Miracle-dz/UniFAR-FTUs huggingface dataset:
Challenge of Humans with Wild-type Salmonella enterica Serovar Typhi Elicits Changes in the Activation and Homing Characteristics of Mucosal-Associated Invariant T Cells

Gastrointestinal infections by Salmonella enterica serovar Typhi (S. Typhi) are rare in industrialized countries. However, they remain a major public health problem in the developing world with an estimated 26.9 million new cases annually and significant mortality when untreated. Recently, we provided the first direct evidence that CD8+ MAIT cells are activated and have the potential to kill cells exposed to S. Typhi, and that these responses are dependent on bacterial load. However, MAIT cell kinetics and function during bacterial infections in humans remain largely unknown. In this study, we characterize the human CD8+ MAIT cell immune response to S. Typhi infection in subjects participating in a challenge clinical trial who received a low- or high dose of wild-type S. Typhi. We define the kinetics of CD8+ MAIT cells as well as their levels of activation, proliferation, exhaustion/apoptosis, and homing potential. Regardless of the dose, in volunteers resistant to infection (NoTD), the levels of CD8+ MAIT cells after S. Typhi challenge fluctuated around their baseline values (day 0). In contrast, volunteers susceptible to the development of typhoid disease (TD) exhibited a sharp decline in circulating MAIT cells during the development of typhoid fever. Interestingly, MAIT cells from low-dose TD volunteers had higher levels of CD38 coexpressing CCR9, CCR6, and Ki67 during the development of typhoid fever than high-dose TD volunteers. No substantial perturbations on the levels of these markers were observed in NoTD volunteers irrespective of the dose. In sum, we describe, for the first time, that exposure to an enteric bacterium, in this case S. Typhi, results in changes in MAIT cell activation, proliferation, and homing characteristics, suggesting that MAIT cells are an important component of the human host response to bacterial infection.
Inhibition of phosphatidylinositol 3-kinase sensitizes ovarian cancer cells to carboplatin and allows adjunct chemotherapy treatment

Signal transduction pathways associated with cancer progression and chemotherapeutic resistance are being investigated as molecular targets for chemotherapy. The phosphatidylinositol 3-kinase (PI3K) pathway has been found to be frequently amplified and have increased activity in ovarian cancer. The current study investigates the efficacy of an antagonist of PI3K, LY294002, in inhibiting ovarian cancer cell growth and survival both in vitro and in vivo. The hypothesis tested is that inhibition of PI3K signaling makes ovarian cancer cells susceptible to the effects of platinum-based chemotherapy. Observations show that LY294002 is an effective inhibitor of ovarian cancer cell growth and survival in vitro. Inhibition of PI3K/Akt signaling increased the sensitivity of ovarian cell cultures to the cytotoxic effects of carboplatin. The combined treatment of LY294002 and carboplatin was needed to optimally promote cellular apoptosis and decrease ovarian cancer cell survival in vitro. To extend these observations, a model involving in vivo i.p. growth of human ovarian tumors in a nude mouse was used. LY294002 in combination with carboplatin was more effective in inhibiting ovarian cancer cell xenograft growth than either agent alone. The results of this study suggest that the combined treatment of carboplatin and LY294002 can effectively decrease ovarian tumor progression and support the use of a PI3K inhibitor (e.g., LY294002) as an adjunct platinum-based drug therapy for treatment of ovarian cancer.
Sequence-Based Screening for Rare Enzymes: New Insights into the World of AMDases Reveal a Conserved Motif and 58 Novel Enzymes Clustering in Eight Distinct Families

Arylmalonate Decarboxylases (AMDases, EC 4.1.1.76) are very rare and mostly underexplored enzymes. Currently only four known and biochemically characterized representatives exist. However, their ability to decarboxylate α-disubstituted malonic acid derivatives to optically pure products without cofactors makes them attractive and promising candidates for the use as biocatalysts in industrial processes. Until now, AMDases could not be separated from other members of the aspartate/glutamate racemase superfamily based on their gene sequences. Within this work, a search algorithm was developed that enables a reliable prediction of AMDase activity for potential candidates. Based on specific sequence patterns and screening methods 58 novel AMDase candidate genes could be identified in this work. Thereby, AMDases with the conserved sequence pattern of Bordetella bronchiseptica’s prototype appeared to be limited to the classes of Alpha-, Beta-, and Gamma-proteobacteria. Amino acid homologies and comparison of gene surrounding sequences enabled the classification of eight enzyme clusters. Particularly striking is the accumulation of genes coding for different transporters of the tripartite tricarboxylate transporters family, TRAP transporters and ABC transporters as well as genes coding for mandelate racemases/muconate lactonizing enzymes that might be involved in substrate uptake or degradation of AMDase products. Further, three novel AMDases were characterized which showed a high enantiomeric excess (>99%) of the (R)-enantiomer of flurbiprofen. These are the recombinant AmdA and AmdV from Variovorax sp. strains HH01 and HH02, originated from soil, and AmdP from Polymorphum gilvum found by a data base search. Altogether our findings give new insights into the class of AMDases and reveal many previously unknown enzyme candidates with high potential for bioindustrial processes.
The Impact of Posting URLs in Disaster-Related Tweets on Rumor Spreading Behavior

Twitter is an example of social media, which allows its users to post text messages, known as "tweets," of up to 140 characters. A tweet can include a shortened URL that provides further information that cannot be included in the tweet. Does including URLs in tweets influence the forwarding of the tweets during disasters, in which social media is flooded with unverified information? We conducted an experiment to answer this question. The results showed that posting URLs in disaster-related tweets increased rumor-spreading behavior even though the URLs lacked the hyperlink function. We identified some psychological factors that could explain this effect. We conclude by discussing the vulnerability of social media to rumor transmission in light of our results.
A double-blind placebo-controlled trial of low-dose ganciclovir to prevent cytomegalovirus disease after heart transplantation.

BACKGROUND The aim of this double-blind, placebo-controlled study was to determine whether a prolonged course of low-dose ganciclovir prevented the development of clinical cytomegalovirus disease after heart transplantation. METHODS Fifty-six consecutive patients were stratified into two groups: cytomegalovirus-positive recipients (n = 40) and cytomegalovirus-negative recipients of organs from cytomegalovirus-positive donors (n = 16). All patients received equine antithymocyte globulin induction for 7 days and maintenance doses of cyclosporine, azathioprine, and prednisolone. Ganciclovir (5 mg/kg intravenously) or matching placebo was given with the premedication, three times weekly for the first 6 weeks after transplantation and for another 2 weeks for each treated rejection episode between 6 and 12 weeks. RESULTS Ganciclovir prophylaxis reduced the actuarial incidence of cytomegalovirus disease from 71% to 11% in cytomegalovirus-mismatched patients (p < 0.01). Ganciclovir prophylaxis did not reduce the incidence of cytomegalovirus disease in cytomegalovirus-positive recipients (25% in both placebo and ganciclovir groups) but did delay its onset and reduce its morbidity. There were no adverse reactions during ganciclovir administration. Gastritis was the most common clinical manifestation of cytomegalovirus disease. Pneumonitis and myocarditis were seen only in placebo-treated cytomegalovirus-mismatched patients. All patients with clinical cytomegalovirus disease responded to ganciclovir, 10 mg/kg/day for 2 weeks. CONCLUSIONS Prolonged low-dose ganciclovir prophylaxis after heart transplantation reduces the incidence of cytomegalovirus disease in cytomegalovirus-mismatched patients and reduces the morbidity of cytomegalovirus disease in cytomegalovirus-positive recipients.
Risk of congenital cytomegalovirus infection among HIV‐exposed uninfected infants is not decreased by maternal nelfinavir use during pregnancy

Background: Congenital cytomegalovirus (cCMV) infection is common among infants born to HIV‐infected women. Nelfinavir (NFV), an antiretroviral drug that is safe during pregnancy, inhibits CMV replication in vitro at concentrations that standard doses achieve in plasma. We hypothesized that infants born to women receiving NFV for prevention of mother‐to‐child transmission of HIV (PMTCT) would have a reduced prevalence of cCMV infection. Methods: The prevalence of cCMV infection was compared among HIV‐uninfected infants whose HIV‐infected mothers either received NFV for >4 weeks during pregnancy (NFV‐exposed) or did not receive any NFV in pregnancy (NFV‐unexposed). CMV PCR was performed on infant blood samples collected at <3 weeks from birth. Results: Of the 1,255 women included, 314 received NFV for >4 weeks during pregnancy and 941 did not receive any NFV during pregnancy. The overall prevalence of cCMV infection in the infants was 2.2%, which did not differ by maternal NFV use. Maternal CD4 T cell counts were inversely correlated with risk of cCMV infection, independent of the time NFV was initiated during gestation. Infants with cCMV infection were born 0.7 weeks earlier (P = 0.010) and weighed 170 g less (P = 0.009) than uninfected infants. Conclusion: Among HIV‐exposed uninfected infants, cCMV infection was associated with adverse perinatal outcomes. NFV use in pregnancy was not associated with protection against cCMV. Safe and effective strategies to prevent cCMV infection are needed. J. Med. Virol. 88:1051–1058, 2016. © 2015 Wiley Periodicals, Inc.
Evaluation of Leymus chinensis quality using near-infrared reflectance spectroscopy with three different statistical analyses

Due to a boom in the dairy industry in Northeast China, the hay industry has been developing rapidly. Thus, it is very important to evaluate the hay quality with a rapid and accurate method. In this research, a novel technique that combines near infrared spectroscopy (NIRs) with three different statistical analyses (MLR, PCR and PLS) was used to predict the chemical quality of sheepgrass (Leymus chinensis) in Heilongjiang Province, China including the concentrations of crude protein (CP), acid detergent fiber (ADF), and neutral detergent fiber (NDF). Firstly, the linear partial least squares regression (PLS) was performed on the spectra and the predictions were compared to those with laboratory-based recorded spectra. Then, the MLR evaluation method for CP has a potential to be used for industry requirements, as it needs less sophisticated and cheaper instrumentation using only a few wavelengths. Results show that in terms of CP, ADF and NDF, (i) the prediction accuracy in terms of CP, ADF and NDF using PLS was obviously improved compared to the PCR algorithm, and comparable or even better than results generated using the MLR algorithm; (ii) the predictions were worse compared to laboratory-based spectra with the MLR algorithmin, and poor predictions were obtained (R2, 0.62, RPD, 0.9) using MLR in terms of NDF; (iii) a satisfactory accuracy with R2 and RPD by PLS method of 0.91, 3.2 for CP, 0.89, 3.1 for ADF and 0.88, 3.0 for NDF, respectively, was obtained. Our results highlight the use of the combined NIRs-PLS method could be applied as a valuable technique to rapidly and accurately evaluate the quality of sheepgrass hay.
Multivariate Statistical Analysis of Audit Trails for Host-Based Intrusion Detection

Intrusion detection complements prevention mechanisms, such as firewalls, cryptography, and authentication, to capture intrusions into an information system while they are acting on the information system. Our study investigates a multivariate quality control technique to detect intrusions by building a long-term profile of normal activities in information systems (norm profile) and using the norm profile to detect anomalies. The multivariate quality control technique is based on Hotelling's T/sup 2/ test that detects both counterrelationship anomalies and mean-shift anomalies. The performance of the Hotelling's T/sup 2/ test is examined on two sets of computer audit data: a small data set and a large multiday data set. Both data sets contain sessions of normal and intrusive activities. For the small data set, the Hotelling's T/sup 2/ test signals all the intrusion sessions and produces no false alarms for the normal sessions. For the large data set, the Hotelling's T/sup 2/ test signals 92 percent of the intrusion sessions while producing no false alarms for the normal sessions. The performance of the Hotelling's T/sup 2/ test is also compared with the performance of a more scalable multivariate technique-a chi-squared distance test.
Siblings' Reports of Conflict and the Quality of Their Relationships.

Associations were investigated between type of conflict resolution strategies (con structive vs. destructive) reported by siblings and relationship qualities, as well as the congruence between siblings' perceptions. Fifthand sixth-grade children (n = 34) and their closest-in-age siblings (a) rated siblings' affective relationship quality, and (b) reported on sibling conflict strategies. Results indicated that (a) focal siblings who engaged in more destructive conflicts reported greater negativism in their relationships, (b) frequency of conflict was positively correlated with destructive conflict, and (c) warmth was positively correlated with prosocial behavior and con structive conflict strategies. Findings reveal that constructive and destructive conflict strategies were differentially related to affective relationship quality and are dis cussed in light of recent conceptualizations.
Okadaic acid mimics a nuclear component required for cyclin B-cdc2 kinase microinjection to drive starfish oocytes into M phase

G2-arrested oocytes contain cdc2 kinase as an inactive cyclin B-cdc2 complex. When a small amount of highly purified and active cdc2 kinase, prepared from starfish oocytes at first meiotic metaphase, is microinjected into Xenopus oocytes, it induces activation of the inactive endogenous complex and, as a consequence, drives the recipient oocytes into M phase. In contrast, the microinjected kinase undergoes rapid inactivation in starfish oocytes, which remain arrested at G2. Endogenous cdc2 kinase becomes activated in both nucleated and enucleated starfish oocytes injected with cytoplasm taken from maturing oocytes at the time of nuclear envelope breakdown, but only cytoplasm taken from nucleated oocytes becomes able thereafter to release second recipient oocytes from G2 arrest, and thus contains M phase-promoting factor (MPF) activity. Both nucleated and enucleated starfish oocytes produce MPF activity when type 2A phosphatase is blocked by okadaic acid. If type 2A phosphatase is only partially inhibited, neither nucleated nor enucleated oocytes produce MPF activity, although both do so if purified cdc2 kinase is subsequently injected as a primer to activate the endogenous kinase. The nucleus of starfish oocytes contains an inhibitor of type 2A phosphatase, but neither active nor inactive cdc2 kinase. Microinjection of the content of a nucleus into the cytoplasm of G2-arrested starfish oocytes activates endogenous cdc2 kinase, produces MPF activity, and drives the recipient oocytes into M phase. Together, these results show that the MPF amplification loop is controlled, both positively and negatively, by cdc2 kinase and type 2A phosphatase, respectively. Activation of the MPF amplification loop in starfish requires a nuclear component to inhibit type 2A phosphatase in cytoplasm.
A Novel Redox Method for Rapid Production of Functional Bi-Specific Antibodies For Use in Early Pilot Studies

We demonstrate here a rapid alternative method for the production of functional bi-specific antibodies using the mild reducing agent 2-mercaptoethanesulfonic acid sodium salt (MESNA). Following reduction of a mixture of two monoclonal antibodies with MESNA to break inter heavy chain bonds, this solution is dialysed under oxidising conditions and antibodies are allowed to reform. During this reaction a mixture of antibodies is formed, including parental antibodies and bi-specific antibody. Bi-specific antibodies are purified over two sequential affinity columns. Following purification, bi-specificity of antibodies is determined in enzyme-linked immunosorbent assays and by flow cytometry. Using this redox method we have been successful in producing hybrid and same-species bi-specific antibodies in a time frame of 6–10 working days, making this production method a time saving alternative to the time-consuming traditional heterohybridoma technology for the production of bi-specific antibodies for use in early pilot studies. The use of both rat and mouse IgG antibodies forming a rat/mouse bi-specific antibody as well as producing a pure mouse bi-specific antibody and a pure rat bi-specific antibody demonstrates the flexibility of this production method.
Weight gain in breastfed infants of mothers taking antidepressant medications.

BACKGROUND Little is known about the physical development of infants who are exposed to antidepressant medications through breast milk. METHOD Seventy-eight breastfeeding women taking antidepressant medications were included in the study. Maternal mood was prospectively evaluated at 6, 12, and 18 months postpartum. Infants' weights were obtained from review of pediatric records. Data were gathered from 1997 to 2002. RESULTS Infants' weights were not significantly different from weights of 6-month-old breastfed infants from normative populations. However, infants of mothers who relapsed to relatively long-lasting major depressive episodes (lasting 2 months or more) following delivery weighed significantly (p =.002) less when compared with infants of mothers who relapsed to brief depressive episodes (< 2 months) and infants of mothers who did not relapse to depression in the postpartum period. This finding remained after including medication dosage and infant birth weight as covariates. CONCLUSION Exposure to antidepressant medications through breast milk does not appear to affect infants' weight. However, infants exposed to maternal depression lasting 2 months or more appear to experience significantly lower weight gain than infants of euthymic mothers or mothers who experience brief (< 2 months) major depressive episodes. Maternal depression following delivery may influence behaviors that, over the course of 2 months or more, affect infants' weight gain.
Automatic data and computation decomposition on distributed memory parallel computers

To exploit parallelism on shared memory parallel computers (SMPCs), it is natural to focus on decomposing the computation (mainly by distributing the iterations of the nested Do-Loops). In contrast, on distributed memory parallel computers (DMPCs), the decomposition of computation and the distribution of data must both be handled---in order to balance the computation load and to minimize the migration of data. We propose and validate experimentally a method for handling computations and data synergistically to minimize the overall execution time on DMPCs. The method is based on a number of novel techniques, also presented in this article. The core idea is to rank the "importance" of data arrays in a program and specify some of the dominant. The intuition is that the dominant arrays are the ones whose migration would be the most expensive. Using the correspondence between iteration space mapping vectors and distributed dimensions of the dominant data array in each nested Do-loop, allows us to design algorithms for determining data and computation decompositions at the same time. Based on data distribution, computation decomposition for each nested Do-loop is determined based on either the "owner computes" rule or the "owner stores" rule with respect to the dominant data array. If all temporal dependence relations across iteration partitions are regular, we use tiling to allow pipelining and the overlapping of computation and communication. However, in order to use tiling on DMPCs, we needed to extend the existing techniques for determining tiling vectors and tile sizes, as they were originally suited for SMPCs only. The overall method is illustrated on programs for the 2D heat equation, for the Gaussian elimination with pivoting, and for the 2D fast Fourier transform on a linear processor array and on a 2D processor grid.
Effects of H2 and Formate on Growth Yield and Regulation of Methanogenesis in Methanococcus maripaludis

ABSTRACT Hydrogenotrophic methanogenic Archaea are defined by an H2 requirement for growth. Despite this requirement, many hydrogenotrophs are also capable of growth with formate as an electron donor for methanogenesis. While certain responses of these organisms to hydrogen availability have been characterized, responses to formate starvation have not been reported. Here we report that during continuous culture of Methanococcus maripaludis under defined nutrient conditions, growth yields relative to methane production decreased markedly with either H2 excess or formate excess. Analysis of the growth yields of several mutants suggests that this phenomenon occurs independently of the storage of intracellular carbon or a transcriptional response to methanogenesis. Using microarray analysis, we found that the expression of genes encoding coenzyme F420-dependent steps of methanogenesis, including one of two formate dehydrogenases, increased with H2 starvation but with formate occurred at high levels regardless of limitation or excess. One gene, encoding H2-dependent methylene-tetrahydromethanopterin dehydrogenase, decreased in expression with either H2 limitation or formate limitation. Expression of genes for the second formate dehydrogenase, molybdenum-dependent formylmethanofuran dehydrogenase, and molybdenum transport increased specifically with formate limitation. Of the two formate dehydrogenases, only the first could support growth on formate in batch culture where formate was in excess.