cssi/SciSciGPT-SciSciNet huggingface dataset:
Vascular endothelial growth factor (VEGF) modulates vascular permeability and inflammation in rat brain.

Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that also induces vascular permeability and macrophage migration. VEGF expression is weak in normal adult brain, but is strongly upregulated in glioma cells and reactive astrocytes, suggesting that chronic overexpression of VEGF in the brain contributes to blood-brain barrier (BBB) breakdown. We examined the effects of chronic VEGF overexposure on the integrity of the BBB using the following approaches: 1) continuous intracerebral infusion of VEGF via miniosmotic pump; and 2) intracerebral injection of an adenoviral vector encoding the VEGF165 gene (AdCMV.VEGF). After 6 days both treatments produced approximately 10-fold breakdown of the BBB (as measured by transport of 14C-aminoisobutyric acid (AIB) from blood into brain) compared with the respective controls (albumin infusion or AdCMV.beta gal virus). BBB disruption in AdCMV.VEGF-treated brains was accompanied by a severe inflammatory response not observed in brains receiving AdCMV.beta gal or VEGF protein infusion, indicating that neither VEGF nor viral particles alone were responsible for the inflammatory response. However, injection of AdCMV.beta gal followed by VEGF infusion to the same site also elicited inflammation. Chronic overexposure of normal brain to VEGF also increased intercellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex (MHC) class I and II expression. Although VEGF itself is not inflammatory, VEGF may modulate immune responses in the central nervous system (CNS) by opening the BBB, altering the immunoprivileged status of the brain, and allowing contact between normally sequestered CNS antigens and blood-borne immune mediators.
Probabilistic simulation for flaw acceptance by dye-penetrant inspection

This paper examines the problems encountered in assessing the reliability of dye-penetrant nondestructive inspection (NDI) techniques in preventing failures due to undetected surface flaws, as well as from flaw acceptance (Fitness-For-Purpose). A Monte Carlo simulation procedure which includes the major variables of the problem is presented as a means of quantifying reliability. Some issues associated with distribution selection are examined. A methodology for selecting the penetrant type and flaw acceptance size for the specific components analyzed using the simulation is proposed. Current methodology limitations are discussed along with possible future effort. Penetrant selection and acceptable sizes of detected flaws are based on a probabilistic assessment of the effect of component and dye-penetrant system variables on structural reliability.
Inpatient Consultation: Results of a Physician Survey and a Proposed Improvement

We undertook the current survey-based study to assess clinicians' views on the determinants of effective inpatient consultation and the existing process of inpatient consultation at the Cleveland Clinic Hospital. A 25-question survey developed for this study using Likert scale responses was completed by 181 (of 404 eligible addressees, a 45% response rate) members of the Cleveland Clinic staff in the divisions of medicine, surgery, and pediatrics. Ratings of the overall value of inpatient consultation reflected moderate satisfaction (mean 6.9 of possible 10). Types of consults that were most valued were those requesting a procedure and those seeking assistance in establishing a diagnosis and in interpreting data. Features deemed most important in making a consult excellent were legibility of the consultant's note, timeliness of the response (i.e., within 24 hours), and direct communication of the consult question. The data showed a trend indicating that physicians regarded the value of direct physician-to-physician communication more highly than they personally practiced such direct communication when requesting a consult. Study findings indicate the opportunity to improve the process of inpatient consultation by implementing measures that enhance direct physician-to-physician communication about the consult, ensure timeliness, facilitate identification of the appropriate consultants, and allow easier auditing. We propose a novel process for requesting inpatient consultations that extends currently available hospital information systems but offers a process improvement that warrants development.
A frictional molecular model for the viscoelasticity of entangled polymer nanocomposites

The dynamics of polymer melts and concentrated solutions reinforced with nanoscale rigid spherical particles is analyzed. Nanocomposites with low filler volume fraction and strong polymer-filler interactions are considered. Entanglement effects are represented by requiring the diffusion in the chain contour direction to be more pronounced than in the direction transverse to the chain primitive path. Filler particles are treated as material points. They reduce the polymer mobility in both longitudinal and transverse tube directions due to short-range energetic filler-polymer interactions. Hence, the contribution to chain dynamics and stress production of both filler-polymer and polymer-polymer interactions is considered to be purely frictional in nature. In the model, the strain rate sensitivity is associated with the thermal motion of chains, with the convective relaxation of entanglement constrains and with the polymer-filler attachment/detachment process. The effect of model parameters is discussed and the predictions are compared with experimental data.
Radiation-induced complications in endovascular neurosurgery: incidence of skin effects and the feasibility of estimating risk of future tumor formation.

BACKGROUND The incidence of radiation-induced complications is increasingly part of the informed consent process for patients undergoing neuroendovascular procedures. Data guiding these discussions in the era of modern radiation-minimizing equipment is lacking. OBJECTIVE To quantify the rates of skin and hair effects at a modern high-volume neurovascular center, and to assess the feasibility of accurately quantifying the risk of future central nervous system (CNS) tumor formation. METHODS We reviewed a prospectively collected database of endovascular procedures performed at our institution in 2008. The entrance skin dose and brain dose were calculated. Patients receiving skin doses >2 Gy were contacted to inquire about skin and hair changes. We reviewed several recent publications from leading radiation physics bodies to evaluate the feasibility of accurately predicting future cancer risk from neurointerventional procedures. RESULTS Seven hundred two procedures were included in the study. Of the patients receiving >2 Gy, 39.6% reported subacute skin or hair changes following their procedure, of which 30% were permanent. Increasing skin dose was significantly associated with permanent hair loss. We found substantial methodological difficulties in attempting to model the risk of future CNS tumor formation given the gaps in our current understanding of the brain's susceptibility to low-dose ionizing radiation. CONCLUSION Radiation exposures exceeding 2 Gy are common in interventional neuroradiology despite modern radiation-minimizing technology. The incidence of side effects approaches 40%, although the majority is self-limiting. Gaps in current models of brain tumor formation after exposure to radiation preclude accurately quantifying the risk of future CNS tumor formation.
Inhibition of cyclin-dependent kinase 6 suppresses cell proliferation and enhances radiation sensitivity in medulloblastoma cells

Medulloblastoma accounts for 20 % of all primary pediatric intracranial tumors. Current treatment cures 50–80 % of patients but is associated with significant long-term morbidity and thus new therapeutic targets are needed. One such target is cyclin-dependent kinase 6 (CDK6), a serine/threonine kinase that plays a vital role in cell cycle progression and differentiation. CDK6 is overexpressed in medulloblastoma patients and is associated with an adverse prognosis. To investigate the role of CDK6 in medulloblastoma, we assayed the effect of CDK6 inhibition on proliferation by depleting expression with RNA interference (RNAi) or by inhibiting kinase function with a small molecule inhibitor, PD0332991. Cell proliferation was assessed by colony focus assay or by the xCELLigence system. We then investigated the impact of CDK6 inhibition on differentiation of murine neural stem cells by immunofluorescence of relevant markers. Finally we evaluated the effects of PD0332991 treatment on medulloblastoma cell cycle and radiosensitivity using colony focus assays. Gene expression analysis revealed that CDK6 mRNA expression is higher than normal cerebellum in fifteen out of sixteen medulloblastoma patient samples. Inhibition of CDK6 by RNAi significantly decreased medulloblastoma cell proliferation and colony forming potential. Interestingly, CDK6 inhibition by RNAi increased differentiation in murine neural stem cells. PD0332991 treatment significantly decreased medulloblastoma cell proliferation and led to a G0/G1 cell cycle arrest. Furthermore, PD0332991 pretreatment sensitized medulloblastoma cells to ionizing radiation. Our findings suggest that targeting CDK6 with small molecule inhibitors may prove beneficial in the treatment of medulloblastoma, especially when combined with radiation.
NFATc2 recruits cJun homodimers to an NFAT site to synergistically activate interleukin-2 transcription

Transcription of interleukin-2 (IL-2), a pivotal cytokine in the mammalian immune response, is induced by NFAT and AP-1 transcriptional activators in stimulated T cells. NFATc2 and cJun drive high levels of synergistic human IL-2 transcription, which requires a unique interaction between the C-terminal activation domain of NFATc2 and cJun homodimers. Here we studied the mechanism by which this interaction contributes to synergistic activation of IL-2 transcription. We found that NFATc2 can recruit cJun homodimers to the -45 NFAT element, which lacks a neighboring AP-1 site. The bZip domain of cJun is sufficient to interact with the C-terminal activation domain of NFATc2 in the absence of DNA and this interaction is inhibited by AP-1 DNA. When the -45 NFAT site was replaced by either an NFAT/AP-1 composite site or a single AP-1 site the specificity for cJun homodimers in synergistically activating IL-2 transcription was lost, and cJun/cFos heterodimers strongly activated transcription. These studies support a model in which IL-2 transcriptional synergy is mediated by the unique recruitment of a cJun homodimer to the -45 NFAT site by NFATc2, where it acts as a co-activator for IL-2 transcription.
A Representation and Economic Interpretation of a Two-Level Programming Problem

This paper first presents a formulation for a class of hierarchial problems that show a two-stage decision making process; this formulation is termed multilevel programming and could be defined, in...
Preparation and friction characteristics of self-lubricating TiN-MoS2 composite coatings

Abstract Composite coatings consisting of discrete phases of TiN and MoS 2 were codeposited on graphite and Ti-6Al-4V substrates from Ti((CH 3 ) 2 N) 4 /NH 3 /MoF 6 /H 2 S gas mixtures. Chemical composition and microstructure of the coatings were characterized by Auger electron spectroscopy, X-ray diffraction, and transmission electron microscopy. Friction coefficients at room temperature in air were typically in the range of 0.07 to 0.3. The friction coefficients remained comparable at 573 K, but increased to 0.7 to 1.0 at 673 K. A friction coefficient value of ∼0.3 was, however, obtained from a composite coating tested at 973 K.
Surface doses for acrylic versus lead acrylic blocking trays for Co-60, 8-MV, and 17-MV photons.

Clear acrylic trays are commonly used on teletherapy units to support freehand and custom‐molded blocks for photon beam irradiation. While these trays have many desirable physical characteristics, they have the disadvantage of degrading the buildup region by contribution of low‐energy electrons to the patient’s surface. Recently, clear leaded acrylic has been introduced and suggested as a replacement for acrylic. The effect of the lead acrylic on the buildup region was investigated for cobalt‐60, 8‐MV, and 17‐MV x‐ray beams. The lead acrylic was found to decrease the surface dose compared to acrylic. Except for cobalt‐60, the lead acrylic results in a higher dose than an open wire tray.
Performance comparison of receivers in a simple partial erasure model

A simple partial erasure model based on the effective reduction of the transition width in a magnetic recording system is presented. This model predicts nonlinear distortion accurately at high recording densities. This paper proposes several detection schemes incorporating this nonlinear model, and compares the performance with receivers designed for a linear channel. Simulations show that the nonlinear equalized maximum likelihood (EML) receiver outperforms other detectors in a nonlinearity-dominant channel. >
Modeling Techniques of Electrical Surge Arrestors for EMP Simulations

Gas filled Electrical Surge Arrestors (ESA's) are used for protection and hardening of systems against such effects as EMP (Electro-Magnetic Pulse from nuclear detonations). In order to effectively utilize ESA's in a sensitive system, the design engineer must have a good understanding of the dynamic capabilities of the device. Unfortunately, existing ESA models, from which such understanding usually is acquired, are either too simple (a switch) or too complex, making their utility slight. The purpose of this paper is to develop ESA models representing a more reasonable compromise between computational simplicity and reality. This is achieved by developing a standard set of experiments for obtaining modeling data with particular relevance to EMP. Model credibility is subsequently assured through verification tests performed in EMP simulated environments.1
Subunit organization and structure in the F0 sector of Escherichia coli F1F0 ATP synthase.

In this review, we summarize recent work from our laboratory which establishes the topology and nearest neighbor organization of subunits in the F0 sector of the H+ transporting ATP synthase of Escherichia coli. The E. coli F0 sector is composed of three subunits in an a1b2c12 stoichiometric ratio. Crosslinking experiments with genetically introduced Cys establish a ring-like organization of the 12 c subunits with subunits a and b lying to the outside of the ring. The results are interpreted using an atomic resolution structural model of monomeric subunit c in a chloroform-methanol-water (4:4:1, v/v/v) solution, derived by heteronuclear NMR (M.E. Girvin, F. Abildgaard, V. Rastogi, J. Markley, R.H. Fillingame, in press). The crosslinking results validate many predictions of the structural model and confirm a front-to-back-type packing of two subunit c into a functional dimer, as was first predicted from genetic studies. Aspartyl-61, the proton translocating residue, lies at the center of the four transmembrane helices of the functional dimer, rather than at the periphery of the subunit c ring. Subunit a is shown to fold with five transmembrane helices, and a functionally important interaction of transmembrane helix-4 with transmembrane helix-2 of subunit c is established. The single transmembrane helices of the two subunit b dimerize in the membrane. The structure of the transmembrane segment of subunit b is predicted from the NMR structure of the monomeric peptide.
Cystometric and perineal electromyography in spinal cord-injured patients☆

The results of combined cystometry and perineal electromyography were reviewed retrospectively in 50 consecutive, traumatic spinal cord-injured patients. Early and frequent urodynamic evaluation was found necessary in order to tailor treatment to the changing cystometric and electromyographic states in these patients.
Eyeblink Conditioning in Healthy Adults: A Positron Emission Tomography Study

Eyeblink conditioning is a paradigm commonly used to investigate the neural mechanisms underlying motor learning. It involves the paired presentation of a tone-conditioning stimulus which precedes and co-terminates with an airpuff unconditioned stimulus. Following repeated paired presentations a conditioned eyeblink develops which precedes the airpuff. This type of learning has been intensively studied and the cerebellum is known to be essential in both humans and animals. The study presented here was designed to investigate the role of the cerebellum during eyeblink conditioning in humans using positron emission tomography (PET). The sample includes 20 subjects (10 male and 10 female) with an average age of 29.2 years. PET imaging was used to measure regional cerebral blood flow (rCBF) changes occurring during the first, second, and third blocks of conditioning. In addition, stimuli-specific rCBF to unpaired tones and airpuffs (“pseudoconditioning”) was used as a baseline level that was subtracted from each block. Conditioning was performed using three, 15-trial blocks of classical eyeblink conditioning with the last five trials in each block imaged. As expected, subjects quickly acquired conditioned responses. A comparison between the conditioning tasks and the baseline task revealed that during learning there was activation of the cerebellum and recruitment of several higher cortical regions. Specifically, large peaks were noted in cerebellar lobules IV/V, the frontal lobes, and cingulate gyri.
Predictive Self-Assembly of Polyhedra into Complex Structures

Predicting structure from the attributes of a material’s building blocks remains a challenge and central goal for materials science. Isolating the role of building block shape for self-assembly provides insight into the ordering of molecules and the crystallization of colloids, nanoparticles, proteins, and viruses. We investigated 145 convex polyhedra whose assembly arises solely from their anisotropic shape. Our results demonstrate a remarkably high propensity for thermodynamic self-assembly and structural diversity. We show that from simple measures of particle shape and local order in the fluid, the assembly of a given shape into a liquid crystal, plastic crystal, or crystal can be predicted.
Underestimation of the presence of breast carcinoma in papillary lesions initially diagnosed at core-needle biopsy.

Purpose: To retrospectively determine the degree of underestimation of breast carcinoma diagnosis in papillary lesions initially diagnosed at core-needle biopsy. Materials and Methods: Institutional review board approval and waiver of informed consent were obtained for this HIPAA-compliant study. Mammographic database review (1994–2003) revealed core biopsy diagnoses of benign papilloma (n = 38), atypical papilloma (n = 15), sclerotic papilloma (n = 6), and micropapilloma (n = 4) in 57 women (mean age, 57 years). Excisional or mammographic follow-up (≥2 years) findings were available. Patients with in situ or invasive cancer in the same breast or patients without follow-up were excluded. Findings were collected from mammography, ultrasonography, core technique, core biopsy, excision, and subsequent mammography. Reference standard was excisional findings or follow-up mammogram with no change at 2 years. Associations were examined with regression methods. Results: In 38 of 63 lesions, surgical excision was ...
Estrogen Protects against Radiation-Induced Cataractogenesis

Cataractogenesis is a complication of radiotherapy when the eye is included in the treatment field. Low doses of densely ionizing space radiation may also result in an increased risk of cataracts in astronauts. We previously reported that estrogen (17-β-estradiol), when administered to ovariectomized rats commencing 1 week before γ irradiation of the eye and continuously thereafter, results in a significant increase in the rate and incidence of cataract formation and a decreased latent period compared to an ovariectomized control group. We therefore concluded that estrogen accelerates progression of radiation-induced opacification. We now show that estrogen, if administered continuously, but commencing after irradiation, protects against radiation cataractogenesis. Both the rate of progression and incidence of cataracts were greatly reduced in ovariectomized rats that received estrogen treatment after irradiation compared to ovariectomized rats. As in our previous study, estradiol administered 1 week prior to irradiation at the time of ovariectomy and throughout the period of observation produced an enhanced rate of cataract progression. Estrogen administered for only 1 week prior to irradiation had no effect on the rate of progression but resulted in a slight reduction in the incidence. We conclude that estrogen may enhance or protect against radiation cataractogenesis, depending on when it is administered relative to the time of irradiation, and may differentially modulate the initiation and progression phases of cataractogenesis. These data have important implications for astronauts and radiotherapy patients.
Comparison of Xenorhabdus bovienii bacterial strain genomes reveals diversity in symbiotic functions

Xenorhabdus bacteria engage in a beneficial symbiosis with Steinernema nematodes, in part by providing activities that help kill and degrade insect hosts for nutrition. Xenorhabdus strains (members of a single species) can display wide variation in host-interaction phenotypes and genetic potential indicating that strains may differ in their encoded symbiosis factors, including secreted metabolites. To discern strain-level variation among symbiosis factors, and facilitate the identification of novel compounds, we performed a comparative analysis of the genomes of 10 Xenorhabdus bovienii bacterial strains. The analyzed X. bovienii draft genomes are broadly similar in structure (e.g. size, GC content, number of coding sequences). Genome content analysis revealed that general classes of putative host-microbe interaction functions, such as secretion systems and toxin classes, were identified in all bacterial strains. In contrast, we observed diversity of individual genes within families (e.g. non-ribosomal peptide synthetase clusters and insecticidal toxin components), indicating the specific molecules secreted by each strain can vary. Additionally, phenotypic analysis indicates that regulation of activities (e.g. enzymes and motility) differs among strains. The analyses presented here demonstrate that while general mechanisms by which X. bovienii bacterial strains interact with their invertebrate hosts are similar, the specific molecules mediating these interactions differ. Our data support that adaptation of individual bacterial strains to distinct hosts or niches has occurred. For example, diverse metabolic profiles among bacterial symbionts may have been selected by dissimilarities in nutritional requirements of their different nematode hosts. Similarly, factors involved in parasitism (e.g. immune suppression and microbial competition factors), likely differ based on evolution in response to naturally encountered organisms, such as insect hosts, competitors, predators or pathogens. This study provides insight into effectors of a symbiotic lifestyle, and also highlights that when mining Xenorhabdus species for novel natural products, including antibiotics and insecticidal toxins, analysis of multiple bacterial strains likely will increase the potential for the discovery of novel molecules
Electrodermal activity and therapeutic response to neuroleptic treatment in chronic schizophrenic in-patients

Electrodermal measures, psychiatric ratings (Brief Psychiatric Rating Scale, Clinical Global Impressions) and several Wechsler subtest scores were obtained for 26 hospitalized chronic schizophrenics during drug ‘washout’. The psychiatric ratings and Wechsler scores were obtained again after 6 months' treatment with thiothixene or thioridazine. Results revealed that those patients who displayed therapeutic benefit from the neuroleptic treatment displayed greater pre-treatment electrodermal activity and higher skin conductance levels, compared with schizophrenics who did not benefit. No effect for laterality was noted.
Effects of ultraviolet–B irradiances on soybean

Soybean [Glycine max (L.) Merr. cv. Hardee] and wheat (Triticum aestivum L. cv. Jori) were grown from seed under four ultraviolet-B irradiances and four levels of photosynthetically active radiation in a factorial design. The effects of ultraviolet-B radiation on leaf number and area, total dry matter production, dry weight of component organs, and plant height were compared between soybean and wheat. Ultraviolet-B radiation effects were dependent upon the level of photosynthetically active radiation incident during growth. Wheat and soybeans were both affected by low ultraviolet-B radiation flux densities; however, they differed markedly in their growth responses and biomass allocation patterns. Substantial interactions between ultraviolet-B and photosynthetically active radiation indicate a need for the measurement of longer wavelength radiation when evaluating the effects of ultraviolet-B radiation on plant growth in natural conditions.
Effect of random background inhomogeneity on observer detection performance.

Many psychophysical studies of the ability of the human observer to detect a signal superimposed upon a uniform background, where both the signal and the background are known exactly, have been reported in the literature. In such cases, the ideal or the Bayesian observer is often used as a mathematical model of human performance since it can be readily calculated and is a good predictor of human performance for the task at hand. If, however, the background is spatially inhomogeneous (lumpy), the ideal observer becomes nonlinear, and its performance becomes difficult to evaluate. Since inhomogeneous backgrounds are commonly encountered in many practical applications, we have investigated the effects of background inhomogeneities on human performance. The task was detection of a two-dimensional Gaussian signal superimposed upon an inhomogeneous background and imaged through a pinhole imaging system. Poisson noise corresponding to a certain exposure time and aperture size was added to the detected image. A six-point rating scale technique was used to measure human performance as a function of the strength of the nonuniformities (lumpiness) in the background, the amount of blur of the imaging system, and the amount of Poisson noise in the image. The results of this study were compared with earlier theoretical predictions by Myers et al. [ J. Opt. Soc. Am. A7, 1279 ( 1990)] for two observer models: the optimum linear discriminant, also known as the Hotelling observer, and a nonprewhitening matched filter. Although the efficiency of the human observer relative to the Hotelling observer was only approximately 10%, the variation in human performance with respect to varying aperture size and exposure time was well predicted by the Hotelling model. The nonprewhitening model, on the other hand, fails to predict human performance in lumpy backgrounds in this study. In particular, this model predicts that performance will saturate with increasing exposure time and drop precipitously with increasing lumpiness; neither effect is observed with human observers.
Autologous hematopoietic stem cell transplantation in refractory rheumatoid arthritis: sustained response in two of four patients.

Objective To investigate the safety and efficacy of immune ablation with subsequent autologous hematopoietic stem cell transplantation (HSCT) in severe rheumatoid arthritis (RA). Methods Four patients with refractory RA and poor prognostic indicators were treated. Stem cells were collected and lymphocytes were depleted by 2.3–4.0 logs. The conditioning regimen included cyclophosphamide (200 mg/kg), antithymocyte globulin (90 mg/kg), and, for 1 patient, total body irradiation (TBI) with 400 cGy. Improvement was evaluated according to the American College of Rheumatology (ACR) preliminary definition of improvement in RA (ACR 20), and also according to the ACR 50 and ACR 70 criteria. Results HSCT was well tolerated. Three patients fulfilled the ACR 70 criteria at 1 month and 3 months post-HSCT. One patient did not fulfill the ACR 20 criteria because of persistent joint tenderness, despite improvement of the joint swelling. At 6 months post-HSCT, 1 patient fulfilled the ACR 70 criteria and 1 fulfilled the ACR 50 criteria, and these 2 patients fulfilled the ACR 70 criteria at 9 months post-HSCT. The other 2 patients (including the patient who received TBI) did not meet the ACR 20 criteria at 6 months and 9 months post-HSCT. The only patient with followup of >9 months fulfilled the ACR 70 criteria at 20 months post-HSCT. Conclusion In this series, autologous HSCT was safe and effective in inducing major clinical response and maintained significant benefit for 2 patients at 9 months and 20 months posttreatment, respectively. Sustained response did not occur for 2 of 4 patients. A regimen dose-response effect may exist, but the addition of TBI did not prevent disease relapse for 1 of the patients. More aggressive T cell depletion of the autograft, use of a myeloablative regimen, or use of an allograft may be necessary to decrease relapse rates.
Multi-Purpose Development and Operation Environments for Natural Language Applications

Interactive user environments have been a central efficiencyenhancing feature of many modem computer applications, including natural language processing. There are two major classes of users for whom NLP environments can be constructed developers and end users, such as technical writers and translators. Developers need help in the various knowledge acquisition tasks, such as dictionary and grammar writing for NLP applications. End users look for efficiency enhancements in document preparation beyond the level of word processing support. There are two approaches to the solution of this problem. A dedicated workstation can be developed for each of the required functionalities. Alternatively, workstations can be configured as sets of application routines attached to a universal user interface. In this report we describe a general-purpose user environment, under development at the Center for Machine Translation of Carnegie Mellon University, capable of supporting a number of dedicated workstation configurations. Among the types of end users whom this system will benefit are technical writers, text revisors and translators. In the framework of NLP system development this tool supports dictionary and ontology acquisition. A number of separate functionalities included in this system have been developed and used either in commercial word processing software packages or in NLP projects (e.g., the translator's tools described in Macklovitch, 1989, ; and the developer environments IRACQ (Ayuso et al., 1987), LUKE (Wrobiewski and Rich, 1988) or ONTOS (Monarch and Nirenburg, 1989), among many others). Our system allows a merge of the two directions in the tool development. One direct reason to put the two previously separate kinds of functionality into a single system was to support the knowledge-based machineaided translation environment which involves an interactive human editor who uses an interface to help the machine understand the source text. A standard Unixand X-windows-based workstation platform has been selected for our system, whose working name is Tws, for "Translator's Workstation." We also used the C-based X11 toolkit called MOTIF (Motif, 1991) and its CommonLisp interface called CLM (Babatz et. al., 1991). In practice, TWS consists of a number of application (functionality) modules which are integrated through the central MOTIF-based user interface module. For reasons of uniformity, each of the applications uses the facilities of the user interface for display and input. Each module uses a standard window to interact with the user, and each window has standard menus which, among other functionalities, allow the user to invoke any other module. Each module also has special menus. The architecture of TWS is presented in Figure 1.
Translational Medicine With a Capital T, Troponin T, That Is

See related article, pages 185–194 Although the quest to translate understanding at the molecular level to the prevention, diagnosis, and therapy of disorders of the heart has been ongoing in many laboratories for many years, the recently popular term “translational medicine” is useful to convey the reality of this objective to our leaders in government, industry, and the academy. In my judgment there is no better example of translational medicine than the identification of sarcomeric mutations linked to cardiomyopathies and sudden death. These myopathies identified by linkage analysis were the first cardiac conditions to be understood at the molecular level of organization.1 “Translation” requires determination of the primary effect of the mutation on function at the level of the cardiac sarcomeres and the cells, and integration of these findings at the level of the organ and the organism. This knowledge sets the stage for rational diagnosis, prevention, and therapy. An extensive analysis of this sort in a mouse model has been performed by Du et al2 and is reported in the present issue. The focus of their work was on troponin T (TnT), a thin filament protein, which, together with troponin-I, troponin-C, and tropomyosin, imposes Ca2+-regulation on the actin-myosin reaction.3 Du et al generated a knock-in mouse model of a deletion mutant of TnT, TNNT2ΔK210/ΔK210, which had been linked to DCM.1 TnT-K210 is localized in a critical region of TnT that has multiple interactions with its neighbors on the thin filament and is critical for regulation by Ca2+.3 The transgenic mice demonstrated a DCM phenotype similar to that documented in patients with this mutation. There was no evidence of cellular or myofibrillar disarray, …
Intergenerational genomic DNA methylation patterns in mouse hybrid strains.

Background: DNA methylation is a contributing factor to both rare and common human diseases, and plays a major role in development and gene silencing. While the variation of DNA methylation among individuals has been partially characterized, the degree to which methylation patterns are preserved across generations is still poorly understood. To determine the extent of methylation differences between two generations of mice we examined DNA methylation patterns in the livers of eight parental and F1 mice from C57BL/6J and DBA/2J mouse strains using bisulfite sequencing. Results: We find a large proportion of reproducible methylation differences between C57BL/6J and DBA/2J chromosomes in CpGs, which are highly heritable between parent and F1 mice. We also find sex differences in methylation levels in 396 genes, and 11% of these are differentially expressed between females and males. Using a recently developed approach to identify allelically methylated regions independently of genotypic differences, we identify 112 novel putative imprinted genes and microRNAs, and validate imprinting at the RNA level in 10 of these genes. Conclusions: The majority of DNA methylation differences among individuals are associated with genetic differences, and a much smaller proportion of these epigenetic differences are due to sex, imprinting or stochastic intergenerational effects. Epigenetic differences can be a determining factor in heritable traits and should be considered in association studies for molecular and clinical traits, as we observed that methylation differences in the mouse model are highly heritable and can have functional consequences on molecular traits such as gene expression.
Comparative analysis of exit interviews and direct clinical observations in pediatric ambulatory care services in Afghanistan.

Objective To assess the receiver operating curves (ROCs) for counseling in the management of common childhood diseases comparing direct observations with exit interviews. Design Eight thousand six hundred and fifty-nine randomly selected new outpatient consultations of sick children under 5 years were assessed by observation using a standardized checklist and an exit interview with their parent/guardian, taken between 2005 and 2007 from 948 health facilities in Afghanistan. The observation checklist was used as a ‘gold standard’ for counseling provided. Main measures Sensitivity, specificity and ROCs were estimated for five counseling items, including explanations of: a working diagnosis; what to do at home; possible adverse reactions to medicine; signs that require a return to the health facility; and a time to return. Results The prevalence of counseling items was relatively low (ranging from 8 to 80%), but generally increasing each year. Exit interviews had relatively low levels of sensitivity for the counseling items, ranging from 33 to 88%, with higher levels of specificity (ranging from 63 to 91%), whereas the ROCs ranged from 61 to 77%. Although ROCs varied significantly from year to year ( P < 0.002 for each item), there was little difference based on the sex or type of the health provider. Conclusions Exit interviews did not provide reliable measurements of provider performance compared with direct observations. Observations identified low prevalence of counseling tasks though increasing over time. The differences between observation and exit interviews identified significant gaps in communication, suggesting that exit interviews are of low accuracy and should not be used alone.
Multilevel Modeling: A Review of Methodological Issues and Applications

This study analyzed the reporting of multilevel modeling applications of a sample of 99 articles from 13 peer-reviewed journals in education and the social sciences. A checklist, derived from the methodological literature on multilevel modeling and focusing on the issues of model development and specification, data considerations, estimation, and inference, was used to analyze the articles. The most common applications were two-level models where individuals were nested within contexts. Most studies were non-experimental and used nonprobability samples. The amount of data at each level varied widely across studies, as did the number of models examined. Analyses of reporting practices indicated some clear problems, with many articles not reporting enough information for a reader to critique the reported analyses. For example, in many articles, one could not determine how many models were estimated, what covariance structure was assumed, what type of centering if any was used, whether the data were consiste...
Phenotypic Diversity of Hydrogen Production in Chlorophycean Algae Reflects Distinct Anaerobic Metabolisms

Several species of green algae use [FeFe]-hydrogenases to oxidize and/or produce H2 during anoxia. To further define unique aspects of algal hydrogenase activity, the well-studied anaerobic metabolisms of Chlamydomonas reinhardtii were compared with four strains of Chlamydomonas moewusii and a Lobochlamys culleus strain. In vivo and in vitro hydrogenase activity, starch accumulation/degradation, and anaerobic end product secretion were analyzed. The C. moewusii strains showed the most rapid induction of hydrogenase activity, congruent with high rates of starch catabolism, and anoxic metabolite accumulation. Intriguingly, we observed significant differences in morphology and hydrogenase activity in the C. moewusii strains examined, likely the result of long-term adaptation and/or genetic drift during culture maintenance. Of the C. moewusii strains examined, SAG 24.91 showed the highest in vitro hydrogenase activity. However, SAG 24.91 produced little H2 under conditions of sulfur limitation, which is likely a consequence of its inability to utilize exogenous acetate. In L. culleus, hydrogenase activity was minimal unless pulsed light was used to induce significant H2 photoproduction. Overall, our results demonstrate that unique anaerobic acclimation strategies have evolved in distinct green algae, resulting in differential levels of hydrogenase activity and species-specific patterns of NADH reoxidation during anoxia.
Engineering Nature's Nanotech

In this paper, the author discussed the possibilities and the advantages of natural nanotechnology over synthethic materials. Proteins for example, as nature's nanomachines is easily accessible and does not require fabrication. nanotechnology is set to open up numerous doors for the future, some of which we will likely not even be able to foresee today. As we begin to venture forth into this new nanoscale world, however, perhaps we should also take the time to appreciate and study the diversity of the nanotechnologies that already exist within and all around us.
Counting objects with biologically inspired regulatory-feedback networks

Neural networks are relatively successful in recognizing individual patterns. However, when images consist of combination of patterns, a preprocessing step of segmentation is required to avoid combinatorial explosion of the training phase. In practical applications, segmentation is a context dependent task which itself requires recognition. In this paper we propose and develop a biologically inspired neural architecture that can recognize and count an arbitrary collection of objects even if trained with individual objects, without making use of additional segmentation algorithms. The two essential features that govern the neurons in this algorithm are 1. dynamical feedback and 2. competition for activation. We show analytically that while the equations governing the output neurons are highly nonlinear in individual feature amplitudes, they are linear in groups of feature amplitudes. We further demonstrate through simulations, that our architecture can precisely count and recognize scenes in which three and four non-overlapping patterns are presented simultaneously. The ability to generalize numerosity outside the training distribution with a simple learning scheme, lack of connection weights and segmentation algorithms prove regulatory feedback networks not only beneficial for machine learning tasks but also for biological modeling of animal vision.
Social buffering in adult male rhesus macaques (Macaca mulatta): Effects of stressful events in single vs. pair housing.

Background The purpose of this study was to test whether long-term pair housing of male rhesus macaques ameliorated negative responses to stressful events that can occur in the course of routine husbandry or research procedures. Methods Twelve singly housed individuals were videotaped during two potentially stressful events before and after social introduction into pairs. During each stressor, abnormal behavior and anxiety-related behavior were quantified from videotape. Results When visually exposed to the restraint and anesthesia of other monkeys, subjects showed significantly reduced frequencies of abnormal behavior when pair-housed in comparison to their reactions when housed singly. Noisy and disruptive conversation between technicians standing immediately in front of the subjects’ cage did not elicit the same reduction in abnormal behavior. Neither test showed a significant difference across housing settings for anxiety-related behaviors. Conclusions These findings suggest that pair housing buffers adult male rhesus macaques against common stressors in the laboratory setting.
Humans Prefer Curved Visual Objects

People constantly make snap judgments about objects encountered in the environment. Such rapid judgments must be based on the physical properties of the targets, but the nature of these properties is yet unknown. We hypothesized that sharp transitions in contour might convey a sense of threat, and therefore trigger a negative bias. Our results were consistent with this hypothesis. The type of contour a visual object possesses—whether the contour is sharp angled or curved—has a critical influence on people's attitude toward that object.
Long-term results of laparoscopic Heller myotomy with partial fundoplication for the treatment of achalasia.

Abstract Background Treatment options for achalasia include medications, endoscopic balloon dilation, injection of botulinum toxin, or surgery. Methods The clinical course of 75 consecutive patients who underwent minimally invasive Heller myotomy and partial fundoplication for achalasia between 1991 and 2001 was reviewed by means of a questionnaire. Results Mean follow-up was 5.3 (range .8 to 10.9) years. Sixty-four percent of questionnaires were returned. Thirty-seven patients (84%) felt much better and 6 (14%) slightly better; 1 (2%) rated the result as unchanged. Twenty-six patients (59%) experienced weight gain. Seven patients (16%) had persistent swallowing problems and 5 (11%) reported frequent reflux. Twenty-five percent underwent additional therapy, including dilation (n = 8, 18%), repeat surgery (n = 2, 5%), and botulinum toxin injection (n = 2, 5%). Eighteen patients (41%) were using a proton pump inhibitor or H2 blocker, three were on a calcium channel blocker (7%), and 1 was using nitroglycerine (2%). Conclusion Laparoscopic Heller myotomy can achieve short- and long-term results comparable to open surgery and should be considered the treatment of choice for patients suffering from achalasia. Despite the frequent need for further therapy, patient satisfaction is good.
Contextualization in Perspective

Instruction abstracted from specific and concrete examples is frequently criticized for ignoring the context-dependent and perspectival nature of learning (e.g., Bruner, 1962, 1966; Greeno, 1997). Yet, in the effort to create personally interesting learning contexts, cognitive consequences have often been ignored. To examine what kinds of personalized contexts foster or hinder learning and transfer, three manipulations of perspective and context were employed to teach participants Signal Detection Theory (SDT). In all cases, application of SDT principles was negatively impacted by manipulations that encouraged participants to consider the perspective of the signal detector (the decision maker in SDT situations): by giving participants active detection experience (Experiment 1), biasing them to adopt a first-person rather than third-person perspective (Experiment 2), or framing the task in terms of a well-known celebrity (Experiment 3). These contexts run the risk of introducing goals and information that ...
The kinetic temperature in the interior of the Xi Ophiuchi cloud from Copernicus observations of interstellar C2

Satellite observations of transitions of C2 at 2312 Angstroms in the spectrum of Xi Ophiuchi were carried out to evaluate the kinetic temperature of the interior cloud. A column density of 1.22 x 10 to the 12th per sq cm is derived from an absorption feature at the 4 sigma level of significance at the position of the R(0) line. This would imply a rotational temperature of not more than 22 K, with a more probable value of less than 16 K. Since total column density (3.2 x 10 to the 12th per sq cm) is found to be lower by a factor of approximately 4 than that which had been previously reported, substantial photo-dissociation of C2 is assumed.