Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptional Profiling of Interferon Regulatory Factor 3 Target Genes: Direct Involvement in the Regulation of Interferon-Stimulated Genes

ABSTRACT Ubiquitously expressed interferon regulatory factor 3 (IRF-3) is directly activated after virus infection and functions as a key activator of the immediate-early alpha/beta interferon (IFN) genes, as well as the RANTES chemokine gene. In the present study, a tetracycline-inducible expression system expressing a constitutively active form of IRF-3 (IRF-3 5D) was combined with DNA microarray analysis to identify target genes regulated by IRF-3. Changes in mRNA expression profiles of 8,556 genes were monitored after Tet-inducible expression of IRF-3 5D. Among the genes upregulated by IRF-3 were transcripts for several known IFN-stimulated genes (ISGs). Subsequent analysis revealed that IRF-3 directly induced the expression of ISG56 in an IFN-independent manner through the IFN-stimulated responsive elements (ISREs) of the ISG56 promoter. These results demonstrate that, in addition to its role in the formation of a functional immediate-early IFN-β enhanceosome, IRF-3 is able to discriminate among ISRE-containing genes involved in the establishment of the antiviral state as a direct response to virus infection.
Rattusin, an Intestinal α-Defensin-Related Peptide in Rats with a Unique Cysteine Spacing Pattern and Salt-Insensitive Antibacterial Activities

ABSTRACT Cationic antimicrobial peptides are essential components of the innate immune system. As a major family of mammalian antimicrobial peptides, defensins are expressed mainly by mucosal epithelial cells and promyelocytes. Despite the capacity to kill a broad spectrum of bacteria through physical disruption of membranes, most defensins show substantially reduced antibacterial activities in the presence of monovalent and divalent cations, thereby limiting their therapeutic potential, particularly for the treatment of systemic infections. Genome-wide computational screening of the rat genome led to the identification of the gene for a novel α-defensin-related peptide that we termed rattusin. Rattusin shares a highly conserved signal and prosequence with mammalian α-defensins, but instead of the canonical α-defensin six-cysteine motif, rattusin consists of five cysteines with a distinctive spacing pattern. Furthermore, rattusin is preferentially expressed in Paneth cells of the distal small intestine with potent antibacterial activity against a broad range of Gram-negative and Gram-positive bacteria, including antibiotic-resistant strains. The MICs were mostly in the range of 2 to 4 μM, with no appreciable toxicity to mammalian cells at up to 100 μM. In contrast to classical α- and β-defensins, rattusin retained its activity in the presence of physiological concentrations of NaCl and Mg2+, making it an attractive antimicrobial candidate for both topical and systemic applications.
Sipuleucel-T and immunotherapy in the treatment of prostate cancer

Introduction: Immunotherapy represents an emerging modality of treatment utilized in patients with prostate cancer, among various other malignancies. Areas covered: Sipuleucel-T is an autologous active cellular immunotherapy that has demonstrated improved survival in patients with metastatic castration-resistant prostate cancer (mCRPC). The IMPACT trial led to the FDA approval of sipuleucel-T as first-line treatment for men with asymptomatic or minimally symptomatic mCRPC. Additional immunotherapies in cancer have shown promising results in clinical studies. These include ProstVac, which is a poxvirus vaccine targeting prostate-specific antigen, and cell cycle checkpoint inhibitors of cytotoxic T lymphocyte antigen-4 and programmed death-1 (PD-1) and its ligand (PD-L1). The combination of sipuleucel-T with both androgen deprivation therapy and androgen signaling agents has demonstrated robust and augmented immune responses. The responses to immunotherapy are often seen via different parameters compared with other therapies, including increased T-cell activation and antibody response. Expert opinion: The role of immunotherapy in cancer continues to grow and encompass agents with different mechanisms, and ongoing efforts to identify appropriate timing of therapy and patients for use is integral to the management of prostate cancer.
Lindenmayer systems and the harmony of fractals

An interactive musical application is developed for realtime improvisation with a machine based on Lindenmayer-systems. This has been used on an installation whose goal is to draw the attention of unexperienced users to the wealth of realtime applications in computer music. Issues on human computer interaction and improvisation grammars had to be dealt with, as well as probabilistic strategies for musical variation. The choice of L-systems as a basis for machine composition is a consequence of their ability to create results that easily have aesthetic appeal, both in the realms of sound and image.
Species Differences in Biliary Clearance and Possible Relevance of Hepatic Uptake and Efflux Transporters Involvement

From a search of the available literature, a database of 22 drugs of all charge types and several different therapeutic classes was compiled to compare rat and human biliary clearance data. Dog biliary excretion data were also found for nine of the drugs. For 19 of the 22 drugs (86%), rat unbound biliary clearance values, when normalized for body weight, exceeded those for humans by factors ranging from 9 to over 2500-fold, whereas human/dog differences were much less dramatic. It was possible to define hepatic uptake and efflux transporter involvement for many of the drugs. On the basis of the findings, it is postulated that regardless of the biliary efflux transporters implicated, when drugs do not require active hepatic uptake to access the liver there may be fairly insignificant differences in rat, dog, and humanbiliary clearance. Conversely, when the organic anion-transporting polypeptide drug transporters are involved, one may expect at least a 10-fold discrepancy in rat to human biliary clearance normalized for body weight and corrected for plasma protein binding.
The nucleoporin Nup205/NPP-3 is lost near centrosomes at mitotic onset and can modulate the timing of this process in Caenorhabditis elegans embryos

Through an RNAi-based modifier screen, we identified the nucleoporin Nup205/NPP-3 as a negative regulator of mitotic onset in Caenorhabditis elegans. Strikingly, NPP-3 is lost from the nuclear envelope at mitotic onset in an AIR-1– and centrosome-dependent manner. We propose a model whereby centrosomes and AIR-1 promote timely mitosis by locally removing NPP-3.
Application of UV nanoimprint lithography in polymer photonic nano-systems

We report an application of UV nanoimprint lithography for the fabrication of two-dimensional polymer photonic crystal slab waveguides. With the aid of optimized resin droplet size and imprint pressure, air-hole photonic crystal structures were replicated on the optical polymer resin. By incorporating buffered oxide etch process, the glass substrate was selectively etched and the imprinted polymer photonic crystal slab waveguides were air-suspended as a membrane. The UV nanoimprinted polymer photonic crystal slab waveguides will be an attractive candidate for the implementations of ultra-compact photonic nano-systems and nano-photonic integrated circuits.
Identification of new Golgi complex specific proteins by direct organelle proteomic analysis

The Golgi complex is in the crossroad of the endocytic and secretory pathways. Its function is to post‐translationally modify and sort proteins and lipids, and regulate the membrane balance in the cell. To understand the structure‐function relationship of the Golgi complex the Golgi proteome has to be identified first. We have used a direct organelle proteomic analysis to identify new Golgi complex proteins. Enriched stacked Golgi membrane fractions from rat livers were isolated, and the proteins from these membranes were subsequently digested into peptides. The peptides were fractionated by cation‐exchange chromatography followed by protein identification by automated capillary‐LC/ESI–MS/MS analysis and database searches. Two different search programs, ProID and MASCOT were used. This resulted in a total of 1125 protein identifications in two experiments. In addition to the known Golgi resident proteins, a significant number of unknown proteins were identified. Some of these were further characterized in silico using different programs to provide insight into their structure, intracellular localization and biological functions. The Golgi localization of two of these newly identified proteins was also confirmed by indirect immunofluorescence.
Constraint solving via fractional edge covers

Many important combinatorial problems can be modelled as constraint satisfaction problems, hence identifying polynomial-time solvable classes of constraint satisfaction problems received a lot of attention. In this paper, we are interested in structural properties that can make the problem tractable. So far, the largest structural class that is known to be polynomial-time solvable is the class of bounded hypertree width instances introduced by Gottlob et al. [20]. Here we identify a new class of polynomial-time solvable instances: those having bounded fractional edge cover number.Combining hypertree width and fractional edge cover number, we then introduce the notion of fractional hypertree width. We prove that constraint satisfaction problems with bounded fractional hypertree width can be solved in polynomial time (provided that a the tree decomposition is given in the input). We also prove that certain parameterized constraint satisfaction, homomorphism, and embedding problems are fixed-parameter tractable on instances having bounded fractional hypertree width.
Stabilization of networked multi-input systems over AWGN channels with channel resource allocation

In this paper, we study stabilization of multi-input networked control systems over additive white Gaussian noise channels. Different from the single-input case, which is available in the literature and boils down to a typical ℋ2 optimal control problem, the multi-input case involves a judicious allocation of the total capacity among the input channels in addition to the design of the feedback controller. With this channel-controller co-design, we successfully show that a networked multi-input system over additive white Gaussian noise channels can be stabilized by state feedback under channel resource allocation, if and only if the total channel capacity is greater than the topological entropy of the plant. A numerical example is given to demonstrate our result.
Intracellular angiotensin II regulates the inward calcium current in cardiac myocytes.

-The influence of intracellular administration of angiotensin II (Ang II) on the inward calcium current (ICa) was investigated in single myocytes isolated from adult rat ventricle. Comparative studies were also made in ventricular cells of Golden hamsters. The ICa was measured in single cells using the whole-cell voltage clamp configuration. The results indicated that Ang II (10(-8) mmol/L) dialyzed into the rat myocytes reduced the peak ICa by 35+/-5.5% (n=20; P<0.05). Losartan (10(-7) mmol/L) added to the bath did not suppress the effects of Ang II, indicating that the peptide is acting intracellularly. Moreover, the intracellular dialysis of losartan (10(-6) mmol/L) or [Sar1Val5Ala8] Ang II (10(-6) mmol/L) did not change the effect of Ang II. Stimulation of ICa by exogenous cAMP or inhibition of protein kinase C did not alter the effect of Ang II on ICa. Zaprinast (100 micromol/L), an inhibitor of cGMP phosphodiesterase, when added to the bath solution increased appreciably the effect of Ang II on ICa (P<0.05). In ventricular myocytes of Golden hamsters, in which Ang II has a positive inotropic action, the intracellular administration of Ang II (10(-8) mmol/L) increased ICa by 36+/-2.4% (n=20; P>0.05). The effect of the peptide was not altered by the intracellular administration of losartan (10(-6) mmol/L), by [Sar1Val5Ala8] Ang II (10(-6) mmol/L), or by the inhibitor of protein kinase A. The inhibition of protein kinase C, however, prevented the effect of Ang II ICa in the hamster myocytes. The results particularly suggest that the activation of the cardiac renin-angiotensin system regulates ICa and myocardial contractility, an effect that varies with the species.
Suicide, deprivation, and unemployment: record linkage study

Abstract Objectives : To investigate the association between suicide and socioeconomic status, unemployment, and chronic illness. Design : Longitudinal study. Setting : England and Wales. Subjects : Individuals from the Office for National Statistics longitudinal study for whom 1981 census data were available. The longitudinal study is a representative 1% sample of the population of England and Wales in which census variables are linked to mortality data. Main outcome measures : Suicide and undetermined deaths occurring between 1983 and 1992. Odds ratios estimated with logistic regression adjusted for attrition of cohort members. Results : There was a strong independent association between suicide and individuals who were unemployed (odds ratio 2.6; 95% confidence interval 2.0 to 3.4) and permanently sick (2.5; 1.6 to 4.0). Those without access to a car had an increased risk (1.3; 1.0 to 1.5), but other measures of socioeconomic status were not associated with suicide. Conclusions : The association between suicide and unemployment is more important than the association with other socioeconomic measures. Although some potentially important confounders were not adjusted for, the findings support the idea that unemployment or lack of job security increases the risk of suicide and that social and economic policies that reduce unemployment will also reduce the rate of suicide.
The effects of highly active antiretroviral therapy on albuminuria in HIV-infected persons: results from a randomized trial.

BACKGROUND Human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) regimens, especially those containing protease inhibitors (PIs), are at increased risk for cardiovascular events. Albuminuria is a known independent predictor for the development of cardiovascular disease and may potentially increase in patients receiving PIs. Alternatively, albuminuria may improve with HAART as a result of treating renal parenchymal HIV infection. Longitudinal studies have not been performed previously addressing the effects of HAART on albuminuria. METHODS We evaluated the effects of HAART on albumin to creatinine ratios (ACRs) during the initial 64 weeks of therapy in 68 previously untreated HIV-infected subjects, without pre-existing diagnosed diabetes or hypertension, enrolled in a randomized trial comparing PI-based (n = 32) with non-PI-based (n = 36) HAART regimens. We also estimated the prevalence of albuminuria, defined as an ACR > or =3.4 mg/mmol, in these subjects prior to initiation of HAART. RESULTS The changes in ACR over the initial 64 weeks of therapy in those receiving PIs [0.0 mg/mmol (-0.4, 0.3)] and in those not receiving PIs [0.0 mg/mmol (-0.5, 0.3)] were not significantly different. There was also no significant difference in the change in the ACR in the group as a whole. However, albuminuria at baseline was found in seven (10%) subjects. Five of these seven subjects had substantial improvements in ACR, ranging from 45 to 95%, with HAART use; three subjects had resolution of albuminuria. ACR at baseline significantly correlated with the baseline HIV-1 RNA level (r = 0.25; P = 0.04) and negatively with CD4 cell count (r = -0.25; P = 0.04). CONCLUSION Albuminuria in HIV-infected, treatment-naïve patients was found more frequently than expected and may be influenced by baseline immune status. Although we did not observe an effect of HAART on ACR during the first 64 weeks of therapy, we cannot exclude the possibility that HAART may be beneficial in those patients with significant albuminuria prior to treatment. Research in larger cohorts is required to investigate more definitively the associations between immune status, antiretroviral therapies and renal function in HIV-infected patients.
Novel Stem/Progenitor Cell Population from Murine Tracheal Submucosal Gland Ducts with Multipotent Regenerative Potential

The airway epithelium is in direct contact with the environment and therefore constantly at risk for injury. Basal cells (BCs) have been found to repair the surface epithelium (SE), but the contribution of other stem cell populations to airway epithelial repair has not been identified. We demonstrated that airway submucosal gland (SMG) duct cells, in addition to BCs, survived severe hypoxic‐ischemic injury. We developed a method to isolate duct cells from the airway. In vitro and in vivo models were used to compare the self‐renewal and differentiation potential of duct cells and BCs. We found that only duct cells were capable of regenerating SMG tubules and ducts, as well as the SE overlying the SMGs. SMG duct cells are therefore a multipotent stem cell for airway epithelial repair This is of importance to the field of lung regeneration as determining the repairing cell populations could lead to the identification of novel therapeutic targets and cell‐based therapies for patients with airway diseases. STEM CELLS 2011;29:1283–1293
Quadratic-Time Hardness of LCS and other Sequence Similarity Measures

Two important similarity measures between sequences are the longest common subsequence (LCS) and the dynamic time warping distance (DTWD). The computations of these measures for two given sequences are central tasks in a variety of applications. Simple dynamic programming algorithms solve these tasks in $O(n^2)$ time, and despite an extensive amount of research, no algorithms with significantly better worst case upper bounds are known. In this paper, we show that an $O(n^{2-\epsilon})$ time algorithm, for some $\epsilon>0$, for computing the LCS or the DTWD of two sequences of length $n$ over a constant size alphabet, refutes the popular Strong Exponential Time Hypothesis (SETH). Moreover, we show that computing the LCS of $k$ strings over an alphabet of size $O(k)$ cannot be done in $O(n^{k-\epsilon})$ time, for any $\epsilon>0$, under SETH. Finally, we also address the time complexity of approximating the DTWD of two strings in truly subquadratic time.
Edinburgh Research Explorer Developmental regulation and extracellular release of a VSG expression-site-associated gene product from Trypanosoma brucei bloodstream forms

Trypanosomes evade host immunity by exchanging variant surface glycoprotein (VSG) coats. VSG genes are transcribed from telomeric expression sites, which contain a diverse family of expression-site-associated genes ( ESAG s). We have discovered that the mRNAs for one ESAG family, ESAG9 , are strongly developmentally regulated, being enriched in stumpy forms, a life-cycle stage in the mammalian bloodstream that is important for the maintenance of chronic parasite infections and for tsetse transmission. ESAG9 gene sequences are highly diverse in the genome and encode proteins with weak similarity to the massively diverse MASP proteins in Trypanosoma cruzi. We demonstrate that ESAG9 proteins are modified by N-glycosylation and can be shed to the external milieu, this being dependent upon coexpression with at least one other family member. The expression profile and extracellular release of ESAG9 proteins represents a novel and unexpected aspect of the transmission biology of trypanosomes in their mammalian host. We suggest that these molecules might interact with the external environment, with possible implications for infection chronicity or parasite transmission.
Feature Selection for Accelerometer-Based Posture Analysis in Parkinson's Disease

Posture analysis in quiet standing is a key component of the clinical evaluation of Parkinson's disease (PD), postural instability being one of PD's major symptoms. The aim of this study was to assess the feasibility of using accelerometers to characterize the postural behavior of early mild PD subjects. Twenty PD and 20 control subjects, wearing an accelerometer on the lower back, were tested in five conditions characterized by sensory and attentional perturbation. A total of 175 measures were computed from the signals to quantify tremor, acceleration, and displacement of body sway. Feature selection was implemented to identify the subsets of measures that better characterize the distinctive behavior of PD and control subjects. It was based on different classifiers and on a nested cross validation, to maximize robustness of selection with respect to changes in the training set. Several subsets of three features achieved misclassification rates as low as 5%. Many of them included a tremor-related measure, a postural measure in the frequency domain, and a postural displacement measure. Results suggest that quantitative posture analysis using a single accelerometer and a simple test protocol may provide useful information to characterize early PD subjects. This protocol is potentially usable to monitor the disease's progression.
Generation of realistic traces for vehicular mobility simulations

Realistic vehicular traces are necessary in reliable VANETs simulations in order to evaluate protocols and applications designed for new technology. Because of the complexity of traffic behaviours, the generation of vehicular traces is one of the biggest challenges in VANETs research. This paper consolidates the current state-of-the art on vehicular mobility generators into three aspects: mobility models, traffic demand model and route assignment method as well as provide and overview of existing generators. The main part of the paper focuses on the improvement of traces generated by the VehiLux model over the city of Luxembourg. The quality of a large set of traces is assessed by the means of realistic traffic simulation and a proposed fitness metric. The influence of the implementation of the Gawron's algorithm---route assignment method on the quality of generated traces is evaluated.
The experimental performance of a mobile manipulator control algorithm

Results of an experimental study of a motion control algorithm for mobile manipulators are presented. The dynamic interactions between a mobile manipulator and its vehicle are shown to lead to poor performance when a conventional fixed-base controller, which neglects these interactions, is used. The mobile manipulator control algorithm, which accounts for dynamic vehicle motions caused by manipulator motions, is shown to be stable and to perform well, while using only limited sensory data, such as would be practically available in highly unstructured field environments. <<ETX>>