Miracle-dz/UniFAR-FTUs huggingface dataset:
Overexpression and Characterization of a Carboxypeptidase from the Hyperthermophilic Archaeon Thermococcus sp. NA1

Genomic analysis of a hyperthermophilic archaeon, Thermococcus sp. NA1, revealed the presence of an 1,497 bp open reading frame, encoding a protein of 499 amino acids. The deduced amino acid sequence was similar to thermostable carboxypeptidase 1 from Pyrococcus furiosus, a member of peptidase family M32. Five motifs, including the HEXXH motif with two histidines coordinated with the active site metal, were conserved. The carboxypeptidase gene was cloned and overexpressed in Escherichia coli. Molecular masses assessed by SDS–PAGE and gel filtration were 61 kDa and 125 kDa respectively, which points to a dimeric structure for the recombinant enzyme, designated TNA1_CP. The enzyme showed optimum activity toward Z-Ala-Arg at pH 6.5 and 70–80 °C (k cat⁄K m=8.3 mM−1 s−1). In comparison with that of P. furiosus CP (k cat⁄K m=667 mM−1 s−1), TNA1_CP exhibited 80-fold lower catalytic efficiency. The enzyme showed broad substrate specificity with a preference for basic, aliphatic, and aromatic C-terminal amino acids. This broad specificity was confirmed by C-terminal ladder sequencing of porcine N-acetyl-renin substrate by TNA1_CP.
Prognostic significance of matrix metalloproteinases 2 and 9 in bladder cancer.

BACKGROUND The levels of matrix metalloproteinases MMP-2 and MMP-9 (type IV collagenases), which degrade the extracellular matrix of the basement membrane, were evaluated as prognostic indicators of metastasis in urothelial carcinoma. MATERIALS AND METHODS Quantitative gel zymography and immunohistochemistry were used and compared with clinical data at the follow-up period of 36 months. RESULTS Zymographical analysis of the levels of MMP-9 and active MMP-2 showed a statistically significant increase with tumor grade and invasiveness. This correlation was confirmed by immunohistochemical analysis of MMP-9 expression. However, the correlation between the levels of both gelatinases with recurrence in superficial tumours or progression in invasive tumours was not statistically significant. CONCLUSION MMPs may have an important role in the invasion mechanism of urothelial cancer and could be useful prognostic markers for patients with bladder carcinoma. The relationship between MMP-2 and MMP-9 expression and the metastatic potential of bladder carcinoma needs further evaluation in subsequent clinical studies.
“Taste and see that the Lord is sweet” (Ps. 33:9): The Flavor of God in the Monastic West*

Which of the senses tells us most about God? Perhaps you will say, “It is a matter of perspective. ” Others might insist, “It is a matter of taste. ” Let us think for a moment about what these two metaphors entail. Perspective is an entailment of vision. We see how and what we do— a text, a devotional image, a spiritual discipline; a person, thing, or event—depending upon our particular vantage point. Clarity of vision is contingent upon not only the relative strength or weakness of our eyes but also an absence of obstacles. We cannot see if something or someone is in our way, nor, because vision is dependent upon relative location, do we as viewers necessarily see the same thing even when we are looking at it at the same time. This is the perceptual metaphor most often invoked by historians as we seek to gain a “view” on the past, recognizing all the while that our view on that past can never be identical with that of the people whom we are studying, nor can their view as they experienced it actually become ours. It is, accordingly, a po-
Psychiatric and cardiovascular comorbidities as causes of long-term work disability among individuals with recent-onset rheumatoid arthritis

Objectives: With the ameliorating prognosis of rheumatoid arthritis (RA), the role of comorbidities as causes of work disability (WD) may increase. The aim of this study was to determine the contribution of psychiatric and cardiovascular (CV) comorbidities as the leading causes of long-term WD among patients with recent-onset RA. Method: Between 2000 and 2007, all incident, working-age and non-retired RA patients were identified from a Finnish nationwide register. From other registers, we identified the RA patients who were granted a permanent or temporary disability pension by 31 December 2008. The incidences of disability pensions with CV diseases (ICD-10 codes I00–I99) or psychiatric disorders (F20–F69) as the leading causes were assessed and compared with the general population. Results: We identified a cohort of 7831 patients with RA. During follow-up, 1095 patients were granted a disability pension. After adjusting for competing risks, the 9-year cumulative incidence of WD caused by RA, a psychiatric comorbidity, or a CV disease was 11.9, 1.3, and 0.5%, respectively. Compared to the general population, the age- and sex-specific standardized incidence ratio (SIR) of WD due to psychiatric comorbidities was 0.99 [95% confidence interval (CI) 0.80–1.23] and due to CV disease 1.75 (95% CI 1.23–2.51). Conclusions: In the study cohort with recent-onset RA, the 9-year cumulative incidence of disability pensions caused by psychiatric or CV comorbidities was only 11% or 4%, respectively, of that caused by RA itself. Compared to the general population, the risk of WD due to CV disease was increased.
Study of nanotribological properties of multilayer graphene by calibrated atomic force microscopy

The nanotribological properties of multilayer graphene oxide (MGO), multilayer reduced graphene oxide (MRGO), and mechanically exfoliated multilayer graphene (MEMG) deposited on SiO2 substrate were comparatively investigated via calibrated atomic force microscopy in ambient conditions. Friction as a function of the applied normal load and sliding velocity was studied. Results show that all three types of multilayer graphene films exhibit good adhesion and friction reduction properties. MEMG exhibits the lowest friction and adhesive force because of its perfect planar lattice. A logarithmic increase in friction was observed at low sliding velocities for all measured graphene films. Friction decreases on MGO and bare SiO2 substrate, whereas it remains approximately constant on MEMG and MRGO, when the sliding velocity exceeds their critical velocities. The possible mechanisms for the experimental results were discussed. Our studies provide a good opportunity to use different types of multilayer graphene films for promising lubricant applications in nanodevices.
The Bicyclic Intermediate Structure Provides Insights into the Desuccinylation Mechanism of Human Sirtuin 5 (SIRT5)*

Background: Human SIRT5 was recently identified as an NAD-dependent demalonylase/desuccinylase. Results: We have determined the crystal structures of SIRT5 with a succinyl peptide and with a bicyclic reaction intermediate. Conclusion: A structure-based mechanism of SIRT5 desuccinylation is delineated. Significance: The structures provide insights into the sirtuin-catalyzed deacylation reaction and benefit the design of specific inhibitors for SIRT5. Sirtuins are pivotal regulators in various cellular processes, including transcription, DNA repair, genome stability, and energy metabolism. Their functions have been generally attributed to NAD-dependent deacetylase activity. However, human SIRT5 (sirtuin 5), which has been reported to exhibit little deacetylase activity, was recently identified as an NAD-dependent demalonylase and desuccinylase. Biochemical studies suggested that the mechanism of SIRT5-catalyzed demalonylation and desuccinylation is similar to that of deacetylation catalyzed by other sirtuins. Previously, we solved the crystal structure of a SIRT5-succinyl-lysine peptide-NAD complex. Here, we present two more structures: a binary complex of SIRT5 with an H3K9 succinyl peptide and a binary complex of SIRT5 with a bicyclic intermediate obtained by incubating SIRT5-H3K9 thiosuccinyl peptide co-crystals with NAD. To our knowledge, this represents the first bicyclic intermediate for a sirtuin-catalyzed deacylation reaction that has been captured in a crystal structure, thus providing unique insights into the reaction mechanism. The structural information should benefit the design of specific inhibitors for SIRT5 and help in exploring the therapeutic potential of targeting sirtuins for treating human diseases.
Isotopic Composition of Neodymium in Waters from the Drake Passage

The isotopic composition of neodymium has been determined in seawaters from the Drake Passage. The Antarctic Circumpolar Current, which controls interocean mixing, flows through this passage. The parameter εNd(0) which is a function of the ratio of neodymium-143 to neodymium-144, is found to be uniform with depth at two stations with a value which is intermediate between the values for the Atlantic and the Pacific and indicates that the Antarctic Circumpolar current consists of about 70 percent Atlantic water. Cold bottom water from a site in the south central Pacific has the neodymium isotopic signature of the waters in the Drake Passage. By using a box model to describe the exchange of water between the Southern Ocean and the ocean basins to the north together with the isotopic results, an upper limit of approximately 33 million cubic meters per second is calculated for the rate of exchange between the Pacific and the Southern Ocean. Concentrations of samarium and neodymium were also determined and found to increase approximately linearly with depth. These results suggest that neodymium may be a valuable tracer in oceanography and may be useful in paleo-oceanographic studies.
Strontium Ranelate Reduces the Fracture Incidence in a Growing Mouse Model of Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by brittle bones with increased fracture risk. Although current treatment options to improve bone strength in OI focus on antiresorptive bisphosphonates, controlled clinical trials suggest they have an equivocal effect on reducing fracture risk. Strontium ranelate (SrR) is a promising therapy with a dual mode of action that is capable of simultaneously maintaining bone formation and reducing bone resorption, and may be beneficial for the treatment of OI. In this study, SrR therapy was investigated to assess its effects on fracture frequency and bone mass and strength in an animal model of OI, the oim/oim mouse. Three‐week‐old oim/oim and wt/wt mice were treated with either SrR or vehicle (Veh) for 11 weeks. After treatment, the average number of fractures sustained by SrR‐treated oim/oim mice was significantly reduced compared to Veh‐treated oim/oim mice. Micro–computed tomographic (μCT) analyses of femurs showed that both trabecular and cortical bone mass were significantly improved with SrR treatment in both genotypes. SrR significantly inhibited bone resorption, whereas bone formation indices were maintained. Biomechanical testing revealed improved bone structural properties in both oim/oim and wild‐type (wt/wt) mice under the treatment, whereas no significant effects on bone brittleness and material quality were observed. In conclusion, SrR was able to effectively reduce fractures in oim/oim mice by improving bone mass and strength and thus represents a potential therapy for the treatment of pediatric OI. © 2015 American Society for Bone and Mineral Research.
Complexité et Performance des Récepteurs MIMO

Le codage espace-temps est une technique qui permet d'exploiter de facon tres efficace la diversite spatiale et temporelle presente dans certains systemes de communication, dont le canal sans fil. Le principal avantage de cette technique est une tres grande efficacite spectrale. Dans nos jours, ou le canal radio-mobile est de plus en plus utilise pour transmettre tout type d'information, les methodes permettant une utilisation plus efficace du spectre electromagnetique ont une importance fondamentale. Les algorithmes de reception connus aujourd'hui sont tres complexes, meme en ce qui concerne les codes espace-temps les plus simples. Cette complexite reste l'un des obstacles principaux a l'exploitation commerciale de ces codes. Cette these presente une etude tres detaillee de la complexite, la performance, et les aspects les plus interessants du comportement des algorithmes de reception pour des codes espace-temps, etude qui presente un moyen rapide pour une eventuelle conception des architectures adaptees a ce probleme. Parmi les sujets presentes dans cette these, une etude approfondie de la performance de ces algorithmes a ete realisee, ayant pour objectif d'avoir une connaisance suffisante pour pouvoir choisir, parmi le grand nombre d'algorithmes connus, le mieux adapte a chaque systeme particulier. Des ameliorations aux algorithmes connus ont aussi ete proposees et analysees.
PI3K/AKT/mTOR inhibitors in patients with breast and gynecologic malignancies harboring PIK3CA mutations.

PURPOSE Mutations of the PIK3CA gene may predict response to phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) inhibitors. Concomitant mutations in the mitogen-activated protein kinase (MAPK) pathway may mediate resistance. PATIENTS AND METHODS Tumors from patients with breast, cervical, endometrial, and ovarian cancer referred to the Clinical Center for Targeted Therapy (Phase I Program) were analyzed for PIK3CA, KRAS, NRAS, and BRAF mutations. Patients with PIK3CA mutations were treated, whenever feasible, with agents targeting the PI3K/AKT/mTOR pathway. RESULTS Of 140 patients analyzed, 25 (18%) had PIK3CA mutations, including five of 14 patients with squamous cell cervical, seven of 29 patients with endometrial, six of 29 patients with breast, and seven of 60 patients with ovarian cancers. Of the 25 patients with PIK3CA mutations, 23 (median of two prior therapies) were treated on a protocol that included a PI3K/AKT/mTOR pathway inhibitor. Two (9%) of 23 patients had stable disease for more than 6 months, and seven patients (30%) had a partial response. In comparison, only seven (10%) of 70 patients with the same disease types but with wild-type PIK3CA treated on the same protocols responded (P = .04). Seven patients (30%) with PIK3CA mutations had coexisting MAPK pathway (KRAS, NRAS, BRAF) mutations (ovarian cancer, n = 5; endometrial cancer, n = 2), and two of these patients (ovarian cancer) achieved a response. CONCLUSION PIK3CA mutations were detected in 18% of tested patients. Patients with PIK3CA mutations treated with PI3K/AKT/mTOR inhibitors demonstrated a higher response rate than patients without mutations. A subset of patients with ovarian cancer with simultaneous PIK3CA and MAPK mutations responded to PI3K/AKT/mTOR inhibitors, suggesting that not all patients demonstrate resistance when the MAPK pathway is concomitantly activated.
The Heterogeneous Multiscale Method Based on the Discontinuous Galerkin Method for Hyperbolic and Parabolic Problems

In this paper we develop a discontinuous Galerkin (DG) method, within the framework of the heterogeneous multiscale method (HMM), for solving hyperbolic and parabolic multiscale problems. Hyperbolic scalar equations and systems, as well as parabolic scalar problems, are considered. Error estimates are given for the linear equations, and numerical results are provided for the linear and nonlinear problems to demonstrate the capability of the method.
An immunochemical analysis of bacterial mucopeptides.

Mucopeptides extracted from gram-positive and gram-negative bacteria which were solubilized by ultrasonic treatment gave precipitin reactions with rabbit antistreptococcal serum. A haptenic inhibitor isolated from S. albus enzymes digest of Group D streptococcal cell walls inhibited this precipitin reaction between the mucopeptides of heterologous bacteria and streptococcal antiserum. Greater than 87% inhibition of the M. lysodeikticus and 65% inhibition of the E. coli quantitative mucopeptide precipitin reactions was achieved with 4 mg/ml of this inhibitor. In double diffusion studies, the mucopeptides from different species of bacteria and streptococcal mucopeptide antiserum formed merging precipitin lines. These results suggest that the mucopeptides of many different species of bacteria possess antigenic determinants which are immunochemically similar to those of streptococci.
Papillary thyroid carcinoma patients assessed to be at low or intermediary risk after primary treatment are at greater risk of long term recurrence if they are thyroglobulin antibody positive or do not have distinctly low thyroglobulin at initial assessment.

BACKGROUND In papillary thyroid carcinoma (PTC), recurrences during long-term follow-up (R-LTFU) occur even in those who appear to have an excellent prognosis after initial thyroid surgery and usually, radioactive iodine (i.e., "primary treatment"). Initial studies that predict R-LTFU are not well defined. Values for serum thyroglobulin (Tg) measurements when serum thyrotropin (TSH) is >30 μU/mL, as a result of either recombinant TSH or L-thyroxine withdrawal, referred to here as stimulated Tg (STg), have been previously evaluated. The aim of the current study was to determine the parameters associated with R-LTFU in patients with PTC categorized as having low-risk disease 9 to 12 months after their primary treatment. METHODS This was a retrospective study of 469 patients with PTC with a mean follow-up 5.8±3.9 years. Study patients had to have no uptake in the first postablative diagnostic (131)iodine whole body scan (WBS) performed 9-12 months after primary treatment, a normal cervical ultrasonography (C-US), and STg of <2 ng/mL if their test for antithyroglobulin antibody (anti-Tg) was negative. The first two criteria were required for patients with a positive anti-Tg test, and their nominal serum Tg concentrations were not analyzed. RESULTS Twelve patients developed recurrences (2.6%) in cervical region. Greater tumor size, higher STg, and positive anti-Tg tests at initial evaluation were associated with greater R-LTFU. The recurrence rates were 1.5% (7/450) and 26% (5/19), respectively, in patients with negative and positive anti-Tg tests at initial evaluation. Recurrence-free survival was lower in the patients with initial lymph node metastases, positive anti-Tg tests, and STg of ≥0.3 ng/mL at the first postablative WBS (p=0.022, 0.001, 0.035, respectively, by log-rank test). Regression analysis in patients who were anti-Tg negative revealed that STg ≥0.3 ng/mL at this first WBS was the only parameter related to recurrence (p=0.031, odds ratio: 10.30, confidence interval: 1.23-83.3). CONCLUSION Patients with PTC traditionally categorized as low risk during their first 9 to 12 months after primary treatment have a greater risk of R-LTFU if their postablative STg is ≥0.3 ng/mL, or they have positive anti-Tg, even at this early stage. Periodic C-US is important in these patients and should probably be more frequent in patients with PTC who have positive anti-Tg tests or STg ≥0.3 ng/mL in the first year after diagnosis.
Retinoic acid – induced cell cycle arrest of human myeloid cell lines is associated with sequential down-regulation of c-Myc and cyclin E and posttranscriptional up-regulation of p 27 Kip 1

Alltrans retinoic acid (ATRA) is a potential therapeutic agent for the treatment of hematopoietic malignancies, because of its function as an inducer of terminal differentiation of leukemic blasts. Although the efficacy of ATRA as an anticancer drug has been demonstrated by the successful treatment of acute promyelocytic leukemia (APL), the molecular mechanisms of ATRA-induced cell cycle arrest of myeloid cells have not been fully investigated. In this study, we show that the onset of ATRAinduced G 0/G1 arrest of human monoblastic U-937 cells is linked to a sharp downregulation of c-Myc and cyclin E levels and an increase in p21 WAF1/CIP1 expression. This is followed by an increase in p27 Kip1 protein expression due to enhanced protein stability. The importance of an early decrease in Myc expression for these events was demonstrated by the failure of a U-937 subline with constitutive exogenous expression of v-Myc to cell cycle arrest and regulate cyclin E and p27 Kip1 in response to ATRA. Preceding the initiation of G 1 arrest, a transient rise in retinoblastoma protein (pRb), p107, and cyclin A levels was detected. Later, a rapid fall in the levels of cyclins A and B and a coordinate dephosphorylation of pRb at Ser780, Ser795, and Ser807/811 coincided with the accumulation of cells in G 1. These results thus identify a decrease in c-Myc and cyclin E levels and a posttranscriptional up-regulation of p27 Kip1 as important early changes, and position them in the complex chain of events regulating ATRA-induced cell cycle arrest of myeloid cells. (Blood. 2002;99:2199-2206)
Silencing of ribonucleotide reductase subunit M1 potentiates the antitumor activity of gemcitabine in resistant cancer cells

Gemcitabine is a deoxycytidine analog used for the treatment of a wide range of solid tumors. Its efficacy is however often reduced due to the development of resistance. Ribonucleotide reductase M1 subunit (RRM1) is a key determinant of gemcitabine resistance, and tumor cells that overexpress RRM1 are resistant to the cytotoxicity of gemcitabine. In the present study, we showed that RRM1-specific small interfering RNA (siRNA), when complexed with polyethylenimine, effectively downregulated the expression of RRM1 protein in mouse tumor cells that overexpress RRM1, both in vitro and in vivo. More importantly, systemic administration of the RRM1-specific siRNA significantly inhibited the growth of RRM1-overexpressing tumors in mice and sensitized the tumors to gemcitabine treatment. These findings suggest that silencing RRM1 expression using siRNA could potentially be an effective strategy to overcome gemcitabine resistance.
A comparison of muscle activity in using touchscreen smartphone among young people with and without chronic neck–shoulder pain

This study aimed to examine differences in muscle activity between young people with and without neck–shoulder pain (n = 20 in each group), when they performed texting on a smartphone. Texting was compared between using both hands (‘bilateral texting’) and with only one hand (‘unilateral texting’). Texting tasks were also compared with computer typing. Surface electromyography from three proximal postural muscles and four distal hand/thumb muscles on the right side was recorded. Compared with healthy controls, young people with neck–shoulder pain showed altered motor control consisting of higher muscle activity in the cervical erector spinae and upper trapezius when performing texting and typing tasks. Generally, unilateral texting was associated with higher muscle loading compared with bilateral texting especially in the forearm muscles. Compared with computer typing, smartphone texting was associated with higher activity in neck extensor and thumb muscles but lower activity in upper and lower trapezius as well as wrist extensors. Practitioner Summary: This study demonstrated that symptomatic individuals had increased muscle activity in the neck–shoulder region when texting on a smartphone. Contemporary ergonomic guidelines should include advice on how to interact with handheld electronic devices to achieve a relaxed posture and reduced muscle load in order to reduce the risk of musculoskeletal disorders.
The acquisition of Japanese r

Cette etude porte sur l'acquisition et le developpement du systeme phonologique japonais chez les enfants. L'A. s'interesse au 'r' qui pose le plus de problemes descriptifs en raison de son acquisition tardive dans le developpement phonologique et qui s'accompagne d'erreurs de substitution, de rhotacismes. L'A. montre qu'une approche par la theorie de l'optimalite de cette etude permet de mieux rendre compte de certains phenomenes qui se revelent necessaires a une meilleure caracterisation de l'acquisition et de la distribution du 'r'