Miracle-dz/UniFAR-FTUs huggingface dataset:
Cobalt-dependent Transcriptional Switching by a Dual-effector MerR-like Protein Regulates a Cobalt-exporting Variant CPx-type ATPase*

CoaR associates with and confers cobalt-dependent activation of the coaToperator-promoter. A CoaR mutant (Ser-Asn-Ser) in a carboxyl-terminal Cys-His-Cys motif bound the coaT operator-promoter but did not activate expression in response to cobalt, implicating thiolate and/or imidazole ligands at these residues in an allosteric cobalt binding site. Deletion of 1 or 2 nucleotides from between near consensus, but with aberrant (20 base pairs) spacing, −10 and −35 elements enhanced expression from the coaToperator-promoter but abolished activation by cobalt-CoaR. It is inferred that cobalt effects a transition in CoaR that underwinds thecoaT operator-promoter to realign promoter elements. In the absence of cobalt, CoaR represses expression (∼50%). CoaR is a fusion of ancestral MerR (mercury-responsive transcriptional activator)- and precorrin isomerase (enzyme of vitamin B12biosynthesis)-related sequences. Expression from the coaToperator-promoter was enhanced in a partial mutant of cbiE(encoding an enzyme preceding precorrin isomerase in B12biosynthesis), revealing that this pathway “inhibits”coaT expression. Disruption of coaT reduced cobalt tolerance and increased cytoplasmic 57Co accumulation. coaT-mediated restoration of cobalt tolerance has been used as a selectable marker.
Optimized Protocol for Gene Expression Analysis in Formalin-fixed, Paraffin-embedded Tissue Using Real-time Quantitative Polymerase Chain Reaction

Formalin-fixed, paraffin-embedded (FFPE) tissue is the most common tissue specimen available after microscopic examination. Molecular methods, such as polymerase chain reaction (PCR) and gene expression examination, serve as a source of diagnostic and prognostic information but require high-quality RNA. However, the increasing application of RNA extracted from FFPE tissue frequently results in very small and degraded quantities of nucleic acid. This study targets gene expression analysis from FFPE specimens using real-time quantitative PCR. The whole protocol consists of several steps, that is, RNA extraction and its quality control, reverse transcription, and fluorescence detection during real-time quantitative PCR. We compared several methods in each step, chose the most effective, and with that combination we successfully examined 95% (62 from 65) FFPE samples for our genes of interest. We reached the best results with RNA isolation by using a commercial kit, carefully interpreted UV spectrophotometric values, and meticulously chose reverse transcriptase and TaqMan fluorescence detection. Our protocol improves the utility of FFPE tissue for molecular profiling studies.
Performance analysis of re-configurable partitioned TLBs

Conventional address translation mechanisms generally use a translation lookaside buffer (TLB) cache of current page translations to provide virtual-to-physical page addressing. This translation cache is generally shared amongst all processes and between reference types, irrespective of whether they relate to instruction or data references. In this paper, we introduce a reconfigurable partitioned TLB which improves TLB performance by removing cache conflict misses between the distinct reference types. Extensive simulations using selected SPEC95 workloads show that data-reference translations unfairly compete with instruction-reference translations by dominating a standard shared TLB. We compare the traditional shared TLB with both fixed partition and reconfigurable fixed partition TLB structures that segregate instruction and data page translation entries. We show that the partitioned TLB operates optimally when the miss ratio of the instruction-reference partition is maintained at a lower level than that for the data-reference partition. By dynamically preserving the balance between the translation performance of the instruction and data components, a protected "working set" of instruction translation entries can be maintained. This can be achieved within the one TLB structure, with soft partitions separating reference types.
Biological characteristics of CD133(+) cancer stem cells derived from human laryngeal carcinoma cell line.

OBJECTIVE To investigate the in vitro invasive capability, clone-forming ability, resistance to anti-tumor treatments of CD133(+) human laryngeal carcinoma stem cells, and characterize the related signaling pathways in these cells. METHODS Human laryngeal carcinoma Hep-2 cells were subjected to flow cytometry sorting to obtain CD133(+) stem cells. Transwell chamber assay and clone-formation forming test were performed to evaluate the invasive capability and the clone-forming ability of CD133(+) laryngeal carcinoma tumor stem cells, respectively. MTT assay was used to assess the resistance of CD133(+) Hep-2 cells to radiotherapy and chemotherapy, respectively. Western blot and real-time PCR were applied to characterize the signaling pathways in these stem cells. RESULTS Our results from the transwell chamber assay indicated that the migrating capability of CD133(+) Hep-2 cells was significantly higher than CD133(-) cells, and the invasive capability of CD133(+) Hep-2 cells was also significantly elevated. Moreover, clone-formation forming test showed higher clone-forming ability for CD133(+) Hep-2 cells, compared with CD133(-) cells. Furthermore, CD133(+) Hep-2 cells displayed significant resistance to radiotherapy and chemotherapy. The Bcl-2/Bax ratio was increased, and Hedgehog, Wnt, and Bmi-l signaling pathways were all activated, in CD133(+) laryngeal carcinoma stem cells, which might be involved in the self-renewal process of these stem cells. CONCLUSION The invasive capability, clone-forming ability, and resistance to anti-tumor treatments are enhanced, and anti-apoptotic and proliferation-related signaling pathways are activated in CD133(+) laryngeal carcinoma tumor stem cells. These findings might provide new insights into the prevention and/or treatment of laryngeal carcinoma, especially concerning target-oriented therapies.
Effect of Climate Change on Isoprene Emissions and Surface Ozone Levels

The effect of climate change on vegetation, isoprene emissions and surface ozone levels was investigated using a global three‐dimensional general circulation model coupled to a dynamic vegetation and chemistry models. Integrations for the 1990s and 2090s were performed. Isoprene emissions increased from 549 Tg yr−1 (1990s) to 736 Tg yr−1 (2090s) as a result of climate change with fixed vegetation. However, the isoprene emissions only increase to 697 Tg yr−1 in the 2090s when vegetation changes were included. Surface ozone levels rose by 20–30 ppbv in some locations with fixed vegetation owing to increases in precursor gases, but only by 10–20 ppbv if the vegetation changes were included. Ozone levels in parts of China, Korea and the eastern USA are predicted to exceed the World Health Organisation health limit of 60 ppbv, however, when changes in vegetation are accounted for, a much smaller area exceeds this limit.
Cardiotoxic effects of anthracycline–taxane combinations

The association of doxorubicin (DOX) and paclitaxel (PTX) is very active in breast cancer. Unfortunately, PTX may potentiate the cardiotoxic effects of anthracyclines: it causes nonlinear disposition of DOX and its metabolites, leading to persistant of elevated plasma concentrations of the anthracyclines. However, this pharmacokinetic interference is not sufficient to explain the enhanced cardiotoxicity of the combination. Recent data suggest that PTX stimulates the conversion of DOX to cardiotoxic metabolites (namely doxorubicinol) inside cardiomyocytes. Docetaxel (DTX) does not have a major influence on DOX plasma concentration because it does not interfere with its elimination. Clinical data suggest that DTX may not enhance anthracycline cardiotoxicity, but patients seldom received a total anthracycline dose compatible with increased risk. Furthermore, there are experimental data indicating that DTX can also stimulate the metabolism of DOX to toxic species in human heart.
Enhanced Yields of Gamma Interferon in Prolactin Treated Human Peripheral Blood Mononuclear Cells

Abstract Prolactin is a peptide hormone with effects on a number of target organs including the immune system. It has been shown that animals rendered hypoprolactinemic have impaired delayed hypersensitivity, impaired macrophage activation and altered secretion of gamma interferon (IFN). Using peripheral blood mononuclear cells (PBMC) and inducing the cells to produce gamma IFN with a range of inducers, we have studied the effects of a number of hormones on IFN production. Using cells from normal donors, we have found that prolactin in concentrations of 10-8 M or greater, can significantly enhance the production of gamma IFN. The effect was dose related and was observed when lectins (PHA and Con A), but not anti CD3 antibodies, ionophones, or IL-2 were used to induce the cells. The presence of prolactin in concentrations above that encountered in the fetal bovine serum used to incubate the cells resulted in a doubling or more of the IFN produced. The tests were performed on 30 occasions with cells drawn from 21 individuals. On all but three occasions, yield enhancement was observed in the presence of prolactin. The mechanism of the effect was investigated, and genistein, a tyrosine kinase inhibitor, was found to abort the influence of prolactin on gamma IFN production. These studies indicate prolactin in physiological concentrations can enhance the production of gamma IFN from cells from normal donors.
Ideality factor behavior between the maximum power point and open circuit

The local ideality factor analysis of dark and light I-V curves has been used in the past to study various performance degradation effects in solar cells. Trapping, edge recombination and injection-level-dependent recombination are expressed as “lumps, humps and bumps” in the plots of the local ideality factor over cell voltage (m-V plots). Earlier applications of this differential technique did not correct the plots for the series resistance effect. Thus, the bumps at the higher voltages introduced by some mechanisms were more difficult to quantify. A possible solution is to analyze ISC-VOC curves, but their measurement is not always possible. We present a formula for calculation of the RS-corrected local ideality factor. The m-I plot can be more informative than the m-V plot which varies strongly with the cell temperature. We present results from several crystalline-silicon (c-Si) PV technologies showing the m-I plot behavior between the MPP and open circuit. For some of the tested modules, the ideality factor is much higher at the MPP.
Regulated Assembly of Vacuolar ATPase Is Increased during Cluster Disruption-induced Maturation of Dendritic Cells through a Phosphatidylinositol 3-Kinase/mTOR-dependent Pathway*

Background: The V-ATPase is induced to assemble during TLR-activated maturation of dendritic cells. Results: Cluster disruption of dendritic cells also induces V-ATPase assembly by a PI3K/mTOR-dependent mechanism. Conclusion: Semi-mature dendritic cells show increased V-ATPase assembly. Significance: Dendritic cell maturation associated with immune tolerance involves V-ATPase assembly. The vacuolar (H+)-ATPases (V-ATPases) are ATP-driven proton pumps composed of a peripheral V1 domain and a membrane-embedded V0 domain. Regulated assembly of V1 and V0 represents an important regulatory mechanism for controlling V-ATPase activity in vivo. Previous work has shown that V-ATPase assembly increases during maturation of bone marrow-derived dendritic cells induced by activation of Toll-like receptors. This increased assembly is essential for antigen processing, which is dependent upon an acidic lysosomal pH. Cluster disruption of dendritic cells induces a semi-mature phenotype associated with immune tolerance. Thus, semi-mature dendritic cells are able to process and present self-peptides to suppress autoimmune responses. We have investigated V-ATPase assembly in bone marrow-derived, murine dendritic cells and observed an increase in assembly following cluster disruption. This increased assembly is not dependent upon new protein synthesis and is associated with an increase in concanamycin A-sensitive proton transport in FITC-loaded lysosomes. Inhibition of phosphatidylinositol 3-kinase with wortmannin or mTORC1 with rapamycin effectively inhibits the increased assembly observed upon cluster disruption. These results suggest that the phosphatidylinositol 3-kinase/mTOR pathway is involved in controlling V-ATPase assembly during dendritic cell maturation.
C-reactive protein and risk of lung cancer.

PURPOSE Chronic inflammation could play a role in lung carcinogenesis, underscoring the potential for lung cancer prevention and screening. We investigated the association of circulating high-sensitivity C-reactive protein (CRP, an inflammation biomarker) and CRP single nucleotide polymorphisms (SNPs) with prospective lung cancer risk. PATIENTS AND METHODS We conducted a nested case-control study of 592 lung cancer patients and 670 controls with available prediagnostic serum and 378 patients and 447 controls with DNA within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N = 77,464). Controls were matched to patients on age, sex, entry year, follow-up time, and smoking. We measured CRP levels in baseline serum samples and genotyped five common CRP SNPs. RESULTS Elevated CRP levels were associated with increased lung cancer risk (odds ratio [OR], 1.98; 95% CI, 1.35 to 2.89; P-trend < .001 for fourth quartile [Q4, > or = 5.6 mg/L] v Q1 [< 1.0 mg/L]). The CRP association did not differ significantly by histology, follow-up time, or smoking status, but was most apparent for squamous cell carcinomas (OR, 2.92; 95% CI, 1.30 to 6.54), 2 to 5 years before lung cancer diagnosis (OR, 2.33; 95% CI, 1.24 to 4.39), and among former smokers (OR, 2.48; 95% CI, 1.53 to 4.03) and current smokers (OR, 1.90; 95% CI, 1.06 to 3.41). Although CRP SNPs and haplotypes were associated with CRP levels, they were not associated with lung cancer risk. Ten-year standardized absolute risks of lung cancer were higher with elevated CRP levels among former smokers (Q4: 2.55%; 95% CI, 1.98% to 3.27% v Q1: 1.39%; 95% CI, 1.07% to 1.81%) and current smokers (Q4: 7.37%; 95% CI, 5.81% to 9.33% v Q1: 4.03%; 95% CI, 3.01% to 5.40%). CONCLUSION Elevated CRP levels are associated with subsequently increased lung cancer risk, suggesting an etiologic role for chronic pulmonary inflammation in lung carcinogenesis.
Topical nipradilol: effects on optic nerve head circulation in humans and periocular distribution in monkeys.

PURPOSE To investigate the effects of topical nipradilol on blood velocity in the optic nerve head (ONH) in normal humans and the ocular and periocular distribution of topically instilled nipradilol in monkeys. METHODS In normal humans, 0.25% nipradilol was instilled in one eye and vehicle in the other twice daily for 7 days, and blood velocity in the ONH was measured by the laser speckle method. In monkeys, after a single instillation of 1% [(14)C]nipradilol in one eye, distribution of radioactivity was evaluated by whole-head autoradiography. RESULTS Twice-daily 7-day instillation of nipradilol temporarily but significantly increased human ONH blood velocity, in the ipsilateral eye only (P = 0.005), independent of a reduction in the intraocular pressure. In monkeys, equivalent nipradilol concentration in the periocular tissue around the optic nerve insertion was higher on the ipsilateral side than on the contralateral side (140 +/- 25 ng/g and 42 +/- 10 ng/g, P = 0.022, n = 5). Radioactivity was higher in the periocular tissue behind the equator than around the optic nerve insertion on the ipsilateral side (P = 0.004), but not on the contralateral side. The equivalent nipradilol concentration in the ipsilateral posterior retina-choroid was 636 +/- 92 ng/g, which was significantly higher than that on the contralateral control side (521 +/- 92 ng/g, P < 0.001). CONCLUSIONS The ipsilateral increase in ONH blood velocity induced by topical nipradilol in humans was attributed to drug that penetrated locally. Whole-head autoradiographic study suggests that topically instilled nipradilol can rapidly reach the posterior periocular tissue at pharmacologic concentrations.
Interpretation of Resistance Assay Results

Resistant viruses may emerge in patients via two different mechanisms [5]. In the first instance, resistant viruses may be transmitted [5‐7]. Alternatively, resistance mutations may be selected for during therapy. This will take place if virus replication occurs in the presence of antiviral drugs, as may be the case due to insufficient drug levels or insufficient inhibitory activity of a regimen [8]. Reasons for suboptimal drug levels include non-adherence, problems with absorption or pharmacokinetic interactions. In this instance, interventions may be more successful by focusing on improving adherence and reducing drug-related toxicities in order to prevent the exhaustion of limited therapy options [5]. The two main types of assay currently used to detect drug-associated resistance are genotypic and phenotypic assays. Genotypic testing uses DNA sequencing or hybridization techniques to identify the presence of individual mutations in the viral genome that are known to be associated with reduced susceptibility to antiretroviral drugs. Phenotypic testing measures the in vitro susceptibility of a viral isolate to one or more drugs. This is generally measured as the concentration of drug required to inhibit replication by 50% in cell culture (IC50). A quantitative measure of isolate susceptibility is derived by comparison of the isolate IC50 with that of a reference wild-type strain, and expressed as the fold-difference between the two. Thus, an isolate displaying a twofold reduction in susceptibility to a particular drug has an IC50 twice as high as the wildtype control. An additional method that combines some of the benefits of both genotyping and phenotyping is the VirtualPhenotype, which relies on a large relational database of genotypes and their corresponding phenotypes [9]. For prevalent mutational patterns this allows an isolate’s genotype to be predictive of a phenotype. For less common mutational patterns, there may be few or no matches in the database and traditional phenotyping assays are required [9]. The application of the results produced by these tests is subject to influence by host factors, pharmacokinetic issues and interactions between mutations [5]. The aim of this article is to review the recent prospective studies and discuss some of the central issues surrounding resistance testing technologies and the interpretation of assay results.
Item-user Preference Mapping with Mixture Models - Data Visualization for Item Preference

In this paper, we propose a visualization technique of a statistical relation of users and preference of items based on a mixture model. In our visualization, items are given as points in a few dimensional preference space, and user specific preferences are given as lines in the same space. The relationship between items and user preferences are intuitively interpreted via projections from points onto lines. As a primitive implementation, we introduce a mixture of the Bradley-Terry models, and visualize the relation between items and user preferences with benchmark data sets.
Comparison of GA Based Heuristic and GRASP Based Heuristic for Total Covering Problem

This paper discusses the comparison of two different heuristics for total covering problem. The total covering problem is a facility location problem in which the objective is to identify the minimum number of sites among the potential sites to locate facilities to cover all the customers. This problem is a combinatorial problem. Hence, heuristic development to provide solution for such problem is inevitable. In this paper, two different heuristics, viz., GA based heuristic and GRASP based heuristic are compared and the best is suggested for implementation.
Spectral Analysis of Bangla Vowels

Spectral analysis of Bangla vowel based on articulatory properties of vocal tract plays a significant role in Bangla speech synthesis and recognition. A vowel system through the spectral analysis is classified into distinct vowel region within articulatory space. This paper synthesize vowel space illustration by spectral analysis of Bangla vowel sounds to locate them in both "acoustic" and "articulatory" space of the vocal tract tube. Measurements of the spectral characteristics and the formant frequencies were made for each vowel from isolated Bangla word spoken by both male and female speakers. All these measurements were tested in synthesis of isolated utterance
Hyperalgesia and opioid switching

Opioids, intended to abolish pain, can unexpectedly produce hyperalgesia, particularly during rapid opioid escalation. Opioid switching could be a therapeutic option in a condition of opioid-induced tolerance or hyperalgesia, but conversion ratios between opioids are difficult to apply in this context and require strict surveillance and expertise. This situation is challenging, because the rapid escalation of opioid doses, possibly due to the development of opioid-induced tolerance, can cause hyperalgesia. To avoid this adverse effect, clinicians need to refine their assessment of pain treatment and consider opioid switching. The authors present a case report in which switching from fentanyl to methadone was effective in a patient who developed hyperalgesia as a consequence of a rapid opioid escalation. Regardless of the expected clinical improvement of opioid switching using lower doses of the second opioid, the final dose of the second opioid was exaggeratedly low, probably as a consequence of the disappearance of hyperalgesia induced by the first opioid. The results of this case and others like it may help practitioners develop a meaningful approach during opioid escalation, possibly anticipating the need for opioid switching or other alternative measures for patients with uncontrolled cancer pain.
Hyper-redundant manipulator dynamics: a continuum approximation

Hyper-redundant, or 'snake-like', manipulators have a very large number of actuatable degrees of freedom. This paper develops an efficient formulation of approximate hyper-redundant manipulator dynamics. The most efficient methods for representing manipulator dynamics in the literature require serial computations proportional to the number of degrees of freedom. Furthermore, these methods are not fully parallelizable. For hyper-redundant manipulators, which may have tens, hundreds or thousands of actuators, these formulations preclude real time implementation. This paper therefore looks at the mechanics of hyper-redundant manipulators from the point of view of an approximation to an 'infinite degree-or-freedom' (or continuum) problem. The dynamics for this case is developed. The approximate dynamics of actual hyper-redundant manipulators is then reduced to a problem which is O(1) in time, i.e. the algorithm is O(n) is the total number of computations, but these computations can be completely distributed o.