Miracle-dz/UniFAR-FTUs huggingface dataset:
Cyclic fatigue and fracture in pyrolytic carbon-coated graphite mechanical heart-valve prostheses: role of small cracks in life prediction.

A fracture-mechanics based study has performed to characterize the fracture toughness and rates of cyclic fatigue-crack growth of incipient flaws in prosthetic heart-valve components made of pyrolytic carbon-coated graphite. Such data are required to predict the safe structural lifetime of mechanical heart-valve prostheses using damage-tolerant analysis. Unlike previous studies where fatigue-crack propagation data were obtained using through-thickness, long cracks (approximately 2-20 mm long), growing in conventional (e.g., compact-tension) samples, experiments were performed on physically small cracks (approximately 100-600 microns long), initiated on the surface of the pyrolytic-carbon coating to simulate reality. Small-crack toughness results were found to agree closely with those measured conventionally with long cracks. However, similar to well-known observations in metal fatigue, it was found that based on the usual computations of the applied (far-field) driving force in terms of the maximum stress intensity, Kmax, small fatigue cracks grew at rates that exceeded those of long cracks at the same applied stress intensity, and displayed a negative dependency on Kmax; moreover, they grew at applied stress intensities less than the fatigue threshold value, below which long cracks are presumed dormant. To resolve this apparent discrepancy, it is shown that long and small crack results can be normalized, provided growth rates are characterized in terms of the total (near-tip) stress intensity (incorporating, for example, the effect of residual stress); with this achieved, in principle, either form of data can be used for life prediction of implant devices. Inspection of the long and small crack results reveals extensive scatter inherent in both forms of growth-rate data for the pyrolytic-carbon material.
Acute Cervical Dystonia Induced by Clebopride

Antidopaminergic drugs are known to induce extrapyramidal symptoms. Clebopride, a dopamine antagonist, also can produce parkinsonism, tardive dyskinesia, tardive dystonia, hemifacial dystonia, or oculogyric crisis; however, acute dystonic reaction caused by clebopride has not been reported in adults. We report two young men who experienced acute cervical dystonia within a few days of taking clebopride. The patients recovered after discontinuation of the drug. Physicians prescribing clebopride should be aware of the adverse effects of this drug.
Morphological effects of mesenchymal stem cells and pulsed ultrasound on condylar growth in rats: a pilot study

Abstract Aim: The aim of this study was to assess and describe the morphological effects of an intra-articular injection of Mesenchymal Stem Cells (MSCs) and/or Low Intensity Pulsed Ultrasound (LIPUS) stimulation on the mandibular condyles of growing rats, using cone beam computed tomography (CBCT) and histology. Methods: Twenty-six young (23-day-old) rats were divided into 5 groups identified as LIPUS-stimulated (20 minutes daily using 50 mW/cm2, 1MHz, 0.2 millisecond pulses), MSCs injected (1 x 105 cells/kg), LIPUS + MSCs, medium injected, and untreated controls. All treatments were performed in the left temporomandibular joint of each rat (TMJs). At day 21, CBCTs were obtained for cephalometric analysis and 3D reconstructions. After animal sacrifice, left and right TMJ sections were histologically prepared and examined. The Wilcoxon sign rank test and the Kruskal-Wallis 2 test were applied for statistical comparison. Results: Imaging results showed that left condyles were wider in all LIPUS-treated groups (p < 0.05), while the LIPUS-only group had a greater left sagittal condylar length. LIPUS-treated groups displayed a lower midline shift to the right (p < 0.02). No significant differences were observed in the MSC group. Bone marrow morphology and vascularity differed between the groups as LIPUS-treated groups exhibited increased vascularity in the erosive cartilage zone. Conclusion: It was established that LIPUS and MSC application to the TMJ region of growing rats favoured transverse condylar growth, while LIPUS application alone may enhance sagittal condylar development. The MSC injection model had little effect on sagittal condylar growth.
Hepatitis C virus continuously escapes from neutralizing antibody and T-cell responses during chronic infection in vivo.

BACKGROUND & AIMS Broadly reactive neutralizing antibodies (nAbs) and multispecific T-cell responses are generated during chronic hepatitis C virus (HCV) infection and yet fail to clear the virus. This study investigated the development of autologous nAb and HCV-glycoprotein-specific T-cell responses and their effects on viral sequence evolution during chronic infection in order to understand the reasons for their lack of effectiveness. METHODS Numerous E1E2 sequences were amplified and sequenced from serum samples collected over a 26-year period from patient H, a uniquely well-characterized, chronically infected individual. HCV pseudoparticles (HCVpp) expressing the patient-derived glycoproteins were generated and tested for their sensitivity to neutralization by autologous and heterologous serum antibodies. RESULTS A strain-specific nAb response developed early in infection (8 weeks postinfection), whereas cross-reactive antibodies able to neutralize HCVpp-bearing heterologous glycoproteins developed late in infection (>33 wk postinfection). The humoral response continuously failed to neutralize viruses bearing autologous glycoprotein sequences that were present in the serum at a given time. The amplified glycoprotein sequences displayed high variability, particularly in regions corresponding to defined linear B-cell epitopes. Mutations in defined neutralizing epitopes were associated with a loss of recognition by monoclonal antibodies against these epitopes and with decreased neutralization of corresponding HCVpp. Viral escape from CD4 and CD8 T-cell responses also was shown for several novel epitopes throughout the glycoprotein region. CONCLUSIONS During chronic infection HCV is subjected to selection pressures from both humoral and cellular immunity, resulting in the continuous generation of escape variants.
Detoxification of Arsenic by Phytochelatins in Plants 1

As is a ubiquitous element present in the atmosphere as well as in the aquatic and terrestrial environments. Arsenite and arsenate are the major forms of As intoxication, and these anions are readily taken up by plants. Both anions efficiently induce the biosynthesis of phytochelatins (PCs) ([g-glutamate-cysteine]n-glycine) in vivo and in vitro. The rapid induction of the metal-binding PCs has been observed in cell suspension cultures of Rauvolfia serpentina, in seedlings of Arabidopsis, and in enzyme preparations of Silene vulgaris upon challenge to arsenicals. The rate of PC formation in enzyme preparations was lower compared with Cd-induced biosynthesis, but was accompanied by a prolonged induction phase that resulted finally in higher peptide levels. An approximately 3:1 ratio of the sulfhydryl groups from PCs to As is compatible with reported As-glutathione complexes. The identity of the As-induced PCs and of reconstituted metal-peptide complexes has unequivocally been demonstrated by electrospray ionization mass spectroscopy. Gel filtration experiments and inhibitor studies also indicate a complexation and detoxification of As by the induced PCs.
Correlation between the prevalence of certain fungi and sick building syndrome.

OBJECTIVE: To examine the role of fungi in the production of sick building syndrome. METHODS: A 22 month study in the United States of 48 schools (in which there had been concerns about health and indoor air quality (IAQ). Building indoor air and surface samples, as well as outdoor air samples were taken at all sites to look for the presence of fungi or their viable propagules. RESULTS: Five fungal genera were consistently found in the outdoor air and comprised over 95% of the outdoor fungi. These genera were Cladosporium (81.5%), Penicillium (5.2%), Chrysosporium (4.9%), Alternaria (2.8%), and Aspergillus (1.1%). At 20 schools, there were significantly more colony forming units per cubic metre (CFU/m3) (p < 0.0001) of propagules of Penicillium species in the air samples from complaint areas when compared with the outdoor air samples and the indoor air samples from noncomplaint areas. At five schools, there were more, although not significant (p = 0.10), Penicillium propagules in the air samples from complaint areas when compared with the outdoor air samples and the indoor air samples from noncomplaint areas. In 11 schools, the indoor air (complaint areas) fungal ratios were similar to that in the outdoor air. In these 11 schools Stachybotrys atra was isolated from swab samples of visible growth under wetted carpets, on wetted walls, or behind vinyl wall coverings. In the remaining 11 schools, the fungal ratios and CFU/m3 of air were not significantly different in different areas. Many of the schools took remedial action that resulted in an indoor air fungal profile that was similar to that outdoors. CONCLUSIONS: Propagules of Penicillium and Stachybotrys species may be associated with sick building syndrome.
Approximal Secondary Caries Lesion Progression, a 20-Week in situ Study

There is no consensus about the definition and progression of outer and wall lesions in secondary caries. In this study we investigated whether lesion progression is influenced by an adjacent composite restoration and whether wall lesions develop at the composite-tooth interface. In order to study the appearance and progression of approximal primary caries lesions and lesions next to composite restorations, 16 samples were placed in a full denture of each of 8 subjects. Each denture housed 4 restored and 4 unrestored enamel samples and similarly 8 dentin samples. All samples were distributed over 2 sample holders, in each of which 4 approximal spaces were simulated. Every 4 weeks the sample holders were microradiographed using transversal wavelength independent microradiography and lesion depth was measured. At the end of the study, after 20 weeks, the lesion depth of the outer lesions was 0–350 µm for enamel and 0–750 µm for dentin. The estimated difference in pro- gression between secondary and primary lesions (1.1 µm/4 weeks, 95% CI: –9.2 to 11.4 µm) was not statistically significant (p = 0.83). Secondary outer lesions appeared and progressed as primary caries lesions. No clear wall lesions were found next to composite, but they were observed next to acrylic resin.
Up-regulation of uncoupling protein 3 (UCP3) mRNA by exercise training and down-regulation of UCP3 by denervation in skeletal muscles.

In skeletal muscles, increased utilization of lipids and carbohydrates accompanied with increased energy expenditure has been observed during and after exercise. UCP3, mitochondrial uncoupling protein, is expressed in skeletal muscles. We investigated UCP3 mRNA levels in exercise training mice which increased energy expenditure and in sciatic nerve-denervated mice which decreased energy expenditure. Mice exercised by 2 wk swimming had 14- to 18-fold increases of UCP3 mRNA in skeletal muscles 3 h after the last swimming, but no increases of UCP1 mRNA in BAT and of UCP2 mRNA in WAT. However, 22 h after exercise, UCP3 mRNA increases observed in skeletal muscles 3 h after exercise returned to sedentary levels. Similar transient increases of UCP3 mRNA were observed in 1 wk treadmill running training or a single exercise bout. In denerved gastrocnemius, GLUT4 and UCP3 mRNA decreased by 58 and 45%, respectively. These data indicate that UCP3 may have a role for fine adjustments of energy expenditure and that up-regulation of UCP3 mRNA may be a defense mechanism against extra energy supply to consume extra energy in skeletal muscles.
Gamma Secretase Inhibition by BMS-906024 Enhances Efficacy of Paclitaxel in Lung Adenocarcinoma

Notch signaling is aberrantly activated in approximately one third of non–small cell lung cancers (NSCLC). We characterized the interaction between BMS-906024, a clinically relevant Notch gamma secretase inhibitor, and front-line chemotherapy in preclinical models of NSCLC. Chemosensitivity assays were performed on 14 human NSCLC cell lines. There was significantly greater synergy between BMS-906024 and paclitaxel than BMS-906024 and cisplatin [mean combination index (CI) value, 0.54 and 0.85, respectively, P = 0.01]. On an extended panel of 31 NSCLC cell lines, 25 of which were adenocarcinoma, the synergy between BMS-906024 and paclitaxel was significantly greater in KRAS- and BRAF-wildtype than KRAS- or BRAF-mutant cells (mean CI, 0.43 vs. 0.90, respectively; P = 0.003). Paclitaxel-induced Notch1 activation was associated with synergy between BMS-906024 and paclitaxel in the KRAS- or BRAF-mutant group. Knockdown of mutant KRAS increased the synergy between BMS-906024 and paclitaxel in heterozygous KRAS-mutant cell lines. Among KRAS- or BRAF-mutant NSCLC, there was a significant correlation between synergy and mutant or null TP53 status, as well as between synergy and a low H2O2 pathway signature. Exogenous overexpression of activated Notch1 or Notch3 had no effect on the enhanced sensitivity of NSCLC to paclitaxel by BMS-906024. In vivo studies with cell line– and patient-derived lung adenocarcinoma xenografts confirmed enhanced antitumor activity for BMS-906024 plus paclitaxel versus either drug alone via decreased cell proliferation and increased apoptosis. These results show that BMS-906024 sensitizes NSCLC to paclitaxel and that wild-type KRAS and BRAF status may predict better patient response to the combination therapy. Mol Cancer Ther; 16(12); 2759–69. ©2017 AACR.
Hierarchical joint learning for natural language generation

Natural Language Generation (NLG) systems typically face an uncertainty regarding the best utterance to communicate to a user in a given context given that the effect of a single utterance depends crucially on the interplay between its physical environment, pragmatic circumstances, addressee and interaction history. NLG system designers have traditionally used a pipeline architecture to divide the generation process into the distinct stages of content selection, utterance planning and surface realisation to choose the semantics, organisation and realisation of an utterance. Unfortunately, this sequential model does not account for the interdependencies that exist among these stages, which in practice has been manifest in inefficient instruction giving and an increased cognitive load for the user. This thesis will advocate a joint optimisation framework for situated NLG that is based on Hierarchical Reinforcement Learning combined with graphical models and will learn the best utterance for a given context by optimising its behaviour through a trial and error search. The joint model considers decisions at different NLG stages in interdependence with each other and thereby produces more contextsensitive utterances than is possible when considering decisions in isolation. To enhance the human-likeness of the model, two augmentations will be made. We will introduce the notion of a Hierarchical Information State to support the systematic pre-specification of prior knowledge and human preferences for content selection. Graphical models—Hidden Markov Models and Bayesian Networks—will then be integrated as generation spaces to encourage natural surface realisation by balancing the proportion of alignment and variation. iv Results from a human evaluation study show that the hierarchical learning agent learns a robust generation policy that adapts to new circumstances and users flexibly leading to smooth and successful interactions. In terms of the comparison between a joint and an isolated optimisation, results indicate that a jointly optimised system achieves higher user satisfaction and task success and is better perceived by human users than its isolated counterpart. To demonstrate the domain-independence and generalisabilty of the hierarchical joint optimisation framework, an additional study will be presented that transfers the model to a new, but related, domain: the generation of route instructions in a real navigation scenario using a situated dialogue system for indoor navigation. Results confirm that the NLG policy can be applied to new domains with limited effort and contribute to high task success and user satisfaction.
A comparison of the placental transfer of ropivacaine versus bupivacaine.

UNLABELLED This study compares the placental transfer of ropivacaine and bupivacaine using the dual perfused, single cotyledon human placental model. We studied the effects of maternal/fetal protein binding, maternal ropivacaine concentration, and fetal pH on ropivacaine transfer. At a clinically relevant maternal concentration (1 microg/mL), the calculated transfer ratios (local anesthetic percent transfer/antipyrine percent transfer) of ropivacaine (0.82 +/- 0.03) and bupivacaine (0.74 +/- 0.01) were comparable at the completion of the perfusion experiment (120 min). When the perfusates were modified to simulate actual in vivo plasma protein binding values, the maternal-to-fetal transfer of ropivacaine and bupivacaine decreased significantly (P < 0.05) as indicated by transfer ratios of 0.42% +/- 0.07% and 0.40% +/- 0.03%, respectively. No saturation of the transfer process was observed for either drug at the maternal concentrations investigated. The placental transfer of both local anesthetic agents increased significantly as the fetal pH decreased. This investigation shows that ropivacaine and bupivacaine cross the human placenta at a similar rate, despite their differences in lipophilicity and stereochemistry. Placental transfer of both compounds is highly influenced by maternal and fetal protein concentration and the fetal pH. IMPLICATIONS The placental transfer of ropivacaine was shown to be similar to that of bupivacaine, and is thus highly influenced by the degree of maternal and fetal protein binding and fetal pH.
Identification of Labile UDP‐Ketosugars in Helicobacter pylori, Campylobacter jejuni and Pseudomonas aeruginosa: Key Metabolites used to make Glycan Virulence Factors

Infectious microorganisms pose an ongoing threat to the health of humans through the development of resistance to antibiotics. Consequently, there is a continual need for novel antimicrobials. Several bacteria produce glycan structures which are attractive therapeutic targets as many are virulence factors that are unique to prokaryotes. Examples can be found in the surface glycans produced by the Gram-negative bacteria Pseudomonas aeruginosa, an opportunistic pathogen that infects individuals whose defenses are compromised, Campylobacter jejuni, a principal cause of acute gastroenteritis, and Helicobacter pylori, a major etiological agent of gastroduodenal disease and the only bacterium to be associated with cancer. Lipopolysaccharides (LPS) produced by many serotypes of P. aeruginosa contain b-l-FucNAc, a deoxyaminohexose that is also a constituent of LPS in Escherichia coli and the capsular polysaccharide (CPS) in Staphylococcus aureus and Streptococcus pneumoniae. C. jejuni is unique amongst bacteria as it generally modifies over 30 proteins with an N-linked heptasaccharide that contains the bacillosamine derivative 2,4-diacetamido-2,4,6-trideoxy-a-d-Glc (a-d-QuiNAc4NAc). H. pylori and C. jejuni both decorate their flagella with the sialic acid-like sugar 5,7-diacetamido-3,5,7,9-tetradeoxy-l-glycero-a-l-mannononulosonic acid or pseudaminic acid (Pse). 7] Pse appears to be necessary for flagellar assembly because mutants deficient in the ability to make this sugar lack flagella and have non-
Failure of nonoperative management of abdominal solid organ injuries

Purpose of reviewNonoperative management of the spleen has been the conventional approach for dealing with blunt splenic injury in children for 25 years. Following acceptance in the field of pediatric surgery, nonoperative management of blunt injury to the liver and spleen became the template in adult trauma surgery. It has proven to be of unequivocal benefit to the majority of hemodynamically stable pediatric and adult patients who have suffered blunt liver or splenic trauma. Offsetting these gains, has been the presence of failures. Recent findingsThe recent literature has focused on factors which may impact the nonoperative management success or failure rate. These factors include initiation of guidelines, risk of overwhelming postsplenectomy infection, character of clinical judgment, role of computed tomography in detecting associated intraabdominal injuries, the presence of more than one solid organ injury, risk of associated hollow viscus injury, and the drawbacks of angioembolization. SummaryDespite the failures of nonoperative management outlined in this review, the approach has been generally successful. Efforts at improving organ salvage rates and diminishing failures with this approach continue. Notwithstanding our enthusiasm to advance this method of patient care, we must avoid imperiling a subpopulation of patients in our attempt to improve nonoperative management success rates.
Contract Theory: Impact on Biopharmaceutical Alliance Structure and Performance

Alliances for new product development have been studied extensively in the operations management literature. Alliances between an innovator and a partner create value by utilizing their complementary capabilities. In this paper, we seek to understand what drives the alliance structure: the choice between collaborative alliances where the parties exert joint efforts and sequential alliances where, for the most part, the partner takes over going forward. Our analysis of a data set of over 2,000 biopharmaceutical alliances reveals our main finding: a key role of operational choices is to address contract theoretic concerns faced by an alliance. We also find that aligning the choice with predictions based on contract theory has consequences for performance. Therefore, our analysis not only has descriptive power about the drivers of alliance choice, but also provides valuable insight into the performance and eventual fate of alliances formed. The online appendix is available at https://doi.org/10.1287/msom.201.