series of organic thiosulfonates were synthesized and studied as sulfur donor substrates for rhodanese encapsulated within murine carrier erythrocytes. Previous studies have indicated that resealed erythrocytes containing rhodanese (CRBC) and sodium thiosulfate can rapidly metabolize cyanide to the less toxic thiocyanate. This thiosulfate - rhodanese system was very efficacious as a new conceptual approach to antagonize cyanide intoxication both in vitro and in vivo. However, its potential is restricted because of the limited availability of thiosulfate due to its poor permeability through RBC membrane. Present studies suggest that there are advantages in using alternative sulfur donors, i.e., organic thiosulfonates in this rhodanese-containing resealed erythrocyte system, since these compounds have higher lipid solubility than inorganic thiosulfates and can readily penetrate the red blood cell membrane. Therefore, this system could provide a virtually unlimited amount of sulfur donor to the encapsulated rhodanese even if the substrates are in solution outside the cells. Moreover, the rhodanese reaction rate of any of these organic thiosulfonates is much faster than the rate observed with the classic cyanide antidote, sodium thiosulfate. This CRBC system will continue to detoxify cyanide even when these encapsulated sulfur donors are depleted, as the lipid soluble organic thiosulfonate outside the cells will diffuse past the membrane into the cell to replenish the sulfur donor. The encapsulation efficiency for rhodanese is about 30%, and the velocity of the rhodanese reaction increases linearly with the volume of enzyme-laden erythrocytes. Similarly, reaction velocity increases linearly with substrate concentration. These results further establish the use of resealed erythrocytes as biodegradable drug carriers, particularly since the sulfur donor is now no longer limiting in this system.
Interest of adolescents in genetic testing for nicotine addiction susceptibility.

Abstract Objectives. Genetic tests for nicotine addiction susceptibility may someday offer preventive medicine specialists new tools to reduce smoking among adolescents. This paper examines adolescents' interest in, and reasons behind interest in, such testing and correlates of interest. Methods. The sample included 211 healthy patients (ages 13–21) recruited from Georgetown University Medical Center's adolescent medicine clinic. Subjects completed a one-time behavioral survey immediately prior to or following a general medical check-up during calendar years 2001–2005. A 4-point self-report survey item served as the dependent variable. Results. Sixty-two percent of adolescents were interested in genetic testing. Among the 72% of adolescents who provided a reason for their interest, 35% would find the information interesting for general or nonspecific reasons, 30% would find it personally useful, 8% noted it would be irrelevant, and 13% stated it would be unimportant; school performance and interest in cancer susceptibility testing were associated with interest in nicotine addiction susceptibility testing (adjusted r2 = 21%; P Conclusions. Adolescent primary care patients will likely be receptive to comprehensive tobacco control programs incorporating genetic testing. Higher levels of educational achievement and greater interest in DNA-based preventive medicine may characterize those most interested. Offering testing will be contingent upon the development of safe and effective genetic tests.
The Therapeutic Use of 2,3-Dimercaptopropane-1-Sulfonate in Two Cases of Inorganic Mercury Poisoning

Two patients had heavy metal intoxication resulting from industrial exposure to mercury vapors. One patient remained asymptomatic despite high urinary mercury levels. The second presented with a documented toxic reaction, including abnormal electromyograms and hematuria. Treatment was begun with 2,3-dimercaptopropane-1-sulfonate, and investigational drug used under Food and Drug Administration guidelines (IND 19,276). Use in both patients resulted in a dramatic change in excretion half-life of the mercury, from 33.1 days before treatment to 11.2 days during therapy. No significant toxic effects related to drug therapy were observed. Clearing of hematuria and reversal of electromyographic abnormalities were prompt in the symptomatic patient. Therapy with 2,3-dimercaptopropane-1-sulfonate was effective in these two patients.
A Global ab Initio Potential Energy Surface for Formaldehyde

We report a global potential energy surface for formaldehyde. The surface is a combination of six local fits joined smoothly by five switching functions. The fits are to roughly 80000 CCSD(T)/aug-cc-PVTZ and 53000 MR−CI/aug-cc-PVTZ calculations of electronic energies. The surface describes the H2CO minimum, the cis and trans HCOH isomers, the molecular channel, H2+CO, and the radical channel, H+HCO. The properties of the potential are evaluated by analyzing the properties of the six stationary points, one-dimensional cuts, and contour plots of the fit.
THE IMPACT OF PHARMACOGENETICS ON THE FUTURE OF HEALTHCARE

Abstract Pharmacogenetics has been promoted as potentially providing benefits to patients, managed care organizations and pharmaceutical companies. This has not translated into products that benecit healthcare developers, providers or consumers. The reasons for this are many, but this will change as the financial incentives become clear for the pharmaceutical industry to develop products that use genetic susceptibility as part of the rationale for products, healthcare providers have increasing incentive to reduce costs, and patients demand up-to-date technologies to optimize healthcare. Recent studies have established genetic contributions that alter the response to therapy for some disease entities, and more will follow as pharmacogenetics becomes increasingly accepted as an important consideration in the therapeutic decision-making process.
Resuscitation with Pressors after Traumatic Brain Injury

Background The purpose of the study was to compare initial resuscitation with arginine vasopressin (AVP), phenylephrine (PE), or isotonic crystalloid fluid alone after traumatic brain injury and vasodilatory shock. Study design Anesthetized, ventilated swine (n = 39, 30 ± 2 kg) underwent fluid percussion traumatic brain injury followed by hemorrhage (30 ± 2mL/kg) to a mean arterial pressure 60mmHg for 30 to 60minutes, then cerebral perfusion pressure > 60mmHg for 60 to 300minutes, either unlimited crystalloid fluid only (n = 9), arginine vasopressin + fluid (n = 9), phenylephrine + fluid (n = 9), arginine vasopressin only (n = 5), or phenylephrine only (n = 5). Heterologous transfusions were administered if hematocrit was 20 mmHg. Cerebrovascular reactivity was evaluated with serial CO 2 challenges. Results In all groups, physiologic variables were similar at baseline and at the end of shock. On resuscitation, all achieved mean arterial pressure and cerebral perfusion pressure goals. Brain tissue PO 2 s were similar. With fluid only, more blood and mannitol were required, intracranial pressure and peak inspiratory pressure were higher, and cerebrovascular reactivity was decreased (all p 2 saturation were similar to fluid only, but total fluid requirements and urine output were both reduced (p 2 saturation, cardiac output, and urine output were decreased (all p Conclusions To correct vasodilatory shock after traumatic brain injury, a resuscitation strategy that combined either phenylephrine or arginine vasopressin plus crystalloid was superior to either fluid alone or pressor alone.
Biological activity of iodinated gastrins

Abstract Mono- and di-iodo heptadecapeptide gastrins were prepared by a modified chloramine-T technique. The iodinated gastrins did not differ significantly from unmodified gastrins in immunoreactivity and in stimulating acid secretion in gastric fistula dogs. The preparations should prove useful in studies of hormone binding to receptors.
Human natural killer cell receptor 2B4 (CD244) down-regulates its own expression by reduced promoter activity at an Ets element

2B4 (CD244), a member of the CD2 subset of the immunoglobulin superfamily, is important for stimulating human natural killer (NK) cell cytotoxicity and cytokine production. It is expressed on all NK cells, a subpopulation of T cells, monocytes, basophils and eosinophils. 2B4 interaction with its ligand CD48 regulates NK, T and B lymphocyte functions and thus plays a central role in various immune responses. Previous study indicated a role for AP-1 and Ets in the transcription of the 2B4 gene. In this study we report that stimulation of NK cells through surface 2B4 down-regulates its own expression due to a reduction in the promoter activity at the Ets element. The down-regulation of 2B4 could be a mechanism to attenuate the co-stimulatory signal from 2B4--CD48 interactions.
Ca2+-dependent Regulation of TrkB Expression in Neurons

The neurotrophin brain-derived neurotrophic factor (BDNF), via activation of its receptor, tyrosine receptor kinase B (trkB), regulates a wide variety of cellular processes in the nervous system, including neuron survival and synaptic plasticity. Although the expression of BDNF is known to be Ca2+-dependent, the regulation of trkB expression has not been extensively studied. Here we report that depolarization of cultured mouse cortical neurons increased the expression of the full-length, catalytically active isoform of trkB without affecting expression of the truncated isoform. This increase in protein expression was accompanied by increased levels of transcripts encoding full-length, but not truncated, trkB. Depolarization also regulated transcription of the gene, TRKB, via entry of Ca2+ through voltage-gated Ca2+ channels and subsequent activation of Ca2+-responsive elements in the two TRKB promoters. Using transient transfection of neurons with TRKB promoter-luciferase constructs, we found that Ca2+ inhibited the upstream promoter P1 but activated the downstream promoter P2. Ca2+-dependent stimulation of TRKB expression requires two adjacent, non-identical CRE sites located within P2. The coordinated regulation of BDNF and trkB by Ca2+ may play a role in activity-dependent survival and synaptic plasticity by enhancing BDNF signaling in electrically active neurons.
Dissection of the protein G B1 domain binding site for human IgG Fc fragment

The contribution to the free energy of binding of each of the residues forming the binding site for a human IgG Fc fragment on the surface of the B1 domain of protein G was determined by alanine-scanning mutagenesis. The interface between these two proteins is atypical in that it is smaller than usual, polar in character, and involves two well-defined "knobs-into-holes" interactions. The bulk of the free energy of binding is contributed by three central residues, which make hydrogen bonds across the interface. Of these, the most critical interaction is formed by Glu27, which acts as a charged knob on the surface of the B1 domain, inserting into a polar hole on the Fc fragment. A single alanine mutation of this residue virtually abolishes stable complex formation. Formation of a stable interface between these two proteins is therefore dominated by a small, polar "hot spot."
Light induced photoreactions with plasmid DNA by Cu/Ru and Cu/Ru/Pt multi-metallic porphyrins

Coordination of two [Ru(bipy)2Cl]+ moieties (where bipy = 2,2′-bipyridine) to the pyridyl nitrogens in the 5,10-positions of meso-5,10,15-(4-Pyridyl)-20-(pentafluorophenyl)porphyrin gives the diruthenium porphyrin complex II. Insertion of copper(II) into the porphyrin center allows for the third pyridyl nitrogen to coordinate to Pt(dmso)Cl2. Electronic transitions associated with the ruthenium porphyrin include an intense Soret band and four less intense Q-bands in the visible region of the spectrum. An intense π–π* transition in the UV region associated with the bipyridyl groups and a metal to ligand charge transfer (MLCT) band appearing as a shoulder to the Soret band are also observed. A slight blue shift of the Soret band and collapse of the Q-bands into one band is observed upon insertion of Cu(II) into the porphyrin center. No change in the electronic spectrum is observed upon coordination of the Pt(dmso)Cl2 moiety. Electrochemical properties associated with the complexes include a redox couple in the cathodic region attributed to the porphyrin and a redox couple in the anodic region due to the RuIII/II couple. DNA titrations of the Cu/Ru and Cu/Ru/Pt porphyrins indicate that both complexes interact strongly with DNA potentially through a partial intercalation mechanism. Gel electrophoresis studies indicate that the Cu/Ru/Pt porphyrin has a greater effect on DNA migration through the gel than the well known DNA binding agent cis-platin. Irradiation of aqueous solutions of the Cu/Ru porphyrin and supercoiled DNA at a 5:1 base pair to complex ratio (in the absence of oxygen) with visible light above 400 nm shows a nicking of the DNA. Repeat experiments in the presence of oxygen show that the Cu/Ru porphyrin photocleaves the DNA, giving the linear form, as evidenced by gel electrophoresis.
The performance of resonant tunnelling transistors

An investigation is reported of the performance of the resonant tunnelling transistor based on the solution of Schrodinger's equation. The calculated J-V (current density-voltage) characteristics have been obtained and from the equivalent circuit, which is derived from these calculations, the cut-off frequency fT and the maximum frequency of oscillation fmax have been estimated.
Gene Array-Based Identification of Changes That Contribute to Ethanol Tolerance in Ethanologenic Escherichia coli: Comparison of KO11 (Parent) to LY01 (Resistant Mutant)

Escherichia coli KO11 (parent) and LY01 (mutant) have been engineered for the production of ethanol. Gene arrays were used to identify expression changes that occurred in the mutant, LY01, during directed evolution to improve ethanol tolerance (defined as extent of growth in the presence of added ethanol). Expression levels for 205 (5%) of the ORFs were found to differ significantly (p < 0.10) between KO11 and LY01 under each of six different growth conditions (p < 0.000001). Statistical evaluation of differentially expressed genes according to various classification schemes identified physiological areas of importance. A large fraction of differentially expressed ORFs were globally regulated, leading to the discovery of a nonfunctional fnr gene in strain LY01. In agreement with a putative role for FNR in alcohol tolerance, increasing the copy number of fnr(+) in KO11(pGS196) decreased ethanol tolerance but had no effect on growth in the absence of ethanol. Other differences in gene expression provided additional clues that permitted experimentation. Tolerance appears to involve increased metabolism of glycine (higher expression of gcv genes) and increased production of betaine (higher expression of betIBA and betT encoding betaine synthesis from choline and choline uptake, respectively). Addition of glycine (10 mM) increased ethanol tolerance in KO11 but had no effect in the absence of ethanol. Addition of betaine (10 mM) increased ethanol tolerance by over 2-fold in both LY01 and KO11 but had no effect on growth in the absence of ethanol. Both glycine and betaine can serve as protective osmolytes, and this may be the basis of their beneficial action. In addition, the marAB genes encoding multiple antibiotic resistance proteins were expressed at higher levels in LY01 as compared to KO11. Interestingly, overexpression of marAB in KO11 made this strain more ethanol-sensitive. Overexpression of marAB in LY01 had no effect on ethanol tolerance. Increased expression of genes encoding serine uptake (sdaC) and serine deamination (sdaB) also appear beneficial for LY01. Addition of serine increased the growth of LY01 in the presence and absence of ethanol but had no effect on KO11. Changes in the expression of several genes concerned with the synthesis of the cell envelope components were also noted, which may contribute to increased ethanol tolerance.