Miracle-dz/UniFAR-FTUs huggingface dataset:
Susceptibility of clinical isolates of Candida lusitaniae to five systemic antifungal agents.

OBJECTIVES The aim of the present study was to expand the MIC database for Candida lusitaniae in order to further determine its antifungal susceptibility pattern. METHODS The activities of amphotericin B, fluconazole, itraconazole, voriconazole and flucytosine were determined in vitro against 80 clinical isolates of C. lusitaniae. A set of 59 clinical isolates of Candida albicans and of 51 isolates of Candida glabrata was included to compare the susceptibilities to amphotericin B. The MICs were determined by Etest with RPMI 1640 agar, and with both this medium and antibiotic medium 3 (AM3) agar for testing of amphotericin B. RESULTS All isolates were highly susceptible to fluconazole. The susceptibility to itraconazole was good; only 4% of isolates had dose-dependent susceptibility (MICs 0.25-0.5 mg/L). Voriconazole was very active in vitro (100% of isolates were inhibited at < or =0.094 mg/L). Flucytosine MICs ranged widely (0.004->32 mg/L). The set included 19% of flucytosine-resistant isolates. For amphotericin B, 100% of isolates were inhibited at < or =0.75 mg/L (MIC(50) 0.047 mg/L; MIC(90) 0.19 mg/L) and at < or =4 mg/L (MIC(50) 0.25 mg/L; MIC(90) 0.75 mg/L) on RPMI and on AM3, respectively. A single isolate was categorized as resistant to amphotericin B (MIC 0.75 and 4 mg/L on RPMI and on AM3, respectively). Amphotericin B thus appeared very active in vitro against C. lusitaniae. Whatever the test medium, the level of susceptibility of C. lusitaniae to amphotericin B did not differ much from those of C. albicans and C. glabrata. CONCLUSION C. lusitaniae appears to be susceptible to amphotericin B, azole antifungal agents, and, to a lesser extent, flucytosine.
Far from the Tree? Do Private Entrepreneurs Agglomerate Around Public Sector Incumbents During Economic Transition?

While it is well known that state enterprises in transition economies were displaced by private enterprises at a macro level, little is known about whether private entrepreneurs emerged in a way that helped preserve or shift preexisting agglomerations of industrial activity at a microgeographic level. To address this question, we integrate competing perspectives on the role of large, bureaucratic incumbents in spawning entrepreneurs. We conceptualize a trade-off between two countervailing effects of large incumbents on potential entrepreneurs: bureaucratic socialization and exposure to capabilities. This yields novel predictions about how different kinds of startups agglomerate around different kinds of incumbents. We test these predictions using fine-grained geographic data on founding rates by private entrepreneurs in China's bicycle manufacturing industry. Consistent with our theorized trade-off, we find evidence of a nonmonotonic effect of incumbent size on local founding rates by private entrepreneurs. Additional moderating effects are consistent with boundary conditions on the hypothesized mechanisms. Our results provide the first empirical investigation of the extent to which entrepreneurial activity agglomerated around public sector incumbents during economic transition. We discuss how these insights add to the understanding of economic transition as well as how the context of economic transition adds to the understanding of entrepreneurial spawning.
Hantavirus Nucleocapsid Protein Has Distinct m7G Cap- and RNA-binding Sites*

Hantaviruses, members of the Bunyaviridae family, are emerging category A pathogens that carry three negative stranded RNA molecules as their genome. Hantavirus nucleocapsid protein (N) is encoded by the smallest S segment genomic RNA (viral RNA). N specifically binds mRNA caps and requires four nucleotides adjacent to the cap for high affinity binding. We show that the N peptide has distinct cap- and RNA-binding sites that independently interact with mRNA cap and viral genomic RNA, respectively. In addition, N can simultaneously bind with both mRNA cap and vRNA. N undergoes distinct conformational changes after binding with either mRNA cap or vRNA or both mRNA cap and vRNA simultaneously. Hantavirus RNA-dependent RNA polymerase (RdRp) uses a capped RNA primer for transcription initiation. The capped RNA primer is generated from host cell mRNA by the cap-snatching mechanism and is supposed to anneal with the 3′ terminus of vRNA template during transcription initiation by single G-C base pairing. We show that the capped RNA primer binds at the cap-binding site and induces a conformational change in N. The conformationally altered N with a capped primer loaded at the cap-binding site specifically binds the conserved 3′ nine nucleotides of vRNA and assists the bound primer to anneal at the 3′ terminus. We suggest that the cap-binding site of N, in conjunction with RdRp, plays a key role during the transcription and replication initiation of vRNA genome.
Contract-Based Incentive Mechanisms for Device-to-Device Communications in Cellular Networks

Device-to-device (D2D) communication is viewed as one promising technology for boosting the capacity of wireless networks and the efficiency of resource management. D2D communication heavily depends on the participation of users in sharing contents. Thus, it is imperative to introduce new incentive mechanisms to motivate such user involvement. In this paper, a contract-theoretic approach is proposed to solve the problem of providing incentives for D2D communication in cellular networks. First, using the framework of contract theory, the users' preferences toward D2D communication are classified into a finite number of types, and the service trading between the base station and users is properly modeled. Next, necessary and sufficient conditions are derived to provide incentives for users' engagement in D2D communication. Finally, our analysis is extended to the case in which there is a continuum of users. Simulation results show that the contract can effectively incentivize users' participation, and increase capacity of the cellular network than the other mechanisms.
Impact of Students Pharmacists on the Medication Reconciliation Process in High-Risk Hospitalized General Medicine Patients

Objective. To compare the accuracy of medication lists obtained by student pharmacists, nurses, and physicians, and quantify the number of discrepancies identified as part of the medication reconciliation process. Methods. Between May and July 2012, patients admitted to an internal medicine team at a 350-bed tertiary academic medical center were assessed for inclusion in the study. Physicians and/or nurses conducted medication reviews for these patients at the time of admission, while student pharmacists conducted medication reconciliation. Results. Eighty-six patients were assessed, and 52 met all inclusion criteria. A total of 268 discrepancies were identified as part of the medication reconciliation performed by the student pharmacists, approximating 5 discrepancies per patient (range 0-13). Student pharmacists identified 532 preadmission medications, significantly more than did nurses (355) or physicians (368), p=0.006. Conclusion. Student pharmacists, with appropriate oversight, can be used in several tasks that previously may have been designated to pharmacists only, such as medication reconciliation.
Kinetics of pharmacologic effects

Mathematical expressions derived from models based on the exponential decline of drug levels in the body and/or on a linear relationship between the intensity of the elicited effect and the logarithm of the dose can frequently be used to describe the rate of decline of a pharmacologic effect, the relationship between dose and duration of pharmacologic activity, and the effect of repeated drug administration. Pharmacokinetic analysis of pharmacologic activity data can lead to better understanding of the relationship between dose and the multiple pharmacologic effects elicited by a drug, and it can facilitate the assessment of factors which account for individual variations in the response to drugs. Under certain conditions, rate constants for drug absorption and drug elimination may be determined from pharmacologic activity rather than from blood levels or urinary excretion rates of the drug. Examples are presented which illustrate the application of these concepts.
Evaluation of potent inhibitors of dihydrofolate reductase in a culture model for growth of Pneumocystis carinii

Many antifolates are known to inhibit dihydrofolate reductase from murine Pneumocystis carinii, with 50% inhibitory concentrations (IC50s) ranging from 10(-4) to 10(-11) M. The relationship of the potency against isolated enzyme to the potency against intact murine P. carinii cells was explored with 17 compounds that had proven selectivity for or potency against P. carinii dihydrofolate reductase. Pyrimethamine and one analog were inhibitory to P. carinii in culture at concentrations two to seven times the IC50s for the enzyme, suggesting that the compounds may enter P. carinii cells in culture. Methotrexate was a potent inhibitor of P. carinii dihydrofolate reductase, but the concentrations effective in culture were more than 1,000-fold higher than IC50s for the enzyme, since P. carinii lacks an uptake system for methotrexate. Analogs of methotrexate in which chlorine, bromine, or iodine was added to the phenyl ring had improved potency against the isolated enzyme but were markedly less effective in culture; polyglutamation also lowered the activity in culture but improved activity against the enzyme. Substitution of a naphthyl group for the phenyl group of methotrexate produced a compound with improved activity against the enzyme (IC50, 0.00019 microM) and excellent activity in culture (IC50, 0.1 microM). One trimetrexate analog in which an aspartate or a chlorine replaced two of the methoxy groups of trimetrexate was much more potent and was much more selective toward P. carinii dihydrofolate reductase than trimetrexate; this analog was also as active as trimetrexate in culture. These studies suggest that modifications of antifolate structures can be made that facilitate activity against intact organisms while maintaining the high degrees of potency and the selectivities of the agents can be made.
Quantum Mechanics_Statistical mechanics

The present understanding of the universe indicates that its fundamental laws are mechanical in nature, and that all physical systems are therefore governed by mechanical laws at a microscopic level. These laws are precise equations of motion that map any given initial state to a corresponding future state at a later time. There is however a disconnection between these laws and everyday life experiences, as we do not find it necessary (nor easy) to know exactly at a microscopic level the simultaneous positions and velocities of each molecule while carrying out processes at the human scale (for example, when performing a chemical reaction). Statistical mechanics is a collection of mathematical tools that are used to fill this disconnection between the laws of mechanics and the practical experience of incomplete knowledge.
Induction of apoptosis in human lymphocytes by human anti-HLA class I antibodies

Background. Ligation of MHC class I molecules expressed on T cells leads to both growth arrest and apoptosis. Although mouse anti-HLA class I monoclonal antibodies (mAbs) have been previously shown to cause apoptosis of human cells, an apoptosis-inducing capacity of human anti-HLA class I antibodies on human lymphocytes has not been reported. Because this is of potential clinical relevance, we tested human anti-HLA class mAbs for their capacity to induce apoptosis. Methods. Twenty-five human HLA class mAbs and mouse mAb W6/32 were tested on resting human peripheral blood mononuclear cells or Jurkat lymphoblastic T cells using the Annexin-V binding and immunobinding assays. Results. We demonstrated that HLA class I human mAbs are able to induce apoptosis as early as 1 hr after treatment of resting human peripheral blood mononuclear cells or Jurkat lymphoblastic T cells. The apoptosis-inducing effect and the binding of anti-HLA mAbs to the cells were strongly increased when lymphoblasts were prestimulated with cytokines, such as interferon-&ggr; and interleukin-2. Induction of apoptosis increased with the dosage and binding of anti-HLA mAbs. Caspase inhibitors did not affect apoptosis induced by MHC class I ligation. Conclusions. Our study showed for the first time that human HLA class I mAbs induce rapid and strong apoptosis in resting human peripheral blood mononuclear cells and Jurkat T lymphoblasts.
Community and Nursing Home Residents with Carbapenemase-Producing Klebsiella pneumoniae Infection

deficits regarding CLABSI prevention, nor were we able to obtain postintervention data on compliance with hand hygiene and central venous catheter access and maintenance bundles. Further work is planned for ongoing collaboration and tracking of infection rates over time. Despite these limitations, the CUORE pilot project demonstrated that real-time interactive conferences for healthcare providers placed in remote pediatric ICUs are feasible and yield a high satisfaction among participants. Future efforts should concentrate on sustaining online training programs for a longer time, eventually involving multiple centers at the same time. We believe this model would also be appropriate for critical care topics other than CLABSI rate reduction. In addition to continuing the CUORE program, we are aiming at developing further online resources (eg, a CUORE Web site containing lecture material).
Effect of AR-R 17477, a potent neuronal nitric oxide synthase inhibitor, on infarction volume resulting from permanent focal ischemia in rats.

OBJECTIVE We tested whether AR-R 17477, a selective inhibitor of neuronal nitric oxide synthase, reduces brain injury in rats subjected to permanent focal ischemia. DESIGN Randomized within cohort; nonblinded study. SETTING University basic science laboratory. SUBJECTS Halothane-anesthetized male Wistar rats (n = 53). INTERVENTIONS Rats were treated with either intravenous saline (diluent) or AR-R 17477 (1 or 3 mg/kg) 30 mins before or 60 mins after the onset of permanent focal cerebral ischemia. Infarction volume was determined at 18 or 48 hrs of ischemia. MEASUREMENTS AND MAIN RESULTS Pretreatment with 1 mg/kg AR-R 17477 was associated with a decreased infarct volume (2,3,5-triphenyltetrazolium chloride staining) in the striatum (saline, 81+/-7 mm3; AR-R 17477, 55+/-3 mm3) but not in the cortex at 18 hrs of occlusion (saline, 302+/-29 mm3; AR-R 17477, 237+/-36 mm3). However, this therapeutic effect of AR-R 17477 was no longer evident if the rats were allowed to survive for 48 hrs before analysis of infarction volume. In fact, in this separate cohort of animals, three of eight AR-R 17477-treated and five of eight saline-treated rats died before completing 48 hrs of ischemia. Efficacy of AR-R 17477 was completely absent (even at 18 hrs of ischemia) when drug treatment was delayed until 1 hr after the onset of ischemia. Infarction volume at 18 hrs of ischemia was similar between rats treated with saline, 1 mg/kg (cortex, 229+/-43 mm3; striatum, 67+/-8 mm3) or 3 mg/kg AR-R 17477 (cortex, 284+/-34 mm3; striatum, 75+/-5 mm3). In addition, only one of eight rats treated with 3 mg/kg AR-R 17477 at 1 hr of ischemia survived 48 hrs of occlusion, compared with three of eight rats treated with saline. CONCLUSIONS Neuronally generated nitric oxide is a mediator of brain injury during permanent focal ischemia in rats. However, severity of the ischemic insult appears to limit the therapeutic efficacy of the specific neuronal nitric oxide synthase inhibitor, AR-R 17477.
Relaxation of the remanent magnetization of dilute anisotropic antiferromagnets.

The relaxation of the remanent magnetization of metastable domains in field-cooled, dilute antiferromagnets is studied with use of Monte Carlo simulations. The relaxation is extremely slow due to strong pinning by magnetic vacancies, as previously observed. The function M τ (t)=M 0 exp{-A[In(t/t')] y }, suggested by results of recent experiments on Fe 0.47 Zn 0.53 F 2 , is used to fit the simulation data and yields excellent fits with a greater than unity value for y, consistent with the experimental results
Does β-Hexosaminidase Function Only as a Degranulation Indicator in Mast Cells? The Primary Role of β-Hexosaminidase in Mast Cell Granules

β-Hexosaminidase, which is generally present in the lysosome, is essential for glycoprotein metabolism in the maintenance of cell homeostasis. In mast cells (MCs), large amounts of β-hexosaminidase are present in the granules as opposed to the lysosome, and the biological role of MC β-hexosaminidase has yet to be fully elucidated. Therefore, we investigated the biological role of β-hexosaminidase in MC granules. Bone marrow-derived MCs from C57BL/6 (BL/6-BMMC) or β-hexosaminidase gene–deficient (hexb−/−-BMMC) mice were transplanted into MC-deficient (WBB6F1/J-KitW/KitW-v [W/Wv]) mice to generate MC-reconstituted models. In asthma model experiments, no differences were observed in the symptoms of BL/6, W/Wv, BL/6-BMMC–reconstituted W/Wv, or hexb−/−-BMMC–reconstituted W/Wv mice. In Staphylococcus epidermidis experimental infection model experiments, the severity of symptoms and frequency of death were markedly higher in W/Wv and hexb−/−-BMMC–reconstituted W/Wv mice than in BL/6 and BL/6-BMMC–reconstituted W/Wv mice. The growth of S. epidermidis in an in vitro study was clearly inhibited by addition of BL/6-BMMC lysate, but not by addition of hexb−/−-BMMC lysate. Moreover, suppression of bacterial proliferation was completely recovered when bacteria were incubated with hexb−/−-BMMC lysate plus β-hexosaminidase. Transmission electron microscopy indicated that the cell wall of S. epidermidis was heavily degraded following coincubation of bacteria with BL/6-BMMC lysate, but not following coincubation with hexb−/−-BMMC lysate. These findings strongly suggest that MC granule β-hexosaminidase is crucial for defense against bacterial invasion, but is not involved in the allergic response. Our results also suggest that the bactericidal mechanism of β-hexosaminidase involves degradation of bacterial cell wall peptidoglycan.
Prenatal diagnosis before implantation: Opportunities and problems

One approach to prenatal diagnosis of hereditary disease is to remove a part of the conceptus for chromosomal or biochemical analysis, allowing the remainder to continue development if the results of the diagnostic procedure are favourable. In the second trimester, for example, fetal blood may be sampled with the aid of fetoscopy, or amniocentesis may be performed to recover amniotic cells. Because second trimester terminations are traumatic both for the patient and her family, and for the medical and nursing staff, methods of diagnosis that could be performed earlier in pregnancy would be greatly preferable. Several diseases can now be diagnosed at 8-12 weeks, on the basis of samples of chorionic villi, recovered usually through the cervix (WHO Report, 1983). If the embryo proves to be affected, the pregnancy can then be terminated before the end of the first trimester, at a stage when the women is less aware of the presence of her fetus, and her pregnancy is not yet apparent to others. Would it be possible to carry out prenatal diagnosis at a still earlier stage, before implantation? This would entail manipulating the conceptus in vitro and then inserting it into the mother’s uterus, since no way can be envisaged at present by which part of the preimplantation conceptus could be removed invivo. If the diagnostic procedure took longer than the conceptus could safely be maintained in culture, it would need to be stored, e.g. by freezing (Whittingham, 1980; Trounson and Mohr, 1983), until the results of the tests were known. Up to the onset of implantation the human conceptus is ‘free-living’ in the sense that it is not attached to the mother in any way, and the environment provided by the reproductive tract can be adequately mimicked by an in vitro culture system. BIastocysts can be recovered from the uterus by trans-cervical flushing (Croxatto et al., 1972; Buster et al., 1983); earlier cleavage stages are located in the Fallopian tube (Croxatto, 1974) from which they cannot be recovered by any simple procedure. Oocytes recovered from the ovary and fertilized in vitro would therefore need to be used if any manipulations were to be carried out during cleavage. Animal experiments suggest two possible approaches to preimplantation embryonic biopsy, one during cleavage and the other at the blastocyst stage. As we shall see, neither is very likely to prove practicable for the human conceptus in the immediate future.
CYP3A and ABCB1 Genetic Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Tacrolimus and Its Metabolites (M-I and M-III)

Background We prospectively studied renal transplant recipients receiving tacrolimus to determine the relationship between the CYP3A4, CYP3A5, and ABCB1 genetic polymorphisms and the pharmacokinetics (PK) and pharmacodynamics (PD) of tacrolimus and its metabolites. Methods Renal transplant recipients receiving tacrolimus were genotyped for CYP3A4*4, CYP3A4*5, CYP3A4*18, CYP3A5*3, ABCB1 c.1236C→T, ABCB1 c.2677G→A/T, and ABCB1 c.3435C→T. Dose-adjusted trough concentration (C0) of tacrolimus and its metabolites (M-I and M-III) and PK and PD (T-cell and monocyte subsets) were determined on transplantation days –2, 5, 30, and 90 and correlated with the corresponding genotypes. Results The dose-adjusted C0 of tacrolimus and its metabolites and AUC0–12 were significantly higher and the mean fluorescence intensity (MFI) of HLA/DR+ in monocytes was significantly lower in patients with CYP3A5*3/*3 than in patients with CYP3A5*1/*1 or CYP3A5*1/*3. However, there was no significant difference in the dose-adjusted C0 of tacrolimus and its metabolites, PK and PD among the ABCB1 genotypes. The MFI of HLA/DR+ in monocytes showed a significant negative correlation with dose-adjusted C0 of tacrolimus and its metabolites and AUC0–12. In a multiple regression analysis, the presence of the CYP3A5*3/*3 genotype was a significant independent variable determining the dose-adjusted C0 of tacrolimus and its metabolites, AUC0–12, and the MFI of HLA/DR+ in monocytes. Conclusions This study demonstrates that the CYP3A5 genetic polymorphisms are associated with the individual differences in PK and PD as well as in C0 of tacrolimus and its metabolites. The MFI of HLA/DR+ in monocytes might be considered to be a significant tool for monitoring tacrolimus efficacy.
Variational Bi-LSTMs

Recurrent neural networks like long short-term memory (LSTM) are important architectures for sequential prediction tasks. LSTMs (and RNNs in general) model sequences along the forward time direction. Bidirectional LSTMs (Bi-LSTMs), which model sequences along both forward and backward directions, generally perform better at such tasks because they capture a richer representation of the data. In the training of Bi-LSTMs, the forward and backward paths are learned independently. We propose a variant of the Bi-LSTM architecture, which we call Variational Bi-LSTM, that creates a dependence between the two paths (during training, but which may be omitted during inference). Our model acts as a regularizer and encourages the two networks to inform each other in making their respective predictions using distinct information. We perform ablation studies to better understand the different components of our model and evaluate the method on various benchmarks, showing state-of-the-art performance.
Prevalence of antibodies to Leptospira serovars in beef cattle in central Queensland

Conclusion These results are broadly similar to those of previous serological surveys. The data suggest that serovars other than hardjo, pomona and tarassovi, are unlikely to have a significant role in bovine subfertility and that cattle are unlikely to be a source of human infection with them in central Queensland. Aust Vet J 2001;79:344-348