Weld microfissuring in Inconel 718 minimized by minor elements

Manganese, silicon, and magnesium markedly reduce the tendency of Inconel 718 to weld microfissuring. By combining a manganese, 0.20 percent by content, with silicon, greater than 0.25 percent content, or by adding 20 ppm of magnesium, the weld microfissuring decreased in the standard alloy

A Practical Entity Linking System for Tables in Scientific Literature

Entity linking is an important step towards constructing knowledge graphs that facilitate advanced question answering over scientific documents, including the retrieval of relevant information included in tables within these documents. This paper introduces a general-purpose system for linking entities to items in the Wikidata knowledge base. It describes how we adapt this system for linking domain-specific entities, especially for those entities embedded within tables drawn from COVID-19-related scientific literature. We describe the setup of an efficient offline instance of the system that enables our entity-linking approach to be more feasible in practice. As part of a broader approach to infer the semantic meaning of scientific tables, we leverage the structural and semantic characteristics of the tables to improve overall entity linking performance

Endemic Acinetobacter baumannii in a New York Hospital

Acinetobacter baumannii is an increasingly multidrug-resistant (MDR) cause of hospital-acquired infections, often associated with limited therapeutic options. We investigated A. baumannii isolates at a New York hospital to characterize genetic relatedness.Thirty A. baumannii isolates from geographically-dispersed nursing units within the hospital were studied. Isolate relatedness was assessed by repetitive sequence polymerase chain reaction (rep-PCR). The presence and characteristics of integrons were assessed by PCR. Metabolomic profiles of a subset of a prevalent strain isolates and sporadic isolates were characterized and compared.We detected a hospital-wide group of closely related carbapenem resistant MDR A. baumannii isolates. Compared with sporadic isolates, the prevalent strain isolates were more likely to be MDR (p = 0.001). Isolates from the prevalent strain carried a novel Class I integron sequence. Metabolomic profiles of selected prevalent strain isolates and sporadic isolates were similar.The A. baumannii population at our hospital represents a prevalent strain of related MDR isolates that contain a novel integron cassette. Prevalent strain and sporadic isolates did not segregate by metabolomic profiles. Further study of environmental, host, and bacterial factors associated with the persistence of prevalent endemic A. baumannii strains is needed to develop effective prevention strategies

Psychometric Properties of an Arabic Pain Anxiety Symptoms Scale-20 (PASS-20) in Healthy Volunteers and Patients Attending a Physiotherapy Clinic.

PURPOSE: The aim of this study was to cross-culturally adapt the PASS-20 questionnaire for use in Libya. METHODS: Participants were 71 patients (42 women) attending the physiotherapy clinic, Ibn Sina Hospital, Sirt, Libya for management of persistent pain and 137 healthy unpaid undergraduate students (52 women) from the University of Sirt, Libya. The English PASS-20 was translated into Arabic. Patients completed the Arabic PASS-20 and the Arabic Pain Rating Scales on two occasions separated by a 14-day interval. Healthy participants completed the Arabic PASS-20 on one occasion. RESULTS: The internal consistency (ICC) for pain patient and healthy participant samples yielded a good reliability for the total score, cognitive anxiety, fear of pain, and physiological anxiety. The test-retest reliability of the Arabic PASS-20 score showed high reliability for the total score (ICC = 0.93, p < 0.001), escape/avoidance (ICC = 0.93, p < 0.001), fear of pain (ICC = 0.94, p < 0.001), and physiological anxiety subscales (ICC = 0.96, p < 0.001) and good reliability for the cognitive anxiety (ICC = 0.85, p < 0.001). Inspection of the Promax rotation showed that each factor comprised of five items were consistent with the theoretical constructs of the original PASS-20 subscales. CONCLUSION: The Arabic PASS-20 retained internal consistency and reliability with the original English version and can be used to measure pain anxiety symptoms in both pain and healthy individual samples in Libya

Hemocompatibility of Silicon-Based Substrates for Biomedical Implant Applications

Silicon membranes with highly uniform nanopore sizes fabricated using microelectromechanical systems (MEMS) technology allow for the development of miniaturized implants such as those needed for renal replacement therapies. However, the blood compatibility of silicon has thus far been an unresolved issue in the use of these substrates in implantable biomedical devices. We report the results of hemocompatibility studies using bare silicon, polysilicon, and modified silicon substrates. The surface modifications tested have been shown to reduce protein and/or platelet adhesion, thus potentially improving biocompatibility of silicon. Hemocompatibility was evaluated under four categories—coagulation (thrombin–antithrombin complex, TAT generation), complement activation (complement protein, C3a production), platelet activation (P-selectin, CD62P expression), and platelet adhesion. Our tests revealed that all silicon substrates display low coagulation and complement activation, comparable to that of Teflon and stainless steel, two materials commonly used in medical implants, and significantly lower than that of diethylaminoethyl (DEAE) cellulose, a polymer used in dialysis membranes. Unmodified silicon and polysilicon showed significant platelet attachment; however, the surface modifications on silicon reduced platelet adhesion and activation to levels comparable to that on Teflon. These results suggest that surface-modified silicon substrates are viable for the development of miniaturized renal replacement systems

A novel chalcone derivative which acts as a microtubule depolymerising agent and an inhibitor of P-gp and BCRP in in-vitro and in-vivo glioblastoma models

<p>Abstract</p> <p>Background</p> <p>Over the past decades, in spite of intensive search, no significant increase in the survival of patients with glioblastoma has been obtained. The role of the blood-brain barrier (BBB) and especially the activity of efflux pumps belonging to the ATP Binding Cassette (ABC) family may, in part, explain this defect.</p> <p>Methods</p> <p>The <it>in-vitro </it>activities of JAI-51 on cell proliferation were assessed by various experimental approaches in four human and a murine glioblastoma cell lines. Using drug exclusion assays and flow-cytometry, potential inhibitory effects of JAI-51 on P-gp and BCRP were evaluated in sensitive or resistant cell lines. JAI-51 activity on <it>in-vitro </it>microtubule polymerization was assessed by tubulin polymerization assay and direct binding measurements by analytical ultracentrifugation. Finally, a model of C57BL/6 mice bearing subcutaneous GL26 glioblastoma xenografts was used to assess the activity of the title compound <it>in vivo</it>. An HPLC method was designed to detect JAI-51 in the brain and other target organs of the treated animals, as well as in the tumours.</p> <p>Results</p> <p>In the four human and the murine glioblastoma cell lines tested, 10 μM JAI-51 inhibited proliferation and blocked cells in the M phase of the cell cycle, via its activity as a microtubule depolymerising agent. This ligand binds to tubulin with an association constant of 2 × 10⁵M^-1, overlapping the colchicine binding site. JAI-51 also inhibited the activity of P-gp and BCRP, without being a substrate of these efflux pumps. These <it>in vitro </it>studies were reinforced by our <it>in vivo </it>investigations of C57BL/6 mice bearing GL26 glioblastoma xenografts, in which JAI-51 induced a delay in tumour onset and a tumour growth inhibition, following intraperitoneal administration of 96 mg/kg once a week. In accordance with these results, JAI-51 was detected by HPLC in the tumours of the treated animals. Moreover, JAI-51 was detected in the brain, showing that the molecule is also able to cross the BBB.</p> <p>Conclusion</p> <p>These <it>in vitro </it>and <it>in vivo </it>data suggest that JAI-51 could be a good candidate for a new treatment of tumours of the CNS. Further investigations are in progress to associate the title compound chemotherapy to radiotherapy in a rat model.</p

Tubulin isoform composition tunes microtubule dynamics

Microtubules polymerize and depolymerize stochastically, a behavior essential for cell division, motility and differentiation. While many studies advanced our understanding of how microtubule-associated proteins tune microtubule dynamics in trans, we have yet to understand how tubulin genetic diversity regulates microtubule functions. The majority of in vitro dynamics studies are performed with tubulin purified from brain tissue. This preparation is not representative of tubulin found in many cell types. Here we report the 4.2Å cryo-EM structure and in vitro dynamics parameters of α1B/βI+βIVb microtubules assembled from tubulin purified from a human embryonic kidney cell line with isoform composition characteristic of fibroblasts and many immortalized cell lines. We find that these microtubules grow faster and transition to depolymerization less frequently compared to brain microtubules. Cryo-EM reveals that the dynamic ends of α1B/βI+βIVb microtubules are less tapered and that these tubulin heterodimers display lower curvatures. Interestingly, analysis of EB1 distributions at dynamic ends suggests no differences in GTP cap sizes. Lastly, we show that the addition of recombinant α1A/βIII tubulin, a neuronal isotype overexpressed in many tumors, proportionally tunes the dynamics of α1B/βI+βIVb microtubules. Our study is an important step towards understanding how tubulin isoform composition tunes microtubule dynamics

MAPK-Activated Protein Kinase 2 Is Required for Mouse Meiotic Spindle Assembly and Kinetochore-Microtubule Attachment

MAPK-activated protein kinase 2 (MK2), a direct substrate of p38 MAPK, plays key roles in multiple physiological functions in mitosis. Here, we show for the first time the unique distribution pattern of MK2 in meiosis. Phospho-MK2 was localized on bipolar spindle minus ends and along the interstitial axes of homologous chromosomes extending over centromere regions and arm regions at metaphase of first meiosis (MI stage) in mouse oocytes. At metaphase of second meiosis (MII stage), p-MK2 was localized on the bipolar spindle minus ends and at the inner centromere region of sister chromatids as dots. Knockdown or inhibition of MK2 resulted in spindle defects. Spindles were surrounded by irregular nondisjunction chromosomes, which were arranged in an amphitelic or syntelic/monotelic manner, or chromosomes detached from the spindles. Kinetochore–microtubule attachments were impaired in MK2-deficient oocytes because spindle microtubules became unstable in response to cold treatment. In addition, homologous chromosome segregation and meiosis progression were inhibited in these oocytes. Our data suggest that MK2 may be essential for functional meiotic bipolar spindle formation, chromosome segregation and proper kinetochore–microtubule attachments

Association of ultra-rare coding variants with genetic generalized epilepsy: A case\u2013control whole exome sequencing study

Objective: We aimed to identify genes associated with genetic generalized epilepsy (GGE) by combining large cohorts enriched with individuals with a positive family history. Secondarily, we set out to compare the association of genes independently with familial and sporadic GGE. Methods: We performed a case\u2013control whole exome sequencing study in unrelated individuals of European descent diagnosed with GGE (previously recruited and sequenced through multiple international collaborations) and ancestry-matched controls. The association of ultra-rare variants (URVs; in 18&nbsp;834 protein-coding genes) with epilepsy was examined in 1928 individuals with GGE (vs. 8578 controls), then separately in 945 individuals with familial GGE (vs. 8626 controls), and finally in 1005 individuals with sporadic GGE (vs. 8621 controls). We additionally examined the association of URVs with familial and sporadic GGE in two gene sets important for inhibitory signaling (19&nbsp;genes encoding \u3b3-aminobutyric acid type A [GABAA] receptors, 113&nbsp;genes representing the GABAergic pathway). Results: GABRG2 was associated with GGE (p&nbsp;=&nbsp;1.8&nbsp; 7&nbsp;10 125), approaching study-wide significance in familial GGE (p&nbsp;=&nbsp;3.0&nbsp; 7&nbsp;10 126), whereas no gene approached a significant association with sporadic GGE. Deleterious URVs in the most intolerant subgenic regions in genes encoding GABAA receptors were associated with familial GGE (odds ratio [OR]&nbsp;=&nbsp;3.9, 95% confidence interval [CI]&nbsp;=&nbsp;1.9\u20137.8, false discovery rate [FDR]-adjusted p&nbsp;=.0024), whereas their association with sporadic GGE had marginally lower odds (OR&nbsp;=&nbsp;3.1, 95% CI&nbsp;=&nbsp;1.3\u20136.7, FDR-adjusted p&nbsp;=.022). URVs in GABAergic pathway genes were associated with familial GGE (OR&nbsp;=&nbsp;1.8, 95% CI&nbsp;=&nbsp;1.3\u20132.5, FDR-adjusted p&nbsp;=.0024) but not with sporadic GGE (OR&nbsp;=&nbsp;1.3, 95% CI&nbsp;=.9\u20131.9, FDR-adjusted p&nbsp;=.19). Significance: URVs in GABRG2 are likely an important risk factor for familial GGE. The association of gene sets of GABAergic signaling with familial GGE is more prominent than with sporadic GGE