cssi/SciSciGPT-SciSciNet huggingface dataset:
Variants in or near KITLG, BAK1, DMRT1, and TERT-CLPTM1L predispose to familial testicular germ cell tumour

Background Familial testicular germ cell tumours (TGCTs) and bilateral TGCTs comprise 1–2% and 5% of all TGCTs, respectively, but their genetic basis remains largely unknown. Aim To investigate the contribution of known testicular cancer risk variants in familial and bilateral TGCTs. Methods and results The study genotyped 106 single nucleotide polymorphisms (SNPs) in four regions ( BAK1 , DMRT1 , KITLG , TERT-CLPTM1L ) previously identified from genome-wide association studies of TGCT, including risk single nucleotide polymorphisms (SNPs) rs210138 ( BAK1 ), rs755383 ( DMRT1 ), rs4635969 ( TERT-CLPTM1L ) in 97 cases with familial TGCT and 22 affected individuals with sporadic bilateral TGCT as well as 871 controls. Using a generalised estimating equations method that takes into account blood relationships among cases, the associations with familial and bilateral TGCT were analysed. Three previously identified risk SNPs were found to be associated with familial and bilateral TGCT (rs210138: OR 1.80, CI 1.35 to 2.41, p=7.03×10 −5 ; rs755383: OR 1.67, CI 1.23 to 2.22, p=6.70×10 −4 ; rs4635969: OR 1.59, CI 1.16 to 2.19, p=4.07×10 −3 ). Evidence for a second independent association was found for an SNP in TERT (rs4975605: OR 1.68, CI 1.23 to 2.29, p=1.24×10 −3 ). Another association with an SNP was identified in KITLG (rs2046971: OR 2.33, p=1.28×10 −3 ); this SNP is in high linkage disequilibrium (LD) with reported risk variant rs995030. Conclusion This study provides evidence for replication of recent genome-wide association studies results and shows that variants in or near BAK1 , DMRT1 , TERT - CLPTM1L , and KITLG predispose to familial and bilateral TGCT. These findings imply that familial TGCT and sporadic TGCT share a common genetic basis.
Differential requirements of MHC and of DCs for endogenous proliferation of different T-cell subsets in vivo

T cells transferred into severe lymphopenic hosts undergo rapid proliferation known as “endogenous proliferation” that are distinct from conventional homeostatic proliferation. Unlike homeostatic proliferation, cytokines, such as IL-7 are dispensable, yet TCR:MHC interaction is essential for this process to occur. However, cell types inducing the proliferation have not formally been addressed. In this study, we report that CD11c+ conventional DCs play irreplaceable roles in inducing endogenous proliferation of both naive and memory phenotype CD4 T cells via TCR-MHC II interaction. By contrast, CD8 T-cell endogenous proliferation was independent of MHC I or CD11c+ DCs. Interestingly, MHC II was necessary to support naive CD8 T-cell proliferation within MHC I-deficient hosts. Depletion of both B cells and DCs was sufficient to abrogate the proliferation of naive but not of memory CD8 T cells. These results suggest that depending on the T-cell lineages, as well as the differentiation status, different mechanisms control endogenous proliferation, revealing in vivo complexity of T-cell proliferation under lymphopenic conditions.
Dynamic prediction of architectural vulnerability from microarchitectural state

Transient faults due to particle strikes are a key challenge in microprocessor design. Driven by exponentially increasing transistor counts, per-chip faults are a growing burden. To protect against soft errors, redundancy techniques such as redundant multithreading (RMT) are often used. However, these techniques assume that the probability that a structural fault will result in a soft error (i.e., the Architectural Vulnerability Factor (AVF)) is 100 percent, unnecessarily draining processor resources. Due to the high cost of redundancy, there have been efforts to throttle RMT at runtime. To date, these methods have not incorporated an AVF model and therefore tend to be ad hoc. Unfortunately, computing the AVF of complex microprocessor structures (e.g., the ISQ) can be quite involved.To provide probabilistic guarantees about fault tolerance, we have created a rigorous characterization of AVF behavior that can be easily implemented in hardware. We experimentally demonstrate AVF variability within and across the SPEC2000 benchmarks and identify strong correlations between structural AVF values and a small set of processor metrics. Using these simple indicators as predictors, we create a proof-of-concept RMT implementation that demonstrates that AVF prediction can be used to maintain a low fault tolerance level without significant performance impact.
Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection

Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for refractory, recurrent Clostridium difficile infection (CDI), which develops following antibiotic treatments. Intestinal microbiota play a critical role in the metabolism of bile acids in the colon, which in turn have major effects on the lifecycle of C. difficile bacteria. We hypothesized that fecal bile acid composition is altered in patients with recurrent CDI and that FMT results in its normalization. General metabolomics and targeted bile acid analyses were performed on fecal extracts from patients with recurrent CDI treated with FMT and their donors. In addition, 16S rRNA gene sequencing was used to determine the bacterial composition of pre- and post-FMT fecal samples. Taxonomic bacterial composition of fecal samples from FMT recipients showed rapid change and became similar to the donor after the procedure. Pre-FMT fecal samples contained high concentrations of primary bile acids and bile salts, while secondary bile acids were nearly undetectable. In contrast, post-FMT fecal samples contained mostly secondary bile acids, as did non-CDI donor samples. Therefore, our analysis showed that FMT resulted in normalization of fecal bacterial community structure and metabolic composition. Importantly, metabolism of bile salts and primary bile acids to secondary bile acids is disrupted in patients with recurrent CDI, and FMT corrects this abnormality. Since individual bile salts and bile acids have pro-germinant and inhibitory activities, the changes suggest that correction of bile acid metabolism is likely a major mechanism by which FMT results in a cure and prevents recurrence of CDI.
An optimized digital frequency synthesizer

We develop an efficient algorithm for generating the complex vector {exp(jω o n)} n=0:N−1 on standard fixed-point systems. The proposed algorithm employs optimal factorization of the recursion step to achieve different optimality criteria. It provides a good compromise between the contradicting requirements of memory, computation, and quantization error.
High-fat/low-carbohydrate diets regulate glucose metabolism via a long-term transcriptional loop

Abstract Insulin sensitivity is characterized by insulin-stimulated glucose metabolism in skeletal muscle. We hypothesized that carbohydrate metabolism and storage might be under transcriptional control. To test this hypothesis, we fed insulin-sensitive males (glucose disposal rate, 14.7 ± 4.1 mg/kg fat-free mass [FFM] per minute) an isoenergetic high-fat/low-carbohydrate diet (HF/LCD) for 3 days with muscle biopsies before and after intervention. Oligonucleotide microarrays revealed a total of 369 genes of 18861 genes on the arrays were differentially regulated in response to diet (Bonferonni adjusted P
The global shape of Europa: Constraints on lateral shell thickness variations

The global shape of Europa is controlled by tidal and rotational potentials and possibly by lateral variations in ice shell thickness. We use limb proles from four Galileo images to determine the best-t hydrostatic shape, yielding a mean radius of 1560.8 ‐ 0.3 km and a radius difference a a c of 3.0 ‐ 0.9 km, consistent with previous determinations and inferences from gravity observations. Adding long-wavelength topography due to proposed lateral variations in shell thickness results in poorer ts to the limb proles. We conclude that lateral shell thickness variations and long-wavelength isostatically supported topographic variations do not exceed 7 and 0.7 km, respectively. For the range of rheologies investigated (basal viscosities from 10 14 to 10 15 Pa s) the maximum permissible (conductive) shell thickness is 35 km. The relative uniformity of Europais shell thickness is due to either a heat ux 7m W m a 2 from the silicate interior, lateral ice o w at the base of the shell, or convection within the shell.
A virtual node algorithm for Hodge decompositions of inviscid flow problems with irregular domains

We present an efficient discrete Hodge decomposition for velocity fields defined over irregular domains in two and three dimensions using a virtual node framework. The method is designed for use in the exact projection discretization of incompressible flow. We leverage the Poisson framework initially developed in [1] and [2]. This approach uses a signed distance function to represent the irregular domain embedded in a Cartesian grid and uses a variational approach to create a symmetric positive definite linear system. We present a novel modification to the previous approach that yields a 5-point stencil (7-point in 3D) across the entire computational domain. The original algorithm required a 9-point stencil (27-point in 3D) near the embedded irregular boundary. We show that this new condensed stencil enables a decomposition of the form A = G T M 1 G, where M is a diagonal weighting matrix and G and D = G T are diagonal scalings of the standard central-difference gradient and divergence operators. We use this factored form as the basis of our discrete Hodge decomposition and show that this can be readily used for exact projection in incompressible flow. Numerical experiments suggest our method is second-order in L ¥ for pressures and first-order in L ¥ , second-order in L 1 for velocities.
Perception of Lightness and Illumination in a World of One Reflectance

Observers looked into a miniature room in which everything was painted matte white, or—in another room—matte black. They made both reflectance and illumination judgments for eight test spots. The test spots (which varied in luminance) were perceived as approximately equal in reflectance—not different, as conventional contrast theories would seem to require. The illumination matches made to the same points, however, closely paralleled the pattern of actual illumination levels, and this result is discussed as evidence that edges are classified as changes in either reflectance or illumination. The white room was correctly perceived as white, and the black room was perceived as middle gray; similar results were obtained even when the luminances in the black room were higher (owing to higher illumination) than the corresponding luminances in the white room. An explanation in terms of differences in gradient patterns is presented and supported with luminance profiles.
Development of a sensitive RT-PCR method for amplifying and sequencing near full-length HCV genotype 1 RNA from patient samples

Direct-acting antiviral (DAAs) agents for hepatitis C virus (HCV) span a variety of targets, including proteins encoded by the NS3/4A, NS4B, NS5A, and NS5B genes. Treatment with DAAs has been shown to select variants with sequence changes in the HCV genome encoding amino acids that may confer resistance to the treatment. In order to assess these effects in patients, a Reverse Transcription Polymerase Chain Reaction (RT-PCR) method was developed to sequence these regions of HCV from patient plasma. A method was developed to amplify and sequence genotype 1 HCV RNA from patient plasma. Optimization of HCV RNA isolation, cDNA synthesis, and nested PCR steps were performed. The optimization of HCV RNA isolation, design of RT-PCR primers, optimization of RT-PCR amplification conditions and reagents, and the evaluation of the RT-PCR method performance is described. The optimized method is able to successfully, accurately, and reproducibly amplify near full-length genotype 1 HCV RNA containing a wide range of concentrations (103 to 108 IU/mL) with a success rate of 97%. The lower limit of detection was determined to be 1000 IU/mL HCV RNA. This assay allows viral sequencing of all regions targeted by the most common DAAs currently in development, as well as the possibility to determine linkage between variants conferring resistance to multiple DAAs used in combination therapy.
On the geometrical multiplication and division of phasors

IN a recent issue of IEEE Circuits and Systems Magazine, Kami described a procedure to multiply two phasors using geometrical methods [1]. Here, we present a procedure to determine the ratio of two phasors, in addition to presenting a simpler form of the procedure for multiplication. The procedure is similar to that of vector addition and subtraction in the sense that the resultant vector is obtained by operating on the given two vectors.
Nine Reasons to go Slow on Bail Bond Reform

The problems of bail bond systems are similar in most states and the proposed solutions are much the same. Bail bond reform by means of establishing an OR (own recognizance) system is becoming a national trend. Once a reform of this kind does become popular with criminal justice personnel, there is a danger that we will stop studying it and assume that it must be good because other states and the federal government are doing it. It is very easy to believe that change itself is progress.Alabama is struggling to join the national trend to overhaul its bail bond system. This paper starts with a brief description of a small empirical study done for the purpose of providing a rationale for introducing reform legislation. This study is used as a vehicle to illustrate how the problems and process of bail bond reform are national in scope.The discussion of the national issues of bail bond reform is conceptually divided into three broad categories of problems: (I) bureaucracy issues; (2) cost effectiveness issues;...
Overexpressed Claudin-1 Can Be Visualized Endoscopically in Colonic Adenomas In Vivo.

Background & Aims Conventional white-light colonoscopy aims to reduce the incidence and mortality of colorectal cancer (CRC). CRC has been found to arise from missed polypoid and flat precancerous lesions. We aimed to establish proof-of-concept for real-time endoscopic imaging of colonic adenomas using a near-infrared peptide that is specific for claudin-1. Methods We used gene expression profiles to identify claudin-1 as a promising early CRC target, and performed phage display against the extracellular loop of claudin-1 (amino acids 53–80) to identify the peptide RTSPSSR. With a Cy5.5 label, we characterized binding parameters and showed specific binding to human CRC cells. We collected in vivo near-infrared fluorescence images endoscopically in the CPC;Apc mouse, which develops colonic adenomas spontaneously. With immunofluorescence, we validated specific peptide binding to adenomas from the proximal human colon. Results We found a 2.5-fold increase in gene expression for claudin-1 in human colonic adenomas compared with normal. We showed specific binding of RTSPSSR to claudin-1 in knockdown and competition studies, and measured an affinity of 42 nmol/L and a time constant of 1.2 minutes to SW620 cells. In the mouse, we found a significantly higher target-to-background ratio for both polypoid and flat adenomas compared with normal by in vivo images. On immunofluorescence, we found significantly greater intensity for human adenomas (mean ± SD, 25.5 ± 14.0) vs normal (mean ± SD, 9.1 ± 6.0) and hyperplastic polyps (mean ± SD, 3.1 ± 3.7; P = 10 -5 and 8 × 10 -12 , respectively), and for sessile serrated adenomas (mean ± SD, 20.1 ± 13.3) vs normal and hyperplastic polyps ( P = .02 and 3 × 10 -7 , respectively). Conclusions Claudin-1 is overexpressed in premalignant colonic lesions, and can be detected endoscopically in vivo with a near-infrared, labeled peptide.
Controls, Trust, and Reciprocity

This study investigates the effects of formal controls on trust and reciprocity within organizations. Prior research finds a positive effect of controls on trust-based cooperative behavior in settings where people work together and may benefit from each other’s behavior. Other work suggests that this result could be driven by control-induced reciprocity rather than control-induced trust. If this is the case, then controls may have less of a positive effect, or no effect, in relationships that do not involve direct interaction. We test the extent to which controls improve trust and reciprocity by comparing the effect of controls in a setting where people do not work together directly, but where behaviors can be observed (in other words, a setting where reciprocity is less likely to influence behavior), to a setting where people work together and can benefit from each other’s work. We find that controls increase cooperative behavior in both settings, but that controls increase this behavior significantly more in the setting where participants work together and can benefit from each other’s work (i.e., where reciprocity is more likely to occur). This suggests that both trust and reciprocity are enhanced by controls, and that controls will enhance cooperative behavior more in more interactive settings.
PATHWAYS OF PROTEIN DEGRADATION IN L6 MYOTUBES

To assess the importance of different proteolytic pathways in anabolic and catabolic states, L6 myotubes were labeled with 3H-phenylalanine for 24 hr, then exposed for another 24 hr to control medium, alone or with one of the following: insulin (1 microgram/ml), insulin-like growth factor-I (IGF-I, 100 ng/ml), clenbuterol (100 microM), or dexamethasone (1 microM). Release of acid-soluble radioactivity and 3-methylhistidine were used to determine rates of total and myofibrillar protein degradation, respectively. Within each hormone treatment, cells were also exposed to none, one, or both of the following protease inhibitors: chloroquine (25 microM); E-64d (100 microM). Chloroquine inhibits lysosomal proteases, and E-64d is a cell-penetrating inhibitor of cysteine proteases (including the calpains). Total protein degradation was reduced by insulin (-33%) and IGF-I (-40%), increased by clenbuterol (+20%), and was unaffected by dexamethasone. Myofibrillar protein degradation was reduced by insulin (-35%), IGF-I (-55%), and clenbuterol (-22%), and was unaffected by dexamethasone. Therefore, total (mainly sarcoplasmic) and myofibrillar protein degradation were regulated independently of one another. The influence of the inhibitors was not consistent across hormone treatments. Chloroquine inhibited total but not myofibrillar proteolysis, indicating that lysosomes may be rate limiting in the former but not the latter. In contrast, E-64d had no effect on total protein degradation, but increased myofibrillar proteolysis. Interactions between anabolic and catabolic hormones and these two protease inhibitors indicate that both lysosomal and nonlysosomal proteolytic pathways are involved in regulation of total protein degradation in myotubes. In contrast, lysosomes are probably not involved in regulating the rate of myofibrillar protein degradation, the initial step likely being due to calpain activity.
Behavioral Impulsivity Does Not Predict Naturalistic Alcohol Consumption or Treatment Outcomes

OBJECTIVE: The purpose of this study was to determine if behavioral impulsivity under multiple conditions (baseline, after alcohol consumption or after serotonin depletion) predicted naturalistic alcohol use or treatment outcomes from a moderation-based contingency management intervention. METHOD: The current data analysis pulls information from three phases of a large study: 1) Phase 1 examined baseline and the effects of alcohol use and serotonin depletion on three types of behavioral impulsivity: response initiation (IMT task), response inhibition (GoStop task), and delay discounting (SKIP task); 2) Phase 2 involved 28 days of naturalistic drinking; and 3) Phase 3 involved 3 months of contingency management. During phases 2 and 3 alcohol use was measured objectively using transdermal alcohol monitors. The results of each individual phase has been previously published showing that at a group level the effects of alcohol consumption on impulsivity were dependent on the component of impulsivity being measured and the dose of alcohol consumed but serotonin depletion had no effect on impulsivity, and that a moderation-based contingency management intervention reduced heavy drinking. RESULTS: The current analysis combining data from those who completed all three phases (n = 67) showed that impulsivity measured at baseline, after alcohol consumption, or after serotonin depletion did not predict naturalistic drinking or treatment outcomes from a moderation-based CM treatment. CONCLUSIONS: Contingency management interventions may prove to be an effective intervention for impulsive individuals, however, normal variations in measured impulsivity do not seem to relate to normal variations in drinking pattern or response to moderation-based contingency management. Language: en
Preloading of GAC by natural organic matter in potable water treatment systems: Mechanisms, effects and design considerations

The existence of complex and highly variable natural organic materials (NOMs) in virtually all potable supply source waters is broadly recognized. It is also general knowledge that granular activated carbon (GAC) adsorbers, integral parts of many potable supply treatment systems, effectively adsorb various molecular fractions of such NOMs. There is strong evidence that the phenomenon of ‘preloading’ of GAC by NOM can have profound effects on its subsequent ability to remove organic contaminants. Such effects on the performance of adsorbers in their primary role of contaminant removal are, nonetheless, seldom factored adequately into their initial design. The objective of this paper is to present a rational approach, a blend of mechanistic modelling and empirical parameter estimation, by which the impacts of NOM preloading can be incorporated into the design of GAC systems on a source-water specific basis. The results of a series of investigations from which a quantitative approach to the integration of preloading effects in the design of such adsorbers has evolved are detailed, and a specific case study application of the approach is described.
Methods to lower formation amount of chlorate during diaphragm electrolysis

Causes of chlorate formation during the production of caustic soda by diaphragm electrolysis were analyzed as well as its damage.Measures to lower the amount of chlorate were put forward emphatically.
Ontogeny of sucrase-isomaltase gene expression in rat intestine: responsiveness to glucocorticoids

The goal of our study was to determine how sucrase-isomaltase (SI) gene expression in the rat small intestine is modulated by glucocorticoids during the second and third postnatal weeks. SI mRNA was quantitated by Northern blot and was compared with sucrase activities in the same tissue samples. The role of endogenous glucocorticoids was assessed by measuring SI mRNA and enzyme activity in rat pups adrenalectomized (ADX) on postnatal day 9. ADX pups showed a retarded appearance of sucrase activity compared with sham-operated control pups, and the appearance of SI mRNA paralleled the enzyme activity. To determine the role of exogenous glucocorticoids, a saturating dose of dexamethasone (Dex) was administered daily in three series of experiments starting on days 10, 16, and 18. In the day 10 series, Dex caused precocious appearance of both SI mRNA and sucrase activity. In the day 16 series, Dex accelerated the rate of rise of the two parameters, whereas by day 18 there was no significant effect of Dex. To investigate whether the accelerated rise in the day 16 series was associated with changes in epithelial cell kinetics, the location of SI protein was assessed by immunofluorescence staining. The results indicated that the effect of Dex at this age was due to faster emergence of SI-bearing enterocytes from the intestinal crypts.(ABSTRACT TRUNCATED AT 250 WORDS)
Overview of bevacizumab: a new cancer therapeutic strategy targeting vascular endothelial growth factor.

PURPOSE: The pharmacology, pharmacokinetics, preclinical and clinical experience to date, and clinical concerns in monitoring patients receiving bevacizumab, recombinant humanized monoclonal antibody to vascular endothelial growth factor (VEGF), are described. SUMMARY: Preclinical research revealed that bevacizumab specifically inhibits VEGF, has activity in multiple cancer cell lines, and is synergistic with several cancer chemotherapeutic agents. In humans, bevacizumab has a long half-life, allowing intravenous administration once every two to three weeks. Dose-limiting toxicities, the formation of antibodies to bevacizumab, and problems with wound healing after surgery have not been observed in clinical trials. A phase II study of bevacizumab in combination with 5-fluorouracil and leucovorin in patients with metastatic colorectal cancer showed promising results (i.e., therapeutic response rate and disease-free progression of survival), although a clear dose-response relationship was not demonstrated and concerns were raised about the potential for thromboembolic events, bleeding, hypertension, and proteinuria. In a phase III study in patients with refractory metastatic breast cancer, bevacizumab doubled the response rate from capecitabine but it did not affect survival. First-line use of bevacizumab with irinotecan, orouracil, and leucovorin produced significant improvements in response rate, duration of response, and survival in a phase III study of patients with metastatic colorectal cancer. Bevacizumab was associated with hypertension, which was readily managed with mild antihypertensive agents, and possibly with gastrointestinal (GI) perforation, but not with serious bleeding, thromboembolism, or proteinuria. Nevertheless, patients receiving bevacizumab should be monitored for GI perforation, bleeding, thromboembolism, hypertension, and proteinuria, especially if they have a condition that predisposes them to these problems (e.g., a history of unusual bleeding or clotting, hypertension, or proteinuria; use of anticoagulants or other medications that affect clotting or coagulation). CONCLUSION: In clinical trials, bevacizumab has shown promise in promoting synergism with other chemotherapeutic agents in the treatment of various cancers.
Why People and Organizations Break Down

One of the most difficult tasks facing humans is to become aware of and challenge their key operating assumptions before a major crisis has occurred. The only way to do this is to study a wide variety of crises both within and outside of one’s industry. In addition, one must continually study and review the assumptions under which one’s organization and technology operate. In this chapter, we focus on several operating assumptions that lead to technological and organizational breakdowns. We investigate why the reliance on technology is not always a good idea, why training is not enough, why organizational culture matters, why organizations mistake the absence of accidents for the presence of safe operations, and why organizations constantly drift away from safety into failure.
Tumor pericyte-associated antigens DLK1 and DLK2 as targets for cancer immunotherapy (VAC13P.1131)

The vasculature of solid tumors is essential for their progressive growth and is abnormal structurally and functionally. Notably, pericytes and vascular endothelial cells (VEC) in tumors exhibit altered epigenetic programming and express antigens that allow for their differential recognition (vs. vascular cells in normal tissues) by therapeutic T cells. Therefore, targeting immune reactivity against these antigens via specific vaccination may be a viable therapeutic approach against solid tumors. We show that pericytes isolated from human and murine renal cell carcinoma (RCC) and melanoma overexpress the antigens Delta-like homologue 1 (DLK1) and its homologue DLK2. Using recombinant lentiviruses and adenoviruses encoding full-length murine DLK1 and DLK2 proteins, we show that coordinate genetic vaccination against these two antigens leads to superior therapeutic inhibition of RENCA and B16 tumor growth in vivo when compared to tumor-bearing mice vaccinated against either DLK1 or DLK2 alone. The coordinate vaccination protocol also resulted in the activation of DLK1- and DLK2-specific CD8+ T cells, recruitment of T cells into the tumor microenvironment, loss of DLK1 and DLK2 expressing pericytes and structural normalization of tumor-associated blood vessels. We conclude that specific vaccination against (oncofetal) DLK1 and/or DLK2 may represent an effective strategy for the treatment of vascularized, solid forms of cancer (including RCC and melanoma, among others).
Bayesian network feature finder (BANFF): an R package for gene network feature selection

Motivation: Network marker selection on genome-scale networks plays an important role in the understanding of biological mechanisms and disease pathologies. Recently, a Bayesian nonparametric mixture model has been developed and successfully applied for selecting genes and gene sub-networks. Hence, extending this method to a unified approach for network-based feature selection on general large-scale networks and creating an easy-to-use software package is on demand. Results: We extended the method and developed an R package, the Bayesian network feature finder (BANFF), providing a package of posterior inference, model comparison and graphical illustration of model fitting. The model was extended to a more general form, and a parallel computing algorithm for the Markov chain Monte Carlo -based posterior inference and an expectation maximization-based algorithm for posterior approximation were added. Based on simulation studies, we demonstrate the use of BANFF on analyzing gene expression on a protein–protein interaction network. Availability: https://cran.r-project.org/web/packages/BANFF/index.html Contact: ude.hcimu@gnaknaij, ude.yrome@uy.iewnait Supplementary information: Supplementary data are available at Bioinformatics online.
CRISPR-Cas9 directed knock-out of a constitutively expressed gene using lance array nanoinjection.

CRISPR-Cas9 genome editing and labeling has emerged as an important tool in biologic research, particularly in regards to potential transgenic and gene therapy applications. Delivery of CRISPR-Cas9 plasmids to target cells is typically done by non-viral methods (chemical, physical, and/or electrical), which are limited by low transfection efficiencies or with viral vectors, which are limited by safety and restricted volume size. In this work, a non-viral transfection technology, named lance array nanoinjection (LAN), utilizes a microfabricated silicon chip to physically and electrically deliver genetic material to large numbers of target cells. To demonstrate its utility, we used the CRISPR-Cas9 system to edit the genome of isogenic cells. Two variables related to the LAN process were tested which include the magnitude of current used during plasmid attraction to the silicon lance array (1.5, 4.5, or 6.0 mA) and the number of times cells were injected (one or three times). Results indicate that most successful genome editing occurred after injecting three times at a current control setting of 4.5 mA, reaching a median level of 93.77 % modification. Furthermore, we found that genome editing using LAN follows a non-linear injection-dose response, meaning samples injected three times had modification rates as high as nearly 12 times analogously treated single injected samples. These findings demonstrate the LAN’s ability to deliver genetic material to cells and indicate that successful alteration of the genome is influenced by a serial injection method as well as the electrical current settings.
Evil in the philosophy of Karl Marx

While a considerable secondary literature revolves around the issue of whether Marx believed that the concepts of “justice” and “injustice” – and hence, by implication, other comparable moral terms as well – had any non-relative meaning, there is really no doubt that a strong moral vision, with emphasis on the evil aspects of the capitalist system as a system of exploitation, undergirded all of his writings, particularly Capital. In understanding the extent to which recognition of evil pervades Marx’s mature thought, the centrality to his analysis of the notion of “exploitation” deserves emphasis. From an historical perspective, it is useful to recall efforts at Marxist-Christian dialogue that occurred during the post-World War II era. Two French philosophers who flourished in the latter part of the Twentieth Century, Michel Henry and Jacques Derrida, deserve special notice for their religious or quasi-religious interpretations of Marx’s philosophy, which in the final analysis can be seen as a critique of profound evil in the world even though it contains nothing resembling a conventional system of ethics. Nor does it, contrary to common assumptions about it, offer a guarantee of a “happy ending” to history. Marx’s greatest contribution to thinking about evil may lie in his insight into the profound immorality of the principle guiding the system of capitalism, both in his day and ours, to wit, that the pursuit of material self-interest is supremely good.
90Y-Ibritumomab Tiuxetan (Zevalin®) in Combination with High-Dose Therapy (HDT) Followed by Autologous Stem Cell Transplant (ASCT) May Improve Survival in Patients with Poor-Risk Follicular Lymphoma (FL) and Diffuse Large B-Cell Lymphoma (DLBCL): Results of a Retrospective Comparative Analysis.

Since NHL is radiosensitive, total body irradiation (TBI) has been used as part of HDT and ASCT for NHL. However, due to short-term and long-term toxicity associated with TBI, alternative regimens have been developed. We have reported that Zevalin at conventional and high doses can be given in combination with HDT and ASCT in patients (pts) with poor-risk or relapsed B-cell NHL without additional toxicity. Given the efficacy of Zevalin in FL and DLBCL, we retrospectively evaluated the outcome of HDT and ASCT in pts with FL and DLBCL who received Zevalin-based HDT regimens (Z-ASCT) and compared to those receiving TBI-based regimen (TBI-ASCT)Between 1/2000 to 1/2006, 187 pts with FL grade I/II (30), FL grade III (20) and DLBCL (137) underwent HDT and ASCT, 62 received Z-ASCT while 125 received TBI-ASCT. For Z-ASCT, pts 60 yrs or with prior RT received conventional dose Zevalin plus high-dose BEAM. TBI-ASCT was performed during the same period for the following reasons: ineligible for Z-ASCT, pt refusal, physician preference and protocol closure. The pt characteristics between the two groups were similar with respect to histology, disease status, prior regimens, bulky disease, B symptoms and performance status. However, the median age was younger for TBI-ASCT (49 vs. 53, p=0.01) and there were more chemo-resistant pts in the Z-ASCT group (p=0.01). Results: At a median follow-up of 28 months (range 2–64) for Z-ASCT and 38 months (range 1–78) for TBI-ASCT, the 2-year overall survival (OS) and disease-free survival (DFS) were 91% (95% CI, 82–96) and 74% (95% CI, 64–82), respectively for Z-ASCT, and 76% (95% CI, 69–80) and 72% (95% CI, 65–77), respectively for TBI-ASCT(Figure 1). OS remained significantly different when first complete remission pts were excluded from analysis (p=0.019). Multivariate models were generated for the primary endpoints of the study (OS and DFS). The results of these analyses showed that the risk of death and/or relapse was less among the Z-ASCT pts after adjusting for baseline differences (ie. Age, performance status and chemosensitivity status at transplant), and other factors (i.e., disease status at transplant, number of previous chemotherapies) previously shown to be associated with survival/disease free survival post transplant (OS: p Conclusion: Zevalin in combination with HDT followed by ASCT was associated with significantly improved survival in pts with poor-risk or relapsed/refractory FL and DLCBL when compared to TBI-ASCT. Further studies and longer follow-up are required to evaluate the long-term efficacy and safety of Zevalin in the HDT/ASCT setting.
Supervision Matters: Collegial, Developmental and Reflective Approaches to Supervision of Teacher Candidates.

This self-study examined the communication approaches of 15 university supervisors who oversaw teacher candidates enrolled in year-long, co-taught P-12 clinical experiences. Supervisors attended 20...
The Present and Future Challenges Facing Urology Departments at Academic Health Centers

Academic health centers (ACHs) represent the pinnacle of health care by providing innovative clinical care, cutting-edge research, and premier education. However, recent changes in health care put their tripartite mission at risk. The coming years will bring immense change to AHCs as they adjust to new market conditions impacting the 3 distinct elements of their mission. Fundamental adaptations are required for AHCs to survive, let alone thrive and continue to represent the best of medical research, education, and health. This paper evaluates the missions and strengths of AHCs, describes the challenges to these missions, and proposes adaptations for future success.
Fish harder; catch more?

Perhaps the most fundamental insight from fishery science is that ecosystems impose important and predictable constraints on food production from the sea. The familiar hump-shaped growth curve implies that the growth rate and carrying capacity of a species limit its production: Once stocks are depleted, further increasing fishing pressure will only lead to decreases in catch. This logic underpins fishery science and economics, nearly all fishery management legislation, and, most importantly, recent calls to restore fish stocks around the world (1). In PNAS, Cao et al. (2) propose a series of concrete steps for ecosystem and fishery restoration in the world’s superpower of fishing, China. Their call is couched within the complex, and often misunderstood, norms of Chinese culture, and appropriately distances itself from the western view of ocean management that is often taken for granted here. A stylized representation of ‘‘western’’ fishery objectives is to optimize the catch of commercially important fish stocks while ensuring a more natural ecosystem and persistence of all species. Under this approach, the fishery economy is believed to be intimately intertwined with natural ecosystems; the former cannot thrive without the latter. We are told that such ecosystem protection increases production, ensures resilience, and delivers a suite of other services (such as carbon sinks or storm protection). However, fishery management objectives can often be quite different in Asia, where a premium is placed on food security, livelihoods of millions of small-scale fishermen, and ensuring fishing opportunities as a backstop in the labor market (3). Also, instead of demanding large, fleshy fish like salmon or halibut, Asian consumers often prefer smaller, bonier, more productive species like yellow croaker ( Larimichthys polyactis ) or largehead hairtail ( Trichiurus lepturus ). These differences in objectives between western and Asian fishery management may seem inconsequential. After all, they are ultimately both subject to … [↵][1]1Email: costello{at}bren.ucsb.edu. [1]: #xref-corresp-1-1
An Exploration of the Relationships between Student Racial Background and the School Sub-Contexts of Office Discipline Referrals: A Critical Race Theory Analysis.

A growing body of research indicates that exclusionary school discipline practices disproportionately impact students of color. Some scholars have theorized that racial disparities likely vary acro...
Optimization of electrospun poly(N-isopropyl acrylamide) mats for the rapid reversible adhesion of mammalian cells

Poly(N-isopropyl acrylamide) (pNIPAM) is a “smart” polymer that responds to changes in altering temperature near physiologically relevant temperatures, changing its relative hydrophobicity. Mammalian cells attach to pNIPAM at 37 °C and detach spontaneously as a confluent sheet when the temperature is shifted below the lower critical solution temperature (∼32 °C). A variety of methods have been used to create pNIPAM films, including plasma polymerization, self-assembled monolayers, and electron beam ionization. However, detachment of confluent cell sheets from these pNIPAM films can take well over an hour to achieve potentially impacting cellular behavior. In this work, pNIPAM mats were prepared via electrospinning (i.e., espNIPAM) by a previously described technique that the authors optimized for cell attachment and rapid cell detachment. Several electrospinning parameters were varied (needle gauge, collection time, and molecular weight of the polymer) to determine the optimum parameters. The espNIPAM mat...
Pelagic zonation of water quality and phytoplankton in the Great Lakes

Analysis of aquatic ecosystem data collected from large water bodies must consider spatial variations. A suite of pelagic survey stations exists for the Laurentian Great Lakes, but little is known about their redundancy. We present a strategy to delineate the lakes into zones based on water quality and phytoplankton biovolume. Water samples were collected from 72 sites in two seasons (spring and summer) from 2007 to 2010 in all five lakes. Integrated samples were analyzed for phytoplankton biovolume and nine water quality parameters. We conducted cluster analysis, principal components analysis and non-metric multidimensional scaling methods for water quality and phytoplankton taxon-specific biovolume for the Great Lakes basin and for each lake separately. There were significant lake-to-lake differences, and based on lake-specific analyses, Lake Superior, Lake Michigan and Lake Erie were each divided into three zones; Lake Huron and Lake Ontario were each grouped into two zones. The zones identified by water quality and phytoplankton provide an understanding of spatial distributions for evaluating monitoring data.
Concomitant Use of Immunosuppressive Therapy with Tumor Necrosis Factor (TNF) Antagonists in Inflammatory Bowel Disease

The treatment paradigm of ulcerative colitis (UC) and Crohn’s disease (CD) has shifted considerably over the past decade. Despite the advancements in our understanding of treatment monitoring and optimization, one of the key questions that continues to be debated is the optimal approach to using concomitant immunosuppressive agents. Well-designed randomized controlled trials have suggested that a clear treatment benefit exists; however, the external validity and applicability of these findings to the general population, and the personalization of treatment decisions based on individual factors and safety, remain to be clarified. In this review, we will discuss the evidence available for treatment efficacy, the impact safety may have on treatment decisions, and opportunities available to optimize the potential application and personalization of concomitant immunosuppressive therapy.
A testimonio of critical race feminista parenting: snapshots from my childhood and my parenting

The author employs a testimonio to partake in the instructive and cathartic tradition of sharing experiences, mistakes, and (mis)understandings of parenting children of color. In doing so, she draw...
Hemispheric Specialization: Language, Space, and Sexual Differentiation

The left and right cerebral hemispheres of the human brain are functionally asymmetric, each side having its own abilities and biases. This article illustrates characteristics of hemispheric asymmetry in humans by focusing on three well-studied topics: language, processing locations in space, and sexual differentiation. In each domain, hemispheric asymmetry can be thought of as complementary, with each side being superior for different, and sometimes, contradictory aspects of a task. Emphasis is on hemispheric asymmetry in humans, while also considering the relationship to asymmetries in other contemporary species that may shed light on the evolutionary origins of hemispheric specialization.
Study of a 3kW high-efficient wide-bandgap DC-DC power converter for solar power integration in 400V DC distribution networks

Direct current (DC) distribution network has a higher efficiency in energy delivery over alternative current (AC) network, when there is a high penetration of dc renewable energy resources and energy storage systems. In this paper, the energy conversion efficiency (n) of a 3kW Silicon Carbide (SiC)-based Boost Cascaded Buck-Boost power converter is analyzed for solar power integration in 400Vdc distribution networks, compared to a Silicon (Si)-based BoCBB prototype. We found that: 1) there is about 2% reduction in n when the switching frequency of MOSFETs increases from 20 kHz to 100 kHz in Si-based prototype. Comparatively, the efficiency reduction with SiC-based MOSFETs is limited within 1% in the same case; 2) under the same switching frequency, the n increases 2.4% in average by replacing Si MOSFETs with SiC MOSFETs. The differences in n increase along the switching frequency. In addition, the switching frequency of 50 kHz is optimal in overall system performance for SiC-based prototype, which makes a good tradeoff between high n, good power quality, and compact size. These conclusions are verified by theoretical analysis and experiment tests. The experiment tests demonstrated a high efficiency of 97% in peak in power conversion.
The Potential Effect of the 21st Century Cures Act on Drug Development

Enacted in December 2016, the 21st Century Cures Act is a pivotal piece of legislation that will influence the FDA drug and device approval process for the foreseeable future. Although this legisla...
Genetic Analysis of Neuronal Migration in the Nematode Caenorhabditis elegans

During metazoan development the migrations of neurons and their growth cones play a major role in generating the final pattern and connectivity of the adult nervous system. Although many migration pathways have been described, the mechanisms regulating these cellular movements are poorly understood. In order to understand how cell migration is regulated, there are several key questions that must be addressed. How do cells decide to migrate? What defines the pathways taken by migrating cells? How do migrating cells know that they have reached their final destinations? One approach to elucidating the mechanisms controlling cell migration is to define the molecules involved by identifying mutations that perturb cell migration. The nematode Caenorhabditis elegans is particularly useful for the study of cell migration because of its anatomical simplicity. Nomarski optics can be used to observe cells as they migrate in living animals (Sulston and Horvitz, 1977; Sulston et al., 1983). Moreover, potential cell interactions involved in both cell migration (Thomas et al., 1990) and axonal guidance (Durbin, 1987; Walthall and Chalfie, 1988; Li and Chalfie, 1990; Garriga et al., 1993a) are easily tested. Our research is directed at understanding how a specific pair of motor neurons, the HSNs, migrate.
Frontiers of Efficiency Research

Efficiency Analysis in general systems theory is an active field of modern research. It covers not only the input-output systems, but other systems in control theory and engineering. Data envelopment analysis (DEA) deals only with a small component of input-output systems. It uses a specific concept of Pareto efficiency and applies it mainly to public sector decision-making units (DMUs) which do not operate under the private market framework governed by market prices and profit maximization.