Metallurgical investigation of cracked Al–5.5Zn–2.5Mg–1.5Cu aluminium alloy valve

AbstractThe high strength aluminium alloy Al–5.5Zn–2.5Mg–1.5Cu (AA7075) is being widely used in realisation of aerospace components. A component ‘fill and vent valve’ used in liquid propulsion system was fabricated from AA 7075 forgings in T7352 temper condition, and subsequently undergone various functional tests, four years back. Recently, during dye penetrant test after proof pressure test at 525bar, a valve indicated presence of a crack. Detailed metallurgical investigation indicated that failure was caused by stress corrosion cracking

Metallurgical analysis of a failed maraging steel shear screw used in the band separation system of a satellite launch vehicle

AbstractMaraging steels have excellent combination of strength and toughness and are extensively used for a variety of aerospace applications. In one such critical application, this steel was used to fabricate shear screws of a stage separation system in a satellite launch vehicle. During assembly preparations, one of the shear screws which connected the separation band and band end block has failed at the first thread. Microstructural analysis revealed that the crack originated from the root of the thread and propagated in an intergranular mode. The failure is attributed to combined effect of stress and corrosion leading to stress corrosion cracking

Identification of RNA bound to the TDP-43 ribonucleoprotein complex in the adult mouse brain

Cytoplasmic inclusions containing TDP-43 are a pathological hallmark of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. TDP-43 is an RNA binding protein involved in gene regulation through control of RNA transcription, splicing and transport. However, the function of TDP-43 in the nervous system is largely unknown and its role in the pathogenesis of ALS is unclear. The aim of this study was to identify genes in the central nervous system that are regulated by TDP-43. RNA-immunoprecipitation with anti-TDP-43 antibody, followed by microarray analysis (RIP-chip), was used to isolate and identify RNA bound to TDP-43 protein from mouse brain. This analysis produced a list of 1839 potential TDP-43 gene targets, many of which overlap with previous studies and whose functions include RNA processing and synaptic function. Immunohistochemistry demonstrated that the TDP-43 protein could be found at the presynaptic membrane of axon terminals in the neuromuscular junction in mice. In conclusion, the finding that TDP-43 binds to RNA that codes for genes related to synaptic function, together with the localization of TDP-43 protein at axon terminals, suggests a role for TDP-43 in the transport of synaptic mRNAs into distal processes

Purification of neural precursor cells reveals the presence of distinct, stimulus-specific subpopulations of quiescent precursors in the adult mouse hippocampus

The activity of neural precursor cells in the adult hippocampus is regulated by various stimuli; however, whether these stimuli regulate the same or different precursor populations remains unknown. Here, we developed a novel cell-sorting protocol that allows the purification to homogeneity of neurosphere-forming neural precursors from the adult mouse hippocampus and examined the responsiveness of individual precursors to various stimuli using a clonal assay. We show that within the Hes5-GFP(+) /Nestin-GFP(+) /EGFR(+) cell population, which comprises the majority of neurosphere-forming precursors, there are two distinct subpopulations of quiescent precursor cells, one directly activated by high-KCl depolarization, and the other activated by norepinephrine (NE). We then demonstrate that these two populations are differentially distributed along the septotemporal axis of the hippocampus, and show that the NE-responsive precursors are selectively regulated by GABA, whereas the KCl-responsive precursors are selectively modulated by corticosterone. Finally, based on RNAseq analysis by deep sequencing, we show that the progeny generated by activating NE-responsive versus KCl-responsive quiescent precursors are molecularly different. These results demonstrate that the adult hippocampus contains phenotypically similar but stimulus-specific populations of quiescent precursors, which may give rise to neural progeny with different functional capacity

Comparative study of nonlinear properties of EEG signals of a normal person and an epileptic patient

Background: Investigation of the functioning of the brain in living systems has been a major effort amongst scientists and medical practitioners. Amongst the various disorder of the brain, epilepsy has drawn the most attention because this disorder can affect the quality of life of a person. In this paper we have reinvestigated the EEGs for normal and epileptic patients using surrogate analysis, probability distribution function and Hurst exponent. Results: Using random shuffled surrogate analysis, we have obtained some of the nonlinear features that was obtained by Andrzejak \textit{et al.} [Phys Rev E 2001, 64:061907], for the epileptic patients during seizure. Probability distribution function shows that the activity of an epileptic brain is nongaussian in nature. Hurst exponent has been shown to be useful to characterize a normal and an epileptic brain and it shows that the epileptic brain is long term anticorrelated whereas, the normal brain is more or less stochastic. Among all the techniques, used here, Hurst exponent is found very useful for characterization different cases. Conclusions: In this article, differences in characteristics for normal subjects with eyes open and closed, epileptic subjects during seizure and seizure free intervals have been shown mainly using Hurst exponent. The H shows that the brain activity of a normal man is uncorrelated in nature whereas, epileptic brain activity shows long range anticorrelation.Comment: Keywords:EEG, epilepsy, Correlation dimension, Surrogate analysis, Hurst exponent. 9 page

Inhibiting Androgen Receptor Splice Variants With Cysteine-Selective Irreversible Covalent Inhibitors To Treat Prostate Cancer

Androgen receptor (AR) and its splice variants (AR-SVs) promote prostate cancer (PCa) growth by orchestrating transcriptional reprogramming. Mechanisms by which the low complexity and intrinsically disordered primary transactivation domain (AF-1) of AR and AR-SVs regulate transcriptional programming in PCa remains poorly defined. Using omics, live and fixed fluorescent microscopy of cells, and purified AF-1 and AR-V7 recombinant proteins we show here that AF-1 and the AR-V7 splice variant form molecular condensates by liquid-liquid phase separation (LLPS) that exhibit disorder characteristics such as rapid intracellular mobility, coactivator interaction, and euchromatin induction. The LLPS and other disorder characteristics were reversed by a class of small-molecule-selective AR-irreversible covalent antagonists (SARICA) represented herein by UT-143 that covalently and selectively bind to C406 and C327 in the AF-1 region. Interfering with LLPS formation with UT-143 or mutagenesis resulted in chromatin condensation and dissociation of AR-V7 interactome, all culminating in a transcriptionally incompetent complex. Biochemical studies suggest that C327 and C406 in the AF-1 region are critical for condensate formation, AR-V7 function, and UT-143\u27s irreversible AR inhibition. Therapeutically, UT-143 possesses drug-like pharmacokinetics and metabolism properties and inhibits PCa cell proliferation and tumor growth. Our work provides critical information suggesting that clinically important AR-V7 forms transcriptionally competent molecular condensates and covalently engaging C327 and C406 in AF-1, dissolves the condensates, and inhibits its function. The work also identifies a library of AF-1-binding AR and AR-SV-selective covalent inhibitors for the treatment of PCa

Dopunska prehrana ribljim uljem poboljšala je funkciju jajnika, koncepciju i određene reprodukcijske pokazatelje kod kobila pasmine marvari

We investigated the effect of dietary fish oil supplementation on the development of the ovarian follicles, corpus luteum (CL), conceptus and certain reproductive events in Marwari mares, since it is reported to improve reproduction in cows. Accordingly, non-lactating mares (n = 20) were randomly assigned into two groups (10 per group) and fed either the control diet (CTR) or a diet enriched with fish oil (FOS) to supplement n-3 polyunsaturated fatty acids (PUFA) at the rate of 64 mg/kg body weight/day for 70 days or until 45 days post-ovulation in the mares that became pregnant. Estrus was detected using a teaser and insemination was performed using frozen thawed semen in the experimental mares. Development of the ovarian follicle, CL and conceptus were recorded using trans-rectal ultrasonography. Plasma concentrations of progesterone and estradiol were estimated by radioimmunoassay. In the FOS group, the diameter of the largest follicle from day 4 of estrus until ovulation, and the diameter of the CL on day 7 post-ovulation (D7PO) were greater (P<0.05). However, on day 15 post-ovulation (D15PO), the CL diameter increased significantly in the pregnant mares. Dietary fish oil significantly improved the development of the embryo as evidenced by an increase in the diameter of the embryonic vesicle on day 15 post-ovulation (D15PO), and the embryo proper on day 28 post ovulation (D28PO). Further, the mean plasma estradiol concentration was higher on the day of estrus onset (P<0.05) and day 4 of estrus (P<0.01) in the FOS group. Similarly, dietary fish oil significantly increased the plasma progesterone on D15PO in the pregnant mares (P<0.01). Although the duration of estrus was shorter by 19 hours (P<0.05), the length of the estrous cycle did not vary in the FOS group. A non-significant increase in the pregnancy rate was observed in the mares that received fish oil. It was concluded that dietary fish oil supplementation improved ovarian function and embryonic development in the Marwari mares.Na temelju prethodnih izvješća o poboljšanju reprodukcije krava, kod kobila pasmine marvari istražili smo učinak ribljeg ulja kao prehrambenog dodatka na razvoj folikula jajnika, žutog tijela, koncepcije i određenih reprodukcijskih pokazatelja. U skladu s ciljem, 20 kobila koje nisu bile u laktaciji je metodom slučajnog izbora podijeljeno u dvije skupine s po 10 kobila. Za razliku od kontrolne skupine, kobile u eksperimentalnoj skupini hranjene su obrokom obogaćenim ribljim uljem u obliku dodatka koji je sadržavao n-3 polinezasićene masne kiseline (PUFA), u dnevnoj količini od 64 mg na jedan kg tjelesne mase. Eksperiment je trajao 70 dana, odnosno za kobile koje su ostale gravidne do 45 dana nakon ovulacije. Estrus je praćen teaserom, a osjemenjivanje je provedeno zamrznutim sjemenom. Razvoj folikula jajnika i žutih tijela te gravidnosti praćeni su transrektalnim ultrazvukom. Koncentracija progesterona i estradiola u plazmi procijenjena je radioimunološkom metodom. U eksperimentalnoj skupini utvrđen je veći (P<0,05) promjer najvećeg folikula od 4. dana estrusa do ovulacije i veći promjer žutog tijela 7. dan nakon ovulacije. No, 15. dan nakon ovulacije promjer žutih tijela bio je signifikantno povećan kod gravidnih kobila. Obrok obogaćen ribljim uljem signifikantno je poboljšao razvoj embrija, što se očitovalo povećanjem promjera embrionalne vezikule 15. dan nakon ovulacije i povećanjem embrija 28. dan nakon ovulacije. Nadalje, u eksperimentalnoj skupini kobila srednja koncentracija estradiola u plazmi bila je veća na dan početka estrusa (P<0,05) i 4. dan estrusa (P<0,01). Slično tome, obrok obogaćen ribljim uljem kod gravidnih je kobila signifikantno (P<0,01) povećao progesteron u plazmi 15. dan nakon ovulacije. U kobila eksperimentalne skupine je, uz varijacije estrusnog ciklusa, utvrđeno i za 19 sati kraće trajanje estrusa (P<0,05). Povećana stopa gravidnosti kod kobila dohranjivanih ribljim uljem nije bila signifikantna. Zaključeno je da je hranidba s dodatkom ribljeg ulja kod kobila pasmine marvari poboljšala funkciju jajnika i razvoj embrija

Indian community health insurance schemes provide partial protection against catastrophic health expenditure

BACKGROUND: More than 72% of health expenditure in India is financed by individual households at the time of illness through out-of-pocket payments. This is a highly regressive way of financing health care and sometimes leads to impoverishment. Health insurance is recommended as a measure to protect households from such catastrophic health expenditure (CHE). We studied two Indian community health insurance (CHI) schemes, ACCORD and SEWA, to determine whether insured households are protected from CHE. METHODS: ACCORD provides health insurance cover for the indigenous population, living in Gudalur, Tamil Nadu. SEWA provides insurance cover for self employed women in the state of Gujarat. Both cover hospitalisation expenses, but only upto a maximum limit of US$23 and US$45, respectively. We reviewed the insurance claims registers in both schemes and identified patients who were hospitalised during the period 01/04/2003 to 31/03/2004. Details of their diagnoses, places and costs of treatment and self-reported annual incomes were obtained. There is no single definition of CHE and none of these have been validated. For this research, we used the following definition; "annual hospital expenditure greater than 10% of annual income," to identify those who experienced CHE. RESULTS: There were a total of 683 and 3152 hospital admissions at ACCORD and SEWA, respectively. In the absence of the CHI scheme, all of the patients at ACCORD and SEWA would have had to pay OOP for their hospitalisation. With the CHI scheme, 67% and 34% of patients did not have to make any out-of-pocket (OOP) payment for their hospital expenses at ACCORD and SEWA, respectively. Both CHI schemes halved the number of households that would have experienced CHE by covering hospital costs. However, despite this, 4% and 23% of households with admissions still experienced CHE at ACCORD and SEWA, respectively. This was related to the following conditions: low annual income, benefit packages with low maximum limits, exclusion of some conditions from the benefit package, and use of the private sector for admissions. CONCLUSION: CHI appears to be effective at halving the incidence of CHE among hospitalised patients. This protection could be further enhanced by improving the design of the CHI schemes, especially by increasing the upper limits of benefit packages, minimising exclusions and controlling costs

An inversion affecting the GCH1 gene as a novel finding in dopa-responsive dystonia

SUPPLEMENTARY FILE : SUPPLEMENTARY FIGURE S1. Pedigree of the family. Arrow indicates proband who underwent genetic studies, filled symbol indicates affected, squares represent males and circles represent females. d. MVA = died in motor vehicle accident. Additional family members were not available for testing. SUPPLEMENTARY FIGURE S2. Illumina short read whole genome sequencing data indicating a structural variant (NC_000014.8:g.[55343254_55346605del;55346606_60822142inv;60822143_60823119del]) on chromosome 14 affecting GCH1. Chimaeric (“split”) reads identified by the ClinSV tool are visualized in the IGV genome browser. To ease interpretation the alignments of segments of two representative reads are highlighted (A00488:195:HGJN7DSX2:3:2336:15573:12743 in red, and A00488:195:HGJN7DSX2:3:2160:31503:1219 in blue). Other tracks show the deletions which flank the inversion, and the exonic structure of GCH1 transcript NM_000161.3. (A) The left-hand (centromere proximal) breakpoint region, associated with a 3.4 kb deletion. (B) The right-hand (centromere distal) breakpoint region, associated with a smaller (1.0 kb) deletion. SUPPLEMENTARY FIGURE S3. Oxford Nanopore long read sequencing (LRS) data supporting the proposed structural variant. Chimaeric nanopore sequences are visualized in the IGV genome browser. The sequence alignments confirm the breakpoints indicated by short read sequencing analysis, and extend wide enough for a high level of confidence in read locations. (A, B) Inversion breakpoint regions as in Fig. S2, but in a 50 kb window.No abstract available.Paul Ainsworth Family Foundation. Open access publishing facilitated by University of New South Wales, as part of the Wiley - University of New South Wales agreement via the Council of Australian University Librarians.https://movementdisorders.onlinelibrary.wiley.com/journal/23301619hj2024School of Health Systems and Public Health (SHSPH)SDG-03:Good heatlh and well-bein