Miracle-dz/UniFAR-FTUs huggingface dataset:
Gastrointestinal Stromal Tumors: Biology and Treatment

Scientific knowledge on gastrointestinal stromal tumors (GIST) has dramatically progressed over the last 10 years. During this period, this distinct disease entity was identified under various acronyms (GIST remaining the most commonly used), the molecular basis of disease transformation (i.e. activating c-kit mutations) was identified in sporadic and familial cases, and finally GIST was identified as the sarcoma subtype most resistant to chemotherapy in both retrospective and prospective studies. Until 2000, surgery was the only reported efficient treatment modality in this disease, both in the localized and metastatic phase. In 2000, the first GIST patient received Glivec, and in the last 3 years, more than 2,000 patients were included in prospective trials evaluating this compound in advanced phases. Disease control is initially achieved in 80–90% of patients, with only 10–15% of patients dying in the first year following the occurrence of metastases, while the median overall survival was less than 12 months with previous treatment options. However, there still remain several questions regarding long-term outcome, tolerance, cure, dose of Glivec, and alternative treatment upon relapse of GIST in patients receiving Glivec. Additional follow-up is necessary. Glivec treatment of GIST is the first example of an efficient targeted treatment in a solid tumor.
Interleukin-6 markedly decreases skeletal muscle protein turnover and increases nonmuscle amino acid utilization in healthy individuals.

CONTEXT IL-6 is a key modulator of immune function and suggested to be involved in skeletal muscle wasting as seen in sepsis. OBJECTIVE Our objective was to determine the role of IL-6 in human in vivo systemic and skeletal muscle amino acid metabolism and protein turnover. SUBJECTS AND METHODS There were 12 healthy men infused for 3 h with saline (saline, n = 6) or recombinant human IL (rhIL)-6 (n = 6). Systemic and muscle protein turnover was determined with a combination of tracer dilution methodology, primed constant infusion of L-[ring-(2)H(5)]phenylalanine, and femoral arterial-venous blood differences and m. vastus lateralis biopsies after 2-h basal, 3-h infusion, and 3 h after infusion. RESULTS The IL-6 concentration after 30-min infusion was approximately 4 (saline) and 140 pg/ml (rhIL-6). Three-hour rhIL-6 infusion caused an approximate 50% decrease in muscle protein turnover, albeit synthesis was more suppressed than breakdown, causing a small increase in net muscle protein breakdown. Furthermore, rhIL-6 decreased arterial amino acid concentration with 20-40%, despite the increase net release from muscle. CONCLUSIONS We demonstrated that IL-6 profoundly alters amino acid turnover. A substantial decrease in plasma amino acids was observed with a concomitant 50% decrease in muscle protein turnover, however, modest increase in net muscle degradation. We hypothesize that the profound reduction in muscle protein turnover and modest increase in net degradation are primarily caused by the reduced plasma amino acid availability and not directly mediated by IL-6.
Positive climate feedbacks of soil microbial communities in a semi-arid grassland.

Soil microbial communities may be able to rapidly respond to changing environments in ways that change community structure and functioning, which could affect climate-carbon feedbacks. However, detecting microbial feedbacks to elevated CO(2) (eCO(2) ) or warming is hampered by concurrent changes in substrate availability and plant responses. Whether microbial communities can persistently feed back to climate change is still unknown. We overcame this problem by collecting microbial inocula at subfreezing conditions under eCO(2) and warming treatments in a semi-arid grassland field experiment. The inoculant was incubated in a sterilised soil medium at constant conditions for 30 days. Microbes from eCO(2) exhibited an increased ability to decompose soil organic matter (SOM) compared with those from ambient CO(2) plots, and microbes from warmed plots exhibited increased thermal sensitivity for respiration. Microbes from the combined eCO(2) and warming plots had consistently enhanced microbial decomposition activity and thermal sensitivity. These persistent positive feedbacks of soil microbial communities to eCO(2) and warming may therefore stimulate soil C loss.
A Quantitative Comparison of DNA Sequence Assembly Programs

We have compared 11 sequence assembly programs for the accuracy and reproducibility with which they assemble DNA fragments into a completed sequence. To test the assemblers under controlled conditions, the rat multidrug resistance (RATMDRM) gene sequence was randomly divided into overlapping 200- to 400-base fragments. Various degrees of error, in the form of miss-identified bases, missed bases, and duplicated bases, were randomly added to these fragments. The probability of an error, and the type of error, was modified using an error distribution template that was developed by comparing the original fragments used to sequence RATMDRM with the final, edited sequence stored in GenBank. From 0 to 15% error was then added to independent sets of fragments, and assemblage was attempted. The quality of the assemblages was evaluated by comparing the number of differences between the assembled sequence and the original sequence. Tests were also done to determine if the order in which fragments were added to a project affected the final sequence and if the quality of assemblage was sequence dependent. Similar results were also obtained using other, unrelated sequences. The programs could be roughly divided into three groups based on the accuracy and reproducibility of assembly. Three (GCG, FAB, and AutoAssembler) consistently produced consensus sequences of low error and high reproducibility. Intermediate results were obtained with five other programs (Sequencher, AssemblyLIGN, XBAP, SeqMan, and AutoAssembler in a mode that made use of an external special processor). Less satisfactory results were obtained with the remaining three programs (GeneWorks, GENeration, and PC/Gene). The ability of the programs to edit the assembled sequence was also compared. Five of the programs were able to display and edit automatic sequencer trace files. The Sequencher program had a particularly well-designed sequence editor that allowed rapid examination and correction of assembly errors.
Circumferential Guided Waves for Defect Detection in Coated Pipe

Circumferential guided wave propagation behavior in a viscoelastic multi‐layered hollow cylinder is studied to provide a baseline for defect detection in tar coated pipelines. Theoretical work was carried out by developing the appropriate dispersion curves and wave structures for circumferential guided waves in a pipe coated with a viscoelastic material. Parameters that affect wave attenuation were investigated with some initial guidelines being established for improved penetration power. Low frequencies are suggested from both attenuation and detection depth points of view. Under this guidance, experiments utilizing a linear transducer array were conducted at a low frequency for successfully detecting delamination and volumetric defects in tar coated pipe. A study was carried out to find the appropriate features for defect detection in coated pipe and a test protocol based on this study is recommended and summarized.
Xenopus laevis actin-depolymerizing factor/cofilin: a phosphorylation- regulated protein essential for development

Two cDNAs, isolated from a Xenopus laevis embryonic library, encode proteins of 168 amino acids, both of which are 77% identical to chick cofilin and 66% identical to chick actin-depolymerizing factor (ADF), two structurally and functionally related proteins. These Xenopus ADF/cofilins (XADs) differ from each other in 12 residues spread throughout the sequence but do not differ in charge. Purified GST- fusion proteins have pH-dependent actin-depolymerizing and F-actin- binding activities similar to chick ADF and cofilin. Similarities in the developmental and tissue specific expression, embryonic localization, and in the cDNA sequence of the noncoding regions, suggest that the two XACs arise from allelic variants of the pseudotetraploid X. laevis. Immunofluorescence localization of XAC in oocyte sections with an XAC-specific monoclonal antibody shows it to be diffuse in the cortical cytoplasm. After fertilization, increased immunostaining is observed in two regions: along the membrane, particularly that of the vegetal hemisphere, and at the interface between the cortical and animal hemisphere cytoplasm. The cleavage furrow and the mid-body structure are stained at the end of first cleavage. Neuroectoderm derived tissues, notochord, somites, and epidermis stain heavily either continuously or transiently from stages 18-34. A phosphorylated form of XAC (pXAC) was identified by 2D Western blotting, and it is the only species found in oocytes. Dephosphorylation of >60% of the pXAC occurs within 30 min after fertilization. Injection of one blastomere at the 2 cell stage, either with constitutively active XAC or with an XAC inhibitory antibody, blocked cleavage of only the injected blastomere in a concentration- dependent manner without inhibiting nuclear division. The cleavage furrow of eggs injected with constitutively active XAC completely regressed. Blastomeres injected with neutralized antibody developed normally. These results suggest that XAC is necessary for cytokinesis and that its activity must be properly regulated for cleavage to occur.
Aldehyde Oxidase-Catalyzed Metabolism of N1-Methylnicotinamide in Vivo and in Vitro in Chimeric Mice with Humanized Liver

Aldehyde oxidase-mediated oxidation of N1-methylnicotinamide to N1-methyl-2-pyridine-5-carboxamide (2-PY) and N1-methyl-4-pyridone-5-carboxamide (4-PY) in chimeric mice constructed by transplanting human hepatocytes into urokinase-type plasminogen activator-transgenic severe combined immunodeficient mice was examined in vivo and in vitro. The activity in liver cytosol of chimeric mice with a high replacement index was approximately 4-fold higher than that in control mice. Furthermore, the oxidation products in control mice were 2-PY and 4-PY, whereas, in chimeric mice, the major product was 2-PY, as in humans. The aldehyde oxidase in chimeric mouse liver was confirmed to be of human type by immunoblotting analysis. The ratio of pyridones (2-PY/4-PY) excreted in the urine of chimeric mice was closer to that of humans than to that of control mice. Thus, the aldehyde oxidase in chimeric mice has human-type functional characteristics.
Active sampling for entity matching

In entity matching, a fundamental issue while training a classifier to label pairs of entities as either duplicates or non-duplicates is the one of selecting informative training examples. Although active learning presents an attractive solution to this problem, previous approaches minimize the misclassification rate (0-1 loss) of the classifier, which is an unsuitable metric for entity matching due to class imbalance (i.e., many more non-duplicate pairs than duplicate pairs). To address this, a recent paper [1] proposes to maximize recall of the classifier under the constraint that its precision should be greater than a specified threshold. However, the proposed technique requires the labels of all n input pairs in the worst-case. Our main result is an active learning algorithm that approximately maximizes recall of the classifier while respecting a precision constraint with provably sub-linear label complexity (under certain distributional assumptions). Our algorithm uses as a black-box any active learning module that minimizes 0-1 loss. We show that label complexity of our algorithm is at most log n times the label complexity of the black-box, and also bound the difference in the recall of classifier learnt by our algorithm and the recall of the optimal classifier satisfying the precision constraint. We provide an empirical evaluation of our algorithm on several real-world matching data sets that demonstrates the effectiveness of our approach.
Squatting facets on the neck of the talus and extensions of the trochlear surface of the talus in late Byzantine males

Remodelling of bone occurs in response to physical stress. Habitual squatting is associated with modifications of the neck of the talus (squatting facets) and its trochlear/malleolar surfaces (trochlear extensions), and individual populations exhibit different incidences of these modifications that reflect their lifestyle. The occurrence of talar modifications was therefore investigated in a population of late Byzantine (13th century AD) adult male skeletons. Lateral squatting facets occurred most frequently (37.7%), but medial (0.6%), combined (0.6%) and continuous (gutter‐like) facets (0.6%) were also observed. Lateral (8.0%), medial (10.9%) and continuous (lateral/central/medial) extensions (4.6%) of the trochlear surface were all present in the late Byzantine population. There was no evidence of side dimorphism. The occurrence of lateral squatting facets in the late Byzantine population was greater than that reported for modern Europeans, but similar to that reported for some populations of modern Indians. The frequency of occurrence of trochlear extensions in the late Byzantine population was substantially less than in modern Indian populations, but similar to modern Europeans. Therefore, it is unlikely that precisely the same factors determine the expression of squatting facets and trochlear extensions.
Nonlinear Instability of Two Superposed Magnetic Fluids in Porous Media Under Vertical Magnetic Fields

The nonlinear analysis of the Rayleigh - Taylor instability of two immiscible, viscous magnetic ∞uids in porous media, is performed for two layers, each has a flnite depth. The system is subjected to both vertical vibrations and normal magnetic flelds. The in∞uence of both surface tension and gravity force is taken into account. Although the motions are assumed to be irrotational in each ∞uid for small perturbations, weak viscous efiects are included in the boundary condition of the normal stress balance. The method of multiple scale expansion is used for the investigation. The evolution of the amplitude is governed by a nonlinear Ginzburg - Landau equation which gives the criterion for modulational instability. When the viscosity and Darcy’s coe‐cients are neglected, the cubic nonlinear Schr}odinger equation is obtained. Further, it is shown that, near the marginal state, a nonlinear difiusion equation is obtained in the presence of both viscosity and Darcy’s coe‐cients. Stability analysis and numerical simulations are used to describe linear and nonlinear stages of the interface evolution and then the stability diagrams are obtained. Regions of stability and instability are identifled.
Eunomia: Scaling Concurrent Search Trees under Contention Using HTM

While hardware transactional memory (HTM) has recently been adopted to construct efficient concurrent search tree structures, such designs fail to deliver scalable performance under contention. In this paper, we first conduct a detailed analysis on an HTM-based concurrent B+Tree, which uncovers several reasons for excessive HTM aborts induced by both false and true conflicts under contention. Based on the analysis, we advocate Eunomia, a design pattern for search trees which contains several principles to reduce HTM aborts, including splitting HTM regions with version-based concurrency control to reduce HTM working sets, partitioned data layout to reduce false conflicts, proactively detecting and avoiding true conflicts, and adaptive concurrency control. To validate their effectiveness, we apply such designs to construct a scalable concurrent B+Tree using HTM. Evaluation using key-value store benchmarks on a 20-core HTM-capable multi-core machine shows that Eunomia leads to 5X-11X speedup under high contention, while incurring small overhead under low contention.
Generation and characterization of a humanized bradykinin B1 receptor mouse

Abstract Antagonists of the B1 bradykinin receptor (B1R), encoded by the BDKRB1 gene, offer the promise of novel therapeutic agents for inflammatory and neuropathic pain. However, the in vivo characterization of the pharmacodynamics of B1R antagonists is hindered by the low level of B1R expression in healthy tissue and the profound species selectivity exhibited by many compounds for the B1R. To circumvent these issues we generated two genetically engineered rodent models. The first is a transgenic rat over-expressing the human B1R under the control of the neuronal-specific enolase promoter; we previously reported the utility of this model in assessing human B1R receptor occupancy in the central nervous system of the rat. The second model, reported here, utilized gene-targeting by homologous recombination to replace the genomic coding sequence for the endogenous mouse B1R with that of the human B1R. The mRNA expression profile of the humanized Bdkrb1 (hBkdrb1) allele is similar to that of the mouse Bdkrb1 (mBkdrb1) in the wild-type animal. Furthermore, in vitro assays indicate that tissues isolated from the humanized mouse possess pharmacological properties characteristic of the human B1R. Therefore, we have generated a humanized B1R mouse model that is suitable for testing the efficacy of human B1R-selective compounds.
Infectious dental diseases in patients with coronary artery disease: an orthopantomographic case-control study.

PURPOSE To investigate a potential association between coronary artery disease (CAD) and a variety of radiographically detectable infectious dental diseases, a hospital-based prospective case-control study was conducted in Kuwait. MATERIALS AND METHODS Eighty-eight consecutive patients with a first attack of unstable angina pectoris or acute myocardial infarction were enrolled as cases and were matched on the basis of age, sex and nationality with control patients who were known not to have CAD. The severity and extent of periodontal bone loss and other radiographic signs of infection in both cases and controls were analyzed with orthopantomograms. RESULTS More cases than controls had teeth needing extraction (p = 0.043), periapical lesions (p = 0.028), molars with furcation lesions (p < 0.001), teeth with marginal bone loss > or = 6 mm (p = 0.001) and teeth with angular (vertical) bone loss (p < 0.001). Analysis of the total dental index showed that the median scores were higher for cases than controls for both radiographically diagnosed periodontitis (p < 0.001) and periapical lesions (p = 0.008). CONCLUSIONS In summary, there was a significant association between radiographically diagnosed periodontal diseases and CAD. These results should not be regarded as indicating a causal relationship, especially given that the diagnosis of periodontitis was based only on a radiographic examination. The true impact of oral infections on CAD should be examined in a large prospective clinical and interventional study.
’ insuffisance rénale aiguë au Burkina Faso Acute renal failure in Burkina Faso

MOTS CLÉS Afrique ; Épidémiologie ; Insuffisance rénale aiguë ; Pronostic Résumé L’insuffisance rénale aiguë est un syndrome dont le pronostic a été amélioré par les méthodes d’épuration extrarénale. Elle demeure néanmoins dramatique dans les pays d’Afrique sub-saharienne. Au Burkina Faso, la pratique néphrologique est récente et les données sur l’insuffisance rénale aiguë peu disponibles. Dans ces conditions, cette étude a été entreprise sur une série consécutive de patients hospitalisés, atteints d’insuffisance rénale aiguë (créatininémie > 240 mmol/L, installation brutale). L’insuffisance rénale aiguë a concerné 121 patients (âge : 38,6 16,3 ans ; créatininémie : 1246,1 870,5 mmol/L ; urée : 40,2 18,3 mmol/L) dont 75 hommes (âge : 41,2 16,4) et 46 femmes (âge : 34,2 15,2) et représentant 18,4 % des admissions. Elle était de causes médicales dans 91 cas, chirurgicales dans 16 cas et gynécoobstétricales dans 14 cas. Plusieurs facteurs physiopathologiques ont été identifiés dont la déshydratation, les infections, les obstructions. L’insuffisance rénale était organique dans 57 cas (âge : 38,2 14,6), prérénale dans 43 cas (âge : 36,8 16,7) dont 21 nécroses tubulaires aiguës, obstructive dans 15 cas (âge : 50,5 15,6) et inclassable dans six cas. Plusieurs morbidités étaient associées dont l’insuffisance cardiaque (13 cas), hépatique (huit cas), tumeurs (quatre cas), HTA sévère (13 cas). La dialyse était indiquée chez 84 malades (créatininémie : 1735,6 868,1 mmol/L ; urée : 51,9 17,5 mmol/L), mais 14 patients en ont bénéficié. La durée d’hospitalisation a été de 20,4 14,9 jours. La mortalité a été de 29 patients (24 %) par insuffisances rénales (13 cas), hépatique (trois cas), infections (10 cas), tumeurs malignes (deux cas) et associées (un cas). # 2009 Association Société de néphrologie. Publié par Elsevier Masson SAS. Tous droits réservés.
Role of Lysyl Oxidase Propeptide in Secretion and Enzyme Activity

Lysyl oxidase (LOX) is secreted as a proenzyme (proLOX) that is proteolytically processed in the extracellular milieu to release the propeptide and mature, active LOX. LOX oxidizes lysyl residues of a number of protein substrates in the extracellular matrix and on the cell surface, which impacts several physiological and disease states. Although the LOX propeptide (LOX‐PP) is glycosylated, little is known about the role of this modification in LOX secretion and activity. To gain insight into this issue, cells were transfected with native, full‐length LOX cDNA (pre‐pro‐LOX), the N‐glycosylation null pre‐[N/Q]pro‐LOX cDNA and the deletion mutant pre‐LOX cDNA, referred to as secretory LOX, in which mature LOX is targeted to the secretory pathway without its N‐terminal propeptide sequence. The results show that glycosylation of the LOX‐PP is not required for secretion and extracellular processing of pro‐LOX but it is required for optimal enzyme activity of the resulting mature LOX. Complete deletion of the propeptide sequence prevents mature LOX from exiting the endoplasmic reticulum (ER). Taken together, our study points out the requirement of the LOX‐PP for pro‐LOX exit from the ER and is the first to highlight the influence of LOX‐PP glycosylation on LOX enzyme activity. J. Cell. Biochem. 111: 1231–1243, 2010. © 2010 Wiley‐Liss, Inc.
GENOTYPE‐ENVIRONMENT INTERACTION FOR JUVENILE GROWTH IN THE HARD CLAM MERCENARIA MERCENARIA (L.)

Offspring from half‐sib and full‐sib families of the hard clam, Mercenaria mercenaria were reared in five locations along the Atlantic Coast to test for the presence of genotype‐environment interaction for juvenile growth rate. Location effects upon growth rate variation were prevalent; of the genetic effects, the additive genetic by location variance was predominant with the nonadditive genetic by location component contributing to a lesser degree to the interaction variance. The additive and nonadditive variation over all environments was negligible. Genotype‐environment interaction was found to be at least partially due to a change in the amount of genetic variation expressed at each location; with significant additive variation detected at Charleston and Georgetown, SC sites and significant nonadditive variation at Millsboro, DE. Genetic covariance/correlation analysis indicated that reversals in relative family performance across locations were prevalent, implying the possibility of habitat specialization among genotypes. In addition, graphical analysis produced no evidence of a ubiquitously superior genotype. These analyses suggest that genotype‐environment interaction should act to constrain the evolution of juvenile growth rate in Mercenaria, preserve any heritable variation associated with this trait and may lead to the development of phenotypic plasticity for growth.