Implementation of Peltier Cooling in Hermetically Sealed Electronic Packaging Unit for Sub-sea Vessel

This paper presents the methodology adopted for implementation of Peltier cooling in hermetically sealed electronic packaging units used in sub-sea vessels. In sub-sea vessels, sonar front-end electronics is packaged in hermetically sealed electronic packaging units. The thermal design of the unit is a highly challenging task considering the heat dissipation of 300W from the electronics, non-availability of chilled air for cooling and IP68 sealing requirements. Cooling fans cannot be integrated, since these units are to be placed in acoustically sensitive pressure capsule area of the subsea vessel. The electronic cooling in this unit is achieved using conduction cooling with external fins. To enhance the cooling, suitable Peltier cooling (Thermo-electric cooling or TEC) module is selected and implemented with the system. Computational fluid dynamic analysis of the unit is carried-out to study the air-flow and thermal performances with Peltier cooler. The unit is realised and the estimated temperatures validated by experimental temperature measurements on the realised unit. The measured temperatures are within the safe operating limits of the electronic components and hence the cooling design of the unit is satisfactory. It is also observed that maximum temperature reduction has occurred at 1.5A current and card edge temperature of Printed circuit board lowered by 9.28 °C by implementing Peltier cooling

Mutation update for the GPC3 gene involved in Simpson-Golabi-Behmel syndrome and review of the literature

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked multiple congenital anomalies and overgrowth syndrome caused by a defect in the glypican-3 gene (GPC3). Until now, GPC3 mutations have been reported in isolated cases or small series and the global genotypic spectrum of these mutations has never been delineated. In this study, we review the 57 previously described GPC3 mutations and significantly expand this mutational spectrum with the description of 29 novel mutations. Compiling our data and those of the literature, we provide an overview of 86 distinct GPC3 mutations identified in 120 unrelated families, ranging from single nucleotide variations to complex genomic rearrangements and dispersed throughout the entire coding region of GPC3. The vast majority of them are deletions or truncating mutations (frameshift, nonsense mutations) predicted to result in a loss-of-function. Missense mutations are rare and the two which were functionally characterized, impaired GPC3 function by preventing GPC3 cleavage and cell surface addressing respectively. This report by describing for the first time the wide mutational spectrum of GPC3 could help clinicians and geneticists in interpreting GPC3 variants identified incidentally by high-throughput sequencing technologies and also reinforces the need for functional validation of non-truncating mutations (missense, in frame mutations, duplications)

Biallelic KITLG variants lead to a distinct spectrum of hypomelanosis and sensorineural hearing loss

BACKGROUND: Pathogenic variants in KITLG, a crucial protein involved in pigmentation and neural crest cell migration, cause non-syndromic hearing loss, Waardenburg syndrome type 2, familial progressive hyperpigmentation and familial progressive hyper- and hypopigmentation, all of which are inherited in an autosomal dominant manner. OBJECTIVES: To describe the genotypic and clinical spectrum of biallelic KITLG-variants. METHODS: We used a genotype-first approach through the GeneMatcher data sharing platform to collect individuals with biallelic KITLG variants and reviewed the literature for overlapping reports. RESULTS: We describe the first case series with biallelic KITLG variants; we expand the known hypomelanosis spectrum to include a 'sock-and-glove-like', symmetric distribution, progressive repigmentation and generalized hypomelanosis. We speculate that KITLG biallelic loss-of-function variants cause generalized hypomelanosis, whilst variants with residual function lead to a variable auditory-pigmentary disorder mostly reminiscent of Waardenburg syndrome type 2 or piebaldism. CONCLUSIONS: We provide consolidating evidence that biallelic KITLG variants cause a distinct auditory-pigmentary disorder. We evidence a significant clinical variability, similar to the one previously observed in KIT-related piebaldism

Interventional research to tackle antimicrobial resistance in Low Middle Income Countries in the era of the COVID-19 pandemic: lessons in resilience from an international consortium

This article summarizes the consequences of the COVID-19 pandemic, on an international project to tackle antimicrobial resistance (AMR). The research leadership and process, the access to data, and stakeholders were deeply disrupted by the national and international response to the pandemic, including the interruption of healthcare delivery, lockdowns, and quarantines. The key principles to deliver the research through the pandemic were mainly the high degree of interdisciplinary engagement with integrated teams, and equitable partnership across sites with capacity building and leadership training. The level of preexisting collaboration and partnership were also keys to sustaining connections and involvements throughout the pandemic. The pandemic offered opportunities for realigning research priorities. Flexibility in funding timelines and projects inputs are required to accommodate variance introduced by external factors. The current models for research collaboration and funding need to be critically evaluated and redesigned to retain the innovation that was shown to be successful through this pandemic

Degradability of cross-linked polyurethanes based on synthetic polyhydroxybutyrate and modified with polylactide

In many areas of application of conventional non-degradable cross-linked polyurethanes (PUR), there is a need for their degradation under the influence of specific environmental factors. It is practiced by incorporation of sensitive to degradation compounds (usually of natural origin) into the polyurethane structure, or by mixing them with polyurethanes. Cross-linked polyurethanes (with 10 and 30%wt amount of synthetic poly([R,S]-3-hydroxybutyrate) (R,S-PHB) in soft segments) and their physical blends with poly([d,l]-lactide) (PDLLA) were investigated and then degraded under hydrolytic (phosphate buffer solution) and oxidative (CoCl2/H2O2) conditions. The rate of degradation was monitored by changes of samples mass, morphology of surface and their thermal properties. Despite the small weight losses of samples, the changes of thermal properties of polymers and topography of their surface indicated that they were susceptible to gradual degradation under oxidative and hydrolytic conditions. Blends of PDLLA and polyurethane with 30 wt% of R,S-PHB in soft segments and PUR/PDLLA blends absorbed more water and degraded faster than polyurethane with low amount of R,S-PHB

The involvement of tau in nucleolar transcription and the stress response

Tau is known for its pathological role in neurodegenerative diseases, including Alzheimer’s disease (AD) and other tauopathies. Tau is found in many subcellular compartments such as the cytosol and the nucleus. Although its normal role in microtubule binding is well established, its nuclear role is still unclear. Here, we reveal that tau localises to the nucleolus in undifferentiated and differentiated neuroblastoma cells (SHSY5Y), where it associates with TIP5, a key player in heterochromatin stability and ribosomal DNA (rDNA) transcriptional repression. Immunogold labelling on human brain sample confirms the physiological relevance of this finding by showing tau within the nucleolus colocalises with TIP5. Depletion of tau results in an increase in rDNA transcription with an associated decrease in heterochromatin and DNA methylation, suggesting that under normal conditions tau is involved in silencing of the rDNA. Cellular stress induced by glutamate causes nucleolar stress associated with the redistribution of nucleolar non-phosphorylated tau, in a similar manner to fibrillarin, and nuclear upsurge of phosphorylated tau (Thr231) which doesn’t colocalise with fibrillarin or nucleolar tau. This suggests that stress may impact on different nuclear tau species. In addition to involvement in rDNA transcription, nucleolar non-phosphorylated tau also undergoes stress-induced redistribution similar to many nucleolar protein

Studies on two polyherbal formulations (ZPTO and ZTO) for comparison of their antidyslipidemic, antihypertensive and endothelial modulating activities

Background Cardiovascular disorders (CVDs) are the leading cause of disease burden worldwide. Apart from available synthetic drugs used in CVDs, there are many herbal formulations including POL-10 (containing 10 herbs), which have been shown to be effective in animal studies but POL-10 was found to cause tachycardia in rodents as its side effect. This study was designed to modify the composition of POL-10 for better efficacy and/or safety profile in CVDs. Methods To assess the antidyslipidemic, antihypertensive and endothelial modulatory properties of two herbal formulations, (ZPTO and ZTO) containing Z: Zingiber officinalis, P: Piper nigrum, T: Terminalia belerica and O: Orchis mascula, different animal models including, tyloxapol and high fat diet-induced dyslipidemia and spontaneously hypertensive rats (SHR) were used. Effect on endothelial function was studied using isolated tissue bath set up coupled with PowerLab data acquisition system. The antioxidant activity was carried out using DPPH radical-scavenging assay. Results Based on preliminary screening of the ingredients of POL-10 in tyloxapol-induced hyperlipidemic rats, ZPTO and ZTO containing four active ingredients namely; Z, P, T and O were identified for further studies and comparison. In tyloxapol-induced hyperlipidemic rats, both ZPTO and ZTO caused significant reduction in serum triglyceride (TG) and total cholesterol (TC). In high fat diet-fed rats, ZPTO decreased TC, low-density lipoproteins cholesterol (LDL-C) and atherogenic index (AI). ZTO also showed similar effects to those of ZPTO with additional merits being more effective in reducing AI, body weight and more importantly raising high-density lipoproteins. In SHR, both formulations markedly reduced systolic blood pressure, AI and TG levels, ZTO being more potent in reversing endothelial dysfunction while was devoid of cardiac stimulatory effect. In addition, ZTO also reduced LDL-C and improved glucose levels in SHR. In DPPH radical-scavenging activity test, ZTO was also more potent than ZPTO. Conclusion The modified formulation, ZTO was not only found more effective in correcting cardiovascular abnormalities than ZPTO or POL-10 but also it was free from tachycardiac side-effect, which might be observed because of the presence of Piper nigrum in ZPTO

The genetic basis of DOORS syndrome: an exome-sequencing study.

Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndrome is a rare autosomal recessive disorder of unknown cause. We aimed to identify the genetic basis of this syndrome by sequencing most coding exons in affected individuals

Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal death

BACKGROUND: We have recently demonstrated a causal link between loss of gonadotropin-releasing hormone (GnRH), the master molecule regulating reproduction, and cognitive deficits during pathological aging, including Down syndrome and Alzheimer's disease. Olfactory and cognitive alterations, which persist in some COVID-19 patients, and long-term hypotestosteronaemia in SARS-CoV-2-infected men are also reminiscent of the consequences of deficient GnRH, suggesting that GnRH system neuroinvasion could underlie certain post-COVID symptoms and thus lead to accelerated or exacerbated cognitive decline. METHODS: We explored the hormonal profile of COVID-19 patients and targets of SARS-CoV-2 infection in post-mortem patient brains and human fetal tissue. FINDINGS: We found that persistent hypotestosteronaemia in some men could indeed be of hypothalamic origin, favouring post-COVID cognitive or neurological symptoms, and that changes in testosterone levels and body weight over time were inversely correlated. Infection of olfactory sensory neurons and multifunctional hypothalamic glia called tanycytes highlighted at least two viable neuroinvasion routes. Furthermore, GnRH neurons themselves were dying in all patient brains studied, dramatically reducing GnRH expression. Human fetal olfactory and vomeronasal epithelia, from which GnRH neurons arise, and fetal GnRH neurons also appeared susceptible to infection. INTERPRETATION: Putative GnRH neuron and tanycyte dysfunction following SARS-CoV-2 neuroinvasion could be responsible for serious reproductive, metabolic, and mental health consequences in long-COVID and lead to an increased risk of neurodevelopmental and neurodegenerative pathologies over time in all age groups. FUNDING: European Research Council (ERC) grant agreements No 810331, No 725149, No 804236, the European Union Horizon 2020 research and innovation program No 847941, the Fondation pour la Recherche Médicale (FRM) and the Agence Nationale de la Recherche en Santé (ANRS) No ECTZ200878 Long Covid 2021 ANRS0167 SIGNAL, Agence Nationale de la recherche (ANR) grant agreements No ANR-19-CE16-0021-02, No ANR-11-LABEX-0009, No. ANR-10-LABEX-0046, No. ANR-16-IDEX-0004, Inserm Cross-Cutting Scientific Program HuDeCA, the CHU Lille Bonus H, the UK Medical Research Council (MRC) and National Institute of Health and care Research (NIHR)