Miracle-dz/UniFAR-FTUs huggingface dataset:
Voriconazole in the management of nosocomial invasive fungal infections

Voriconazole is a new triazole developed for the treatment of life-threatening fungal infections. The drug is available for both oral and intravenous administration; the oral formulation has excellent bioavailability. The side-effect profile of voriconazole presents an acceptable safety and tolerability spectrum: transient visual disturbances, liver enzyme abnormalities, and skin rashes are the most frequently reported side effects but rarely lead to discontinuation. The potential for drug–drug interactions is high, because of its extensive hepatic metabolism. Careful attention to dosage is required, and serum levels and the effects of interacting drugs should be monitored. Review of 25 470 isolates of yeasts and 3216 isolates of filamentous fungi showed voriconazole to have broad-spectrum activity against pathogenic yeasts including intrinsically fluconazole-resistant isolates such as Candida krusei, dimorphic fungi, and opportunistic moulds like Aspergillus spp, amphotericin-B-resistant Aspergillus terreus, Fusarium spp, and Scedosporium apiospermum. It displays excellent clinical efficacy in patients with fluconazole-resistant and -susceptible Candida infections, invasive bone and central nervous system aspergillosis, and various refractory fungal infections. Voriconazole has been approved by the US Food and Drug Administration and by the European Medicines Agency for the treatment of invasive aspergillosis, serious infections caused by Fusarium and S. apiospermum, fluconazole-resistant invasive Candida infections, and candidemia in nonneutropenic patients.
Severe preeclampsia and delivery outcomes: is immediate cesarean delivery beneficial?

OBJECTIVE This study was designed to determine whether immediate cesarean delivery for patients with severe preeclampsia confers any benefit to the mother or neonate. STUDY DESIGN This retrospective chart review included all deliveries complicated by severe preeclampsia between July 1, 1999, and June 30, 2000. Cesarean deliveries performed for malpresentation, previous classic incision, multiple gestation, placenta previa, and herpetic outbreak were not included. Demographic variables, maternal outcomes, and neonatal outcomes were collected. RESULTS Of 114 patients, 93 had an option regarding route of delivery. Thirty-four had an immediate cesarean section and 59 had induction of labor. Thirty-seven of 59 were delivered vaginally and 22 of 59 underwent cesarean delivery. Pulmonary complications in the mother and neonate were more common in cesarean delivery (P <.05). No morbidity was decreased by cesarean delivery. Bishop score and gestational age did not affect the labor induction success rate. CONCLUSION Immediate cesarean delivery confers no benefit to patients with severe preeclampsia.
Understanding the Evolutionary Fate of Finite Populations: The Dynamics of Mutational Effects

The most consistent result in more than two decades of experimental evolution is that the fitness of populations adapting to a constant environment does not increase indefinitely, but reaches a plateau. Using experimental evolution with bacteriophage, we show here that the converse is also true. In populations small enough such that drift overwhelms selection and causes fitness to decrease, fitness declines down to a plateau. We demonstrate theoretically that both of these phenomena must be due either to changes in the ratio of beneficial to deleterious mutations, the size of mutational effects, or both. We use mutation accumulation experiments and molecular data from experimental evolution to show that the most significant change in mutational effects is a drastic increase in the rate of beneficial mutation as fitness decreases. In contrast, the size of mutational effects changes little even as organismal fitness changes over several orders of magnitude. These findings have significant implications for the dynamics of adaptation.
The University of Birmingham ( Live System ) The time course of task-specific memory consolidation effects in resting state networks

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A Design Science Approach for Creating Mobile Applications

In addressing competition, telecommunications opera tors are faced with the challenge of creating products that lure customers from their competitors and keeping their existing customers. Researchers posit that the successful implementatio n and wide scale adoption of mobile commerce services is best achieved by understanding consumer s’ attitude, interests and needs. The purpose of this study is to utilize the design science paradigm to address the creation of a mobile valueadded service that meet the need of consumers and t o evaluate the said service for its suitability and potential adoption in Jamaica using the Technol ogy Acceptance Model. The results suggest that consumer interest is driven by events that are related to social experiences. The evaluation of the artifact highlighted that perceived ease of use , perceived usefulness, attitude and demographic variables, age and gender, play a role in the behav iour intention to adopt the service.
Current-Driven Domain Wall Motion : Velocity , Current and Phase Transition

The relation between domain wall motion and intensity of driven current is examined in a phenomenological theory where the kinetic energy is expanded as a series of polynomial function of current density just as the Landau phase transition theory. The dependency of velocity on current density is square root which degenerates into linear if the current is much higher than the critical value. The theory result is consistent with several previous experiments and also can explain the change of critical current in the presence of temperature. The role of temperature playing in the dynamics of domain wall motion is also discussed. The phase transition theory in terms of current density is employed to explain the critical behavior of domain wall motion.
Gap junction-mediated transfer of left-right patterning signals in the early chick blastoderm is upstream of Shh asymmetry in the node

The elaboration of left-right (LR) asymmetry during animal embryogenesis involves cascades of asymmetrically expressed genes (Fujinaga, 1996; Levin, 1998b). These genes regulate each others’ expression in sequential pathways consisting of inductions and repressions on the left and right sides of the embryo (Levin et al., 1995, 1997; Isaac et al., 1997; Levin, 1998a; Logan et al., 1998). Distinct left and right programs of gene expression have suggested that the left and right sides of the embryo function autonomously. This paradigm includes the notion of a midline barrier to prevent the inappropriate crossover of secreted signaling molecules (Danos and Yost, 1996; Levin et al., 1996; Harvey, 1998; Meno et al., 1998). Hensen’s node is an important signaling center for the orientation of LR asymmetry. During normal chick development, the left side of the node expresses higher levels of Shh which in turn activates a cascade of gene expression in the left lateral plate, eventually inducing Nodal and Pitx2 (Harvey, 1998; Levin, 1998b). Several lines of evidence suggest that LR pattern does not originate in the node but, rather, that it responds to signals from elsewhere in the blastoderm. When the node is ablated, it regenerates with correct LR asymmetry, as assessed by expression of the leftsided gene Shh (Psychoyos and Stern, 1996). In contrast, portions of the blastoderm, when cultured separately, also regenerate the node, but without proper patterning of the LR axis (Levin and Mercola, 1998b; Yuan and Schoenwolf, 1998). One interpretation of these observations is that signals from potentially distant regions of the blastodisc may be required upstream of LR patterning of Hensen’s node. In this paper, we describe experiments directed at 4703 Development 126, 4703-4714 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 DEV4222
Tailoring Lexical Choice to the User’s Vocabulary in Multimedia Explanation Generation

In this paper, we discuss the different strategies used in COMET (COordinated Multimedia Explanation Testbed) for selecting words with which the user is familiar. When pictures cannot be used to disambiguate a word or phrase, COMET has four strategies for avoiding unknown words. We give examples for each of these strategies and show how they are implemented in COMET.
Age‐dependent generation of reactive oxygen species in the skin of live hairless rats exposed to UVA light

Abstract: Aging proceeds by highly complicated biochemical processes, in which the involvement of the reactive oxygen species (ROS) and free radicals has been implicated. Although the relationship between UV‐induced photoaging and ROS generation has been proposed, it has been difficult to establish direct proof of the generation of ROS in the skin under UV exposure. Recently, we reported finding endogenously generated ROS in the skin of live mice after UVA light exposure by a method of in vivo chemiluminescent detection, in which superoxide anion radical (·O2–) and singlet oxygen species (1O2) are contributed. In light of the results, we tried to understand the age‐dependent changes in ROS generation in the skin of hairless rats under UVA exposure. Chemiluminescent levels due to ROS in the untreated and UVA‐exposed skin decreased age dependently, and the signal intensities in old rats were significantly lower than those in young rats. However, the ratios of chemiluminescent intensities in the UVA‐exposed skin to those in the untreated skin were significantly enhanced in an age‐dependent manner. These results suggest that the antioxidative ability against ROS generation in the skin, possessed by antioxidant enzymes and low molecular weight antioxidants, is lowered age dependently.
CECOS: A Chinese-English code-switching speech database

With the increase on the demands for code-switching automatic speech recognition (ASR), the design and development of a code-switching speech database becomes highly desirable. However, it is not easy to collect sufficient code-switched utterances for model training for code-switching ASR. This study presents the procedure and experience for the design and development of a Chinese-English COde-switching Speech database (CECOS). Two different methods for collecting Chinese-English code-switched utterances are employed in this work. The applications of the collected database are also introduced. The CECOS database not only contains the speech data with code-switch properties but also accents due to non-native speakers. This database can be applied to several applications, such as code-switching speech recognition, language identification, named entity detection, etc.
Efficacy of Nucleot(s)ide Analogs Therapy in Patients with Unresectable HBV-Related Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Aim. To determine whether nucleot(s)ide analogs therapy has survival benefit for patients with HBV-related HCC after unresectable treatment. Method. A systematic search was conducted through seven electronic databases including PubMed, OVID, EMBASE, Cochrane Databases, Elsevier, Wiley Online Library, and BMJ Best Practice. All studies comparing NA combined with unresectable treatment versus unresectable treatment alone were considered for inclusion. The primary outcome was the overall survival (OS) after unresectable treatment for patients with HBV-related HCC. The secondary outcome was the progression-free survival (PFS). Results were expressed as hazard ratio (HR) for survival with 95% confidence intervals. Results. We included six studies with 994 patients: 409 patients in nucleot(s)ide analogs therapy group and 585 patients without antiviral therapy in control group. There were significant improvements for the overall survival (HR = 0.57; 95% CI = 0.47–0.70; p < 0.001) and progression-free survival (HR = 0.84; 95% CI = 0.71–0.99; p = 0.034) in the NA-treated group compared with the control group. Funnel plot showed that there was no significant publication bias in these studies. When it comes to antiviral drugs and operation method, it also showed benefit in NA-treated group. At the same time, overall mortality as well as mortality secondary to liver failure in NA-treated group was obviously lesser. Sensitivity analyses confirmed the robustness of the results. Conclusions. Nucleot(s)ide analogs therapy after unresectable treatment has potential beneficial effects in terms of overall survival and progression-free survival. NA therapy should be considered in clinical practice.
Electrical impedance tomography problem with inaccurately known boundary and contact impedances

In electrical impedance tomography (EIT) the conductivity function inside a body is reconstructed based on current and voltage data on the boundary of the body. The traditional setting for the EIT problem assumes that the boundary of the body and the electrode-skin contact impedances are known a priori. However, in clinical experiments one usually lacks the exact knowledge of the boundary and contact impedances, and it has been noticed that even small errors in the shape of the computation domain or contact impedances can cause large systematic artefacts in the reconstructed images. In this paper, we propose a novel reconstruction method in which the systematic errors caused by inaccurately known boundary and contact impedances are eliminated as part of the image reconstruction. The method is tested with real EIT data
Specific regulation of rat glial cell line‐derived neurotrophic factor gene expression by riluzole in C6 glioma cells

Contrasting with its robust expression during embryogenesis, the glial cell line‐derived neurotrophic factor (GDNF) is repressed in the adult organism. However, rapid induction of this neuronal growth factor is observed following diverse neuronal insults and it is now widely accepted that the control of its expression could constitute a powerful target in neuropharmacology. We investigated the effects of the neuroprotective drug, riluzole, on the GDNF gene expression in glial cells. Exposure of C6 glioma cells to riluzole (1 µm) significantly increased GDNF protein and mRNA levels. Using luciferase reporter gene constructs encoding fragments of the 5′ untranslated region of the rat GDNF gene, we demonstrated that riluzole mediates its effect at the transcription level. Furthermore, luciferase assays revealed the presence of a negative regulatory region within the +343/+587 region of exon 1. This region was shown to contribute to the high sensitivity and specificity of the induction mediated by riluzole in the C6 glioma cell line at pharmacologically relevant concentrations. The effects of riluzole were inhibited by the mitogen‐activated protein kinase extracellular signal‐related kinase (MEK) inhibitor PD 98059. Together, these results indicated that the induction of GDNF release by riluzole in the C6 glioma cells results from the activation of its corresponding gene promoter through a signalling pathway involving MEK activity. This study suggests that the regulation of GDNF gene transcription in glial cells could contribute to the pharmacological properties of riluzole and possibly other neuroprotective drugs.
Conditioned place preference and locomotor activity in response to methylphenidate, amphetamine and cocaine in mice lacking dopamine D4 receptors

Methylphenidate (MP) and amphetamine (AMPH) are the most frequently prescribed medications for the treatment of attention-deficit/hyperactivity disorder (ADHD). Both drugs are believed to derive their therapeutic benefit by virtue of their dopamine (DA)-enhancing effects, yet an explanation for the observation that some patients with ADHD respond well to one medication but not to the other remains elusive. The dopaminergic effects of MP and AMPH are also thought to underlie their reinforcing properties and ultimately their abuse. Polymorphisms in the human gene that codes for the DA D4 receptor (D4R) have been repeatedly associated with ADHD and may correlate with the therapeutic as well as the reinforcing effects of responses to these psychostimulant medications. Conditioned place preference (CPP) for MP, AMPH and cocaine were evaluated in wild-type (WT) mice and their genetically engineered littermates, congenic on the C57Bl/6J background, that completely lack D4Rs (knockout or KO). In addition, the locomotor activity in these mice during the conditioning phase of CPP was tested in the CPP chambers. D4 receptor KO and WT mice showed CPP and increased locomotor activity in response to each of the three psychostimulants tested. D4R differentially modulates the CPP responses to MP, AMPH and cocaine. While the D4R genotype affected CPP responses to MP (high dose only) and AMPH (low dose only) it had no effects on cocaine. Inasmuch as CPP is considered an indicator of sensitivity to reinforcing responses to drugs these data suggest a significant but limited role of D4Rs in modulating conditioning responses to MP and AMPH. In the locomotor test, D4 receptor KO mice displayed attenuated increases in AMPH-induced locomotor activity whereas responses to cocaine and MP did not differ. These results suggest distinct mechanisms for D4 receptor modulation of the reinforcing (perhaps via attenuating dopaminergic signalling) and locomotor properties of these stimulant drugs. Thus, individuals with D4 receptor polymorphisms might show enhanced reinforcing responses to MP and AMPH and attenuated locomotor response to AMPH.
Src Kinases Regulate De Novo Actin Polymerization during Exocytosis in Neuroendocrine Chromaffin Cells

The cortical actin network is dynamically rearranged during secretory processes. Nevertheless, it is unclear how de novo actin polymerization and the disruption of the preexisting actin network control transmitter release. Here we show that in bovine adrenal chromaffin cells, both formation of new actin filaments and disruption of the preexisting cortical actin network are induced by Ca2+ concentrations that trigger exocytosis. These two processes appear to regulate different stages of exocytosis; whereas the inhibition of actin polymerization with the N-WASP inhibitor wiskostatin restricts fusion pore expansion, thus limiting the release of transmitters, the disruption of the cortical actin network with cytochalasin D increases the amount of transmitter released per event. Further, the Src kinase inhibitor PP2, and cSrc SH2 and SH3 domains also suppress Ca2+-dependent actin polymerization, and slow down fusion pore expansion without disturbing the cortical F-actin organization. Finally, the isolated SH3 domain of c-Src prevents both the disruption of the actin network and the increase in the quantal release induced by cytochalasin D. These findings support a model where a rise in the cytosolic Ca2+ triggers actin polymerization through a mechanism that involves Src kinases. The newly formed actin filaments would speed up the expansion of the initial fusion pore, whereas the preexisting actin network might control a different step of the exocytosis process.
Mechanism of activation of protein kinase B by insulin and IGF‐1.

Insulin activated endogenous protein kinase B alpha (also known as RAC/Akt kinase) activity 12‐fold in L6 myotubes, while after transfection into 293 cells PKBalpha was activated 20‐ and 50‐fold in response to insulin and IGF‐1 respectively. In both cells, the activation of PKBalpha was accompanied by its phosphorylation at Thr308 and Ser473 and, like activation, phosphorylation of both of these residues was prevented by the phosphatidylinositol 3‐kinase inhibitor wortmannin. Thr308 and/or Ser473 were mutated to Ala or Asp and activities of mutant PKBalpha molecules were analysed after transfection into 293 cells. The activity of wild‐type and mutant PKBalpha was also measured in vitro after stoichiometric phosphorylation of Ser473 by MAPKAP kinase‐2. These experiments demonstrated that activation of PKBalpha by insulin or insulin‐like growth factor‐1 (IGF‐1) results from phosphorylation of both Thr308 and Ser473, that phosphorylation of both residues is critical to generate a high level of PKBalpha activity and that the phosphorylation of Thr308 in vivo is not dependent on phosphorylation of Ser473 or vice versa. We propose a model whereby PKBalpha becomes phosphorylated and activated in insulin/IGF‐1‐stimulated cells by an upstream kinase(s).
The Status of Teaching as a Profession

Teachers are often considered the backbone of schools; without them there would be no school. Thus, understanding teachers’ roles is key to understanding the educational system. Discussions of organizations often include information about the roles people occupy within them. One aspect of roles that distinguishes organizations is the type of workers they employ. Professionals have a high degree of control over their work environments, high prestige, and relatively high compensation compared to nonprofessionals. This designation is not without controversy, and it is often at the foundation of many labor disputes. Whether teachers qualify as professionals is one of these debates. Richard M. Ingersoll evaluates each criterion of professionalization as it applies to teachers and concludes that teachers generally fall into a category called “semiprofessionals. ”
Performance Degradation Assessment of Rolling Element Bearings Based on an Index Combining SVD and Information Exergy

Performance degradation assessment of rolling element bearings is vital for the reliable and cost-efficient operation and maintenance of rotating machines, especially for the implementation of condition-based maintenance (CBM). For robust degradation assessment of rolling element bearings, uncertainties such as those induced from usage variations or sensor errors must be taken into account. This paper presents an information exergy index for bearing performance degradation assessment that combines singular value decomposition (SVD) and the information exergy method. Information exergy integrates condition monitoring information of multiple instants and multiple sensors, and thus performance degradation assessment uncertainties are reduced and robust degradation assessment results can be obtained using the proposed index. The effectiveness and robustness of the proposed information exergy index are validated through experimental case studies.
A 0.4-V 0.2 pJ/step 90-dB SNDR 20-kHz CT delta-sigma modulator using class-AB amplifier with a novel local common-mode feedback

This paper presents a 0.4-V continuous-time delta-sigma modulator for high-quality power-efficient audio applications. A new ultra-low voltage amplifier for high linearity and low power consumption is proposed by exploring class-AB topology with a novel local common-mode-feedback loop. A low V T self-body-biased PMOS switch is employed in feedback digital-to-analog converter to improve the linearity performance against PVT-induced on resistance variation, which avoids clock boosting that may harm long-term reliability. A simple and robust non-overlapping clock generation circuit is proposed for high SNDR performance of modulator at 0.4-V or below. Fabricated in a 130-nm CMOS process, the modulator achieves 90.2dB signal-to-noise-plus-distortion ratio (SNDR) with 0.2pJ/step Figure-of-Merit (FoM) over a 20- k Hz signal bandwidth, outperforming the reported audio delta-sigma modulators operating at 0.5-V or below. Furthermore, the modulator can operate with a supply down to 0.34-V while achieving an 86.1dB SNDR at 0.17pJ/step.