cssi/SciSciGPT-SciSciNet huggingface dataset:
Activation of Dendritic Cells by Surrogate T Cell Interactions Leads to Enhanced Costimulation, Secretion of TH1-Associated Cytokines, and CTL Inductive Capacity

Dendritic cells (DC), as professional antigen presenting cells (APC), have the capacity to capture antigen and migrate to lymphoid organs, where antigen presentation to and priming of naive T cells takes place (reviewed in 1). It is currently believed that effective induction of antigen-specific T cell responses requires a dynamic dialogue of multiple, sequential interactions between the DC as APC and a given T cell clone in order to prime the cell for expansion and effector function. The first interaction (signal 1) is felt to involve the MHC I/II-peptide on APC with the T cell receptor (TCR) on the effector lymphocyte, with a second signal being the costimulatory interaction between CD80 (B7.1)/CD86(B7.2) on DC with CD28 on the T cell. Signals 1 and 2 combine to activate the T cell, upregulating the expression of CD4OL which can interact with DC-expressed CD40 (reviewed in 2). This DC-T cell interaction results in the generation of an antigen-specific T cell responses. The ability of DC to prime naive T cells has been attributed to several factors, most notably the high levels of expression of MHC and costimulatory molecules such as B7.1 and B7.2. It has also been shown that DC are capable of producing several cytokines, among them IL-12, a cytokine critical for the development of Thl responses (3,4). Recently, ligation of CD40 on both human (5) and murine (6) DC has been reported to result in the upregulation of costimulatory molecules and the induction of IL-12. These findings suggest that the interaction of T cells with DC result in signals to DC which are critical for induction of the cellular immune response. Whereas many of the signals required by T cells for activation and proliferation have been described, the signaling requirements for optimal DC activation remain poorly defined.
Real-Time Stochastic Lightcuts

We present real-time stochastic lightcuts, a real-time rendering method for scenes with many dynamic lights. Our method is the GPU extension of stochastic lightcuts [Yuksel 2019], a state-of-art hierarchical light sampling algorithm for offline rendering. To support arbitrary dynamic scenes, we introduce an extremely fast light tree builder. To maximize the performance of light sampling on the GPU, we introduce cut sharing, a way to reuse adaptive sampling information in light trees in neighboring pixels.
Therapeutic Alliance in Substance Dependence Treatment: HAq-II Comparisons between Social Workers and Nurses

As social workers and nurses comprise much of the substance dependence treatment team, it is critical to evaluate how well they perform in a context where they bring different professional orientat...
Strategies and Tools to Enhance Patient Safety: HROs, HEROs, and Safety Culture.

Introduction The Institute of Medicine has defined multiple domains to improve safety, efficiency, and effectiveness of health care. High-Reliability Organizations (HROs) address these issues and promote safety/reliability at the highest level. Methods HROs create a bottom-up, top-down culture that focuses upon continuous improvement by withholding blame on individuals yet requiring all members to be accountable for continuous improvement. Results Supporting staff to speak up, identify, and engage on the path to perfect care and zero harm are elements of a safety culture. In addition to safety, HROs can also focus on effectiveness and efficiency. This may be accomplished by creating consistent care practices that reduce irrational variation, decrease complexity, and lower risk. Discussion Developing a culture focused upon reliability, safety, and staff resilience is critical for HROs. HROs support and empower all staff to be vigilant and report concerns about any issue related to safety and support the development of a "Safety Culture." HROs focus upon safety will be enhanced by an expanded focus upon effectiveness and efficiency to improve value. A focus on standard clinical practices and clinician integration into the supply chain will help organizations produce better value and be an essential tool to reduce complexity and risk within health care systems.
Ionization Chambers for Monitoring in High-Intensity Charged Particle Beams

Radiation-hard ionization chambers were tested using an intense electron beam from the accelerator test facility (ATF) at the Brookhaven National Laboratory (BNL). The detectors were designed to be used as the basic element for monitoring muons in the Main Injector Neutrino beamline (NuMI) at the Fermi National Accelerator Laboratory (FNAL). Measurements of linearity of response, voltage dependence, and the onset of ionization saturation as a function of gap voltage were performed.
Transcriptomic Regulations Underlying Pair-bond Formation and Maintenance in the Socially Monogamous Male and Female Prairie Vole.

Abstract Background The ability to form enduring social bonds is characteristic of human nature, and impairments in social affiliation are central features of severe neuropsychiatric disorders including autism spectrum disorder and schizophrenia. Owing to its ability to form long-term pair-bonds, the socially monogamous prairie vole has emerged as an excellent model to study the neurobiology of social attachment. Despite the enduring nature of the bond, however, surprisingly few genes have been implicated in the pair-bonding process in either sex. Methods Male and female prairie voles (Microtus ochrogaster) were cohabitated with an opposite-sex partner for 24 hours or 3 weeks, and transcriptomic regulations in the nucleus accumbens were measured by RNA sequencing. Results We found sex-specific response patterns despite similar behavioral indicators of pair-bond establishment. Indeed, 24 hours of cohabitation with an opposite-sex partner induced widespread transcriptomic changes that remained sustained to some extent in females after 3 weeks but returned to baseline before a second set of regulations in males. This led to a highly sexually biased nucleus accumbens transcriptome at 3 weeks related to processes such as neurotransmission, protein turnover, and DNA transcription. In particular, we found sex-specific alterations of mitochondrial dynamics following cohabitation, with a shift toward fission in males. Conclusions In addition to identifying the genes, networks, and pathways involved in the pair-bonding process in the nucleus accumbens, our work illustrates the vast extent of sex differences in the molecular mechanisms underlying pair-bonding in prairie voles and paves the way to further our understanding of the complex social bonding process.
Using ordinal regression for advancing the understanding of distinct suicide outcomes.

OBJECTIVE As recent advances in suicide research have underscored the importance of studying distinct suicide outcomes (i.e., suicidal thinking vs. behavior), there is a need to consider the theoretical meaningfulness of our statistical approach(es). As an alternative to more popular statistical methods, we introduce ordinal regression, detailing specific forms that are well-aligned to examine outcomes specific to suicide research. METHOD Ordinal regression models allow for assessment of the influences of covariates on the experience of lower (i.e., suicidal ideation) to higher (i.e., suicidal planning) suicide risk outcomes. RESULTS As an empirical application, we fit a sequential ordinal regression model with 17 theoretically selected covariates and modeled category specific effects for each covariate. CONCLUSIONS Results detailed from depression and presence of nonsuicidal self-injury demonstrate the utility of ordinal regression in consideration of transitions across suicide outcomes. Ordinal regression models may be particularly informative in identifying risk factors unique to each suicide outcome, which has the potential to meaningfully inform theoretical models of suicide and suicide risk prediction.
Considerations on activity assay discrepancies in factor VIII and factor IX products.

New modified coagulation factor VIII (FVIII) and factor IX (FIX) products have been designed to improve the treatment of individuals with hemophilia A and B by increasing the interval between dosing. Although these FVIII and FIX molecules have been structurally modified to improve the circulation time, the changes have also influenced their behavior in functional assays in comparison with traditional plasma-derived or recombinant coagulation factors. The assignment of potencies for these products can be problematic because discordance in factor activity values between the commonly used one-stage clotting (OC) and chromogenic substrate (CS) assays is often observed. Discrepancies in potency assay values also exist when different assay kits and reagents are used in the same assay type. Ideally, all FVIII and FIX products should be calibrated against the World Health Organization (WHO) International Standards (IS) because the assignment of potencies in International Units (IU) helps maintain treatment tradition and meaningful references for manufacturers, patients, and clinicians. The discrepant measurements, attributed to the modified structural and functional properties of these products, are manifested in their lack of commutability with the WHO IS for FVIII or FIX. Herein, we discuss the considerations upon which an assay is chosen for potency assignment and post-administration monitoring of a new factor product, which include the validity of the assay calibrated with the IS, the meaning of the potency values in IU, standards of care for patients, clinical relevance between the assigned potency value and recovery value from clinical labs, and patient safety.
Methods-Motivational Interviewing Approach for Enhanced Retention and Attendance.

Introduction Suboptimal and differential participant engagement in randomized trials—including retention at primary outcome assessments and attendance at intervention sessions—undermines rigor, internal validity, and trial conclusions. Methods First, this study describes Methods-Motivational Interviewing approach and strategies for implementation. This approach engages potential participants before randomization through interactive, prerequisite orientation sessions that illustrate the scientific rationale behind trial methods in accessible language and use motivational interviewing to diffuse ambivalence about participation. Then, this study examines the potential improvements in retention (proportion of participants assessed at follow-up visits) and attendance (e.g., mean percentage of intervention sessions attended, percentage of participants who attended 0 sessions) in 3 randomized weight-management trials that quickly added prerequisite orientations to their protocols following early signs of suboptimal or differential participant engagement (Supporting Health by Integrating Nutrition and Exercise [2009–2013, n=194]; Get Social [2016–2020, n=217]; GestationaL Weight Gain and Optimal Wellness [2014–2018, n=389]). Using a pre–post analytical design, adjusted estimates from regression models controlling for condition and assessment timepoint (analyses from 2020) are reported. Results After adding prerequisite orientations, all 3 trials attained higher participant engagement. Retention at assessments was 11.4% and 17.3% higher (Get Social and Supporting Health by Integrating Nutrition and Exercise, respectively). Mean percentage of attendance at intervention sessions was 8.8% higher (GestationaL Weight Gain and Optimal Wellness), and 10.1% fewer participants attended 0 intervention sessions (Get Social). Descriptively, all the remaining retention and attendance outcomes were consistently higher but were nonsignificant. Across the trials, adding prerequisite orientations did not impact the proportion of eligible participants enrolled or the baseline demographics. Conclusions The Methods-Motivational Interviewing approach shows promise for increasing the rigor of randomized trials and is readily adaptable to in-person, webinar, and conference call formats. Trial Registration All 3 trials are registered at www.clinicaltrials.gov (Supporting Health by Integrating Nutrition and Exercise: NCT00960414; Get Social: NCT02646618; and GestationaL Weight Gain and Optimal Wellness: NCT02130232).
Examining SARS-CoV-2 Interventions in Residential Colleges Using an Empirical Network

Objectives Universities have turned to SARS-CoV-2 models to examine campus reopening strategies. While these studies have explored a variety of modeling techniques, none have used empirical data. Methods In this study, we use an empirical proximity network of college freshmen obtained using smartphone Bluetooth to simulate the spread of the virus. We investigate the role of immunization, testing, isolation, mask wearing, and social distancing in the presence of implementation challenges and imperfect compliance. Results We show that frequent testing could drastically reduce the spread of the virus if levels of immunity are low, but its effects are limited if immunity is more ubiquitous. Furthermore, moderate levels of mask wearing and social distancing could lead to additional reductions in cumulative incidence, but their benefit decreases rapidly as immunity and testing frequency increase. However, if immunity from vaccination is imperfect or declines over time, scenarios not studied here, frequent testing and other interventions may play more central roles. Conclusions Our findings suggest that although regular testing and isolation are powerful tools, they have limited benefit if immunity is high or other interventions are widely adopted. If universities can attain even moderate levels of vaccination, masking, and social distancing, they may be able to relax the frequency of testing to once every four weeks.
Integrating Satellite Thermal Imagery and Global Weather Datasets for Operational Actual Evapotranspiration Mapping and Drought Early Warning Applications

The development and online access to an operational global actual evapotranspiration (ETa) is described. The global ETa is generated using the Operational Simplified Surface Energy Balance (SSEBop) model with inputs from the Moderate Resolution Imaging Spectroradiometer (MODIS) land surface temperature and gridded weather datasets. Global and regional ETa, as well as anomaly graphics and data, are posted at https://earlywarning.usgs.gov/fews at dekadal, monthly, and annual aggregation periods at 1 km spatial resolution since 2003. As part of the convergence of evidence, the Famine Early Warning Systems Network (FEWS NET) consults these products along with precipitation- and vegetation-derived products for drought monitoring and early warning applications to avert food insecurity crises around the world.
Representation and American Governing Institutions

AbstractWe isolate two limitations of the existing literature on representation and then move toward some important remedies. The first limitation is that typical representation studies assess the extent to which policymakers’ issue positions correspond to those of the public, but do not investigate whether the issue priorities of policymakers correspond to those of the public. The second limitation is that existing studies do not consider the full policymaking process, from agenda setting to enactment. Using data provided by the Policy Agendas and Congressional Bills Projects, we investigate how well the public's policy priorities have been represented in national policymaking over a 47-year time period. We first assess public concern about 18 major issues using Most Important Problem data (1956–2002) and then correlate these concerns with changing issue attention across 10 policymaking channels that are ordered by differences in institutional friction. We find much closer correspondence where friction i...
Epidemiology of FMF Worldwide

The familial Mediterranean fever (FMF) is the primarily described and most prevalent autoinflammatory disease known in the world. FMF was so named by Heller, because of its high prevalence in the Mediterranean population [1]. Indeed, it was previously denominated as benign paroxysmal peritonitis by Siegal, a New York allergist of Jewish origin [2], whereas it has been described as Maladie periodique by French authors [3].
Optimal Depreciation Policy Under the Tax Reform Act of 1986

Abstract Mathematical expressions for allowable depreciation are developed for the Modified Accelerated Cost Recovery System (MACRS) as well as the allowed alternate method (AMACRS), two capital recovery methods permitted under the Tax Reform Act of 1986. The choice between MACRS or AMACRS is rigorously analyzed with respect to normal asset disposition, premature asset disposition, monotone decreasing tax rates and monotone increasing tax rates. Conditions under which either MACRS or AMACRS is optimal are specified, and the economic value of the optimal policy is determined. Numerical illustrations are provided throughout the paper to demonstrate the underlying methodology. Handled by the Department of Engineering Economics.
Old issues confront biotechnology and new products

Abstract Few decisions have had such a far-reaching effect on the development and production of biological products as that made in 1954 by the Armed Forces Epidemiological Board. It was at that point that a decision had to be made regarding the use of HeLa cells as the substrate for an experimental adenovirus vaccine. Because HeLa cells were rejected in favour of ‘normal cells’, a philosophy emerged which equated anything other than primary cell cultures from normal tissues of normal animals as dangerous and unacceptable. It was a philosophy which probably made sense at the time, and which had the general support of the biomedical community. However, once it became established as a standard of practice, any suggestion to depart from that position was met with significant obstacles as exemplified by the diploid cell line saga.
Is the Addiction Severity Index a Reliable and Valid Assessment Instrument Among Clients with Severe and Persistent Mental Illness and Substance Abuse Disorders

Objective: This study examined aspects of reliability, validity and utility of Addiction Severity Index (ASI) data as administered to clients with severe and persistent mental illness (SMI) and concurrent substance abuse disorders enrolled in a publicly-funded community mental health center. Methods: A total of 62 clients with SMI volunteered to participate in an interobserver and test-retest reliability study of the ASI. Spearman-Brown and Pearson correlation coefficients were calculated to examine the extent of agreement among client responses. Results: Overall 16% of the composite scores could not be calculated due to missing data and 31% of the clients misunderstood or confused items in at least one of the seven ASI domains. As a whole, the interobserver reliability of the ASI composite scores for those subjects where sufficient data were available was satisfactory. However, there was more variance in the stability of client responses, with four composite scores producing test-retest reliability coefficients below .65. Conclusion: Evidence from this study suggests that the ASI has a number of limitations in assessing the problems of clients with severe and persistent mental illness, and it is likely that other similar instruments based on the self-reports of persons with severe and persistent mental illness would also encounter these limitations.
Hot piston ring/cylinder liner materials: selection and evaluation

In current designs of the automotive (kinematic) Stirling engine, the piston rings are made of a reinforced polymer and are located below the pistons because they cannot withstand the high temperatures in the upper cylinder area. Theoretically, efficiency could be improved if hot piston rings were located near the top of the pistons. Described is a program to select piston ring and cylinder coating materials to test this theory. Candidate materials were screened, then subjected to a pin or disk friction and wear test machine. Tests were performed in hydrogen at specimen temperatures up to 760 C to simulate environmental conditions in the region of the hot piston ring reversal. Based on the results of these tests, a cobalt based alloy, Stellite 6B, was chosen for the piston rings and PS200, which consists of a metal-bonded chromium carbide matrix with dispersed solid lubricants, was chosen as the cylinder coating. Tests of a modified engine and a baseline engine showed that the hot ring reduced specific fuel consumption by up to 7 percent for some operating conditions and averaged about 3 percent for all conditions evaluated. Related applications of high-temperature coatings for shaft seals and as back-up lubricants are also described.
Abstract 1532: A Microbiomic analysis in African American with colonic lesions reveals bacterial markers with potential diagnostic value

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Background: Increasing evidence suggests a role of the gut microbiota in colorectal carcinogenesis. However, no specific bacteria have been unequivocally linked to either initiation or progression of colorectal cancer (CRC). Aim: To analyze the taxonomic composition and functional potential of the gut microbiome in African Americans with colorectal lesions with the goal of detecting markers of diagnostic value. Materials & Methods: DNA extracts from 10 stool samples of colon adenoma patients, 10 healthy subjects’ stool samples and from 10 CRC tumors and their matched normal tissues were analyzed for their microbiota composition and genomic content using Illumina MiSeq. Metagenomic Linkage Groups (MLGs) were established and those with high discriminative power between healthy and neoplastic specimens were analyzed for their genetic content. Metagenomic reads from stool samples were mapped against bacterial genes from tissues and vice-versa to identify common markers with discriminative power. Results: The microbiota in both cancer vs. normal tissues and adenoma vs. normal stool samples were different at the 16S rRNA gene level. The metagenomic analysis led to 5 statistically significant MLGs in each set of samples. There was little overlap between the stool-based and tissue-based significant MLGs. Mapping stools reads to annotated tissue genes and vice-versa revealed a panel of 9 bacterial markers with statistically significant discriminative power between normal and adenoma in the stool dataset and visually striking (though non-significant) discriminative power between normal and tumor samples in the tissue dataset. Conclusion: We defined MLGs with discriminative power among cancers vs. normal and adenomas vs. normals and identified 9 bacterial markers that can potentially be used as a panel for non-invasive colorectal cancer screening tests. These findings will need to be validated in a larger population of patients at different stages of the carcinogenic process and from different ethnic/racial backgrounds. Citation Format: Hassan Brim, Sudhir Varma, Adeinko Laiyemo, Zaki Sharif, Edward L. Lee, Hassan Ashktorab. A Microbiomic analysis in African American with colonic lesions reveals bacterial markers with potential diagnostic value. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1532. doi:10.1158/1538-7445.AM2015-1532
Properties of a Highly Crosslinked Elastomer

The properties of a highly crosslinked polyurethane elastomer, based on ricinoleic acid (castor oil) as the backbone, have been measured. The rubber, termed Galcit I, has been proposed as a standardized, highly birefringent, nearly elastic rubber for use in testing new apparatus on a material with known properties, and in checking or calibrating existing instruments. Various characterizations have been carried out and the results will be presented briefly. These include stress relaxation and dynamic shear modulus, uniaxial and uniform biaxial tests to failure, some additional biaxial tests in combined shear and tension, and swelling. in several liquids. The tensile modulus at 25°C is high, about 37 bar (535 psi). Mc ≈ 2300g/mole as determined from swelling and ultimate properties. This corresponds to 112 carbon atoms between crosslinks, which would be equivalent to Mc ≈ 1500 in a polybutadiene or 2000 in natural rubber. This is a high enough crosslink density to virtually eliminate the effects of chain entanglements on the time dependence of the modulus and to render the elastomer almost brittle. The stress/strain response is neo-Hookean, i.e. at 25°C and above the material appears to obey the classic, Gaussian-chain theory of rubberlike elasticity for strains up to rupture, though these are only of the order of 60%. At very small strains in biaxial tests, however, there appears to be a departure from the simple kinetic theory response.
The GENIE is out! (Who needs fitness to evolve?)

"Survival of the fittest" is often seen as the driving force behind adaptation and evolution. For sure, all evolutionary algorithms use fitness based selection. However, it is not necessary to know where you are, to know where you are going. Similarly, it is not necessary to know the fitness of a solution, to find a better solution. The GENIE algorithm uses random parent selection and a non-elitist generational replacement scheme. Experiments on a non-trivial instance of the Traveling Salesman Problem show that heuristic operators in GENIE can converge to the optimal solution without evaluating fitness.
Peripheral alpha-1 and alpha-2 adrenergic receptors in three models of hypertension in rats: an in vitro autoradiography study

In vitro autoradiography was used to compare peripheral alpha-1 and alpha-2 adrenergic receptor binding in various tissues using [3H]prazosin and [3H]rauwolscine, respectively, in three models of experimental hypertension in rats. Models studied included two-kidney, one-clip hypertension, one-kidney, one-clip hypertension, desoxycorticosterone-salt hypertension, and three normotensive control groups: two-kidney control, one-kidney control and salt-loaded control. Blood pressures at death were significantly higher in all three hypertensive groups compared with normotensive controls, but there were no significant differences among the hypertensive or normotensive groups. Plasma norepinephrine levels were significantly elevated in all three hypertensive groups compared with respective controls, with no significant differences among hypertensive or control groups. In all three hypertensive groups, there were significant reductions in binding of aortic and mesenteric vascular alpha-1 receptors, renal tubular alpha-1 and alpha-2 receptors, and adrenal cortical alpha-2 receptors when compared with respective control groups. Reduced binding of cardiac ventricular alpha-1 and alpha-2 receptors was also found in all hypertensive groups, but not to statistically significant levels. No significant differences in intestinal alpha-1 and alpha-2 receptor binding were detected in either hypertensive or normotensive groups. The results suggest increased peripheral sympathetic activity in all three models of experimental hypertension, which is associated with down-regulation of alpha-1 and alpha-2 receptors in a number of peripheral tissues, especially those that control cardiovascular hemodynamics and fluid and salt balance. There is no evidence of an increase in peripheral alpha receptor binding as has often been found in some models of genetic or spontaneous hypertension.
Bulimia nervosa and evidence for striatal dopamine dysregulation: A conceptual review

Objective This article reviews concepts and evidence, based in particular on the work of Bartley G. Hoebel and colleagues, which suggest that a better understanding of the role of striatal dopamine (DA) in the initiation and/or maintenance of bulimia nervosa (BN) may result in a clearer characterization of mechanisms underlying BN.
The great migration and changes in the northern black family 1940 to 1990.

There is a strong tradition in the social sciences that links the migration of southern [U.S.] blacks to northern cities with changes in family structure in the North. This article examines that assumption by comparing the living arrangements of children and women for migrants and nonmigrants in northern central cities. Data from the newly available Integrated Public Use Microdata Series for the period 1940 through 1990 are used for this purpose. The findings show that northern urbanites with `southern origins actually exhibited more traditional family patterns--more children living with two parents more ever-married women living with their spouses and fewer never-married mothers. It is concluded that the evidence yields no support for the longstanding assumption that southern migrants contributed disproportionately to changes in the African American family in northern cities during this century. (EXCERPT)
The reduction of vitamin B12a by carbon monoxide

Abstract Vitamin B12a is reduced by CO to vitamin B12r according to the Eq. (2): B12a + CO + H2O → 2B12r + CO2 + 2H+. The reaction represents the first example of a product-autocatalyzed reduction of a corrin. The reduction of the Co (III) ion in vitamin B12a by CO is initiated by the spontaneous generation of Co(II) corrin derivatives in aqueous solutions by a self-reduction process. The reduced species act as the catalysts of the CO reduction of vitamin B12a. Derivatives of vitamin B12a in which self-reduction is impaired through structural modifications at the periphery of the corrin ring, e.g., vitamin B12a-lactam or autoxidized vitamin B12a, are not reduced by CO even in the presence of catalytic amounts of vitamin B12r. This suggests that electron-transfer reactions between reduced and oxidized corrins take place with corrin ligand participation. Acyloins, certain ketosugars, and hydroquinone display a similar selectivity for vitamin B12a as CO and apparently reduce vitamin B12a by a related autocatalytic mechanism.
Toxic RNA as a driver of disease in a common form of ALS and dementia

A recent and very stimulating finding in the field of neurodegenerative disease is the discovery that expansion of a hexanucleotide microsatellite DNA repeat (GGGGCC) in an intron of the C90RF72 gene is a common cause of two devastating neurodegenerative diseases for which there are no cures: frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) (1, 2). With this observation arose a fascinating question—how does expansion of this repeat induce a disease that can manifest as ALS, a motor neuron disease, as well as FTD, a leading cause of presenile dementia? Adding to the mystery is the almost complete absence of information on the C9ORF72 gene or the function of the protein it encodes. However, initial characterization of C9ORF72-FTD/ALS combined with work on some other neurodegenerative diseases suggests three pathogenic mechanisms (Fig. 1). First is the evidence indicating that mRNA levels of C9ORF72 transcripts are decreased in C9ORF72-FTD/ALS (1⇓–3). Thus, a loss of C9ORF72 function might contribute to disease. Second, accumulation of RNA transcripts containing the GGGGCC repeat within nuclear foci in frontal cortex and spinal cord material in C9ORF72-FTD/ALS patients suggests a toxic RNA gain of function (1). This pathogenic mechanism is patterned after other noncoding expansion disorders where RNA foci lead to the sequestration and altered activity of RNA-binding proteins (4). A third possible pathogenic mechanism is repeat-associated non-ATG translation (RAN translation). RAN translation, a mode of translation that occurs in the absence of an initiating ATG codon, was first reported to occur across expanded CAG repeats to produce potentially toxic homopolymeric peptides (5). It is among these competing possibilities that now enters the work of Xu et al. in PNAS (6), showing that expression of the expanded C9ORF72 repeat is sufficient to cause neurodegeneration and that its ability to sequester the …
The induction of GSH synthesis by nanomolar concentrations of NO in endothelial cells: a role for γ-glutamylcysteine synthetase and γ-glutamyl transpeptidase

Nitric oxide protects cells from oxidative stress through a number of direct scavenging reactions with free radicals but the effects of nitric oxide on the regulation of antioxidant enzymes are only now emerging. Using bovine aortic endothelial cells as a model, we show that nitric oxide, at physiological rates of production (1–3 nM/s), is capable of inducing the synthesis of glutathione through a mechanism involving γ-glutamylcysteine synthetase and γ-glutamyl transpeptidase. This novel nitric oxide signalling pathway is cGMP-independent and we hypothesize that it makes an important contribution to the anti-atherosclerotic and antioxidant properties of nitric oxide.
Evaluation of a rayleigh-number-based freckle criterion for Pb-Sn alloys and Ni-base superalloys

A criterion for predicting the formation of freckles for Pb-Sn and Ni-base superalloys is evaluated using available experimental data. The criterion is based on a maximum value of the Rayleigh number, which indicates that the magnitude of buoyancy forces is largest with respect to the retarding frictional forces. The definition of the Rayleigh number involves a characteristic length scale. The two options explored in this study are the distance from the liquid mush interface and the scale represented by the ratio of thermal diffusivity to the casting speed. Additionally, two alternative ways of computing the mushy-zone permeability are explored. Only two of the possible combinations of length scales and permeability relations provide a maximum value within the mush that can be chosen as a representative value for the given conditions. It is found that the Rayleigh number that uses the ratio of thermal diffusivity to the casting speed as a length scale provides the best separation between freckled and nonfreckled data. Critical values for the Rayleigh number are in the range of 38 to 46 for vertically solidified Pb-Sn and within the range of 30 to 33 for Ni-base superalloys. Although not exactly the same, the proximity of these intervals indicates that the critical Rayleigh number is not very sensitive to alloy-specific system parameters. The influence of sample pulling inclination angle on this critical value is assessed for Ni-base superalloys. A preliminary relationship between the critical Rayleigh number and the inclination angle is developed.
Novel microfluidic technologies for portable diagnostics systems

Novel microfluidic technologies being developed for portable diagnostic systems have potential for use in TB serodiagnosis or as platforms for cell and biomolecular assays. Using microfluidics, with its miniaturized channels and reservoirs for portable devices, offers many advantages, including: high surface-to-volume ratio; a low Reynolds number; increased speed of reaction; reduced cost of reagents; decreased cost of power consumption; precise mixing/dosage and heating. Its integration capability offers advantages as well, such as low manufacturing cost and multiplex capability, i.e. an increased number of parameters can be monitored per sample. Two microfluidic platforms may be helpful in protein microarray analysis. Microfluidic electrical sensing platforms are capable of detecting antigen/antibody binding in real time. The development of this platform will allow for faster detection of certain diseases with a patient’s sample compared to standard techniques such as ELISA. This platform requires microchannel-sealed microarrays with electrical detection capability. By measuring electrical charges, the scientists can determine protein-binding activity. Additionally, microfluidic colorimetric platforms are being developed using acoustic micromixing instead of fluorescence scanning. The process uses a scanner that detects an enzyme–based change of color that allows measurement of the protein-binding event. Our team is developing these platforms using components that have very small energy requirements, which means the device may not require batteries to operate. A ‘lab-in-a-droplet’ technique using digital microfluidics rather than using microarrays, which produce a static substrate, diffuses samples into as many as millions of droplets, presenting a three-dimensional picoliter reactor array. This process has several advantages including: rapid mixing, homogeneous reactions, precise control of volumes and concentrations, and an ability to mimic cellular reactions. Our team is using this technique in the development of lipoplexes and to encapsulate a cell in a single droplet. Lastly, a platform is under development for cell sorting using electrodes to track cells in order to determine what function the cell will take on. In addition to its value in the diagnosis of TB, microfluidics technology has several other applications, including: broader distribution of new assays to biologic labs, rapid analyses in the field for epidemiologic studies, and the ability to study hybridization of molecules on microarrays. For example, Lab-on-a-chip technologies are an excellent vehicle for integrating diagnostic and therapeutic functions. Digital (droplet) microfluidics enables high throughput cellular and molecular assays and cell sorting technologies enable more practical cellular analyses and therapies.
Single-pulse measurement of synchrotron radiation using an ultrafast x-ray streak camera.

We have demonstrated that a newly developed, ultrafast x-ray streak camera is sensitive to single x-ray pulses of highly monochromatic and unfocused synchrotron radiation at 8 keV. The high sensitivity was achieved by using CsI as the photocathode material. The individually measured x-ray pulses revealed that the bunch length was 120 ps long (full-width-at-half-maximum) and about 20-30 photon events were registered by streak camera in each pulse at the experimental conditions. The results demonstrated the feasibility of using this streak camera for single-shot experiments and using single x-ray pulses from the third-generation synchrotron sources with microfocused and/or polychromatic beams.
Mission Impossible? Advising and Institutional Culture

The structure of undergraduate advising at private institutions that offer degrees beyond the baccalaureate level is considered. Shared advising models are found to be suitable for highly selective, extensive doctoral institutions with sizeable full-time undergraduate populations and relatively basic programmatic structures. Similar but more pro-grammatically complex institutions with larger full-time undergraduate populations might benefit more from the decentralized satellite model. Smaller, less selective, more residential, liberal arts institutions may find the decentralized faculty-only model most appropriate.
Monoclonal Antibody Interaction with the Third Immunoglobulin-like Domain of N-CAM Is Sufficient to Cause Cell Migration ☆

Abstract Cellular adhesion molecules can influence a variety of biological mechanisms in the nervous system. These range from the processes of normal development and maintenance to neural plasticity and recovery following injury. The elucidation of the intricate contributions of these molecules will require the correlation of functional assays with specific molecules and the specific binding domains of such molecules with multiple signaling pathways. The data presented in this paper show that the monoclonal antibody anti-NCAM16, directed against the third immunoglobulin-like domain of the neural cell adhesion molecule N-CAM, is capable of stimulating the complex biological process of cell migration in primary embryonic motor neurons and human neuronal cell lines
Laboratory criteria for the completeness of vagotomy.

Various laboratory procedures for the evaluation of gastric function as an index of the completeness of vagotomy were reviewed. The Hollander test is presently the only method in general use; however, there are no well-established limiting values between a negative and a positive result. Repeated attempts to apply gastric motility recording as a method for demonstrating successful vagotomy failed in our hands for the reason that no consistent augmentation of motility was demonstrable following the production of hypoglycemia in the nonoperated subject. Hollander tests in 55 subjects after vagotomy and pyloroplasty yielded responses varying throughout the complete range from zero to the level of the nonoperated duodenal ulcer patient, whether analyzed on the basis of volume, acid concentration, or acid output. Thus, no secretory values could be recognized as the definite dividing line between an incomplete and a complete vagotomy. It is concluded that pending the development of a better test procedure, the Hollander test should be applied with due appreciation of its limitations and of the need for exercising judgment in interpreting the results of the test. Some suggestions are made as a working basis for such interpretation.
Relationship between hydrocarbon structure and induction of P450: effect on RNA levels

1. Exposure to simple aromatic hydrocarbons has been shown to induce P450-dependent activities and the expression of particular P450 isozymes in a manner related to the molecular structure of the inducing hydrocarbon. In an attempt to identify the structural relationship controlling P450 induction, the effect of hydrocarbon treatment on the RNA levels for specific P450 isozymes was examined.2. Rats were treated with daily injections of hydrocarbons (benzene, toluene, ethylbenzene, n-propylbenzene, m- and p-xylene) for 3 days, and the effects on specific RNA levels were examined by Northern blot hybridization.3. Although P4502B1 mRNA was not elevated after hydrocarbon treatment, a significant elevation in 2B2 mRNA was observed after exposure to the larger aromatic hydrocarbons, ethylbenzene and m-xylene. It is interesting to note that despite the substantial elevation of P4502B protein levels, only a small elevation of P4502B1 and 2B2 RNA was observed.4. P4502C11 mRNA was only suppressed by ethylbenzene ad...
An infrared spectroscopic study of some carbonaceous materials

Abstract IR photothermal beam deflection spectroscopy (PBDS) was used to record spectra of intermediate-temperature carbon materials having greatly different properties and origins. A good charcoal, anthracite coal, bituminous coal, and two Chromatographic carbons were studied in a cell under the controlled conditions required for surface studies. PBD spectra recorded after various heat treatments in vacuum, and after oxidation, were compared with those of cellulose-derived chars. IR data concerning the degree of carbonication, the formation and changes of the various species making up the surface layers, and inorganic materials within the carbons, were obtained easily and are discussed. IR-PBDS is a valuable technique for the study of intermediate carbons and their reactions.
Adaptive informatics for multifactorial and high-content biological data

Whereas genomic data are universally machine-readable, data from imaging, multiplex biochemistry, flow cytometry and other cell- and tissue-based assays usually reside in loosely organized files of poorly documented provenance. This arises because the relational databases used in genomic research are difficult to adapt to rapidly evolving experimental designs, data formats and analytic algorithms. Here we describe an adaptive approach to managing experimental data based on semantically typed data hypercubes (SDCubes) that combine hierarchical data format 5 (HDF5) and extensible markup language (XML) file types. We demonstrate the application of SDCube-based storage using ImageRail, a software package for high-throughput microscopy. Experimental design and its day-to-day evolution, not rigid standards, determine how ImageRail data are organized in SDCubes. We applied ImageRail to collect and analyze drug dose-response landscapes in human cell lines at single-cell resolution.
Modulated oscillatory hardening and dynamic recrystallization in cryomilled nanocrystalline Zn

Abstract Oscillatory variation of the hardness with milling time was observed in cryomilled nanocrystalline Zn. Transmission electron microscopy showed that large variations in the dislocation density and grain-size distribution occurred during cryomilling. The observations suggest that recrystallization takes place in larger grains when the dislocation density due to strain-hardening reaches a critical level. A reaction-rate model was developed which accounts for the dynamic recrystallization effect and the observed oscillations in hardness. Good agreement was obtained with the experimental data. The results provide unique insight into grain-size effects and the interplay of these with deformation mechanisms and recrystallization effects in nanocrystalline materials.
Diffusivity in chaos-induced turbulent diffusion

Abstract A pattern in relative diffusion characteristic of turbulent diffusion, e.g. Richardson's law of pair diffusion, can be generated by a deterministic chaotic map, the amplified climbing-sine map. This map has previously been shown to exhibit the long-term growth in variance that is also characteristic of turbulent diffusion.
The role of social supports in medical care

Increasingly, medicine has regarded social networks not just as a site for disease transmittance but also as a resource that affects morbidity, mortality, and the utilization of medical care. Support systems interact with all specialties in the medical network variously by competing, cooperating, or opposing.
Toxicity of methyl-tert-butyl ether to freshwater organisms

Increased input of the fuel oxygenate methyl-tert-butyl ether (MTBE) into aquatic systems has led to concerns about its effect(s) on aquatic life. As part of a study conducted by University of California scientists for the State of California, the Aquatic Toxicology Laboratory, UC Davis, reviewed existing literature on toxicity of MTBE to freshwater organisms, and new information was generated on chronic, developmental toxicity in fish, and potential toxicity of MTBE to California resident species. Depending on time of exposure and endpoint measured, MTBE is toxic to various aquatic organisms at concentrations of 57-> 1000 mg/l (invertebrates), and 388-2600 mg/l (vertebrates). Developmental effects in medaka (Oryzias latipes) were not observed at concentrations up to 480 mg/l, and all fish hatched and performed feeding and swimming in a normal manner. Bacterial assays proved most sensitive with toxicity to Salmonella typhimurium measured at 7.4 mg/l within 48 h. In microalgae, decreased growth was observed at 2400 and 4800 mg/l within 5 days. MTBE does not appear to bioaccumulate in fish and is rapidly excreted or metabolized. Collectively, the available data suggests that at environmental MTBE exposure levels found in surface waters (< 0.1 mg/l) this compound is likely not acutely toxic to aquatic life. However, more information is needed on chronic and sublethal effects before we can eliminate the possibility of risk to aquatic communities at currently detected concentrations.