Miracle-dz/UniFAR-FTUs huggingface dataset:
Bone morphogenetic proteins 4, 6, and 7 are up‐regulated in mouse spinal cord during experimental autoimmune encephalomyelitis

Although spontaneous remyelination occurs in multiple sclerosis (MS), the extent of myelin repair is often inadequate to restore normal function. Oligodendrocyte precursors remaining in nonremyelinating MS plaques may be restricted by an inhibitory signal. Bone morphogenetic proteins (BMPs) have been implicated as repressors of oligodendrocyte development and inducers of astrogliogenesis. We hypothesized that BMPs are up‐regulated in MS lesions and play a role in demyelination and astrogliosis. We examined expression of BMPs in an animal model of MS, chronic experimental autoimmune encephalomyelitis (EAE) induced by the myelin oligodendrocyte glycoprotein (MOG) peptide in C57BL/6 mice. By 14 days postimmunization, compared to those of control mice, the lumbar spinal cords of MOG‐peptide EAE mice demonstrated prominent astrogliosis, infiltration of inflammatory cells, and disrupted expression of myelin proteins. Quantitative RT‐PCR showed that expression of BMP4, BMP6, and BMP7 mRNA increased 2‐ to 4‐fold in the lumbar spinal cords of animals with symptomatic EAE versus in vehicle‐treated and untreated controls on days 14, 21, and 42 postimmunization. BMP2 mRNA expression was not altered. BMP4 mRNA was much more abundant in the spinal cords of all animals than was mRNA encoding BMP2, BMP6, and BMP7. Immunoblot analysis confirmed the increased expression of BMP4 in the EAE animals. Immunohistochemistry revealed increased BMP4 immunoreactivity in areas of inflammation in MOG‐peptide EAE animals. BMP4 labeling was mostly limited to macrophages but was sometimes associated with astrocytes and oligodendrocytes. These results indicate that members of the BMP family are differentially expressed in adult spinal cord and are up‐regulated during EAE. © 2007 Wiley‐Liss, Inc.
Extracellular matrix and the regulation of lung development and repair 1

During lung development the extracellular matrix regulates cellular growth, migration, and differentiation. Pulmonary cells reciprocate and regulate extracellular matrix formation by elaborating a variety of peptides that affect gene transcription, RNA processing, translation, and posttranslational modifications of proteins. This regulation involves prenatal events such as the branching of airways and postnatal events such as alveolar septal formation. Normal airway branching requires multiple extracellular matrix proteins, proteoglycans, and the expression of cellular receptors for these molecules. Alveolar septal formation exemplifies how cells regulate the production, export, and deposition of an important structural protein, elastin, which is essential for the development of normal gas exchange units. Repair after injury to the adult lung engages some of the same factors that regulate lung development. However, in this case, inflammatory cells that enter the lung after injury elaborate many of these regulatory peptides. The effects of these peptides on the resident cells, which produce extracellular matrix, are a major determinant of whether the repair restores normal pulmonary architecture or progresses to fibrosis and additional impairment of gas exchange. — McGowan, S. E. Extracellular matrix and the regulation of lung development and repair. FASEB J. 6: 2895‐2904; 1992.
Extending BITA Maturity Model from Organizational Culture Perspective

Business-IT alignment (BITA) has gained attention during the past few years. As a result, a number of theoretical models that can be applied as supportive tools for assessing different components of BITA have been developed. However, most of these efforts have been produced either in Anglo-Saxon Countries or rooted in the experiences gained from these countries. Consequently, they ignore the factor that is subjected to change due to difference in cultural contexts. Therefore, the purpose of this paper is to investigate the impact of organizational culture on achieving BITA and influences its maturity. The research method and process that was followed, namely an in-depth literature survey followed by an empirical study of 51 Swedish multinational organizations.
Concordance of HIV-1 RNA Values by Amplicor and TaqMan 2.0 in Patients With Confirmed Suppression in Clinical Trials.

BACKGROUND The COBAS AMPLICOR HIV-1 MONITOR Test, version 1.5 (Amplicor) has been replaced with the COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, version 2.0 (TaqMan 2.0), a real-time polymerase chain reaction human immunodeficiency virus type 1 (HIV-1) assay with higher sensitivity and broader dynamic range. HIV-1 RNA values at the 50 copies/mL cutoff drive major patient management decisions and clinical study outcomes. METHODS A total of 2217 samples were collected from 1922 HIV-1-infected subjects taking antiretroviral therapy for at least 48 weeks and had at least 2 consecutive samples with HIV-1 RNA <50 copies/mL by Amplicor from 7 recent clinical trials. HIV-1 RNA results were obtained from the Amplicor and TaqMan 2.0 assays in parallel by a reference laboratory. RESULTS The overall concordance between assay results was 96% at the cutoff of 50 copies/mL. However, statistically significant discordance at the 50 copies/mL cutoff was found between the assays for 3.9% of samples (n = 87). By TaqMan 2.0, virologic failure defined as HIV-1 RNA ≥ 50 copies/mL was reported for 2.8% more samples than Amplicor. Of these 87 samples, 68 samples fell within the predicted range of assay variability. Retesting of HIV-1 RNA by TaqMan 2.0 confirmed the discordance in only 28 of the 87 samples. CONCLUSIONS The TaqMan 2.0 assay reports fewer subjects below the clinical endpoint of HIV-1 RNA <50 copies/mL in HIV clinical trials than the Amplicor assay. This difference must be considered when assessing disease progression, designing clinical trials, and comparisons with historical trials that used the Amplicor assay.
Recommendations for Generating, Evaluating, and Implementing Drug‐Drug Interaction Evidence

In October 2009, a 2‐day, multistakeholder, national conference was held in Rockville, Maryland, to discuss and propose methods to improve the drug‐drug interaction (DDI) evidence base and its evaluation and integration into clinical decision support (CDS) systems. The conference featured participants representing consumers, health care providers, those responsible for relevant policies and guidelines, and developers and vendors of DDI compendia, databases, and CDS systems. One desired outcome of the conference was to prepare recommendations on critical issues surrounding DDI evidence. A set of recommendations was developed to improve the generation, evaluation, and translation of DDI evidence into CDS systems based on presentations by experts and the supporting literature. These recommendations were reviewed initially by conference moderators, speakers, and Scientific Steering and Planning Committee members, and subsequently by all attendees. The following recommendations were developed to increase patient safety by improving the relevance and assessment of DDI evidence: conduct well‐designed studies to determine the incidence, outcomes, and patient‐level risk factors for DDIs; use a systematic and transparent process for evaluating the DDI evidence in order to estimate the severity and risks of DDIs; and improve the integration of DDI evidence into electronic CDS. Opportunities exist to improve the DDI evidence base, develop and promote a systematic approach for evaluating the evidence, and integrate this evidence into meaningful CDS.
Genesis of Sindbis virus by in vivo recombination of nonreplicative RNA precursors

Genetically engineered RNA transcripts coding for various Sindbis virus (SIN) genes were used to study structure and sequence requirements of RNA recombination in BHK cells. Three different groups of RNA transcripts were made: (i) RNAs which retain the ability to replicate and which carry sequences coding for either viral polymerase or viral structural proteins; (ii) RNAs which lack the complete 3' end of the SIN genome and thus are incapable of replicating; and (iii) RNAs which lack the complete 5' end of the SIN genome and also are incapable of replicating. BHK cells were transfected with specific combinations of these precursor RNAs, and virus production and RNA synthetic abilities of the released virus were determined. We demonstrate in vivo generation of infectious SIN by fusion of (i) replicative RNAs to nonreplicative RNAs and (ii) two nonreplicative RNA precursors. Both homologous and nonhomologous types of recombinations were observed. In the homologous type of recombination, a 694-nucleotide overlap at the crossover region of the first pair of precursors resulted in the addition of an A residue converting the UAG stop codon of nonstructural protein P4 to a UAA stop codon. In the nonhomologous type of recombination, the crossover sites contained deletion of up to 76 nucleotides from one of the precursors and complete preservation of junction sequence from the other precursor. This is also the first report that a cytoplasmic RNA virus can be generated from biologically nonreplicative RNA precursors. These results have implications for initiation of viral RNA synthesis and recombination between RNA viral genomes in general. We favor template switching as a mechanism for the fusion events described here and suggest inclusion of polymerase scanning of diverse nonreplicative RNAs as an inherent feature of the copy choice model of RNA recombination. Very importantly, the facile nature of RNA recombination occurring between nonreplicative RNA precursors should speed up the production and analysis of targeted mutants of SIN and possibly other RNA viruses.
Pseudo-active sites of protease domains: HGF/Met and Sonic hedgehog signaling in cancer

Abstract Proteases represent a large class of enzymes with crucial biological functions. Although targeting various relevant proteases for therapeutic intervention has been widely investigated, structurally related proteins lacking proteolytic activity (pseudo-proteases) have received relatively little attention. Two distinct clinically relevant cancer pathways that contain signaling proteins with pseudo-protease domains include the Met and Hedgehog (Hh) pathways. The receptor tyrosine kinase Met pathway is driven by hepatocyte growth factor (HGF), a plasminogen-related ligand that binds Met and activates intracellular pathways resulting in cell proliferation, angiogenesis, motility and survival. HGF is a disulfide-linked α/β-heterodimer having a trypsin serine protease-like β-chain. The Hh pathway is driven by Sonic hedgehog (Shh), which has a Zn2+ metalloprotease fold and binds Patched1 (Ptc1), which de-represses Smoothened and ultimately activates Gli-dependent transcription. Although HGF and Shh differ in structure and function, the pseudo-catalytic sites of both HGF and Shh are crucial for signal transduction. For HGF, this region binds the Met β-propeller domain, which leads to Met dimerization and signaling. For Hh, this region binds to the antagonist receptor Hedgehog-interacting protein (Hhip) and most probably to Ptc1 as well. Thus, for both HGF and Hh pathways, targeting ligand pseudo-active sites represents a new strategy for regulation.
Cardiovascular autonomic control in endurance‐trained and sedentary young women

This study aimed to investigate whether endurance‐trained (ET) female athletes demonstrate differences in cardiovascular autonomic control compared with sedentary controls. Eighteen healthy eumenorrhoeic subjects, nine trained (22·4 ± 3 years) and nine sedentary (21·0 ± 1 years), volunteered for the study. Heart rate variability (HRV) and cardiovagal baroreflex sensitivity (BRS) measures were adopted to assess cardiac autonomic control. HRV was recorded for 30 min under both controlled (0·25 Hz) and spontaneous breathing conditions. Cardiovagal BRS was assessed using the Valsalva manoeuvre. Analysis of the HRV showed a longer R‐R interval (1089 ± 114 ms versus 865 ± 100 ms; P<0·001) in the trained subject but only in the spontaneous breathing condition. Conversely, athletes exhibited higher normalized low frequency (LFnu, 44·2 ± 8·5% versus 29·5 ± 6·8%; P<0·001) and lower normalized high frequency (HFnu, 55·8 ± 8·5% versus 69·9 ± 7·7%; P<0·01) only during the controlled breathing condition, consequently the LF/HF ratio was also higher in the trained group in the same condition (0·83 ± 0·3 versus 0·47 ± 0·1, P<0·01). BRS was significantly lower in the ET group (7·95 ± 4·0 ms mmHg−1 versus 13·00 ± 4·4 ms mmHg−1, P<0·05). Further studies are necessary to elucidate the potential role of training and altered hormonal profile in the genesis of the observed differences in cardiovascular autonomic control between highly trained and sedentary control female subjects.
Liver Transplantation Criteria For Hepatocellular Carcinoma Should Be Expanded: A 22-Year Experience With 467 Patients at UCLA

Objective:To assess the efficacy of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) and the impact of current staging criteria on long term survival. Summary Background Data:HCC is becoming an increasingly common indication for OLT. Medicare approves OLT only for HCCs meeting the Milan criteria, thus limiting OLT for an expanding pool of potential liver recipients. We analyzed our experience with OLT for HCC to determine if expansion of criteria for OLT for HCC is warranted. Methods:All patients undergoing OLT for HCC from 1984 to 2006 were evaluated. Outcomes were compared for patients who met Milan criteria (single tumor ≤5 cm, maximum of 3 total tumors with none >3 cm), University of California, San Francisco (UCSF) criteria (single tumor <6.5 cm, maximum of 3 total tumors with none >4.5 cm, and cumulative tumor size <8 cm), or exceeded UCSF criteria. Results:A total of 467 transplants were performed for HCC. At mean follow up of 6.6 ± 0.9 years, recurrence rate was 21.2%, and overall 1, 3, and 5-year survival was 82%, 65%, and 52%, respectively. Patients meeting Milan criteria had similar 5-year post-transplant survival to patients meeting UCSF criteria by preoperative imaging (79% vs. 64%; P = 0.061) and explant pathology (86% vs. 71%; P = 0.057). Survival for patients with tumors beyond UCSF criteria was significantly lower and was below 50% at 5 years. Multivariate analysis showed that tumor number (P < 0.001), lymphovascular invasion (P < 0.001), and poor differentiation (P = 0.002) independently predicted poor survival. Conclusions:This largest single institution experience with OLT for HCC demonstrates prolonged survival after liver transplantation for tumors beyond Milan criteria but within UCSF criteria, both when classified by preoperative imaging and by explant pathology. Measured expansion of OLT criteria is justified for tumors not exceeding the UCSF criteria.
Single-Nucleotide Polymorphisms : an overview of the analytical power of SNP ’ s in genomic research and the preliminary results of its application

The Human Genome Project (HGP), a $3 billion federal program launched in 1990, is an effort designed to sequence the entire human genome by the year 2001. While there are diverse and profound implications of such an achievement, the HGP will actually produce very little information about DNA sequence variation within the human population. From a bioinformatics perspective, this issue clearly needs to be addressed since a key aspect of research in genetics is associating sequence variations with heritable phenotypes. Information about genetic variation is critical for understanding how genes function or malfunction and for understanding how genetic and functional variation are related. In addition, analysis of DNA sequence variation is becoming an increasingly important source of information for identifying the genes involved in both disease and in normal biological processes. Since the most common sequence variations are single nucleotide polymorphisms (SNP’s), it is not surprising that recent advents of mutation detection and highly efficient genotyping technologies (Chee et al. 1996) have coincided with the emergence of the new generation of markers based on single-nucleotide polymorphisms and has subsequently generated great interest in SNP discovery and detection. In addition to their frequency, SNP’s have several other properties that make it an attractive candidate to be the primary analytical reagent in the study of human sequence variation. In this report, the value of SNPs in generating information about genetic variation will first be set in the historical context of positional cloning. In conjunction with a brief description of past generations of genetic markers, the potential powers and limitations of SNP will be discussed in context of genetic analysis. Lastly, a general perspective of the feasibility of low-cost and large-scale discovery and detection of SNPs will be discussed in light of the current state of technology.
A fast CMOS voltage-controlled ring oscillator

A voltage-controlled ring oscillator based on variable capacitive loading is described. A prototype, fabricated in a 1.2 /spl mu/m CMOS-technology, has been tested. The results showed that it is capable to operate at a maximum frequency of 560 MHz. This design operates at 92% of the speed achievable by the same ring oscillator, but where the speed control circuits have been removed. An important feature of this oscillator is its tunability range, which goes from 277 to 560 MHz, or a factor of 2.0 between f/sub max/ and f/sub min/. This paper presents the simulations performed to optimize the performance of the circuit. <<ETX>>
Profile of Philip Cohen. Interview by Carrie Arnold.

Sir Philip Cohen, a biochemist elected as a foreign associate to the National Academy of Sciences in 2008, remembers the moment in his distinguished career when his studies in cell signaling and protein phosphorylation took off. The moment arrived during a 1978 seminar given by Thomas Vanaman at the University of Dundee (Dundee, Scotland, UK). At that time, Cohen had been working on the first kinase to be studied, phosphorylase kinase, which helps to regulate the breakdown of glycogen. Cohen had purified the kinase to study how it was regulated by cAMP and calcium, but he could not untangle the mechanisms by which calcium activated it. That afternoon, Vanaman spoke about work he had done on calmodulin, a calcium-binding protein and a known intermediary in calcium-regulated processes. Vanaman's descriptions of calmodulin—its small size and heat stability—gave Cohen a better idea of the perplexing faint blue smear that he had observed at the bottom of his polyacrylamide gels. Cohen had been so focused on the massive kinase subunits controlled by cAMP that he had missed the small protein that ran off the end of the gel. Philip Cohen Rushing back to his laboratory after Vanaman's seminar, Cohen prepared a different type of gel and identified a small band ahead of the dye front—a band that appeared even after the sample had been boiled, indicating the component was heat-stable. “Then I knew what the answer was going to be,” Cohen said. “This must be the missing component. ” Shortly after, Cohen's hypothesis was confirmed: calmodulin mediated the action of calcium ions on phosphorylase kinase. Cohen has remained at the University of Dundee since 1971 and has worked on many areas of signal transduction, from protein phosphorylation to ubiquitination. His inaugural article, published in a recent issue of PNAS, identifies the phosphorylation sites on Pellino that activate this signaling protein that controls ubiquitination events in the innate immune system (1).
Netropsin . dG-dG-dA-dA-dT-dT-dC-dC complex. Antibiotic binding at adenine . thymine base pairs in the minor groove of the self-complementary octanucleotide duplex.

The structure of the netropsin . dG-dG-dA-dA-dT-dT-dC-dC complex (one antibiotic molecule/self-complementary octanucleodide duplex) and its dynamics as a function of temperature have been monitored by the nuclear magnetic resonances of the Watson-Crick protons, the nonexchangeable base and sugar protons and the backbone phosphates. The antibiotic forms a complex with the nucleic acid duplex at the dA . dT-containing tetranucleotide segment dA-dA-dT-dT, with slow migration amongst potential binding sites at low temperature. The downfield shifts in the exchangeable protons of netropsin on complex formation demonstrate the contributions of hydrogen-bonding interactions between the antibiotic and the nucleic acid to the stability of the complex. Complex formation results in changes in the glycosidic torsion angles of both thymidine residues and one deoxyadenosine residue as monitored by chemical shift changes in the thymine C-6 and adenine C-8 protons. The close proximity of the pyrrole rings of the antibiotic and the base-pair edges in the minor groove is manifested in the downfield shifts (0.3--0.5 ppm) of the pyrrole C-3 protons of netropsin and one adenine C-2 proton and one thymine N-3 base-pair proton on complex formation. The internucleotide phosphates of the octanucleotide undergo 31P chemical shift changes on addition of netropsin and these may reflect, in part, contributions from electrostatic interactions between the charged ends of the antibiotic and the backbone phosphates of the nucleic acid.
Running "fsck" in the Background

Traditionally, recovery of a BSD fast filesystem after an uncontrolled system crash such as a power failure or a system panic required the use of the filesystem checking program, "fsck". Because the filesystem cannot be used while it is being checked by "fsck", a large server may experience unacceptably long periods of unavailability after a crash. Rather than write a new version of "fsck" that can run on an active filesystem, I have added the ability to take a snapshot of a filesystem partition to create a quiescent filesystem on which a slightly modified version of the traditinal "fsck" can run. A key feature of these snapshots is that they usually require filesystem write activity to be suspended for less than one second. The suspension time is independent of the size of the filesystem. To reduce the number and types of corruption, soft updates were added to ensure that the only filesystem inconsistencies are lost resources. With these two additions it is now possible to bring the system up immediately after a crash and then run checks to reclaim the lost resources on the active filesystems. Background "fsck" runs by taking a snapshot and then running its traditional first four passes to calculate the correct bitmaps for the allocations in the filesystem snapshot. From these bitmaps, "fsck" finds any lost resources and invokes special system calls to reclaim them in the underlying active filesystem.
Stability analysis of sensorless BLDC motor drive using digital PWM technique for electric vehicles

Electric vehicles are attractive for future transportation due to sustainability, efficiency and zero greenhouse gases emission. The Brushless DC (BLDC) motor has been used for propulsion system of electric vehicles in the last decade. This paper proposes a new optimized sensorless drive of BLDC motor. This technique is based on back-EMF zero crossing detection (ZCD) from voltage of one phase suitable for EV application. This paper presents a novel commutation technique of BLDC which significantly reduces sensing circuits and cost of motor drive. Digital PWM technique with a PI duty cycle controller is implemented for speed control. The stability of BLDC motor drive is analyzed by Lyapunov stability method. A novel condition is derived for digital PWM controller system being stable with respect to Lyapunov stability criterion. Further cost reduction is also possible by implementing proposed technique and speed controller on a single chip microcontroller. The effectiveness of stability analysis for proposed sensorless technique is verified through simulation and experiment.