cssi/SciSciGPT-SciSciNet huggingface dataset:
Silencing of end-joining repair for efficient site-specific gene insertion after TALEN/CRISPR mutagenesis in Aedes aegypti

Conventional control strategies for mosquito-borne pathogens such as malaria and dengue are now being complemented by the development of transgenic mosquito strains reprogrammed to generate beneficial phenotypes such as conditional sterility or pathogen resistance. The widespread success of site-specific nucleases such as transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 in model organisms also suggests that reprogrammable gene drive systems based on these nucleases may be capable of spreading such beneficial phenotypes in wild mosquito populations. Using the mosquito Aedes aegypti, we determined that mutations in the FokI domain used in TALENs to generate obligate heterodimeric complexes substantially and significantly reduce gene editing rates. We found that CRISPR/Cas9-based editing in the mosquito Ae. aegypti is also highly variable, with the majority of guide RNAs unable to generate detectable editing. By first evaluating candidate guide RNAs using a transient embryo assay, we were able to rapidly identify highly effective guide RNAs; focusing germ line-based experiments only on this cohort resulted in consistently high editing rates of 24–90%. Microinjection of double-stranded RNAs targeting ku70 or lig4, both essential components of the end-joining response, increased recombination-based repair in early embryos as determined by plasmid-based reporters. RNAi-based suppression of Ku70 concurrent with embryonic microinjection of site-specific nucleases yielded consistent gene insertion frequencies of 2–3%, similar to traditional transposon- or ΦC31-based integration methods but without the requirement for an initial docking step. These studies should greatly accelerate investigations into mosquito biology, streamline development of transgenic strains for field releases, and simplify the evaluation of novel Cas9-based gene drive systems.
Seafood omega-3 intake and risk of coronary heart disease death: an updated meta-analysis with implications for attributable burden

Abstract Background Uncertainty exists in understanding the relation between omega-3 polyunsaturated fatty acids and major cardiovascular outcomes. An updated meta-analysis on the relation between intake of seafood omega-3 fatty acids and the risk of coronary heart disease (CHD) death was undertaken as part of the Global Burden of Disease (GBD) 2010 Study. Methods We conducted an update of an earlier meta-analysis by Mozaffarian and Rimm. Medline and PubMed were searched for articles published between April, 2006, and August, 2012. Randomised clinical trials (RCTs) and observational studies evaluating the effect of omega-3 on CHD death were included. The relative risk per 100 mg/day eicosapentaenoic acid and docosahexaenoic acid (EPA+DHA) was estimated using restricted cubic splines; the estimates were weighted by the inverse variance. The relative risks were used with other data from the GBD 2010 Study to estimate the burden attributable to a diet low in seafood omega-3s. Findings Of the 1085 citations retrieved, 22 studies, including those from previous analyses, with 5 772 809 person-years and 5822 CHD deaths, were included. While the effect of seafood omega-3s was lower in RCTs than in observational studies, this difference was not statistically significant (p=0·057). The effect size based on all studies was 0·89 (95% CI 0·86–0·92) per 100 mg/day EPA+DHA. When the analysis was restricted to RCTs, the effect was 0·95 (95% CI 0·87–1·05) per 100 mg/day EPA+DHA. The global attributable burden of a diet low in seafood was 1·1% of global disability-adjusted life-years (DALYs; 95% CI 0·8–1·5), with 22% of ischaemic heart disease DALYs attributable to low seafood intake. The global burden was reduced by more than half when using the relative risk from RCTs (0·5%, 95% CI −0·5 to 1·4). Interpretation This research makes the connection between relative risks and their health impact at the population level. Our all-study results are comparable to those of Rizos and colleagues, who found a 0·91 (95% CI 0·85–0·98; p=0·01) per 100 mg EPA+DHA reduction in risk of CHD death. Mozaffarian and Rimm report larger results of 0·85 (95% CI 0·79–0·92) per 100 mg EPA+DHA. Our results differ when restricted to RCTs, thereby necessitating a degree of caution when interpreting burden estimates. The differences between previous studies and our all-study and RCT-restricted results illustrate the importance of further research to understand the value of seafood intake. Funding Bill & Melinda Gates Foundation.
Effect of subcutaneous recombinant human erythropoietin in cancer patients receiving radiotherapy: Preliminary results of a randomized, open-labeled, phase II trial

Abstract Purpose : To determine the efficacy and safety of subcutaneous administration of recombinant human erythropoietin (r-HuEPO) at a dose of 200 units/kg/day to cancer patients undergoing radiotherapy. Methods and Materials : This is a randomized, open-labeled, Phase II study. Only patients receiving radiotherapy ± chemotherapy are included. Eligibility is restricted to patients with lung cancer, carcinoma of the uterine cervix, prostatic adenocarcinoma, or adenocarcinoma of the breast. Patients in the control and treatment arms receive radiotherapy with similar policies, and their doses of radiotherapy and treatment volumes are determined by the site and stage of the disease. Patients in the “treatment arm” receive 200 units/kg/day of r-HuEPO, subcutaneously, five times a week with iron (Fe SO4, 325 mg. p.o., t.i.d.) supplements. Complete blood counts are obtained weekly. Quality of life is assessed weekly by the patients themselves by a few simple entries on an analog scale. Results : Twenty-six patients have been entered in the study so far. Twelve patients were placed in the control arm and 14 in the treatment arm. Pre-randomization demographic and laboratory mean values in both arms were comparable, with none of 16 parameters compared reaching statistical significance. Our results can be summarized as follows: (a) Mean hemoglobin, hematocrit, and red blood cell values increased gradually in the treatment arm patients. Week-by-week comparison showed that mean values for these three parameters were significantly higher in the treatment arm than in the control arm. For example, the p values for the differences in hemoglobin mean values for weeks 1–6 were 0.015, 0.002, 0.003, 0.0002, 0.0006, and 0.007, respectively. Similar trends were observed for red blood cells and the hematocrit values. (b) No significant toxicity has been encountered. (c) No significant differences in the mean values of white blood cells and platelet counts were seen between the two arms. The values of these two parameters declined over the course of radiotherapy. (d) The mean weekly increase in hemoglobin levels in the treatment arm was 0.43 gm/dl. Conclusion : (a) The safety and efficacy of r-HuEPO, with 200 units/kg/day of subcutaneous administration, have been confirmed in our study group. (b) However, the rate of increase in hemoglobin levels is not very rapid with the doses used. (c) Dose escalation studies are needed for determination of the feasibility of improving hemoglobin levels by about 1 gm/dl/week. (d) The question whether improvement in hemoglobin with r-HuEPO therapy can improve outcome by improving tumor oxygenation needs to be studied in carcinoma of the uterine cervix and squamous cell carcinoma of the head and neck.
From placode to polarization: new tunes in inner ear development

The highly orchestrated processes that generate the vertebrate inner ear from the otic placode provide an excellent and circumscribed testing ground for fundamental cellular and molecular mechanisms of development. The recent pace of discovery in developmental auditory biology has been unusually rapid, with hundreds of papers published in the past 4 years. This review summarizes studies addressing several key issues that shape our current thinking about inner ear development, with particular emphasis on early patterning events, sensory hair cell specification and planar cell polarity.
Immunosuppressive and Anti-Inflammatory Effects of Nicotine Administered by Patch in an Animal Model

To study the immunological effects of nicotine, there are several rodent models for chronic nicotine administration. These models include subcutaneously implanted miniosmotic pumps, nicotine-spiked drinking water, and self-administration via jugular cannulae. Administration of nicotine via these routes affects the immune system. Smokers frequently use nicotine patches to quit smoking, and the immunological effects of nicotine patches are largely unknown. To determine whether the nicotine patch affects the immune system, nicotine patches were affixed daily onto the backs of Lewis rats for 3 to 4 weeks. The patches efficiently raised the levels of nicotine and cotinine in serum and strongly inhibited the antibody-forming cell response of spleen cells to sheep red blood cells. The nicotine patch also suppressed the concanavalin A-induced T-cell proliferation and mobilization of intracellular Ca2+ by spleen cells, as well as the fever response of animals to subcutaneous administration of turpentine. Moreover, immunosuppression was associated with chronic activation of protein tyrosine kinase and phospholipase C-γ1 activities. Thus, in this animal model of nicotine administration, the nicotine patch efficiently raises the levels of nicotine and cotinine in serum and impairs both the immune and inflammatory responses.
ON THE (RE)DISCOVERY OF FUZZY GOAL PROGRAMMING

An earlier paper and subsequent commentaries in Decision Sciences described purportedly new methods for formulating and solving goal programming problems with fuzzy goals. This note suggests that much of what these articles propose is but a rediscovery of well-known results.
The influence of salt and solvent concentrations on electrospun polyvinylpyrrolidone fiber diameters and bead formation

Abstract The electrospinning process is a useful technique to fabricate nanoscale filaments from polymeric solution. Its versatility and simplicity allows engineers and scientists to synthesize fibers for many applications. The diameters and morphologies of the electrospun fibers are dependent upon the electrospinning conditions and the composition of the electrospinning solution. In this work, the composition of the electrospinning solution for fabricating Polyvinylpyrrolidone (PVP) fibers was experimentally modified with the goal of fabricating smaller diameter fibers without the formation of bead structures in the fibers. The results show the average fiber diameter can be reduced significantly, from about 700 nm to about 100 nm, by adding deionized water to a solution of PVP in ethanol. However, the addition of deionized water into the PVP-ethanol solution increased the formation of beads in the fiber morphology. Further modification of the solution with ionic salts successfully reduced the formation of beads in the morphology of the electrospun fibers with average diameter less than 300 nm.
Victim Selection in the Jeffrey Dahmer Slayings: An Example of Repetition in the Paraphilias?

It has been suggested that Jeffrey Dahmer, who was convicted for the serial murders of 15 people, carefully selected most of his victims on the basis of their external phenotype. Although the sample size is small, both univariate and multivariate methods support the possibility that similarity in craniofacial architecture strongly influenced his choice of victims. Because necrophilia played a key role during expert testimony at his trial, and because Dahmer retained most of the skulls and one postcranial skeleton, the results suggest that his actions represent an example of repetition in the paraphilias.
Mouse Gli1 mutants are viable but have defects in SHH signaling in combination with a Gli2 mutation

The secreted factor Sonic hedgehog (SHH) is both required for and sufficient to induce multiple developmental processes, including ventralization of the CNS, branching morphogenesis of the lungs and anteroposterior patterning of the limbs. Based on analogy to the Drosophila Hh pathway, the multiple GLI transcription factors in vertebrates are likely to both transduce SHH signaling and repress Shh transcription. In order to discriminate between overlapping versus unique requirements for the three Gli genes in mice, we have produced a Gli1 mutant and analyzed the phenotypes of Gli1/Gli2 and Gli1/3 double mutants. Gli3(xt) mutants have polydactyly and dorsal CNS defects associated with ectopic Shh expression, indicating GLI3 plays a role in repressing Shh. In contrast, Gli2 mutants have five digits, but lack a floorplate, indicating that it is required to transduce SHH signaling in some tissues. Remarkably, mice homozygous for a Gli1(zfd )mutation that deletes the exons encoding the DNA-binding domain are viable and appear normal. Transgenic mice expressing a GLI1 protein lacking the zinc fingers can not induce SHH targets in the dorsal brain, indicating that the Gli1(zfd )allele contains a hypomorphic or null mutation. Interestingly, Gli1(zfd/zfd);Gli2(zfd/+), but not Gli1(zfd/zfd);Gli3(zfd/+) double mutants have a severe phenotype; most Gli1(zfd/zfd);Gli2(zfd/+) mice die soon after birth and all have multiple defects including a variable loss of ventral spinal cord cells and smaller lungs that are similar to, but less extreme than, Gli2(zfd/zfd) mutants. Gli1/Gli2 double homozygous mutants have more extreme CNS and lung defects than Gli1(zfd/zfd);Gli2(zfd/+) mutants, however, in contrast to Shh mutants, ventrolateral neurons develop in the CNS and the limbs have 5 digits with an extra postaxial nubbin. These studies demonstrate that the zinc-finger DNA-binding domain of GLI1 protein is not required for SHH signaling in mouse. Furthermore, Gli1 and Gli2, but not Gli1 and Gli3, have extensive overlapping functions that are likely downstream of SHH signaling.
Prevalence and Clinical Implications of Improper Filter Settings in Routine Electrocardiography

High- and low-filter bandwidth governs the fidelity of electrocardiographic waveforms, including the durations used in established criteria for infarction, the amplitudes used for the diagnosis of ventricular hypertrophy, and the accuracy of the magnitudes of ST-segment elevation and depression. Electrocardiographs allow users to reset high- and low-filter settings for special electrocardiographic applications, but these may be used inappropriately. To examine the prevalence of standard and nonstandard electrocardiographic filtering at 1 general medical community, 256 consecutive outpatient electrocardiograms (ECGs) submitted in advance of ambulatory or same-day admission surgery during a 3-week period were examined. ECGs were considered to meet standards for low-frequency cutoff when equal to 0.05 Hz and to meet standards for high-frequency cutoff when equal to 100 Hz, according to American Heart Association recommendations established in 1975. Only 25% of ECGs (65 of 256) conformed to recommended standards; 75% of ECGs (191 of 254) did not. The most prevalent deviation from standard was reduced high-frequency cutoff, which was present in 96% of tracings with nonstandard bandwidth (most commonly 40 Hz). Increased low-frequency cutoff was present in 62% of ECGs in which it was documented. In conclusion, improper electrocardiographic filtering, with potentially adverse clinical consequences, is highly prevalent at 1 large general medical community and is likely a generalized problem. This problem should be resolvable by targeted educational efforts to reinforce technical standards in electrocardiography.
Scalable Certification Framework for Behavioral Synthesis Front-End

Behavioral synthesis entails application of a sequence of transformations to compile a high-level description of a hardware design (e.g., in C/C++/SystemC) into a register-transfer level (RTL) implementation. In this paper, we present a scalable equivalence checking framework to validate the correctness of compiler transformations employed by behavioral synthesis front-end. Our approach makes use of dual-rail symbolic simulation of the input and output of a transformation, together with identification and inductive verification of their loop structures. We have evaluated our framework on transformations applied by an open source behavioral synthesis tool to designs from the CHStone benchmark. Our tool can automatically validate more than 75 percent of the total of 1008 compiler transformations applied, taking an average time of 1.5 seconds per transformation.
Induction of tolerance to sheep red blood cells

Adult mice injected with a sheep red blood cell hemolysate supernatant fraction were found to have a severely reduced responsiveness to subsequent immunization with sheep red blood cells. The induced unresponsiveness was found to be specific, as tested by reciprocal experiments involving horse and sheep erythrocyte preparations. The tolerogenic material did not appear to be immunogenic.
PARALLEL WOLFF CLUSTER ALGORITHMS

The Wolff single-cluster algorithm is the most efficient method known for Monte Carlo simulation of many spin models. Due to the irregular size, shape and position of the Wolff clusters, this method does not easily lend itself to efficient parallel implementation, so that simulations using this method have thus far been confined to workstations and vector machines. Here we present two parallel implementations of this algorithm, and show that one gives fairly good performance on a MIMD parallel computer.
Face Matching and Retrieval in Forensics Applications

This article surveys forensic face-recognition approaches and the challenges they face in improving matching and retrieval results as well as processing low-quality images.
Global Warming and Infectious Disease

Global warming has serious implications for all aspects of human life, including infectious diseases. The effect of global warming depends on the complex interaction between the human host population and the causative infectious agent. From the human standpoint, changes in the environment may trigger human migration, causing disease patterns to shift. Crop failures and famine may reduce host resistance to infections. Disease transmission may be enhanced through the scarcity and contamination of potable water sources. Importantly, significant economic and political stresses may damage the existing public health infrastructure, leaving mankind poorly prepared for unexpected epidemics. Global warming will certainly affect the abundance and distribution of disease vectors. Altitudes that are currently too cool to sustain vectors will become more conducive to them. Some vector populations may expand into new geographic areas, whereas others may disappear. Malaria, dengue, plague, and viruses causing encephalitic syndromes are among the many vector-borne diseases likely to be affected. Some models suggest that vector-borne diseases will become more common as the earth warms, although caution is needed in interpreting these predictions. Clearly, global warming will cause changes in the epidemiology of infectious diseases. The ability of mankind to react or adapt is dependent upon the magnitude and speed of the change. The outcome will also depend on our ability to recognize epidemics early, to contain them effectively, to provide appropriate treatment, and to commit resources to prevention and research.
Epigenetic regulation of cardiac muscle-specific genes in H9c2 cells by Interleukin-18 and histone deacetylase inhibitor m -carboxycinnamic acid bis -hydroxamide

Interleukin-18 (IL-18) elicited a robust hypertrophy response in H9c2 cardiomyocytes as judged by their accelerated rates of protein synthesis and increased cell size. Evidently, IL-18 treatment also induced a cardiac hypertrophy-specific program of gene expression in H9c2 cardiomyocytes since they elicited enhanced expression of atrial naturetic factor (ANF), desmin, and skeletal α-actin genes accompanied by a canonical switch in the transcription of α- and β-myosin heavy chain (MyHC) genes. Co-treatment of H9c2 cells with m-carboxycinnamic acid bis-hydroxamide (CBHA), an inhibitor of histone deacetylases, significantly blocked both morphological and molecular manifestations of IL-18-induced cardiac hypertrophy in vitro. IL-18 treatment led to activation of phosphoinositide-3-kinase and phosphorylated Akt/protein kinase B, while CBHA blunted this pathway via inducing the expression of its upstream regulator, PTEN (phosphatase and tensin homolog). The architecture of bulk chromatin of H9c2 cells exposed to IL-18 and/or CBHA was significantly altered as judged by the extent of covalent modifications of its constituent histones. The chromatin immuno-precipitation (ChIP) assays revealed that IL-18-induced specific epigenetic changes in the chromatin of ANF, desmin, skeletal α-actin, and MyHC genes that were largely neutralized by CBHA. We demonstrate for the first time that ‘histone code’ of the entire ∼50 kb genomic DNA encoding the α- and β-MyHC genes and the intergenic DNA that generates anti-β-MyHC RNA was uniquely modulated by pro- and anti-hypertrophy signals of IL-18 and CBHA, respectively.
Could climate change precipitate peace

Growing interest in the social consequences of climate change has fueled speculation that global warming could lead to an increase in various forms of political violence. This article examines the ...
Semantic relatedness study using second order co-occurrence vectors computed from biomedical corpora, UMLS and WordNet

Automated measures of semantic relatedness are important for effectively processing medical data for a variety of tasks such as information retrieval and natural language processing. In this paper, we present a context vector approach that can compute the semantic relatedness between any pair of concepts in the Unified Medical Language System (UMLS). Our approach has been developed on a corpus of inpatient clinical reports. We use 430 pairs of clinical concepts manually rated for semantic relatedness as the reference standard. The experiments demonstrate that incorporating a combination of the UMLS and WordNet definitions can improve the semantic relatedness. The paper also shows that second order co-occurrence vector measure is a more effective approach than path-based methods for semantic relatedness.
Cops and Spooks: The Role of Police in Counterterrorism

This chapter examines the role of full-service or general-duties policing in combating terrorism. In particular we are concerned with whether the counterterrorism activities of covert intelligence gathering and disruption are playing a larger role in the activities of police agencies today, and if so to what extent such a role is impacting the services that police are expected to provide in Western democracies. We begin with a comparison of national structures for conducting counterterrorism in Western democracies. Then, we explore the impact of counterterrorism post 9/11 on policing and specify specific factors that affect the strength of its impact. Finally, drawing heavily on information from the United States and Israel, the chapter discusses arguments for and against the involvement of police in covert terrorism prevention. Overall, we conclude that general duties police agencies should be cautious in adopting a strong counterterrorism function.
Impact of Completion Lymph Node Dissection on Patients with Positive Sentinel Lymph Node Biopsy in Melanoma

Background Whether patients with positive SLNB should undergo complete lymph node dissection (CLND) is an important unanswered clinical question. Study Design Patients diagnosed with positive SLNB at a melanoma referral center from 1991 to 2013 were studied. Outcomes of patients who underwent CLND were compared with those who did not undergo immediate CLND (observation [OBS] group). Results There were 471 patients who had positive SLNB; 375 (79.6%) in the CLND group and 96 (20.4%) in the OBS group. The groups were similar except that the CLND group was younger and had more sentinel nodes removed. Five-year nodal recurrence-free survival was significantly better in the CLND group compared with the OBS group (93.1% vs 84.4%; p = 0.005). However, 5-year (66.4% vs 55.2%) and 10-year (59.5% vs 45.0%) distant metastasis-free survival rates were not significantly different (p = 0.061). The CLND group's melanoma-specific survival (MSS) rate was superior to that of the OBS group; 5-year MSS rates were 73.7% vs 65.5% and 10-year MSS rates were 66.8% vs 48.3% (p = 0.015). On multivariate analysis, CLND was associated with improved MSS (hazard ratio = 0.60; 95% CI, 0.40–0.89; p = 0.011) and lower nodal recurrence (hazard ratio = 0.46; 95% CI, 0.24–0.86; p = 0.016). Increased Breslow thickness, older age, ulceration, and trunk melanoma were all associated with worse outcomes. On subgroup analysis, the following factors were associated with better outcomes from CLND: male sex, nonulcerated primary, intermediate thickness, Clark level IV or lower extremity tumors. Conclusions Treatment of positive SLNB with CLND was associated with improved MSS and nodal recurrence rates. Follow-up beyond 5 years was needed to see a significant difference in MSS rates.
Joint hypocentral determination and the detection of low-velocity anomalies. An example from the Phlegraean Fields earthquakes

Abstract Arrival time data from the Phlegraean Fields (Italy) earthquake swarm recorded by the University of Wisconsin array in 1983 to 1984 were reanalyzed using a joint hypocentral determination (JHD) technique. The P - and S -wave station corrections computed as part of the JHD analysis show a circular pattern of central positive values surrounded by negative values whose magnitudes increase with distance from the center of the pattern. This center roughly coincides with the point of the maximum uplift (almost 2 m) associated with the swarm. Corrections range from −0.85 to 0.10 sec for P -wave arrivals and from −1.09 to 0.70 sec for S -wave arrivals. We interpret these patterns of corrections as caused by a localized low-velocity anomaly in the epicentral area, which agrees with the results of a previous 3-D velocity inversion of the same data set. The relocated (JHD) epicenters show less scatter than the epicenters obtained in the velocity inversion, and move more of the seismic activity to the vicinity of the only presently active fumarolic feature. The capability of the JHD technique to detect low-velocity anomalies and at the same time to give reliable locations, particularly epicenters, was verified using synthetic data generated for a 3-D velocity model roughly resembling the model obtained by velocity inversion.
Inhibition of hyaluronidase activity by factors associated with blood clotting.

Summary1. Proconvertin preparations were found to function as hyaluronidase inhibitors. The inhibition of hyaluronic acid depolymerization by proconvertin requires a cofactor and is enhanced by prior incubation with platelet material, which, when tested alone, is inactive. 2. Tissue thromboplastin is also shown to inhibit hyaluronidase. This inhibitory activity seems to be inherent mainly in the lipid moiety, and although always associated with the fraction containing the thromboplastic principle, is independent of its activity. 3. It is suggested that the nonspecific serum hyaluronidase inhibitor is associated with a part of the thromboplastic complex of the blood.
Vertically oriented Ti-Pd mixed oxynitride nanotube arrays for enhanced photoelectrochemical water splitting.

In recent years, considerable efforts have been made to design and discover photoactive nanostructured materials that can be used as anodes in water photoelectrolysis cells. Herein, we report on th...
The Teaching of Medical Entomology

The teaching of a subject which is growing as rapidly as medical entomology cannot be reduced to a common formula. Even if such a standardization were possible, there is little basis for supposing that any real progress would result through it.
Alterations of Red-Cell Glycolytic Intermediates and Oxygen Transport as a Consequence of Hypophosphatemia in Patients Receiving Intravenous Hyperalimentation

Abstract Within seven to 10 days after initiation of total intravenous hyperalimentation with solutions lacking added inorganic phosphate, five of eight adults were found to be significantly hypophosphatemic (serum inorganic phosphate less than 1 mg per 100 ml). Associated with this hypophosphatemia was a decrease in erythrocyte glucose-6-phosphate, fructose-6-phosphate, 3-phosphoglyceric acid, 2-phosphoglyceric acid, phosphoenolpyruvate, 2,3-diphosphoglycerate and adenosine triphosphate, and a marked increase in the concentration of "total triosre phosphates." The reduction in 2,3-diphosphoglycerate and adenosine triphosphate was accompanied by a striking increase in the red cell's affinity for oxygen. In an additional patient studied prospectively, the changes in erythrocyte metabolism were initially manifested by a slight rise in the "total triose phosphates," which was rapidly followed by alterations similar to those described above. These findings suggest that in vivo red-cell glucose metabolism is c...
Determination of chlorobenzenes and hexachlorobutadiene in drinking water with headspace gas chromatography

Objective:To establish a method for the determination of chlorobenzenes and hexachlorobutadiene in drinking water with headspace gas chromatography. Methods:Chlorobenzenes and hexachlorobutadiene in water was extracted by headspace technology,then analyzed with Rtx-1701 capillary column. At the same time,chlorobenzenes and hexachlorobutadiene was determined with GC with temperature programming. The retention time of the peaks was used for qualitative analysis,while external standard method was used for quantitative analysis. Results:The linear range was 0. 38 μg/L ~ 40. 0 μg/L for 1,3-dichlorobenzene,0. 96 μg/L ~ 100. 0 μg/L for 1,4-dichlorobenzene,0. 42 μg/L ~ 70. 0 μg/L for 1,2-dichlorobenzene,0. 03 μg/L ~ 5. 0 μg/L for 1,3,5-trichlorobenzene,0. 04 μg/L ~ 9. 0 μg/L for 1,2,4-trichlorobenzene,0. 004 μg/L ~ 0. 60 μg/L for hexachlorobutadiene,0. 03 μg/L ~ 6. 0 μg/L for 1,2,3-trichlorobenzene,0. 01 μg/L ~ 2. 0 μg/L for pentachlorobenzene,0. 02 μg/L~ 2. 0 μg/L for hexachlorobenzene respectively,while the detection limits were 0. 11 μg/L,0. 29 μg/L,0. 13 μg /L,0. 009 μg/L,0. 012 μg/L,0. 001 μg/L,0. 009 μg/L,0. 004 μg/L,0. 006 μg/L,respectively,the recovery rate was 100% ~ 114%,and RSD was 1. 0% ~ 2. 9%. Conclusion:This method is simple,accurate,sensitive and applicable to the determination of chlorobenzenes in drinking water,without organic solvent.
Conventional-intensity was more effective than low-intensity warfarin therapy for preventing recurrent venous thromboembolism.

Source Citation Kearon C, Ginsberg JS, Kovacs MJ, et al. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous throm...
Entry Dynamics: Theory and Implications

Entry and exit behavior of firms tends to determine the pattern of industry evolution. Industries grow when new firms enter the industry; they decline when the incumbent firms exit. The entry process necessarily involves competition between the incumbent and the new entrants. Models of perfect competition where firms are price takers, assume that entry and exit are more or less costless and under conditions of free flow of market information this yields an industry equilibrium. The Walrasian model of competitive equilibrium introduces two types of adjustments: price—cost adjustment and demand—supply adjustment. First, if price exceeds marginal cost where the latter could be viewed as minimal average cost, the profitability continues and this provides incentives for new firms to enter the market till the excess profits are eliminated by new entry. Secondly, if excess demand persists and the capacity ceiling is hit, prices tend to rise thus causing profits to rise. This again provides incentives for new entry or the expansion of output by the existing incumbents.
Educating Health Care Providers in Treatment of Patients With Ebola Virus Disease

Nurses manage patients with common infectious diseases by following institutional guidelines based on expert advice, evidence in the literature, and a wealth of experience. Today nurses are challenged to provide care to patients with multidrug-resistant organisms and virulent infectious diseases such as Ebola virus disease. Management of some patients with virulent infectious diseases occurs in the context of minimal experience with the pathogen, course of infection, diagnostics, nursing care, and treatment. Limited evidence exists in the US or international literature about direct nursing care of patients with virulent infectious diseases in the community, clinic, or hospital. Workplaces may have insufficient supplies, equipment, and knowledge of the management of patients with these diseases. At the National Institutes of Health Clinical Center in Bethesda, Maryland, nursing education strategies for enhanced experiential learning are used to prepare staff to care for patients with virulent infectious diseases, especially Ebola virus disease.
A whole-plant perspective reveals unexpected impacts of above- and belowground herbivores on plant growth and defense

Trade-offs between plant growth and defense are central to theoretical frameworks used to study the ecology and evolution of plant defense against herbivores. However, these frameworks, as well as the experiments designed to test them, rarely include belowground herbivores. We experimentally challenged seedlings of the tropical shrub Solanum lycocarpum (Solanaceae) with either aboveground foliar herbivores (Spodoptera caterpillars) or belowground root herbivores (the nematode Meloidogyne incognita) and measured the resulting changes in plant growth rates, biomass allocation, and the concentration of defensive terpenoids in roots and leaves. We found that plants that suffered aboveground herbivory responded with aboveground growth but belowground defense. Similarly, belowground herbivory resulted in root growth but elevated defenses of leaves. These results underscore the importance of belowground plant-herbivore interactions, and suggest that, in contrast to theoretical predictions, plants can simultaneously invest in both growth and defense. Finally, they emphasize the need for a "whole-plant" perspective in theoretical and empirical evaluations of plant-herbivore interactions.
Model-Mismatch Instability in Adaptive Control Systems

It has long been recognized that any adaptive controller can be characterized by an admissible controller set and a data-dependent cost function that partially orders these controllers. In this talk we discuss the unfalsified control concept, which involves expressing adaptive control cost functions in terms of certain controller-dependent `fictitious' signals used to evaluate stability and performance. We also define a new plant-independent property for adaptive controllers called cost-detectability. We prove that when cost-detectable unfalsified controllers are constructed using hysteresis-type adaptive algorithms, then closedloop stability of the adaptive control system is guaranteed with no assumption on the plant other than the trivial assumption of feasibility, i.e., that there exists a controller in the candidate controller set that would stabilize the plant if it were known. Cost detectable adaptive control designs circumvent the robustness problems and model-mismatch instability risks inherent with other popular adaptive design methods. Design studies and simulations demonstrate remarkably rapid convergence with unfalsified adaptive designs, often within a fraction of a plant time constant.
Polymeric nanospheres for topical delivery of vitamin D3

This study investigates the potential application of polymeric nanospheres (known as TyroSpheres) as a formulation carrier for topical delivery of cholecalciferol (i.e., Vitamin D3, VD3) with the goal to improve the skin delivery and stability of VD3. High drug loading and binding efficiencies were obtained for VD3 when loaded in TyroSpheres. VD3 was released from TyroSpheres in a sustained manner and was delivered across the stratum corneum, which occurred independent of the initial drug loading. An ex vivo skin distribution study showed that TyroSphere formulations delivered 3-10μg of active into the epidermis which was significantly higher than that delivered from Transcutol® (the control vehicle). In addition, an in vitro cytotoxicity assay using keratinocytes confirmed that VD3 encapsulation in the nanoparticles did not alter the drug activity. Photodegradation of VD3 followed zero-order kinetics. TyroSpheres were able to protect the active against hydrolysis and photodegradation, significantly enhancing the stability of VD3 in the topical formulation.
Proof Without Words: Factorial Sums

We provide a visual proof of a factorial sum identity implying the existence of the factorial base number system.
microRNA dependent and independent deregulation of long non-coding RNAs by an oncogenic herpesvirus.

Kaposi’s sarcoma (KS) is a highly prevalent cancer in AIDS patients, especially in sub-Saharan Africa. Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of KS and other cancers like Primary Effusion Lymphoma (PEL). In KS and PEL, all tumors harbor latent KSHV episomes and express latency-associated viral proteins and microRNAs (miRNAs). The exact molecular mechanisms by which latent KSHV drives tumorigenesis are not completely understood. Recent developments have highlighted the importance of aberrant long non-coding RNA (lncRNA) expression in cancer. Deregulation of lncRNAs by miRNAs is a newly described phenomenon. We hypothesized that KSHV-encoded miRNAs deregulate human lncRNAs to drive tumorigenesis. We performed lncRNA expression profiling of endothelial cells infected with wt and miRNA-deleted KSHV and identified 126 lncRNAs as putative viral miRNA targets. Here we show that KSHV deregulates host lncRNAs in both a miRNA-dependent fashion by direct interaction and in a miRNA-independent fashion through latency-associated proteins. Several lncRNAs that were previously implicated in cancer, including MEG3, ANRIL and UCA1, are deregulated by KSHV. Our results also demonstrate that KSHV-mediated UCA1 deregulation contributes to increased proliferation and migration of endothelial cells.
Clear speech and lexical competition in younger and older adult listeners

This study investigated whether clear speech reduces the cognitive demands of lexical competition by crossing speaking style with lexical difficulty. Younger and older adults identified more words in clear versus conversational speech and more easy words than hard words. An initial analysis suggested that the effect of lexical difficulty was reduced in clear speech, but more detailed analyses within each age group showed this interaction was significant only for older adults. The results also showed that both groups improved over the course of the task and that clear speech was particularly helpful for individuals with poorer hearing: for younger adults, clear speech eliminated hearing-related differences that affected performance on conversational speech. For older adults, clear speech was generally more helpful to listeners with poorer hearing. These results suggest that clear speech affords perceptual benefits to all listeners and, for older adults, mitigates the cognitive challenge associated with identifying words with many phonological neighbors.
Disorders of Calcium, Phosphate, and Magnesium Metabolism

There have been substantial recent advances in the pathophysiology of calcium, phosphate, and magnesium disorders. These include the identification of novel transport pathways for magnesium, characterization of the many genetic causes of hypomagnesemia, and the discovery of FGF23, a potent phosphaturic hormone with pleiotropic effects on calcium and phosphate homeostasis. These advances are incorporated in a comprehensive review of the pathophysiology, clinical presentation, and management of these important disorders.
Just-So Stories and Origin Myths: Phosphorylation and Structural Disorder in Circadian Clock Proteins

Some longstanding dogmas in the circadian field warrant reexamination in light of recent studies focused on the role of post-translational modifications and intrinsic disorder in core circadian clock proteins of mice and fungi. Such dogmas include the role of turnover in circadian feedback loops and the origin myths describing evolutionary relatedness among circadian clocks. In this Essay, the authors recapitulate recent findings on circadian clock protein regulation by taking an unconventional approach in the form of a dialog between Wizard and Apprentice.
Prophylactic Cranial Irradiation for Limited-Stage Small-Cell Lung Cancer: Survey of US Radiation Oncologists on Current Practice Patterns.

Abstract Purpose Prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (LS-SCLC) is considered the standard of care. Meta-analysis of 7 clinical trials indicates a survival benefit to PCI, but all of these trials were conducted in the pre–magnetic resonance imaging (MRI) era. Therefore, routine brain imaging with MRI before PCI—as recommended by National Comprehensive Cancer Network guidelines—is not directly supported by the evidence. Current US practice patterns for patients with LS-SCLC are unknown. Materials and Methods We surveyed practicing US radiation oncologists via an institutional review board–approved online questionnaire. Questions covered demographic information and treatment recommendations for LS-SCLC. Results We received 309 responses from US radiation oncologists. Ninety-eight percent recommended PCI for patients with LS-SCLC, 96% obtained brain MRI before PCI, 33% obtained serial brain imaging with MRI after PCI to detect new metastases, and 35% recommended memantine for patients undergoing PCI. Recommending memantine was associated with fewer years of practice (P Conclusion Almost all responding radiation oncologists recommended PCI and pre-PCI brain MRI for LS-SCLC patients with disease responsive to initial therapy. Only a third of respondents followed these patients with serial brain MRI. Approximately one third provided memantine therapy to try to limit neurocognitive effects of PCI. Further research is warranted to determine the best treatment for patients with LS-SCLC. This survey can inform the development of future trials that depend on participation from radiation oncologists.
Condensate Reuse: Phase II

During the 1976 edition of the Citrus Engineering Conference, Mr. Dave Hamrick, Technical Vice President of Tropicana Products, delivered a paper entitled “Condensate Reuse in Citrus Plants”. In this paper, he described the nature and composition of process condensate, showed the quantity which might be available for reuse, and recommended several areas where this water might be used.Paper published with permission.Compilation Copyright © 2018 ASME
Towards Personalized Medicine in Pediatric Cancer: Genome-Wide Strategies to Investigate Cancer Risk and Response to Therapy

Cancer results from the complex actions and interactions of multiple genetic, epigenetic and environmental factors that lead to the acquisition of somatic alterations abrogating the function of a variety of normal regulatory networks. While there has been considerable progress in understanding the genetic basis of cancer, only rarely has this knowledge translated to the development of rational therapeutics. In fact, the majority of children with cancer are still treated with nonspecific cytotoxic agents, and the remarkable strides made in curing these diseases have come largely from improvements in chemotherapy, radiation, cellular transplantation, and supportive care rather than from the use of targeted therapies.
Slotting Contracts and Consumer Welfare

Slotting contracts involve manufacturer payments to retailers for shelf space. Slotting contracts are an important part of the competitive process in many product markets. While slotting contracts have been the subject of congressional hearings, agency investigations, antitrust litigation, and scholarly debate, very little is known about their competitive consequences. This article analyzes military commissary sales before and after a natural experiment in which commissaries ceased to accept slotting payments. This natural experiment provides a rare opportunity to directly observe the crucial policy counterfactual: would a prohibition on slotting contracts increase consumer welfare? This analysis measures the impact of slotting, at both the product and category levels, on prices, output, and product variety. The results are inconsistent with anticompetitive theories of slotting contracts. Slotting contracts are primarily associated with brand-shifting of sales within a product category, but not increases in category level prices or a reduction in category output or variety. To the extent that slotting contract revenue is passed on to consumers in competitive retail markets, an assumption generally warranted in the grocery retail industry, the results imply that slotting contract competition is likely to benefit consumers.
Treg, Chemokines, and Other Small Molecules: Role in Metastasis and Its Prevention

It has long been known that malignant tumors contain variable numbers of lymphocytes referred to as tumor-infiltrating lymphocytes (TIL). In melanoma, the intensity of this lymphocytic infiltrate is correlated with outcome measures, though there is some debate in the literature that such an association may only exist for certain melanomas, for example, of a certain thickness. However, early studies on melanoma TIL did not immunophenotype these cells, and recent data have revealed that the composition of the tumoral lymphocytic infiltrate is not homogenous, but rather represents varying contributions from many lymphocytic subsets. Furthermore, the function of CD8 TIL is often compromised as a result of the accumulation of immunoregulatory cells and various tumor escape mechanisms. Nevertheless, the increase in our understanding of immunobiology has facilitated the development of logical immunotherapeutic strategies to overcome such hurdles. Examples of these strategies which are currently being tested in clinical trials and which are discussed in-depth include blocking antibodies against CTLA-4 and therapies to deplete Foxp3+ regulatory T cells (Treg), which will hopefully enhance existing immunotherapeutical protocols such as tumor immunization. In addition to strategies designed to tip the balance between antitumor immunity and regulatory T-cell function, a greater understanding of the small molecules which govern the migration of immunocytes and tumor cells (chemokines) has made possible the development of strategies to selectively impede certain immunocyte populations into the tumor microenvironment, as well as to abrogate the chemokine-mediated metastasis of tumor cells. This chapter highlights some of these current developments occurring in the field of immunological cancer therapy, and illustrates how these developments resulted from a greater understanding of basic immunobiology.
Do Radical Discoveries Require Ontological Shifts

Abstract: The theoretical stance explicated in this chapter assumes that scientific discoveries often require that the problem-solver (either the scientist or the inventor) re-conceptualizes the problem in a way that crosses ontological categories. Examples of the highest level of ontological categories are ENTITIES, PROCESSES, and MENTAL STATES. Discoveries might be explained as the outcome of the process of switching the problem representation to a different ontological category. Examples from contemporary and the history of science will be presented to support this radical ontological change hypothesis.