cssi/SciSciGPT-SciSciNet huggingface dataset:
Cloning of Streptococcus pneumoniae DNA fragments in Escherichia coli requires vectors protected by strong transcriptional terminators.

Unstable recombinant plasmids are frequently encountered when cloning pneumococcal DNA into ordinary Escherichia coli plasmid vectors (e.g., pBR325, pMB9, pHC79). Stassi and Lacks [Gene 18 (1982) 319-328] have shown that the pneumococcal mal region, which exhibits strong promoter activity, interferes with maintenance of a recombinant plasmid in E. coli. In this paper, we report that random pneumococcal DNA fragments cloned in E. coli exhibited a higher frequency of strong promoter activity than did similarly cloned E. coli fragments. Furthermore, shotgun cloning yields for pneumococcal DNA were found to be higher with cloning vectors containing efficient transcriptional terminators surrounding the insertion site than with vectors lacking such protection. Therefore, vectors which carry an efficient transcriptional terminator are likely to be valuable for cloning pneumococcal DNA and stabilizing the recombinants. A new vector, pJDC9, was constructed, containing a lacZ alpha' multiple cloning site surrounded by transcriptional terminators, and an erythromycin-resistant marker expressed both in E. coli and Streptococcus. This plasmid was shown to be unusually effective for cloning of streptococcal genes in E. coli, and is designed to permit excisional cloning of streptococcal DNA in E. coli.
Nonpersuasive communication about matters of greatest urgency : Climate change

Scientists can become the trusted source for credible, relevant, comprehensible information by avoiding advocacy and letting the science speak for itself.
The association of ENPP1 K121Q with diabetes incidence is abolished by lifestyle modification in the diabetes prevention program

Context: Insulin resistance is an important feature of type 2 diabetes. Ectoenzyme nucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) inhibits insulin signaling, and a recent meta-analysis reported a nominal association between the Q allele in the K121Q (rs1044498) single nucleotide polymorphism in its gene ENPP1 and type 2 diabetes. Objective and Intervention: We examined the impact of this polymorphism on diabetes incidence as well as insulin secretion and sensitivity at baseline and after treatment with a lifestyle intervention or metformin vs. placebo in the Diabetes Prevention Program (DPP). Design, Setting, Participants, and Outcome: We genotyped ENPP1 K121Q in 3548 DPP participants and performed Cox regression analyses using genotype, intervention, and interactions as predictors of diabetes incidence. Results: Fasting glucose and glycated hemoglobin were higher in QQ homozygotes at baseline (P < 0.001 for both). There was a significant interaction between genotype at rs1044498 and intervention under the dominant model (P = 0.03). In analyses stratified by treatment arm, a positive association with diabetes incidence was found in Q allele carriers compared to KK homozygotes [hazard ratio (HR), 1.38; 95% confidence interval (CI), 1.08–1.76; P = 0.009] in the placebo arm (n = 996). Lifestyle modification eliminated this increased risk. These findings persisted after adjustment for body mass index and race/ethnicity. Association of ENPP1 K121Q genotype with diabetes incidence under the additive and recessive genetic models showed consistent trends [HR, 1.10 (95% CI, 0.99–1.23), P = 0.08; and HR, 1.16 (95% CI, 0.92–1.45), P = 0.20, respectively] but did not reach statistical significance. Conclusions: ENPP1 K121Q is associated with increased diabetes incidence; the DPP lifestyle intervention eliminates this increased risk.
Secophalloidin as a novel activator of skinned cardiac muscle.

Abstract Secophalloidin (SPH) is known to activate skinned cardiac muscle in the absence of Ca 2+ . We hypothesized that SPH-induced changes in cross-bridge properties underlie muscle activation. We found that force responsiveness to orthovanadate was drastically reduced in SPH activated muscles compared to Ca 2+ -activated contraction. Moreover, SPH caused ∼30% increase in Ca 2+ -independent force in muscles where Ca 2+ sensitivity was totally destroyed by troponin I extraction with 10 mM vanadate. Thus, SPH and Ca 2+ activation differ in both properties of the cross-bridge cycle and protein requirements for thin filament regulation. In addition, we tested the relationship between the activating effects SPH and EMD 57033, a Ca 2+ sensitizer that increases resting force in cardiac muscle. After maximal activation by either SPH or EMD 57033, the other compound was found to further increase force, indicating that SPH activates muscle via a novel mechanism.
Electrocardiographic observations on the tuatara, Sphenodon punctatus.

Abstract 1. 1. Electrocardiograms were obtained from two unrestrained tuataras at body temperatures from 7 to 26°C. 2. 2. Heart rates were lower than previously reported for resting Sphenodon , but were similar to resting rates of large lizards. 3. 3. EGG intervals (P–R, R–T, P i –T f ) did not differ greatly from those of Iguana iguana , except that duration of ventricular depolarization was more sensitive to temperature in Sphenodon . 4. 4. In general, the electrocardiology of Sphenodon closely resembles that of squamate reptiles. 5. 5. An unusual feature was an occasional increase in the absolute duration of R–T when heart rate increased slightly in response to disturbance.
Crystallization and vitrification in aqueous systems

SUMMARY Some key ideas and experimental findings concerning the probability that crystallization of a liquid or its binary solutions will occur at moderate cooling rates are discussed. The use of cryoprotectants and of pressure to favourably influence these probabilities is rationalized, and some of the newer findings on small sample supercooling phenomena are reviewed.
Reevaluation of transcriptional regulation by TATA-binding protein oligomerization: predominance of monomers.

The TATA-binding protein (TBP) plays an important role in transcriptional initiation by all three nuclear RNA polymerases. TBP contains a conserved C-terminal domain (cTBP) that binds DNA. Crystallographic studies of cTBP (i.e., TBP without the N-terminal domain) from various species and molecular biology studies of cTBP and mixed cTBP/TBP species have led to the view that DNA binding by TBP is regulated by TBP dimerization. Using sedimentation equilibrium, we show that yeast cTBP forms dimers in solution at 5 degrees C with a dissociation constant of 7 +/- 1 microM. This observation of cTBP dimers in solution is in accord with the dimeric state observed in crystal structures of cTBP. In contrast, physiologically relevant, full-length yeast TBP is monomeric at 5 degrees C and forms dimers at 30 degrees C with a dissociation constant of 51 +/- 16 microM. This dissociation constant precludes formation of stable full-length TBP dimers at physiological concentrations. In addition, we tested for yeast TBP oligomerization in the presence of TBP-associated factors in the context of TFIID. No evidence for TBP oligomers was found using immunoprecipitation techniques from yeast whole-cell extracts. We conclude that yeast TBP is predominantly monomeric under physiological conditions, arguing against a role for TBP dimerization in the regulation of transcriptional initiation.
Klinefelter syndrome and other sex chromosomal aneuploidies

The term Klinefelter syndrome (KS) describes a group of chromosomal disorder in which there is at least one extra X chromosome to a normal male karyotype, 46,XY. XXY aneuploidy is the most common disorder of sex chromosomes in humans, with prevalence of one in 500 males. Other sex chromosomal aneuploidies have also been described, although they are much less frequent, with 48,XXYY and 48,XXXY being present in 1 per 17,000 to 1 per 50,000 male births. The incidence of 49,XXXXY is 1 per 85,000 to 100,000 male births. In addition, 46,XX males also exist and it is caused by translocation of Y material including sex determining region (SRY) to the X chromosome during paternal meiosis. Formal cytogenetic analysis is necessary to make a definite diagnosis, and more obvious differences in physical features tend to be associated with increasing numbers of sex chromosomes. If the diagnosis is not made prenatally, 47,XXY males may present with a variety of subtle clinical signs that are age-related. In infancy, males with 47,XXY may have chromosomal evaluations done for hypospadias, small phallus or cryptorchidism, developmental delay. The school-aged child may present with language delay, learning disabilities, or behavioral problems. The older child or adolescent may be discovered during an endocrine evaluation for delayed or incomplete pubertal development with eunuchoid body habitus, gynecomastia, and small testes. Adults are often evaluated for infertility or breast malignancy. Androgen replacement therapy should begin at puberty, around age 12 years, in increasing dosage sufficient to maintain age appropriate serum concentrations of testosterone, estradiol, follicle stimulating hormone (FSH), and luteinizing hormone (LH). The effects on physical and cognitive development increase with the number of extra Xs, and each extra X is associated with an intelligence quotient (IQ) decrease of approximately 15–16 points, with language most affected, particularly expressive language skills.
Optical antennas for vector near-field imaging

A new method for nano-engineering the optical antenna properties of scanning probe tips by combining focused ion beam milling with nano-CVD is presented. We demonstrate the capabilities by probing specific vector-field components of plasmonic nanostructures.
FAMILIAL MEDITERRANEAN FEVER PRESENTING AS RECURRENT ACUTE PELVIC INFLAMMATORY DISEASE

Abstract Background Recurrent acute episodes of pelvic inflammatory disease (PID) often present a diagnostic dilemma. The differential diagnosis should include reinfection, appendicitis, endometriosis, irritable bowel syndrome, colitis, persistent ovarian cyst, and antibiotic-resistant bacterial strains. Case A young Palestinian woman presented with recurrent episodes of pelvic pain with rebound tenderness, fever, and elevated white blood cell count, erythrocyte sedimentation rate, and C-reactive protein. The patient underwent extensive workup, multiple courses of intravenous and oral antibiotics, and diagnostic laparoscopies, with continued recurrent episodes. Treatment with colchicine for suspected familial Mediterranean fever resulted in resolution of symptoms. Conclusion In patients of Mediterranean ancestry who have symptoms of recurrent PID that are refractory to conventional treatment, familial Mediterranean fever should be included in the differential diagnosis.
IL-1α and IL-1β Are Endogenous Mediators Linking Cell Injury to the Adaptive Alloimmune Response

Preoperative or perioperative ischemic injury of allografts predisposes to graft arteriosclerosis, the major cause of late graft failure. We hypothesize that injured tissues release mediators that increase the production of pathogenic cytokines by alloreactive T cells. We find that freeze-thaw lysates of human endothelial cells (EC) increase both IFN-gamma and IL-17 production by human CD4(+) T cells activated by HLA-DR(+) allogeneic EC. Immunoadsorption of high-mobility group box 1 protein (HMGB1) reduces this activity in the lysates by about one-third, and recombinant HMGB1 increases T cell cytokine production. HMGB1 acts by inducing IL-1beta secretion from contaminating monocytes via TLR4 and CD14. Upon removal of contaminating monocytes, the remaining stimulatory activity of EC lysates is largely attributable to IL-1alpha. Recombinant IL-1 directly augments IFN-gamma and IL-17 production by activated memory CD4(+) T cells, which express IL-1R1. Furthermore, IL-1 increases the frequency of alloreactive memory CD4(+) T cells that produce IL-17, but not those that produce IFN-gamma, in secondary cultures. Our results suggest that IL-1, released by injured EC or by HMGB1-stimulated monocytes, is a key link between injury and enhanced alloimmunity, offering a new therapeutic target for preventing late graft failure.
Dam Policy: The Need For Global Governance

Dams have long fascinated engineers, policymakers, and citizens-at-large. No doubt the engineering and architectural details of physical construction of dams are worth study and scrutiny, but it is the human dimension that complicates dam policies. Dams can result in tremendous negative impacts on human populations. Yet, dams provide a source of renewable energy, hydroelectric power. Analyzing these issues in a global perspective offers strategies for policy makers to consider. This paper will analyze the negative impact dams have on humans, illustrate the hydroelectric push for dams and how they impact food production. Finally, global policy strategies will be offered with consideration of environmental accounting and an indication of the future of water and food.
Perceived Self-Efficacy of Licensed Counselors to Provide Substance Abuse Counseling

This nationwide, quantitative study documented licensed counselors' perceived self-efficacy of adequately providing substance abuse services. Despite their lack of substance abuse training, counselors were highly confident in their ability to provide quality substance abuse services. Counselor training implications are discussed.
On the Repeated Test-Retest Reliability of the End-User Computing Satisfaction Instrument: A Comment*

This comment extends the test-retest reliability of the end-user computing satisfaction (EUCS) instrument by Torkzadeh and Doll [10]. Whereas Torkzadeh and Doll [10] reportedstability for two hour and two week EUCS test-retest reliability, we investigate the test-retest reliability of the EUCS instrument at two points in time, separated by a two yearinterval. We assess the end user computing satisfaction of personal computer, as well as mainframe, administrative end users in a large public organization. The results of the repeated test-retest using differing application platforms add further support for the reliability of the EUCS measure and highlight some areas of concern for managers of information systems.
State and Local Antipoverty Expenditures

State and local antipoverty expenditures are functionally related to the needs Abstract of the poor, state fiscal capacity and willingness to meet these needs, economies of scale, and external financial assistance. This study examines that multi-variate relationship for 1957 through 1972. The evidence indicates a sharp decline in state and local antipoverty expenditures per poor person. However, federal effort has grown enormously and has more than compensated for the decrease in lower level expenditures. There is wide variation across the country in popular support for aiding the poor. Affordability of antipoverty programs is the key to explaining expenditures. Needs do not play the major role in stimulating spending.
On the behavior of the surface tension for spin systems in a correlated porous medium

We investigate the behavior of various spin-systems that are subject to the highly correlated and extremely diluted quenched disorder as provided by the fractal aerogel model. For these systems, it is (easily) established that, at all temperatures, the free energy is identical to that of the corresponding uniform system. The surface tension, however, behaves quite differently. Foremost, at any fixed temperature corresponding to the low temperature phase in the uniform system, there is a non-trivial curve in the aerogel phase plane dividing high-temperature behavior (zero surface tension) from low-temperature behavior (positive surface tension). The fractal aerogel has two distinctive phases in its own right: gel and sol. In the gel phase, the spin system has zero surface tension at all temperatures. In one region of the sol phase, the surface tension is shown to be equal to its value in the uniform system. Since part of this region borders on the gel phase, a certain portion of the sol/gel phase boundary is also the dividing line between high- and low-temperature behavior. Evidently, in this case, the surface tension is discontinuous at the phase boundary. on the other hand, there are well-defined length scales that diverge as the phase boundary is approached. This demonstrates an absence of scaling in these systems.
Lunar science: The Apollo Legacy

The progress made in answering a list of fundamental lunar problems is considered, taking into account the nature of the differences in highlands and mare materials, the chemical composition of the moon, the density and internal structure of the moon, and the state of evolution of the moon. Attention is also given to a number of unanticipated results provided by lunar science. Findings concerning an ancient paleomagnetic field are discussed along with the characteristics of exotic components in the regolith, fundamental material differences observed in lunar surface layers, microcraters, and questions regarding an enhanced iron emission in solar flares.
Triidothyronine and epinephrine rapidly modify myocardial substrate selection: a 13C isotopomer analysis

Triiodothyronine (T3) exerts direct action on myocardial oxygen consumption (MV˙o 2), although its immediate effects on substrate metabolism have not been elucidated. The hypothesis, that T3 regula...
Variable quantitation of Haemophilus influenzae type b anticapsular antibody by radioantigen binding assay

The measurement of antibody to Haemophilus influenzae type b capsular polysaccharide is important in the study of natural immunity and in the immunogenicity evaluation of H. influenzae type b vaccines. Several radioantigen binding assays (RABA) have been developed to measure H. influenzae type b anticapsular antibody, but recent immunogenicity data obtained with structurally similar vaccines suggest major differences in antibody quantitation in different laboratories. To evaluate interlaboratory variability in the measurement of anticapsular antibody levels, we blindly evaluated a sample of 40 pre- and postimmunization sera by eight RABAs in different laboratories. Evaluation of RABA methods revealed differences in polysaccharide antigens, radiolabeling methods, concentration and volume of antigen and antibody, and other assay methods. The reported results of assays varied significantly between laboratories (up to sixfold differences in geometric means), in part because of differences in assay sensitivity and different proportions of samples having undetectable levels of antibody (0 to 65% of specimens with undetectable levels). After standardizing the limit of sensitivity for all assays (0.125 microgram/ml), the results of all combinations of paired analyses of RABA assays correlated well (r = 0.88 to 0.99) but the geometric mean levels still varied as much as twofold. For individual sera, the differences between paired assays often were substantial (P less than or equal to 0.0001, paired t test), with some results varying as much as 64-fold. Differences were greatest for lower levels of antibody. There was good comparability and interlaboratory reproducibility of some assays but not of others. Intrinsic or extrinsic labeling of the antigen was not a major determinant of comparability. In most instances, the current variation in the quantitation of antibody levels by these assays precludes interassay comparisons. A standardized measurement of antibody needs to be developed to adequately compare results between different H. influenzae type b immunogenicity studies.
Students' Response to Ethical Dilemmas

The teaching of ethics in hospitality curricula is an important part of students’ overall education. Past research has indicated that college students are generally as ethically aware as their professional counterparts. The authors replicated a study by Damitio and Schmidgall (1993) in which over 700 college students were asked if they agreed with decisions in 15 hypothetical scenarios. Students were also asked if the decisions were in fact ethical. Results are reported. The authors use these results as further evidence that ethical awareness in hospitality students needs to be raised. There does not appear to be any change in students’ ethical awareness since the original study in the early 1990s. A discussion of the direction ethics education might take follows. Implications for hospitality curricula and hospitality students are analyzed. A course of action is
Contrasting the Material Chemistry of Cu2ZnSnSe4 and Cu2ZnSnS(4–x)Sex

Earth-abundant sustainable inorganic thin-film solar cells, independent of precious elements, pivot on a marginal material phase space targeting specific compounds. Advanced materials characterization efforts are necessary to expose the roles of microstructure, chemistry, and interfaces. Herein, the earth-abundant solar cell device, Cu2ZnSnS(4-x)Se x , is reported, which shows a high abundance of secondary phases compared to similarly grown Cu2ZnSnSe4.
A New Computational Method to Track a Liquid/Vapor Interface With Mass Transfer, Demonstrated on the Concentration Driven Evaporation From a Capillary Tube, and the Marangoni Effect

A new computational liquid/vapor interface tracking technique is developed to model an interface between a liquid and a vapor including mass transfer. This technique does not require the use of an additional transport equation, as does the VOF method, while still being implemented without a complicated solution procedure. This new interface tracking technique is used to capture the liquid/vapor interface in a capillary tube of 100 μm scale. The diffusion driven evaporation process is studied, along with the Marangoni convection that is caused by the temperature gradient along the interface. The results are qualitatively and quantitatively compared to existing experimental data.Copyright © 2005 by ASME
Abstract 4451: Targeted therapy of lung cancer using ScFvEGFR-Heparin-Cisplatin nanoparticles

The clinical use of cis-diamminedichloridoplatinum(II) (cisplatin, CDDP) is restricted by severe side effects, including nephrotoxicity, peripheral neuropathy, and ototoxicity. Although the nanoparticles has been used for CDDP delivery in animal models and demonstrated to reduce the side effects and increase the antitumor effects of CDDP, most of studies used none-targeted nanoparticles for CDDP delivery via enhanced permeability and retention (EPR) effect. However, utilizing EPR effect for delivery of CDDP achieves only passive tumor targeting. We have developed novel nanoparticles by conjugating single-chain antibodies to epidermal growth factor receptor (ScFvEGFR) to modified heparin, and loaded CDDP into the targeted nanoparticles (EHDDP). Our results showed that the intracellular Pt was significantly higher in EHDDP treated cells (27.91± 2.45 ng Pt/105 cells) than that of free DDP (2.49± 0.39 ng Pt/105 cells) (P=0.004) and non-targeted nanopartcles HDDP(2.14± 0.20 ng Pt/105 cells) (P=0.003) at 4 hrs, while the internalization of Pt in free CDDP treated cells didn9t show any significant difference as compared with that in HDDP (P=0.25). The Pt (166.05±21.17pg Pt/ug DNA) which was intercalated into DNA in EHDDP treated cells increased significantly as compared with that in CDDP(42.34±10.57pg Pt/ug DNA) (P=0.015) and HDDP(20.27±2.88 pg Pt/ug DNA) (P=0.008) treated cells. We found that the CDDP-loaded nanoparticles could significantly change the biodistribution of Pt in mice comparing with the free CDDP. Accumulation of Pt in subcutaneous tumor lesions in EHDDP group (13.45±2.15ng/mg dry tissue) was significant higher than that in HDDP (4.87±0.67ng/mg dry tissue) (P=0.026) and CDDP groups (1.48±0.52ng/mg dry tissue) (P=0.02) 24 hours after the intravenously injection (Pt, 2.5mg/kg) into nude mice bearing H292 tumors. The systemic delivery of EHDDP (2.5 mg/kg; 5 times treatment at 3 days intervals) to mice showed significant enhanced antitumor activity with no body weight loss or damages to kidney, liver, and spleen, while the mice that received free CDDP had significant weight loss and massive organ damages. Our results suggest that EHDDP nanoparticles have the potential to be used for targeted therapy of cancer which expresses EGFR with reduced side effects. (Supported by P50CA128613). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4451. doi:10.1158/1538-7445.AM2011-4451
Nutritional Status: An Overview of Methods for Assessment

This chapter focuses on the whole area of nutritional assessment and explores the wide spectrum of testing available that can aid in determining the health of an individual. This process typically includes in-depth evaluation of both subjective data and objective evaluations of an individual’s food and nutrient intake, components of lifestyle, and medical history. A nutritional assessment provides an overview of nutritional status; it focuses on nutrient intake analysis of the diet, which is then compared with blood tests and physical examination.
Instructor’s Use of Social Presence, Teaching Presence, and Attitudinal Dissonance: A Case Study of an Attitudinal Change MOOC

This study examines a MOOC instructor’s use of social presence, teaching presence, and dissonance for attitudinal change in a MOOC on Human Trafficking, designed to promote attitudinal change. Researchers explored the MOOC instructor’s use of social presence and teaching presence, using the Community of Inquiry (CoI) framework as a lens, and examined the facilitation of attitudinal dissonance within the discussion forum, announcements and blog postings in the course. The instructor entered the MOOC with the idea of serving as a co-participant and a facilitation choice was made to address the issue of multiple perspectives and experiences. The instructional design focused on establishing a collaborative community of learners and this was demonstrated through a high number of social presence indicators but with significant use of all three areas in evidence. Findings present a detailed examination of instructor strategies in a MOOC designed to focus on the establishment of a collaborative learning community and can inform future instructional design and instruction of MOOCs in general and MOOCs for attitudinal change specifically.
Ebonics and Advertising to the Black Consumer: A Need for Research to Analyze Language and Communication Styles in a Linguistic Framework

Advertisers face the problem of identifying the most appropriate copy strategies to reach Black consumers. There are varying approaches but few clear-cut guidelines that will help advertisers avoid mistakes. Marketers cannot afford to risk using advertising language that may offend this substantial market segment. This paper develops a conceptual framework for examining these issues by drawing on the disciplines of linguistics and speech communication, with particular emphasis on the concept of Ebonics, or Black English. Background on the history and characteristics of Ebonics and a research design to measure effects are discussed.
Tolerance of Microbial Biocatalysts to Feedstocks, Products, and Environmental Conditions

Bioreactor conditions and environmental stressors present during fermentation can negatively impact the productivity of industrial biocatalysts. Robustness of biocatalysts in fermentation conditions is thus important for the economical viability of bio-based production. Temperature, pH, and osmotic pressure inside the bioreactor are often not optimal for cell growth. Feedstocks (particularly sustainably sourced) and products (desired or side) often contain toxic components that further reduce biocatalyst performance. The physiological effects of many industrially relevant environmental stressors have been studied extensively. However, due to the complexity of cellular processes and the significant knowledge gap in genotype-phenotype relationships associated with these complex phenotypes, the rational engineering of robust biocatalysts is currently limited. Traditional strain developments rely on random approaches, and have been successful at generating more robust biocatalysts. Random approaches combined with new genomic technologies will start to fill the genotype-phenotype knowledge gap, making the rational engineering of robust biocatalysts for industrial applications more readily achievable. This chapter will focus on the common environmental stressors present in industrial fermentation; the stressors will be divided into three sections: feedstock toxicity, fermentation conditions, and product toxicity. Each section will describe the known mechanisms of toxicity associated with each stressor followed by examples of successful development of strains with enhanced tolerance, with a focus on the tools used, and discussions of the known molecular mechanisms associated with tolerance.
Primary Care Screening and Treatment for Latent Tuberculosis Infection in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force

Importance Five to ten percent of individuals with latent tuberculosis infection (LTBI) progress to active tuberculosis (TB) disease. Identifying and treating LTBI is a key component of the strategy for reducing the burden of TB disease. Objective To review the evidence about targeted screening and treatment for LTBI among adults in primary care settings to support the US Preventive Services Task Force in updating its 1996 recommendation. Data Sources MEDLINE, Cochrane Library, and trial registries, searched through August 3, 2015; references from pertinent articles; and experts. Literature surveillance was conducted through May 31, 2016. Study Selection English-language studies of LTBI screening, LTBI treatment with recommended pharmacotherapy, or accuracy of the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). Studies of individuals for whom LTBI screening and treatment is part of public health surveillance or disease management were excluded. Data Extraction and Synthesis Two investigators independently reviewed abstracts and full-text articles. When at least 3 similar studies were available, random-effects meta-analysis was used to generate pooled estimates of outcomes. Main Outcomes and Measures Sensitivity, specificity, reliability, active TB disease, mortality, hepatotoxicity, and other harms. Results The review included 72 studies (n = 51 711). No studies evaluated benefits and harms of screening compared with no screening. Pooled estimates for sensitivity of the TST at both 5-mm and 10-mm induration thresholds were 0.79 (5-mm: 95% CI, 0.69-0.89 [8 studies, n = 803]; 10 mm: 95% CI, 0.71-0.87 [11 studies; n = 988]), and those for IGRAs ranged from 0.77 to 0.90 (57 studies; n = 4378). Pooled estimates for specificity of the TST at the 10-mm and 15-mm thresholds and for IGRAs ranged from 0.95 to 0.99 (34 studies; n = 23 853). A randomized clinical trial (RCT) of 24 weeks of isoniazid in individuals with pulmonary fibrotic lesions and LTBI (n = 27 830) found a reduction in absolute risk of active TB at 5 years from 1.4% to 0.5% (relative risk [RR], 0.35 [95% CI, 0.24-0.52]) and an increase in absolute risk for hepatoxicity from 0.1% to 0.5% (RR, 4.59 [95% CI, 2.03-10.39]) for 24 weeks of daily isoniazid compared with placebo. An RCT (n = 6886) found that 3 months of once-weekly rifapentine plus isoniazid was noninferior to 9 months of isoniazid alone for preventing active TB. The risk difference for hepatoxicity comparing isoniazid with rifampin ranged from 3% to 7%, with a pooled RR of 3.29 (95% CI, 1.72-6.28 [3 RCTs; n = 1327]). Conclusions and Relevance No studies evaluated the benefits and harms of screening compared with no screening. Both the TST and IGRAs are moderately sensitive and highly specific within countries with low TB burden. Treatment reduced the risk of active TB among the populations included in this review. Isoniazid is associated with higher rates of hepatotoxicity than placebo or rifampin.
Exploring the Relationship Between Varieties of Variety and Weight Loss: When More Variety Can Help People Lose Weight

AbstractPrior research has indicated that greater dietary variety in a single eating episode increases caloric intake, contributing to weight gain and obesity. This study presents a novel conceptual framework for investigating dietary variety across the entire diet according to time frame (cumulative vs. daily), aggregation level (overall vs. episode-specific), and categorization level (individual foods vs. food groups). This framework is used to assess how naturally occurring dietary variety relates to weight loss among overweight/obese women enrolled in a 16-week trial to achieve weight loss. Acknowledging this is a first exploratory attempt to test such relationships using correlational analyses, the authors uncover several key findings. First, whereas cumulative overall variety was not associated with weight loss, daily overall variety was positively associated with weight loss. Second, this relationship was strongest for variety during breakfast and afternoon snacks and was particularly driven by con...
Molecular Dynamics Study of Cubic Boron Nitride Nanoparticles: Decomposition with Phase Segregation during Melting

The relative stability and melting of cubic boron nitride (c-BN) nanoparticles of varying shapes and sizes are studied using classical molecular dynamics (MD) simulation. Focusing on the melting of octahedral c-BN nanoparticles, which consist solely of the most stable {111} facets, decomposition is observed to occur during melting, along with the formation of phase segregated boron clusters inside the c-BN nanoparticles, concurrent with vaporization of surface nitrogen atoms. To assess this MD prediction, a laser-heating experiment of c-BN powders is conducted, manifesting boron clusters for the post-treated powders. A general analysis of the geometrical and surface dependence of the nanoparticle ground-state energy using a Stillinger-Weber potential determines the relative stability of cube-shaped, octahedral, cuboctahedral, and truncated-octahedral c-BN nanoparticles. This stability is further examined using transient MD simulations of the melting behavior of the differently shaped nanoparticles, providing insights and revealing the key roles played by corner and edge initiated disorder as well as surface reconstruction from {100} to the more stable {111} facets in the melting process. Finally, the size dependence of the melting point of octahedral c-BN nanoparticles is investigated, showing the well-known qualitative trend of depression of melting temperature with decreasing size, albeit with different quantitative behavior from that predicted by existing analytical models.
Countercurrent enzymatic saccharification of pretreated corn stover part 2: Lime + shock pretreated corn stover and commercial approach

Abstract Corn stover was pretreated with submerged lime plus shock, a mechanical treatment that subjects biomass to a detonation wave. In a series of bottles, pretreated corn stover was countercurrently saccharified with enzyme loadings of CTec3 (1 mg protein/g dry biomass), CTec3 (1 mg protein/g dry biomass) + HTec3 (1 mg protein/g dry biomass), and CTec3 (2 mg protein/g dry biomass) + HTec3 (2 mg protein/g dry biomass). To reach a given glucan conversion at low enzyme loadings, countercurrent saccharification reduced enzyme loadings by 1.9 times compared with batch saccharification but was not helpful at high enzyme loadings. To preserve the sugars during saccharification, volatile anti-microbials (chloroform and essential oils from thyme and oregano) prevent the growth of contaminating microorganisms. A simple packed column is proposed to perform commercial-scale countercurrent saccharification.
Impact on CDC Guideline Compliance After Incorporating Pharmacy in a Pneumococcal Vaccination Screening Process.

ABSTRACT Background: Centers for Disease Control and Prevention (CDC) guidelines for pneumococcal vaccinations were updated in 2014. Given the complexity of the guidelines and the fact that hospitals are no longer required to keep records for pneumococcal vaccinations, many hospitals are determining whether to continue this service. Objective: The primary objective of this study was to determine the impact on compliance with the revised pneumococcal vaccination guidelines from the CDC after involving pharmacy in the screening and selection processes. Secondary objectives were to determine the impact of the new process on inappropriate vaccination duplications, the time spent by pharmacy on assessments, and financial outcomes. Methods: This institutional review board (IRB)–approved, retrospective, cohort study examined all patients who received a pneumococcal vaccination from January to February 2016 after implementing a new process whereby pharmacy performed pneumococcal vaccination screening and selectio...
An EPIC electronic decision support tool to identify percentage of patients with stage IV thoracic or gastrointestinal malignancy who would benefit from concurrent palliative care but do not currently receive it.

133Background: In 2016 ASCO updated its guideline for early integration of palliative care (PC) into standard oncologic care for all “inpatients and outpatients with advanced cancer.” PC has been shown to improve quality of life, align care at the end of life with patient preferences, and reduce health-care utilization. In preparation for the expansion of our palliative care service into ambulatory disease-based practices at Smilow Cancer Hospital at Yale-New Haven, we sought to create a decision support tool (DST) in the EPIC Electronic Health Record (EHR) that would identify patients for PC referral. Methods: This DST identifies patients with a GI or thoracic malignancy who have had an ICD-10 diagnosis of metastatic or stage IV disease, have not had a palliative care visit in the last 6 months, and are not enrolled in hospice. If the patient meets criteria, the DST will remind providers that “this patient meets ASCO and IOM criteria for concurrent palliative care with oncologic care ” and offers a one-c...
Quasi-Dome: A Self-Calibrated High-NA LED Illuminator for Fourier Ptychography

We demonstrate an inexpensive programmable color LED array illuminator with 0.98 numerical aperture (NA), coupled with an auto-calibration procedure, to enable a simple and efficient setup for high-angle Fourier Ptychography in a commercial microscope.
A comparison of five methods for pretest item selection in online calibration

Many long-term testing programs rely on large item banks that need to be replenished regularly with new items, and these new items need to be pretested before being used operationally. Online calibration is a pretesting strategy in computerised adaptive testing, which embeds pretest items in operational tests and adaptively matches the pretest items with examinees. This paper compares five existing methods for pretest item selection in online calibration. A simulation study was conducted under the one-, two-, and three-parameter logistic models. The effects of two estimation methods, three seeding locations, and five calibration sample sizes were also investigated. Findings from the simulation study are mixed. However, overall, the simplest random selection method appears to be a potential best choice.
Refractory pouchitis improves after administration of the green tea polyphenol EGCG: a retrospective review.

Ulcerative colitis (UC) is a common, chronic, inflammatory process limited to the colon. UC affects up to 1 million individuals in the USA alone and requires resection in up to 30% of patients. Resection is often followed by creation of a pouch. Pouchitis is the most common complication of ileal pouch-anal anastomosis (IPAA) following total proctocolectomy, affecting up to 50% of patients. Symptoms include increased stool frequency, urgency, cramping, and bleeding. Management of pouchitis is complex in antibiotic refractory cases. Plant-based polyphenolic compounds have shown protective effects against UC. We conducted a retrospective review of pouchitis patients treated with EGCG 200–400 mg twice daily. Seven of nine (78%) patients experienced significant improvement based on reduced frequency of bowel movements and bleeding, while five of nine (56%) experienced complete relief. One patient experienced no improvement with EGCG, and one had progression of pouchitis symptoms while taking EGCG. No significant adverse events were noted by patients while taking EGCG. The green tea-derived molecule EGCG exhibits an efficacy signal in the IBD-related condition of pouchitis. Impressively, 78% of patients experienced noticeable improvement in pouchitis symptoms after initiation of EGCG, while 56% of treated patients entered complete remission. These positive responses to EGCG in patients with pouchitis suggests the need to confirm these findings in a formal, controlled trial. Based on recent findings documenting its effects on epithelial permeability and mucosal inflammation, combined with its favorable safety profile, a possible preventative role could also be explored.
The "final common pathway" hypothesis and inherited cardiovascular disease. The role of cytoskeletal proteins in dilated cardiomyopathy.

The genetic basis of a number of inherited cardiovascular diseases has been elucidated over the last few years, including the long QT syndromes, hypertrophic cardiomyopathy and dilated cardiomyopathy. While genetic heterogeneity has been demonstrated in most of these diseases, a pattern has emerged, specifically that genes encoding proteins with similar functions or involved in the same pathway are responsible for a particular disease or syndrome. Based on this observation we proposed the “final common pathway” hypothesis. In the case of the arrhythmogenic disorders, the long QT syndromes and Brugada syndrome, mutations have been described in a number of ion channel proteins, including cardiac potassium (KVLQT1, HERG and minK) and sodium (SCN5A) channels. Thus, using the “final common pathway” hypothesis we have proposed these diseases to be “ion channelopathies”. Hypertrophic cardiomyopathy appears to be a disease of the sarcomere (“sarcomyopathy”) since all the disease-causing mutations have been identified in the gene encoding many of the sarcomeric proteins, including β-myosin heavy chain, α-tropomyosin, troponin I and troponin T, as well as in actin, close to the β-myosin heavy chain binding site. The genes responsible for familial dilated cardiomyopathy have been less well characterized. For X-linked dilated cardiomyopathy, mutations in the dystrophin and G4.5 genes have been reported. In addition, mutations in actin (close to the dystrophin binding domain) and desmin, a component of the intermediate filaments, have been reported. However, the genes at a further 6 loci associated with autosomal dominant dilated cardiomyopathy (associated with conduction disease in 2 cases) remain unidentified. Due to the mutations in dystrophin, actin and desmin, we have proposed that dilated cardiomyopathy is a “cytoskeletalopathy”, and we are currently investigating the involvement of these genes in patients.
The impact of earthquake cycle variability on neotectonic and paleoseismic slip rate estimates

Abstract. Because of the natural (aleatoric) variability in earthquake recurrence intervals and coseismic displacements on a fault, cumulative slip on a fault does not increase linearly or perfectly step-wise with time; instead, some amount of variability in shorter-term slip rates results. Though this variability could greatly affect the accuracy of neotectonic (i.e., late Quaternary) and paleoseismic slip rate estimates, these effects have not been quantified. In this study, idealized faults with four different, representative, earthquake recurrence distributions are created with equal mean recurrence intervals (1000 years) and coseismic slip distributions, and the variability in slip rate estimates over 500- to 100 000-year measurement windows is calculated for all faults through Monte Carlo simulations. Slip rates are calculated as net offset divided by elapsed time, as in a typical neotectonic study. The recurrence distributions used are quasi-periodic, unclustered and clustered lognormal distributions, and an unclustered exponential distribution. The results demonstrate that the most important parameter is the coefficient of variation ( CV = standard deviation ∕ mean) of the recurrence distributions rather than the shape of the distribution itself. Slip rate variability over short timescales (< 5000 years or 5 mean earthquake cycles) is quite high, varying by a factor of 3 or more from the mean, but decreases with time and is close to stable after ∼40 000 years (40 mean earthquake cycles). This variability is higher for recurrence distributions with a higher CV. The natural variability in the slip rate estimates compared to the true value is then used to estimate the epistemic uncertainty in a single slip rate measurement (as one would make in a geological study) in the absence of any measurement uncertainty. This epistemic uncertainty is very high (a factor of 2 or more) for measurement windows of a few mean earthquake cycles (as in a paleoseismic slip rate estimate), but decreases rapidly to a factor of 1–2 with > 5 mean earthquake cycles (as in a neotectonic slip rate study). These uncertainties are independent of, and should be propagated with, uncertainties in fault displacement and geochronologic measurements used to estimate slip rates. They may then aid in the comparison of slip rates from different methods or the evaluation of potential slip rate changes over time.
Iron and Manganese

Iron (Fe) and manganese (Mn) are present in relatively high concentrations in freshwater ecosystems and in many respects can be viewed as ‘master metals’ owing to their ability to strongly influence the cycles of other biologically important elements through both microbially mediated and abiotic chemical reactions. Iron and manganese play major roles in determining the forms and cycling of phosphorous (P), sulfur (S), and trace metals in lakes, rivers, streams, and bogs. In some systems they also serve as important alternative oxidants for the degradation of carbon. Fe and Mn are also essential micronutrients, although they rarely appear to limit primary production in freshwater ecosystems. Fe is present in higher concentrations than Mn in most aquatic systems but chemically, Fe and Mn exhibit similar behavior in natural systems. Both have relatively soluble reduced forms that are present in significant quantities in anoxic sediments and waters. When oxygen is present, both metals form insoluble oxyhydroxides. However, Fe oxidizes much more rapidly than Mn and reduces at a lower redox potential and interacts more strongly with the P and S cycles.
Association with c-Myc: an alternated mechanism for c-Myc function.

The c-myc proto-oncogene encodes a ubiquitously expressed nuclear phospho-protein that is involved in the control of cellular proliferation and differentiation (1, 2, 3). Alteration of the c-myc locus by chromosomal translocation, amplification or retroviral insertion is often associated with tumorigenesis in different species including humans (1, 3). In normal cells c-MYC plays a crucial role in determining whether cells divide or undergo programmed cell death (4).