Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinetic Analysis of Translesion Synthesis Opposite Bulky N2- and O6-Alkylguanine DNA Adducts by Human DNA Polymerase REV1*

REV1, a Y family DNA polymerase (pol), is involved in replicative bypass past DNA lesions, so-called translesion DNA synthesis. In addition to a structural role as a scaffold protein, REV1 has been proposed to play a catalytic role as a dCTP transferase in translesion DNA synthesis past abasic and guanine lesions in eukaryotes. To better understand the catalytic function of REV1 in guanine lesion bypass, purified recombinant human REV1 was studied with two series of guanine lesions, N2-alkylG adducts (in oligonucleotides) ranging in size from methyl (Me) to CH2(6-benzo[a]pyrenyl) (BP) and O6-alkylG adducts ranging from Me to 4-oxo-4-(3-pyridyl)butyl (Pob). REV1 readily produced 1-base incorporation opposite G and all G adducts except for O6-PobG, which caused almost complete blockage. Steady-state kinetic parameters (kcat/Km) were similar for insertion of dCTP opposite G and N2-G adducts but were severely reduced opposite the O6-G adducts. REV1 showed apparent pre-steady-state burst kinetics for dCTP incorporation only opposite N2-BPG and little, if any, opposite G, N2-benzyl (Bz)G, or O6-BzG. The maximal polymerization rate (kpol 0.9 s–1) opposite N2-BPG was almost the same as opposite G, with only slightly decreased binding affinity to dCTP (2.5-fold). REV1 bound N2-BPG-adducted DNA 3-fold more tightly than unmodified G-containing DNA. These results and the lack of an elemental effect ((Sp)-2′-deoxycytidine 5′-O-(1-thiotriphosphate)) suggest that the late steps after product formation (possibly product release) become rate-limiting in catalysis opposite N2-BPG. We conclude that human REV1, apparently the slowest Y family polymerase, is kinetically highly tolerant to N2-adduct at G but not to O6-adducts.
Age-Dependent Increase in Ischemic Brain Injury in Wild-Type Mice and in Mice Lacking the Inducible Nitric Oxide Synthase Gene

The authors investigated the influence of age on the outcome of cerebral ischemia in wild-type mice and in mice with a deletion of the inducible nitric oxide synthase (iNOS) gene. The middle cerebral artery was permanently occluded in iNOS-null mice and in wild-type (C57BL/6) controls aged 4, 8, 16, and 24 weeks. Infarct volume was determined in thionin-stained brain sections 4 days after permanent middle cerebral artery occlusion. No differences in forebrain volume were found among wild-type and iNOS-null mice at the ages studied (P> 0.05). In C57BL/6 mice (n = 5 to 6/group), neocortical infarct volume corrected for swelling was 28 ± 5 mm3 in 4-week-old mice, 28 ±3 at 8 weeks, 35 ±4 at 16 weeks, and 37 ± 6 at 24 weeks (mean ± SD). iNOS-null mice (n = 5 to 6/group) had smaller infarcts than wild-type controls at all ages (P < 0.05). However, the magnitude of the reduction was greater in 4-week-old (–29% ± 10%) or 8-week-old mice (–24% ± 8%), than in 16-week-old (–14% ± 10%) or 24-week-old mice (–11% ± 6%). Neurologic deficit scores improved significantly between 24 and 96 hours in 4- and 8-week-old iNOS-null mice compared with age-matched wild-type mice (P < 0.05). However, in 16- or 24-week-old iNOS-null mice, neurologic deficits did not improve (P > 0.05). The authors conclude that in iNOS–/– and in wild-type mice, the size of the infarct produced by occlusion of the middle cerebral artery is larger in older than in younger mice. However, the reduction in infarct volume observed in iNOS-null mice is age-dependent and is greatest at 1 to 2 months of age. Therefore, age is a critical variable in studies of focal cerebral ischemic damage, both in wild-type mice and in mouse mutants.
Surgical Management of Massive Hemoptysis: A Ten‐year Experience

Pulmonary bleeding was defined as massive when the collected blood was 600 ml or more in 24 hours. Hemoptysis of this magnitude carries more than 50% mortality when managed without surgical intervention. For this reason all patients admitted, bleeding massively, in the past ten years were considered candidates for surgical therapy. Localization of the bleeding was done by bronchoscopy. Pulmonary reserve was evaluated by clinical and radiological observation and, when feasible, by spirometry. Of the 75 patients seen with massive hemoptysis, 68 were operated. Seven patients were excluded for various reasons. Five of these patients died during the acute bleeding episode. Sixty-five resections were performed with 11 deaths (17%) and three cavernostomies with one death. Of 51 lobectomies, seven expired (14%). One segmentectomy survived. Other than the magnitude of the surgical resection, the mortality was related to the amount of bleeding in the 24 hours preceding the surgical procedure. Severe bleeding at the time of resection requiring one-lung ventilation also significantly influenced the mortality (33% against 7%). This experience shows that pulmonary resection is the treatment of choice in patients with massive hemoptysis.
Early detection of Parkinson's disease through Voice

This paper present different methods of diagnosis of Parkinson's disease through voice in early stages. The aim of this study is to provide a simple, fast, cheaper method of detection of Parkinson's disease for the patients as there is no cure for this disease and the available therapies which provide some relief to them are too much costlier for this disease. Voice has different parameters that tell meaningful variations between normal people and Parkinson's patient like pitch, jitter, formant, shimmer, Mel-frequency Cepstral Coefficient (MFCC) and glottal pulse were founded out and analyzed.
Prediction of recurrent venous thromboembolism by the activated partial thromboplastin time

Summary. Background: Venous thromboembolism (VTE) is a multi‐factorial disease. Extensive thrombophilia screening is costly and often inconclusive. Simple laboratory methods are required to predict the risk of recurrence. Objective: To assess if measurement of activated partial thromboplastin time (APTT) allows stratification of patients with VTE into high‐ and low‐risk categories with regard to recurrence. Patients and methods: We prospectively followed 918 patients with a first unprovoked VTE and studied the relationship between recurrence and an APTT after discontinuation of anticoagulation. APTT was expressed as a ratio of test to reference coagulation times. Study endpoint was symptomatic recurrent VTE. Results: Venous thromboembolism recurred in 101 (11%) patients. Patients without recurrence had a greater APTT ratio than those with recurrence (0.97 ± 0.09 vs. 0.93 ± 0.09, P = 0.001). After 4 years, probability of recurrent VTE was 8.5% (95% CI: 5.5–11.5%) among patients with a ratio equal to or > 0.95 and 15.6% (95% CI: 11.4–19.9%) among patients with a lower ratio (P = 0.005). Compared with patients with an APTT ratio < 0.95, the relative risk (RR) of recurrence among patients with a ratio equal to or > 0.95 was 0.56 (95% CI: 0.38–0.84, P = 0.005) before and 0.58 (95% CI: 0.39–0.87, P = 0.009) after adjustment for sex, age, factor V Leiden, and factor II G20210A. Conclusions: Measurement of APTT allows stratification of patients with VTE into high‐ and low‐risk categories with regard to recurrence.
The combination stretching function technique with simulated annealing algorithm for global optimization

A stretching function technique is combined with the simulated annealing (SA) algorithm for the global optimization problems. In the presented algorithm, the obtained local optimum information by SA search is used to build a stretching function. To speed up the convergence of SA, SA is executed iteratively on the stretching function constructed with respect to the previously found local minima instead of on the original objective function. Furthermore, a new next trial point generation scheme in SA is designed to increase the diversity of the trial points to make the introduced technique more effective. In the numerical experiments, we first investigate and compare the effectiveness and efficiency of the combination of the stretching technique with a newly designed SA (SSA), with particle swarm optimization and with differential evolution algorithm, respectively, on eight typical test functions in terms of the average number of the function evaluations and its standard deviation, and the success rate. Second, we systematically compare the numerical results of SSA with the traditional SA with elitist and SA with new generation scheme on 37 benchmark problems. The numerical results show that the hybrid method is effective for global optimization.
The Dynamics of Tectonic Modelling of Some Caves in the Karst Region (Croatia)

Deformational processes resulted in the formation of certain caves in the carbonate rocks of the karst area are analysed. Some of the caves were formed by deformational processes connected to extension of the area, while others were formed by processes that followed compression during structural formation of the Dinarides. In the first case, the caves were infilled by calcite material and/or by debris from the surrounding rocks mixed with terra rossa. The second group is mostly represented by caves forming open spelaeological objects.
Inhibition of prostaglandin synthesis in intact cells by paracetamol (acetaminophen)

Despite its wide use, the mechanism of action of paracetamol (acetaminophen) is uncertain. It is commonly stated to be a weak inhibitor of the synthesis of prostaglandins (PGs) by the prostaglandin H synthases (COX-1 and COX-2) but paracetamol inhibits the synthesis of PGs in stimulated cultured cells with IC50 values ranging from 4 to 200 μM. Paradoxically, it generally stimulates PG production in broken cell preparations. Here we show that paracetamol inhibits the production of PGs in human rheumatoid synoviocytes during stimulation by interleukin1β (0.1ng/ml) for 18 h. Paracetamol inhibited the production of both PGE2 and PGF2αwith median IC50 values of 7.2 and 4.2 μM respectively, without affecting the or the level of the constitutive enzyme, COX-1 or the interleukin-1β mediated induction of both COX-2 and cytosolic phospholipase A2-α (cPLA2-α). These data indicate that paracetamol suppresses delayed PG production by direct modulation of the cPLA2-α /COX-2 pathway at therapeutic concentrations. Paracetamol is a substituted phenol and its effects on the synthesis of PGs are very similar to those of other phenols. Paracetamol should be considered to inhibit the production of PGs although the cause of its selectivity; analgesic and antipyretic effects with weak antiplatelet and anti-inflammatory effects is unknown.
A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of the Augmentation of a Nicotinic Acetylcholine Receptor Partial Agonist in Depression: Is There a Relationship to Leptin Levels?

Abstract This randomized, double-blind, placebo-controlled trial evaluated the efficacy of CP-601,927, an &agr;4&bgr;2 nicotinic acetylcholine receptor partial agonist and an augmenting agent of antidepressants in major depressive disorder patients with insufficient response to selective serotonin reuptake inhibitors (SSRIs). After open-label treatment with an SSRI for 8 weeks, subjects with a Hamilton Depression Scale 17 score greater than or equal to 16 were entered into a double-blind phase and randomized to CP-601,927 2 mg twice daily or placebo for 6 weeks. The primary end point was the change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from double-blind baseline to week 14. There was no significant difference in change from baseline to week 14 in the MADRS score for CP-610,927 versus placebo (least square mean difference [80% confidence interval], −1.30 [−3.32–0.71]). Post hoc analyses revealed that the drug-placebo difference in change from baseline (SE) to week 14 in MADRS score was greater in subjects with body mass index (BMI) less than or equal to 35 kg/m2 (−3.43 [1.87], P = 0.069) than those with BMI greater than 35 kg/m2 (3.37 [2.8], P = 0.230). Analysis of biomarkers associated with increased BMI suggests that baseline leptin had a significant effect on treatment outcome. P values for the effect of treatment on mean change in MADRS score for subjects with baseline leptin levels below and above the median were 0.055 and 0.0055, respectively. CP-601,927 was equivalent to placebo as an augmenting agent of antidepressants in major depressive disorder patients with insufficient response to SSRIs. However, post hoc analyses suggest that BMI, particularly elevated leptin levels, may have affected the response to CP-601,927; however, further study may be needed to confirm these results.
A Randomized, Double-Blind Placebo-Controlled Trial Evaluating the Effects of Vitamin E and Selenium on Arsenic-Induced Skin Lesions in Bangladesh

Objective: We sought to determine whether supplementation of vitamin E (α-tocopherol), selenium (L-selenomethionine), or their combination improves arsenical skin lesions. Methods: A 2 × 2 randomized, placebo-controlled, double-blind trial among 121 men and women chronically exposed to arsenic in drinking water was conducted in rural Bangladesh. Participants were randomized to one of four treatment arms: vitamin E, selenium, vitamin E and selenium (combination), or placebo and were treated for 6 months. Results: At baseline, the average skin lesion scores were 2.23, 2.26, and 2.63 and at follow-up, the average skin lesion scores went down to 2.00, 2.06, and 2.47 in those receiving vitamin E, selenium, and the combination, respectively. Conclusions: Supplementation with vitamin E and selenium, either alone or in combination, slightly improved skin lesion status, although the improvement was not statistically significant.
Humanizing the Self: Moderators of the Attribution of Lesser Humanness to Others

Three studies investigated moderators of the tendency to attribute greater humanness to the self than to others, an interpersonal counterpart of outgroup infra-humanization. Study 1 demonstrated that this self-humanizing effect is reduced when the other is the focus of comparison. Study 2 showed that the effect is reduced when the other is individuated. Study 3 indicated that empathy does not moderate self-humanizing: Self-humanizing failed to correlate negatively with dispositional empathy or perspective-taking. Study 3 also indicated that abstract construal moderates the self-humanizing effect using a temporal comparison. Participants rated their future self, but not their past self, as less human than their present self. Studies 1 and 3 also showed that self-humanizing is greater for undesirable traits: People may view their failings as “only human. ” All findings were distinct from those attributable to self-enhancement. Self-humanizing may reflect a combination of egocentrism, focalism, abstract representation of others, and motivated processes.
Cross-Linguistic Distinctions Between Professional and Non-Professional Speaking Styles

This work investigates acoustic and perceptual differences in four language varieties by using a corpus of professional and non-professional speaking styles. The professional stimuli are composed of excerpts of broadcast news and political discourses from six subjects in each case. The non-professional stimuli are made up of recordings of 10 subjects who read a long story and narrated it subsequently. All this material was obtained in four language varieties: Brazilian and European Portuguese, standard French and German. The corpus is balanced for gender. Eight melodic and intensity parameters were automatically obtained from excerpts of 10 to 20 seconds. We showed that 6 out of 8 parameters partially distinguish professional from non-professional style in the four language varieties. Classification and discrimination tests carried out with 12 Brazilian listeners using delexicalised speech showed that these subjects are able to distinguish professional style from non-professional style with about 2/3 of hits irrespective of language. In comparison, an automatic classification using an LDA model performed better in classifying non-professional (96 %) against professional styles, but not in classifying professional (42 %) against non-professional styles.
Heat Shock Protein 10 Inhibits Lipopolysaccharide-induced Inflammatory Mediator Production*

Heat shock protein 10 (Hsp10) and heat shock protein 60 (Hsp60) were originally described as essential mitochondrial proteins involved in protein folding. However, both proteins have also been shown to have a number of extracellular immunomodulatory activities. Here we show that purified recombinant human Hsp10 incubated with cells in vitro reduced lipopolysaccharide (LPS)-induced nuclear factor-κB activation and secretion of several inflammatory mediators from RAW264.7 cells, murine macrophages, and human peripheral blood mononuclear cells. Induction of tolerance by contaminating LPS was formally excluded as being responsible for Hsp10 activity. Treatment of mice with Hsp10 before endotoxin challenge resulted in the reduction of serum tumor necrosis factor-α and RANTES (regulated upon activation, normal T cell expressed and secreted) levels and an elevation of serum interleukin-10 levels. Hsp10 treatment also delayed mortality in a murine graft-versus-host disease model, where gut-derived LPS contributes to pathology. We were unable to confirm previous reports that Hsp10 has tumor growth factor properties and suggest that Hsp10 exerts anti-inflammatory activity by inhibiting Toll-like receptor signaling possibly by interacting with extracellular Hsp60.
Advances in Brief Photofrin Photodynamic Therapy Can Significantly Deplete or Preserve Oxygenation in Human Basal Cell Carcinomas during Treatment , Depending on Fluence Rate 1

At high fluence rates in animal models, photodynamic therapy (PDT) can photochemically deplete ambient tumor oxygen through the generation of singlet oxygen, causing acute hypoxia and limiting treatment effectiveness. We report that standard clinical treatment conditions (1 mg/kg Photofrin, light at 630 nm and 150 mW/cm), which are highly effective for treating human basal cell carcinomas, significantly diminished tumor oxygen levels during initial light delivery in a majority of carcinomas. Oxygen depletion could be found during at least 40% of the total light dose, but tumors appeared well oxygenated toward the end of treatment. In contrast, initial light delivery at a lower fluence rate of 30 mW/cm increased tumor oxygenation in a majority of carcinomas. Laser treatment caused an intensityand treatment time-dependent increase in tumor temperature. The data suggest that high fluence rate treatment, although effective, may be inefficient.
Multibaseline Polarimetric SAR Tomography of a Boreal Forest at P- and L-Bands

Longer wavelength synthetic aperture radars (SARs) are precious in the remote sensing of forested areas, being sensitive to contributions from the whole vegetation layer and from the ground below. The electromagnetic properties of such contributions are retrieved from multipolarimetric acquisitions, whereas their vertical structure is retrieved from multibaseline acquisitions through tomographic imaging. Combining baseline and polarization diversity provides most information, allowing the decomposition of the SAR signal into ground- and volume-only contributions. A formal treatment of this problem is provided with the algebraic synthesis technique, which extends the concepts of PolInSAR. The decomposition, however, is shown to be ambiguous in that different solutions are equally consistent with the data. The main goal of this paper is to discuss this topic in light of the experimental results from a tomographic and polarimetric analysis of the boreal forest within the Krycklan River catchment, Northern Sweden, investigated at P- and L-bands during the ESA campaign BioSAR 2008. Different solutions to the decomposition problem will be discussed by examining the corresponding vertical structures accessible through tomographic techniques. Elements are shown supporting the idea that ground-volume interactions play a nonnegligible role at P-band, and a solution is proposed to isolate contributions from direct volume backscattering. The retrieval of forest top height is discussed as well, leading to the conclusion that such parameter is robust against erroneous choices in the identification of volume-only contributions, thus corroborating the PolInSAR approach for the analysis of single-baseline data.
International Uveitis Study Group (IUSG) Clinical Classification of Uveitis

A simplified clinical classification system of uveitis has been proposed by the International Uveitis Study Group. Its aim is to assist in the diagnosis and evaluation of patients with uveitis. Used in conjunction with other recognized classification systems it will also enable enrollment of patients for clinical trials, and contribute to clinical guidelines.
Sample preparation in patients receiving uric acid oxidase (rasburicase) therapy.

With the advances in medicine and the development of newer therapeutic agents, the laboratorian needs to be constantly aware of the potential analytical interferences from these medications. Here we demonstrate a potential analytical interference with a case report of a patient who received the recombinant uric acid oxidase Rasburicase (Sanofi-Synthelabo) and the sample handling requirements for uric acid analysis. Rasburicase is a potent uricolytic agent that catalyzes the enzymatic oxidation of uric acid to allantoin, a water soluble metabolite that is readily excreted by the kidney (1). It is used in the treatment and prevention of hyperuricemia, predominantly in patients with hematologic malignancies (1)(2)(3)(4)(5). The half-life of Rasburicase is estimated to be between 16 and 22 h (2). A 28-year-old man presented with ascites to the emergency department at Sir Charles Gairdner Hospital, a tertiary teaching hospital in Western Australia. The patient was subsequently diagnosed with B-cell non-Hodgkin lymphoma 7 days postadmission. The day before commencement of the patient’s scheduled chemotherapy (day 8 of admission), he developed tumor lysis syndrome. The patient had severe metabolic acidosis (9 mmol/L plasma bicarbonate; reference interval, 22–32 mmol/L), a plasma uric …
Expansion of T cells targeting multiple antigens of cytomegalovirus, Epstein-Barr virus and adenovirus to provide broad antiviral specificity after stem cell transplantation.

BACKGROUND AIMS Hematopoietic stem cell transplant (HSCT) is the treatment of choice for a proportion of patients with hematologic malignancies as well as for non-malignant diseases. However, viral infections, particularly Epstein-Barr virus (EBV), cytomegalovirus (CMV) and adenovirus (Ad), remain problematic after transplant despite the use of antiviral drugs. We have shown that cytotoxic T lymphocytes (CTL) generated against CMV-pp65, EBV and Ad antigens in a single culture are capable of controlling infections with all three viruses after HSCT. Although pp65-specific CTL have proved efficacious for the control of CMV infection, several reports highlight the importance of targeting additional CMV antigens. METHODS To expand multivirus-specific T cells with activity against both CMV-pp65 and CMV-IE-1, peripheral blood mononuclear cells (PBMC) were transduced with the adenoviral vector (Ad5f35-IE-1-I-pp65). After 9-12 days the CTL were restimulated with autologous EBV-transformed B cells transduced with the same Ad vector. RESULTS After 18 days in culture nine CTL lines expanded from less than 1.5 × 10(7) PBMC to a mean of 6.1 × 10(7) T cells that recognized CMV antigens pp65 [median 273 spot-forming cells (SFC), range 47-995] and IE-1 (median 154 SFC, range 11-505), the Ad antigens hexon (median 153 SFC, range 26-465) and penton (median 37 SFC, range 1-353), as well as EBV lymphoblastoid cell lines (median 55 SFC, range 9-301). Importantly, the T cells recognized at least two antigens per virus and lysed virus peptide-pulsed targets. CONCLUSIONS CTL that target at least two antigens each of CMV, EBV and Ad should have clinical benefit with broad coverage of all three viruses and enhanced control of CMV infections compared with current protocols.