Miracle-dz/UniFAR-FTUs huggingface dataset:
Rifampicin induces MDR1 expression in Candida albicans.

OBJECTIVES Overexpression of efflux pumps such as MDR1 has been identified as an important mechanism contributing to fluconazole resistance in Candida albicans. This phenomenon is frequently observed in fluconazole-resistant strains isolated from AIDS patients treated with various pharmaceuticals. Therefore, we hypothesized that some of these compounds might influence the expression of genes responsible for fluconazole resistance. METHODS We examined a variety of clinically relevant compounds for their in vitro effects on MDR1 expression with a C. albicans reporter strain containing a transcriptional fusion of the MDR1 promoter (MDR1P) with the gfp gene. Activation of the MDR1 promoter and subsequent green fluorescent protein production was determined by fluorescence microscopy and flow cytometry. Additionally, MDR1 transcription was confirmed and quantified by RT-PCR analysis, followed by Mdr1p detection by western blot. Finally, the effect of a selected agent on resistance to fluconazole was tested by chequerboard titration of both substances. RESULTS Of 15 compounds tested, only rifampicin induced a rapid and dose-dependent increase in MDR1 expression (up to 122-fold induction), whereas structurally related molecules such as rifabutin and rifamycin were not active. Induction of MDR1 expression upon rifampicin exposure was also observed in 10 blood culture isolates. In contrast, rifampicin exposure did not markedly affect the expression of the transporters CDR1 and CDR2. Increased MDR1 expression was accompanied by elevated MICs for fluconazole after exposure of C. albicans to rifampicin, whereas Mdr1p expression was only moderately induced. CONCLUSIONS Out of the compounds examined, only rifampicin specifically induced MDR1 expression in all C. albicans strains tested. Rifampicin may play a general role in signal transduction or another means of modulation of gene expression in C. albicans.
Methods to study degradation of ruminant feeds

Ruman degradation is crucial in the supply of dietary nutrients to meet the nutrient demands of the anaerobic microbes and body tissues of ruminant animals. Therefore, it is essential to study the dynamics of rumen degradation of various feeds before their potential use to formulate nutritious diets for ruminant animals. Amongst many methods that have been used in the past, the in sacco method has been the most effective method to study rumen degradation. However, this method is undesirable due to its implications for animal welfare and costs. While many in vitro methods have been tested as possible alternatives to the in sacco method to study rumen degradation of feeds, they were unable to remove the need to use fistulated animals to obtain rumen fluid. Although solubility, enzyme- and faeces-based in vitro methods do not require rumen fluid, they still need data from either the in sacco method or the rumen fluid-based in vitro methods for comparison and validation. Therefore, there is a need to develop in vitro methods that do not require the need to surgically modify ruminants to obtain rumen fluid to study rumen degradation. We review the potentials and problems associated with the existing methods to study rumen degradation and their implications for the animal industry in different situations.
From Conventional to Stealth Liposomes a new Frontier in Cancer Chemotherapy

Many attempts have been made to achieve good selectivity to targeted tumor cells by preparing specialized carrier agents that are therapeutically profitable for anticancer therapy. Among these, liposomes are the most studied colloidal particles thus far applied in medicine and in particular in antitumor therapy. Although they were first described in the 1960s, only at the beginning of 1990s did the first therapeutic liposomes appear on the market. The first-generation liposomes (conventional liposomes) comprised a liposome-containing amphotericin B, Ambisome (Nexstar, Boulder, CO, USA), used as an antifungal drug, and Myocet (Elan Pharma Int, Princeton, NJ, USA), a doxorubicin-containing liposome, used in clinical trials to treat metastatic breast cancer. The second-generation liposomes (“pure lipid approach”) were long-circulating liposomes, such as Daunoxome, a daunorubicin-containing liposome approved in the US and Europe to treat AIDS-related Kaposi's sarcoma. The third-generation liposomes were surface-modified liposomes with gangliosides or sialic acid, which can evade the immune system responsible for removing liposomes from circulation. The fourth-generation liposomes, pegylated liposomal doxorubicin, were called “stealth liposomes” because of their ability to evade interception by the immune system, in the same way as the stealth bomber was able to evade radar. Actually, the only stealth liposome on the market is Caelyx/Doxil (Schering-Plough, Madison NJ, USA), used to cure AIDS-related Kaposi's sarcoma, resistant ovarian cancer and metastatic breast cancer. Pegylated liposomal doxorubicin is characterized by a very long-circulation half-life, favorable pharmacokinetic behavior and specific accumulation in tumor tissues. These features account for the much lower toxicity shown by Caelyx in comparison to free doxorubicin, in terms of cardiotoxicity, vesicant effects, nausea, vomiting and alopecia. Pegylated liposomal doxorubicin also appeared to be less myelotoxic than doxorubicin. Typical forms of toxicity associated to it are acute infusion reaction, mucositis and palmar plantar erythrodysesthesia, which occur especially at high doses or short dosing intervals. Active and cell targeted liposomes can be obtained by attaching some antigen-directed monoclonal antibodies (Moab or Moab fragments) or small proteins and molecules (folate, epidermal growth factor, transferrin) to the distal end of polyethylene glycol in pegylated liposomal doxorubicin. The most promising therapeutic application of liposomes is as non-viral vector agents in gene therapy, characterized by the use of cationic phospholipids complexed with the negatively charged DNA plasmid. The use of liposome formulations in local-regional anticancer therapy is also discussed. Finally, pegylated liposomal doxorubicin containing radionuclides are used in clinical trials as tumor-imaging agents or in positron emission tomography.
Virulence Profiles of Vibrio vulnificus in German Coastal Waters, a Comparison of North Sea and Baltic Sea Isolates

Vibrio vulnificus is a halophilic bacterium of coastal environments known for sporadically causing severe foodborne or wound infections. Global warming is expected to lead to a rising occurrence of V. vulnificus and an increasing incidence of human infections in Northern Europe. So far, infections in Germany were exclusively documented for the Baltic Sea coast, while no cases from the North Sea region have been reported. Regional variations in the prevalence of infections may be influenced by differences in the pathogenicity of V. vulnificus populations in both areas. This study aimed to compare the distribution of virulence-associated traits and genotypes among 101 V. vulnificus isolates from the Baltic Sea and North Sea in order to assess their pathogenicity potential. Furthermore, genetic relationships were examined by multilocus sequence typing (MLST). A high diversity of MLST sequences (74 sequence types) and differences regarding the presence of six potential pathogenicity markers were observed in the V. vulnificus populations of both areas. Strains with genotypes and markers associated with pathogenicity are not restricted to a particular geographic region. This indicates that lack of reported cases in the North Sea region is not caused by the absence of potentially pathogenic strains.
University of Twente at the TREC 2007 Enterprise Track: Modeling Relevance Propagation for the Expert Search Task

This paper describes several approaches which we used for the expert search task of the TREC 2007 Enterprise track. We studied several methods of relevance propagation from documents to related candidate experts. Instead of one-step propagation from documents to directly related candidates, used by many systems in the previous years, we do not limit the relevance flow and disseminate it further through mutual documents-candidates connections. We model relevance propagation using random walk principles, or in formal terms, discrete Markov processes. We experiment with innite and nite number of propagation steps. We also demonstrate how additional information, namely hyperlinks among documents, organizational structure of the enterprise and relevance feedback may be utilized by the presented techniques.
Membrane Curvature Sensing by Amphipathic Helices Is Modulated by the Surrounding Protein Backbone

Membrane curvature is involved in numerous biological pathways like vesicle trafficking, endocytosis or nuclear pore complex assembly. In addition to its topological role, membrane curvature is sensed by specific proteins, enabling the coordination of biological processes in space and time. Amongst membrane curvature sensors are the ALPS (Amphipathic Lipid Packing Sensors). ALPS motifs are short peptides with peculiar amphipathic properties. They are found in proteins targeted to distinct curved membranes, mostly in the early secretory pathway. For instance, the ALPS motif of the golgin GMAP210 binds trafficking vesicles, while the ALPS motif of Nup133 targets nuclear pores. It is not clear if, besides curvature sensitivity, ALPS motifs also provide target specificity, or if other domains in the surrounding protein backbone are involved. To elucidate this aspect, we studied the subcellular localization of ALPS motifs outside their natural protein context. The ALPS motifs of GMAP210 or Nup133 were grafted on artificial fluorescent probes. Importantly, ALPS motifs are held in different positions and these contrasting architectures were mimicked by the fluorescent probes. The resulting chimeras recapitulated the original proteins localization, indicating that ALPS motifs are sufficient to specifically localize proteins. Modulating the electrostatic or hydrophobic content of Nup133 ALPS motif modified its avidity for cellular membranes but did not change its organelle targeting properties. In contrast, the structure of the backbone surrounding the helix strongly influenced targeting. In particular, introducing an artificial coiled-coil between ALPS and the fluorescent protein increased membrane curvature sensitivity. This coiled-coil domain also provided membrane curvature sensitivity to the amphipathic helix of Sar1. The degree of curvature sensitivity within the coiled-coil context remains correlated to the natural curvature sensitivity of the helices. This suggests that the chemistry of ALPS motifs is a key parameter for membrane curvature sensitivity, which can be further modulated by the surrounding protein backbone.
Index compression using 64-bit words

Modern computers typically make use of 64-bit words as the fundamental unit of data access. However the decade-long migration from 32-bit architectures has not been reflected in compression technology, because of a widespread assumption that effective compression techniques operate in terms of bits or bytes, rather than words. Here we demonstrate that the use of 64-bit access units, especially in connection with word-bounded codes, does indeed provide the opportunity for improving the compression performance. In particular, we extend several 32-bit word-bounded coding schemes to 64-bit operation and explore their uses in information retrieval applications. Our results show that the Simple-8b approach, a 64-bit word-bounded code, is an excellent self-skipping code, and has a clear advantage over its competitors in supporting fast query evaluation when the data being compressed represents the inverted index for a large text collection. The advantages of the new code also accrue on 32-bit architectures, and for all of Boolean, ranked, and phrase queries; which means that it can be used in any situation. Copyright © 2010 John Wiley & Sons, Ltd.
Biofilm Formation by Campylobacter jejuni Is Increased under Aerobic Conditions

ABSTRACT The microaerophilic human pathogen Campylobacter jejuni is the leading cause of food-borne bacterial gastroenteritis in the developed world. During transmission through the food chain and the environment, the organism must survive stressful environmental conditions, particularly high oxygen levels. Biofilm formation has been suggested to play a role in the environmental survival of this organism. In this work we show that C. jejuni NCTC 11168 biofilms developed more rapidly under environmental and food-chain-relevant aerobic conditions (20% O2) than under microaerobic conditions (5% O2, 10% CO2), although final levels of biofilms were comparable after 3 days. Staining of biofilms with Congo red gave results similar to those obtained with the commonly used crystal violet staining. The level of biofilm formation by nonmotile aflagellate strains was lower than that observed for the motile flagellated strain but nonetheless increased under aerobic conditions, suggesting the presence of flagellum-dependent and flagellum-independent mechanisms of biofilm formation in C. jejuni. Moreover, preformed biofilms shed high numbers of viable C. jejuni cells into the culture supernatant independently of the oxygen concentration, suggesting a continuous passive release of cells into the medium rather than a condition-specific active mechanism of dispersal. We conclude that under aerobic or stressful conditions, C. jejuni adapts to a biofilm lifestyle, allowing survival under detrimental conditions, and that such a biofilm can function as a reservoir of viable planktonic cells. The increased level of biofilm formation under aerobic conditions is likely to be an adaptation contributing to the zoonotic lifestyle of C. jejuni.
Application of PID controller based on the localization method for ancillary service provision

The work deals with usage of classical PID controller to maintain balance between electricity consumption and production using concepts of smart grid and virtual power plant. Aggregated control of large groups of thermostatically controlled loads can be used for ancillary services provision. The focus is on secondary control and peak-shaving, which are a part of the power balance problem. Calculation of PID controller parameters are based on the localization method. The main idea of the localization method is using a derivatives vector of the controlled variable for manipulated variable calculation. The highest derivative implicitly contains full information about plant's state at the current moment. The dynamics of individual building with heaters is described by second order equivalent thermal parameters (ETP) model. The obtained results show that aggregate response of large population of electrical space heaters can meet the requirements on both of the problems. Nevertheless, there are still a lot of issues remaining open: influence of the hysteresis parameter, and using suitable sampling time in order to lower demand on the communication infrastructure.
Fostering a career development culture: reflections on the roles of managers, employees and supervisors (Поддержка культуры развития карьеры: рефлексия ролей менеджера, служащего и супервизора)

The culture of an organization can be positive and supportive, or threatening and destructive. A career development culture helps address productivity, competitiveness, affirmative action, and succession planning. It helps people redefine their talents to realize the full potential of their jobs. Supervisors should play a key role in creating a career development culture, but many feel their careers are going nowhere and see career development efforts to be an added burden. Supervisors seldom do performance appraisals properly because they are afraid of their workers and the workers are virtually paranoid about the slightest negative note on their files. A better way is to organize a system of mentorship. Evaluation of initiatives can be calculated on the basis of savings that can be attributed to the program and its actual costs. A managed career development culture can pay great rewards to an organization and the people working in it.
Development of 3D stack package using silicon interposer for high power application

Stacking of many functional chips in a 3D stack package leads to high heat dissipation. Therefore a new platform technology is required to assemble chips vertically and remove the heat effectively. A 3D stacked package with silicon interposers is developed to integrate one ASIC and two memory chips in a package. Electrical connections in the silicon interposer are formed by through silicon via. Silicon has much high thermal conductivity than organic interposers, which reduces drastically the package thermal resistance. Thermal performances of the 3D package are analyzed and thermal enhancement methods like thermal vias, thermal bridging are evaluated. The designed package is having 5 times lesser thermal resistance compared to the package with organic substrate. An additional silicon heat spreader is attached to the package for high power application. Numerical analysis and experimental validation are carried out. The designed 3D stack package is found suitable for 20 watts heat dissipation
Model Character Development Training (CDT) untuk Meningkatkan Perilaku Anti Plagiat Mahasiswa

Telah dikembangkan sebuah model character development training (CDT) untuk meningkatkan perilaku anti plagiat mahasiswa. Penelitian ini bertujuan mengetahui efektivitas model CDT untuk meningkatkan perilaku anti plagiat mahasiswa. Penelitian ini melibatkan 50 orang mahasiswa (pra-eksperimen). Instrumen penelitian yang digunakan adalah skala perilaku anti plagiat. Data dianalisis dengan menggunakan uji t test untuk melihat perbedaan skor rerata prates dan pascates. Hasil penelitian menunjukan adanya peningkatan perilaku anti plagiat mahasiswa sebelum dan sesudah diberikan perlakuan berupa CDT. Hasil ini menunjukan bahwa model CDT yang dikembangkan efektif untuk meningkatkan perilaku anti plagiat mahasiswa. Kata-kata Kunci: moral dan karakter, character development training , perilaku plagiat
CSP and Takeout Genes Modulate the Switch between Attraction and Repulsion during Behavioral Phase Change in the Migratory Locust

Behavioral plasticity is the most striking trait in locust phase transition. However, the genetic basis for behavioral plasticity in locusts is largely unknown. To unravel the molecular mechanisms underlying the behavioral phase change in the migratory locust Locusta migratoria, the gene expression patterns over the time courses of solitarization and gregarization were compared by oligonucleotide microarray analysis. Data analysis revealed that several gene categories relevant to peripheral olfactory perception are strongly regulated in a total of 1,444 differentially expressed genes during both time courses. Among these candidate genes, several CSP (chemosensory protein) genes and one takeout gene, LmigTO1, showed higher expression in gregarious and solitarious locusts, respectively, and displayed opposite expression trends during solitarization and gregarization. qRT-PCR experiments revealed that most CSP members and LmigTO1 exhibited antenna-rich expressions. RNA interference combined with olfactory behavioral experiments confirmed that the CSP gene family and one takeout gene, LmigTO1, are involved in the shift from repulsion to attraction between individuals during gregarization and in the reverse transition during solitarization. These findings suggest that the response to locust-emitted olfactory cues regulated by CSP and takeout genes is involved in the behavioral phase change in the migratory locust and provide a previously undescribed molecular mechanism linked to the formation of locust aggregations.
Reducing the Network Load of Replicated Data

In the Internet today, transfer rates are often limited by the bandwidth of a bottleneck link rather than the computing power available at the ends of the links. To address this problem, we have designed a novel link layer protocol that employs computation at the ends of the link to reduce bandwidth consumption across the link. Our scheme is motivated by the prevalence of repeated transfers of the same information, as typically occurs in the form of HTTP, FTP, and DNS traffic. The protocol complements existing link compression and application-level caching schemes by combining aspects of both. It is able to detect and remove redundancy at the packet level and across large timescales. 'We make three contributions in this thesis. First, to motivate our scheme we show by packet trace analysis that there is significant replication of data at the packet level, mainly due to Web traffic. Second, we present an innovative link compression protocol that is well-suited to traffic with such long-range correlation. Third, we demonstrate by experimentation that the availability of inexpensive memory and general-purpose processors in PCs makes our protocol practical and useful at rates exceeding T3 (45 Mbps). Thesis Supervisor: John V. Guttag Title: Professor and Associate Head, Computer Science and Engineering Thesis Supervisor: David J. Wetherall Title: Research Assistant
What makes a gene name? Named entity recognition in the biomedical literature

The recognition of biomedical concepts in natural text (named entity recognition, NER) is a key technology for automatic or semi-automatic analysis of textual resources. Precise NER tools are a prerequisite for many applications working on text, such as information retrieval, information extraction or document classification. Over the past years, the problem has achieved considerable attention in the bioinformatics community and experience has shown that NER in the life sciences is a rather difficult problem. Several systems and algorithms have been devised and implemented. In this paper, the problems and resources in NER research are described, the principal algorithms underlying most systems sketched, and the current state-of-the-art in the field surveyed.
Tissue distribution of products of the mouse decay‐accelerating factor (DAF) genes. Exploitation of a Daf1 knock‐out mouse and site‐specific monoclonal antibodies

Decay‐accelerating factor (DAF) is a membrane regulator of C3 activation that protects self cells from autologous complement attack. In humans, DAF is uniformly expressed as a glycosylphosphatidylinositol (GPI)‐anchored molecule. In mice, both GPI‐anchored and transmembrane‐anchored DAF proteins are produced, each of which can be derived from two different genes (Daf1 and Daf2). In this report, we describe a Daf1 gene knock‐out mouse arising as the first product of a strategy for targeting one or both Daf genes. As part of the work, we characterize recently described monoclonal antibodies against murine DAF protein using deletion mutants synthesized in yeast, and then employ the monoclonal antibodies in conjunction with wild‐type and the Daf1 knock‐out mice to determine the tissue distribution of the mouse Daf1 and Daf2 gene products. To enhance the immunohistochemical detection of murine DAF protein, we utilized the sensitive tyramide fluorescence method. In wild‐type mice, we found strong DAF labelling of glomeruli, airway and gut epithelium, the spleen, vascular endothelium throughout all tissues, and seminiferous tubules of the testis. In Daf1 knock‐out mice, DAF labelling was ablated in most tissues, but strong labelling of the testis and splenic dendritic cells remained. In both sites, reverse transcription‐polymerase chain reaction analyses identified both GPI and transmembrane forms of Daf2 gene‐derived protein. The results have relevance for studies of in vivo murine DAF function and of murine DAF structure.