Miracle-dz/UniFAR-FTUs huggingface dataset:
Human genetic variation altering anthrax toxin sensitivity

The outcome of exposure to infectious microbes or their toxins is influenced by both microbial and host genes. Some host genes encode defense mechanisms, whereas others assist pathogen functions. Genomic analyses have associated host gene mutations with altered infectious disease susceptibility, but evidence for causality is limited. Here we demonstrate that human genetic variation affecting capillary morphogenesis gene 2 (CMG2), which encodes a host membrane protein exploited by anthrax toxin as a principal receptor, dramatically alters toxin sensitivity. Lymphoblastoid cells derived from a HapMap Project cohort of 234 persons of African, European, or Asian ancestry differed in sensitivity mediated by the protective antigen (PA) moiety of anthrax toxin by more than four orders of magnitude, with 99% of the cohort showing a 250-fold range of sensitivity. We find that relative sensitivity is an inherited trait that correlates strongly with CMG2 mRNA abundance in cells of each ethnic/geographical group and in the combined population pool (P = 4 × 10−11). The extent of CMG2 expression in transfected murine macrophages and human lymphoblastoid cells affected anthrax toxin binding, internalization, and sensitivity. A CMG2 single-nucleotide polymorphism (SNP) occurring frequently in African and European populations independently altered toxin uptake, but was not statistically associated with altered sensitivity in HapMap cell populations. Our results reveal extensive human diversity in cell lethality dependent on PA-mediated toxin binding and uptake, and identify individual differences in CMG2 expression level as a determinant of this diversity. Testing of genomically characterized human cell populations may offer a broadly useful strategy for elucidating effects of genetic variation on infectious disease susceptibility.
Study on Effective Microorganisms Bacteria for Acrylonitrile Wastewater Treatment

In this study, according to the specific characteristics of acrylonitrile wastewater, Effective Microorganisms (EM) was used as Contact oxidation strain. The optimum conditions of EM bacteria domestication and contact oxidation treatment, such as pH, concentration and temperature, was confirmed. In addition, the results of aerobic treatment of wastewater suggested that COD effluent reduced to below 100mg/L, the removal efficiency to 99.4% and the chromaticity reduced from 300 times to less than 20 times. And the final effluent quality can be satisfied with the first-class discharge standard stipulated in the State Integrated Sewage Discharge Standard&#65288;GB 8978-199&#65289;
Inhibition of Intestinal Bile Acid Transporter Slc10a2 Improves Triglyceride Metabolism and Normalizes Elevated Plasma Glucose Levels in Mice

Interruption of the enterohepatic circulation of bile acids increases cholesterol catabolism, thereby stimulating hepatic cholesterol synthesis from acetate. We hypothesized that such treatment should lower the hepatic acetate pool which may alter triglyceride and glucose metabolism. We explored this using mice deficient of the ileal sodium-dependent BA transporter (Slc10a2) and ob/ob mice treated with a specific inhibitor of Slc10a2. Plasma TG levels were reduced in Slc10a2-deficient mice, and when challenged with a sucrose-rich diet, they displayed a reduced response in hepatic TG production as observed from the mRNA levels of several key enzymes in fatty acid synthesis. This effect was paralleled by a diminished induction of mature sterol regulatory element-binding protein 1c (Srebp1c). Unexpectedly, the SR-diet induced intestinal fibroblast growth factor (FGF) 15 mRNA and normalized bile acid synthesis in Slc10a2−/− mice. Pharmacologic inhibition of Slc10a2 in diabetic ob/ob mice reduced serum glucose, insulin and TGs, as well as hepatic mRNA levels of Srebp1c and its target genes. These responses are contrary to those reported following treatment of mice with a bile acid binding resin. Moreover, when key metabolic signal transduction pathways in the liver were investigated, those of Mek1/2 - Erk1/2 and Akt were blunted after treatment of ob/ob mice with the Slc10a2 inhibitor. It is concluded that abrogation of Slc10a2 reduces hepatic Srebp1c activity and serum TGs, and in the diabetic ob/ob model it also reduces glucose and insulin levels. Hence, targeting of Slc10a2 may be a promising strategy to treat hypertriglyceridemia and diabetes.
Leucine kinetics from [2H3]- and [13C]leucine infused simultaneously by gut and vein.

In amino acid tracer kinetic studies of the fed state, ingested amino acid may be taken up during its initial transit through splanchnic tissues and thus not enter the plasma compartment where tracer is infused. To investigate this possibility, adult human subjects received simultaneous intravenous (iv) and intragastric (ig) leucine tracer infusions, first during a postabsorptive (PA) 4-h primed continuous ig infusion of L-[1-13C]-leucine and L-[5,5,5-2H3]leucine iv, followed on a separate day by a fed infusion, in which an ig infusion of a liquid formula was started 2 h before the tracer infusion and continued throughout the tracer study. Subjects were accustomed to a constant experimental diet supplying 1.5 g protein.kg-1.day-1 and 41-45 kcal.kg-1.day-1 for 7 and 12 days before the PA and fed studies, respectively. For the PA study, plasma enrichment for the ig tracer was 3.34 +/- 0.27 (SE) mol + excess and for the iv tracer it was 4.18 +/- 0.10 (P less than 0.02). Enrichments of alpha-keto-isocaproic acid (KIC) were 3.24 +/- 0.16 (ig) and 3.02 +/- 0.14 (iv), respectively [not significant (NS)]. For the fed study, plasma leucine enrichment for the ig tracer was 2.15 +/- 0.14 and for the iv tracer was 2.84 +/- 0.09 (P less than 0.02). KIC enrichments were 2.02 +/- 0.08 (ig) and 2.24 +/- 0.08 (iv), respectively (NS). In the PA study, the ratio of the plasma leucine enrichments for the ig and iv tracers was 0.80 +/- 0.06 and in the fed experiment, 0.76 +/- 0.05, respectively. (ABSTRACT TRUNCATED AT 250 WORDS)
Step-Indexed Relational Reasoning for Countable Nondeterminism

Programming languages with countable nondeterministic choice are computationally interesting since countable nondeterminism arises when modeling fairness for concurrent systems. Because countable choice introduces non-continuous behaviour, it is well-known that developing semantic models for programming languages with countable nondeterminism is challenging. We present a step-indexed logical relations model of a higher-order functional programming language with countable nondeterminism and demonstrate how it can be used to reason about contextually defined may- and must-equivalence. In earlier step-indexed models, the indices have been drawn from omega. Here the step-indexed relations for must-equivalence are indexed over an ordinal greater than omega.
Retrospective study of two biochemical markers for the risk assessment of oral bisphosphonate-related osteonecrosis of the jaws: can they be utilized as risk markers?

PURPOSE the purpose of this retrospective study was to examine the possibility of utilizing serum C-terminal telopeptide cross-link of type I collagen (s-CTX) and serum osteocalcin (s-OC) as risk markers for oral bisphosphonate-related osteonecrosis of the jaws (BRONJ). PATIENTS AND METHODS the s-CTX values and the s-OC values were measured from 23 patients (one male, 22 females) diagnosed with BRONJ using clinical and radiographic examinations. The two biochemical markers were evaluated during a regular checkup for osteoporosis management. For the control group of s-CTX study, s-CTX values were obtained from 61 independently recruited postmenopausal women who have been on bisphosphonate therapy for >6 months. The s-CTX values of the ONJ group and the control group were compared. Because of retrospective nature of this study, the control group for s-OC study could not be established. A single sample t-test was performed for the s-OC value from the ONJ group. RESULT twenty-three ONJ patients had taken alendronate for osteoporosis treatment, and the s-CTX testing results were low levels of 10-192 pg/ml (mean: 93.2 ± 49.4 pg/ml). Mean of s-CTX of the control (n=61) was 125 ± 85.7 pg/ml. The duration of BP therapy ranged between 1 and 10 years (4.82 ± 2.6). The s-OC level was estimated between 0.2 and 5.4 ng/ml (1.91 ± 1.51 ng/ml). The mean s-CTX value of the control group was higher but without significance (P=0.12). The s-OC values of the ONJ group were significantly lower than the lowest value of the reference range (P<0.001). CONCLUSION as a result of the s-CTX and s-OC testings at the diagnosis of BRONJ, the values of the two markers were decreased. The decrease of the s-OC values implies a problem during the bone-formation process. Therefore, we can assume that in this patient group, invasive dental surgery contributes to an increase in the risk of BRONJ incidence. This result may imply that, during bisphosphonate therapy, simultaneous consideration of s-CTX showing inhibition of bone resorption and s-OC indicating the degree of bone formation might be a set of risk markers assessing risk prediction for BRONJ before invasive dental surgery.
Cerebral Metabolic Alterations in Rats With Diabetic Ketoacidosis

OBJECTIVE Cerebral edema is a life-threatening complication of diabetic ketoacidosis (DKA) in children. Recent data suggest that cerebral hypoperfusion and activation of cerebral ion transporters may be involved, but data describing cerebral metabolic alterations during DKA are lacking. RESEARCH DESIGN AND METHODS We evaluated 50 juvenile rats with DKA and 21 normal control rats using proton and phosphorus magnetic resonance spectroscopy (MRS). MRS measured cerebral intracellular pH and ratios of metabolites including ATP/inorganic phosphate (Pi), phosphocreatine (PCr)/Pi, N-acetyl aspartate (NAA)/creatine (Cr), and lactate/Cr before and during DKA treatment. We determined the effects of treatment with insulin and intravenous saline with or without bumetanide, an inhibitor of Na-K-2Cl cotransport, using ANCOVA with a 2 × 2 factorial study design. RESULTS Cerebral intracellular pH was decreased during DKA compared with control (mean ± SE difference −0.13 ± 0.03; P < 0.001), and lactate/Cr was elevated (0.09 ± 0.02; P < 0.001). DKA rats had lower ATP/Pi and NAA/Cr (−0.32 ± 0.10, P = 0.003, and −0.14 ± 0.04, P < 0.001, respectively) compared with controls, but PCr/Pi was not significantly decreased. During 2-h treatment with insulin/saline, ATP/Pi, PCr/Pi, and NAA/Cr declined significantly despite an increase in intracellular pH. Bumetanide treatment increased ATP/Pi and PCr/Pi and ameliorated the declines in these values with insulin/saline treatment. CONCLUSIONS These data demonstrate that cerebral metabolism is significantly compromised during DKA and that further deterioration occurs during early DKA treatment—consistent with possible effects of cerebral hypoperfusion and reperfusion injury. Treatment with bumetanide may help diminish the adverse effects of initial treatment with insulin/saline.
Novel Nuclear Shuttle Proteins, HDBP1 and HDBP2, Bind to Neuronal Cell-specific cis-Regulatory Element in the Promoter for the Human Huntington's Disease Gene*

Huntington's disease (HD) is a neurodegenerative disease caused by a CAG repeat expansion in exon 1 of the HD gene, and the expression level of either normal or mutant huntingtin is implicated in the pathogenesis of HD. However, a molecular base of the HD gene transcription has not been elucidated as yet. In this study, we identified two proteins, HDBP1 and HDBP2, which bind to the promoter region for the HD gene using a yeast one-hybrid system. Amino acid sequence analysis of the proteins deduced the presence of nuclear localization signal, nuclear export signal, zinc finger, serine/proline-rich region, and highly conserved C-terminal region. In vitro DNA binding assay indicated that the C-terminal conserved regions of the proteins were responsible for binding to the unique promoter DNA sequences of the HD gene. The DNA sequence protected from DNase I digestion was a 7-bp consensus sequence (GCCGGCG), which resides in triplicate at intervals of 13 bp within and proximal to the 20-bp direct repeat sequences of the HD promoter region. The mutation of 7-bp consensus sequence abolishes the HD promoter function in a neuronal cell line (IMR32). In human cultured cells, ectopically expressed green fluorescent protein-fused HDBP1 and HDBP2 localized in the cytoplasm, but both proteins totally shift from cytoplasm to nucleus by the treatment with an inhibitor of the nuclear export, leptomycin B, and mutagenesis of the putative nuclear export signals. Taken together, HDBP1 and HDBP2 are novel transcription factors shuttling between nucleus and cytoplasm and bind to the specific GCCGGCG, which is an essential cis-element for HD gene expression in neuronal cells.
Flow cytometry in the diagnosis and classification of malignant lymphoma and leukemia

DNA content and light scatter were measured by flow cytometry (FCM) in 103 patients including 43 patients with non‐Hodgkin's lymphoma (NHL), eight patients with Hodgkin's disease (HD), 17 patients with acute lymphoblastic leukemia (ALL), ten patients with acute nonlymphocytic leukemia (ANLL), and 25 patients with chronic lymphoid leukemias. Controls consisted of 42 nonneoplastic specimens obtained from lymph nodes, spleen, bone marrow, and peripheral blood. Each specimen was analyzed after staining with a hypotonic solution of propidium iodide using nuclei isolated from chicken erythrocytes as an internal standard. The DNA content and light scatter of the human populations was expressed as a ratio between the DNA content (or light scatter) of the human G0‐G1 cells and that of the chicken erythrocyte nuclei. The mean DNA ratio for the 42 nonneoplastic samples was 2.58 ± 0.045 (SD). In these samples the DNA coefficient of variation of the human G0‐G1 peak ranged from 1.48–3.28% (mean, 2.33 ± 0.54%). The FCM data in the NHL was compared to morphologic diagnoses made according to the “working formulation of NHL for clinical usage” recently proposed by a panel of international experts. Eight of 17 (47%) low grade NHL, one of two (50%) mycosis fungoides, ten of 14 (71%) intermediate grade NHL, nine of ten (90%) high grade NHL, nine of 17 (53%) ALL, three of ten (30%) ANLL, and seven of 25 (28%) chronic lymphoid leukemias had abnormal DNA ratios indicative of aneuploidy. In addition, several cases had normal DNA ratios but G0−G1 coefficients of variation outside of the normal range. All cases of HD had normal DNA values except one case with a small percentage of near tetraploid cells. The mean percentage of cells with S‐phase DNA content for the low grade NHL (2.2 ± 0.8%) was significantly lower than that of the intermediate grade NHL (12.1 ± 4.9%; P < 0.0001). The mean S‐phase value for the intermediate grade NHL was significantly lower than that of the high grade NHL (22.6 ± 11.1%; P < 0.001). The three prognostic categories of NHL designated by the new formulation were clearly distinguishable by the FCM data. Light scatter was not particularly useful for distinguishing nonneoplastic from neoplastic populations. The mean light scatter coefficient of variation of the ALL (15.2%) was significantly lower than that of ANLL (20.5%), however (P < 0.04).
Electromagnetic modeling of terahertz quantum cascade laser waveguides and resonators

Finite-element numerical modeling and analysis of electromagnetic waveguides and resonators used in terahertz quantum cascade lasers are presented. Both metal-metal and semi-insulating (SI) surface-plasmon ridge waveguide geometries were investigated. Simulations and analysis of two types were performed: two-dimensional waveguides (eigenmode calculation), and two- and three-dimensional resonators (facet reflectivity calculation for infinite width and finite width waveguides, respectively). Waveguide simulations extend previous transverse one-dimensional analyses to two dimensions (for the lateral and transverse dimensions), and quantify the breakdown of the one-dimensional approximation as the ridge width is reduced. Resonator simulations in two and three dimensions are presented and are used to obtain facet reflectivities and output radiation patterns. For the metal-metal waveguide structures, these resonator simulations quantitatively show strong deviations for terahertz facet reflectivities from those .
Data Science for Software Maintenance

Maintaining and evolving modern software systems is a difficult task: their scope and complexity mean that seemingly inconsequential changes can have far-reaching consequences. Most software development companies attempt to reduce the number of faults introduced by adopting maintenance processes. These processes can be developed in various ways. In this thesis, we argue that data science techniques can be used to support process development. Specifically, we claim that robust development processes are necessary to minimize the number of faults introduced when evolving complex software systems. These processes should be based on empirical research findings. Data science techniques allow software engineering researchers to develop research insights that may be difficult or impossible to obtain with other research methodologies. These research insights support the creation of development processes. Thus, data science techniques support the creation of empiricallybased development processes. We support this argument with three examples. First, we present insights into automated malicious Android application (app) detection. Many of the prior studies done on this topic used small corpora that may provide insufficient variety to create a robust app classifier. Currently, no empirically established guidelines for corpus size exist, meaning that previous studies have used anywhere from tens of apps to hundreds of thousands of apps to draw their conclusions. This variability makes it difficult to judge if the findings of any one study generalize. We attempted to establish such guidelines and found that 1,000 apps may be sufficient for studies that are concerned with what the majority of apps do, while more than a million apps may be required in studies that want to identify outliers. Moreover, many prior studies of malicious app detection used outdated malware corpora in their experiments that, combined with the rapid evolution of the Android API, may have influenced the accuracy of the studies. We investigated this problem by studying 1.3 million apps and showed that the evolution of the API does affect classifier accuracy, but not in the way we originally predicted. We also used our API usage data to identify the most infrequently used API methods. The use of data science techniques allowed us to study an order of magnitude more apps than previous work in the area; additionally, our insights into infrequently used methods illustrate how data science can be used to guide API deprecation. Second, we present insights into the costs and benefits of regression testing. Regression test suites grow over time, and while a comprehensive suite can detect faults that are introduced into the system, such a suite can be expensive to write, maintain, and execute. These costs may or may not be justified, depending on the number and severity of faults the suite can detect. By studying 61 projects that use Travis CI, a continuous integration system, we were able to characterize the cost/benefit tradeoff of their test suites. For
Baseline evidence-based practice use, knowledge, and attitudes of allied health professionals: a survey to inform staff training and organisational change.

AIM Evidence-based practice (EBP) is fundamental to improving patient outcomes. Universal adoption of EBP into the allied health clinical setting has not yet occurred. The primary aim of this project was to capture baseline measurements of the level of EBP self-efficacy, outcome expectancy, knowledge and use at our health service prior to training and organisational changes to support EBP. METHODS All allied health staff (n=252) employed across the campus were invited to participate in an online survey consisting of a battery of validated and reliable survey tools. Professional background, knowledge and previous training in EBP and research processes were collected. RESULTS One hundred eighty-two allied health staff completed the survey (response rate 72%). One-way ANOVAs were used to compare levels of self-efficacy, outcome expectancy, knowledge and use, according to allied health discipline and experience with EBP and research processes. Mean scores for EBP attitudes (self-efficacy and outcome expectancy) and knowledge were higher than for use. Professional group differences were noted in the post-hoc analysis of the significant EBP constructs. Regression analyses indicated that EBP course attendance as well as training in research design and analysis impacted positively on EBP construct scores. CONCLUSIONS Despite positive attitudes about, a belief in and knowledge of EBP, self-reports of EBP processes do not indicate systematic application in the allied health workplace. The results of this research will inform a targeted intervention to foster ongoing training in EBP and research activity for allied health staff.
Lymphovascular Invasion in Colorectal Cancer: An Interobserver Variability Study

Background Lymphovascular invasion (LVI) in colorectal cancer (CRC) is considered a strong stage-independent prognostic factor and influences decisions regarding adjuvant chemotherapy in patients with stage II tumors. However, the degree of interobserver agreement among pathologists for LVI in CRC is largely unknown. This study was undertaken to examine such interobserver variability, and we hypothesized that the use of immunohistochemical markers for vascular and lymphatic channels could improve interobserver agreement. Design Fifty cases of American Joint Committee on Cancer stage II moderately differentiated CRC from 1990 to 2005 from the pathology archives were selected; mucinous, medullary, and other recognized special subtypes were excluded. Fifty hematoxylin and eosin (H&E) slides (1 from each case) were circulated to 6 gastrointestinal pathologists, who independently assessed small and large vessel invasion. No diagnostic guidelines were given to the participating pathologists; each was instructed to apply the criteria for LVI that he or she used in daily practice. Immunohistochemistry (IHC) for D2-40 and CD31 was performed on corresponding paraffin blocks. The IHC slides were randomized, recirculated, and rescored for LVI. Results were analyzed by kappa (κ) statistics, which correct for agreement by chance, and for percentage agreement. Results The average κ values were determined for the H&E slides (large and small vessel), CD31 (small vessel), and D2-40 (small vessel) (Fig. 1). Agreement was fair for H&E small vessel invasion [κ=0.28; 95% confidence interval (CI): 0.22-0.34]. The least agreement was seen in interpretation of H&E large vessel invasion (κ=0.18; 95%CI: 0.11-0.26). Agreement was not improved by use of immunohistochemical stains: CD31 (large vessel, κ=0.42, 95%CI: 0.20-0.63, small vessel, κ=0.26, 95%CI: 0.10-0.42) and D2-40 (κ=0.32, 95%CI: 0.21-0.42). Conclusions Interobserver variability in diagnosis of LVI was substantial on H&E slides and did not improve upon use of IHC. Agreement in evaluation of large vessel invasion was only slightly higher than would be seen by chance alone. This study highlights the need for criteria in evaluation of LVI, as this assessment may impact patient prognosis and thus change the course of clinical treatment.