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Purpose: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the ongoing global COVID-19 disease pandemic. Convalescent plasma therapy (CPT) is one of the promising therapies being tried for COVID-19 patients. However, the presence or disappearance of SARS-CoV-2 RNA (RNAemia) in convalescent plasma is unclear and the prognostic implication of viral RNA detection in these samples is not fully understood. Hence, we aimed to investigate SARS-CoV-2 RNAemia in the convalescent plasma of COVID-19 patients. Methods & Materials: Convalescent plasma samples from donors with a previous laboratory-confirmed SARS-CoV-2 infection were included in the study. Samples were screened for the presence of Anti-SARS CoV-2 IgG antibodies using a commercially available enzyme-linked immunosorbent assay targeting the whole-cell antigen of SARS-CoV-2. Then plasma samples were pooled by the mixing of five samples. RNA extraction and real-time RT-PCR for SARS-CoV-2 specific gene targets was performed for pooled plasma samples. Results: A total of 250 convalescent plasma samples of COVID-19 patients with different disease severity were included in the study; of these, 149 (59.6%) were found to have anti-SARS-CoV-2 antibodies using serological tests. SARS-CoV-2 RNA was not detected in any of the convalescent plasma samples. Conclusion: SARS-CoV-2 RNAemia was not found in individuals with a previous laboratory-confirmed SARS-CoV-2 infection at least 28 days after the resolution of their symptoms. All RT-PCR positive COVID-19 patients subsequently may not develop antibodies. Our study showed that screening for neutralizing antibody titres is more important rather than SARS-CoV-2 RNA detection in convalescent plasma samples for therapeutic use.

The theoretical aspects of predicting the development of an energy cluster are investigated in the article, since the energy cluster itself should create conditions for basic, complex development within the objective function aimed at activating it technological, scientific, technical, industrial, commercial and human resources, as well as prejudice, minimization of active and passive economic threats related, for example, to fragmented state policy in the sphere of supporting the functioning of integration entities. The problems of formation of new models of organization of joint activity of enterprises, namely the energy cluster as one of the tools for creation of innovative high-tech economy and attraction of investments, have been updated. Grouping of approaches to economic and mathematical development of the energy cluster is carried out, which highlights the advantages and disadvantages of groups of models of innovative economic development in the form of a vector linear programming problem, models based on one or a group of criteria indicators or on the concept of balance, and based on the analysis of the structure of economic object. The organizational and economic system of elements of the energy cluster is provided, which ensures the stability of its operation, achievement of financial and commercial success, progressive scientific and technical and social development taking into account the current tendencies of the world economic, industrial and scientific transformations. The complex of factors of development of energy cluster and princes of adaptation are presented, the use of which will contribute to the effective solution of problems of rational use of energy resources within the framework of integration formation.

Abstract Three years after SARS-CoV-2 emerged as a global infectious threat, the virus has become endemic. The neurological complications such as depression, anxiety, and other CNS complications after COVID-19 disease are increasing. The brain, and CSF have been shown as viral reservoirs for SARS-CoV-2, yielding a potential hypothesis for CNS effects. Thus, we investigated the CNS pharmacology of orally dosed nirmatrelvir/ritonavir (NMR/RTV). Using both an in vitro and an in vivo rodent model, we investigated CNS penetration and potential pharmacodynamic activity of NMR. Through pharmacokinetic modeling, we estimated the median CSF penetration of NMR to be low at 18.11% of plasma with very low accumulation in rodent brain tissue. Based on the multiples of the 90% maximal effective concentration (EC90) for SARS-CoV-2, NMR concentrations in the CSF and brain do not achieve an exposure level similar to that of plasma. A median of only 16% of all the predicted CSF concentrations in rats were > 3xEC90 (unadjusted for protein binding). This may have implications for viral persistence and neurologic post-acute sequelae of COVID-19 if increased NMR penetration in the CNS leads to decreased CNS viral loads and decreased CNS inflammation.

Material Extrusion (MEX) 3D printing is revolutionizing manufacturing by transforming digital designs into tangible innovations by its layer-by-layer approach. However, an important issue impeding the adoption of this technology is the limited size of the prints due to the machine's small bed. An appropriate polymer joining technique can be used as a post-fabrication step to circumvent this issue. This paper explores the findings related to the joining of MEX-3D printed parts fabricated from generally preferred thermoplastics, Acrylonitrile Butadiene Styrene (ABS), and Polylactic acid (PLA) by the Spin Friction Welding (SFW) technique. The critical parameters involved in the process are identified and optimized using statistical tools including Design of Experiments (DOE), Taguchi, and Analysis of Variance (ANOVA). The results revealed that the type of material combination as well as the number of perimeter shells had the highest effect on the joint strength and cylindricity of the welds, resulting in the joint efficiency going up to 93.16 %. The practicability of the research was further approved by implementing the results to weld the sections of a service saddle point of a pipeline, wherein the weld displayed good strength and integrity. With the suggested method, it is expected that in the future, joining and welding procedures will gain more acceptance with SFW in particular showing great promise for joining cylindrical and rotary MEX-3D printed parts.

Abstract Background The aim of the study was to determine the facial divergence and lip position combinations that are most and least preferred, and to investigate whether age or gender has an impact on these preferences. Methods The current investigation was carried out on a sample of 1077 individuals who were not experts in the field (253 men and 824 females). The research employed black silhouette photographs of profiles featuring different lip locations and profile divergences. The recruitment of participants was conducted in order to assess the attractiveness of the profiles, employing a Likert scale. The various positions of the lips and variations in facial profiles were thoroughly categorized. Results were analyzed using the Chi-square test. Results The findings of the research demonstrated that aesthetic perceptions displayed diversity when considering different lip locations and profile divergences. It was shown that neutral lip positions were predominantly favored, accounting for approximately 40.2% of the total frequencies in the anterior diverging group. It is noteworthy to highlight the aesthetically pleasing features exhibited by those with the most prominent lip position, occurring at a frequency of 10.9% in straight-diverging group. In the posterior divergent group, the most protruded lip position, showed very attractive aesthetics with frequency (7.1%). Gender, age, region, and level of education had significant influence on aesthetic perception. Conclusions The variety of aesthetic preferences is influenced by the location of the lips and the divergence of the facial profile, resulting in different outcomes within the categories of anterior, straight, and posterior divergence. Clinicians are advised to customize the treatment regimen in order to correspond with the unique desires and preferences of the patient.

Ion channel TRPM8 mediates thermoregulatory adaptations to cold in poikilotherms by coordinating changes to skin pigmentation and locomotor activity.

Abstract In the present study, chitosan (CH) based biodegradable films were developed enriched with thyme essential oil (TEO) incorporated with different additives including zinc oxide (ZnO), polyethylene glycol (PEG), nano clay (NC), and calcium chloride (CaCl2) and characterize the postharvest quality of ‘collard greens’ during refrigerated storage. The results indicated that the incorporation of ZnO/PEG/NC/CaCl2 in CH-based films significantly decreased water vapor transmission rate, increased tensile strength, and were water soluble and biodegradable in nature. Moreover, CH-TEO based films incorporated with ZnO/PEG/NC/CaCl2 were significantly effective in reducing physiological weight loss, retained total soluble solids, titratable acidity, and preserved chlorophyll contents as well as showed lesser a* values, suppressed microbial growth, and preserving appearance/sensory quality of collard greens for 24 days than LDPE and other biodegradable films. Our results suggest that CH-based films enriched with TEO and additives such as ZnO/CaCl2/NC/PEG are an ecological, environmental friendly, and effective alternative approach to retain shelf life of collard greens during refrigerated storage.

Abstract We diagnosed 66 peripheral nerve injuries in 34 patients who survived severe coronavirus disease 2019 (COVID-19). We combine this new data with published case series re-analyzed here (117 nerve injuries; 58 patients) to provide a comprehensive accounting of lesion sites. The most common are ulnar (25.1%), common fibular (15.8%), sciatic (13.1%), median (9.8%), brachial plexus (8.7%) and radial (8.2%) nerves at sites known to be vulnerable to mechanical loading. Protection of peripheral nerves should be prioritized in the care of COVID-19 patients. To this end, we report proof of concept data of the feasibility for a wearable, wireless pressure sensor to provide real time monitoring in the intensive care unit setting.

Additive Manufacturing (colloquially: 3D printing) is ready to emerge from its niche status and become a feasible mainstream technology due to its increasing number of industrial applications. However, the restricted size of the prints, resulting from the printer's limited bed size is an aspect hindering the acceptance of this technology. Splitting the CAD model and joining them with some viable technique can be an evocative solution to this challenge. This article investigates the welding of MEX-AM parts made from frequently chosen thermoplastics (Acrylonitrile Butadiene Styrene/Polylactic Acid) ABS/PLA with the assistance of electromagnetic microwave radiations, employing inexpensive Fe2O3 as the absorbent material. The foremost objective of the investigation was to counterbalance the dimension limits of MEX 3D printers by microwave welding and simultaneously optimize the parameters involved in the process. Critical parameters including microwave power level, absorbent quantity, welding pressure, infill percentage and material combination were optimized via (Design of Experiments/Analysis of Variance) DOE/ANOVA statistical tools. The outcome resulted in the joint efficiency reaching upto 99.53%. ABS being amorphous, responded well to the microwaves displaying better shear strength and ductility compared to PLA. Further, it was observed that a temperature of 120 to 165 °C with lead-times of 5 to 8 min was approximately required for the successful welds to happen. The predicted and validated results revealed that for maximum joint efficiency, the parameters to be set should be 1000 W, 0.2 g absorbent, 400 g dead weight and 35% infill percentage with ABS/ABS as the printing material. The results when applied to repair a drone body, weld a (Unmanned Aerial Vehicle) UAV wingspan, helmet sections as well as pump flanges displayed good structural strength and integrity. The proposed technique displayed enormous potential as it could easily be reproduced even on a household microwave oven obtaining complex 3D structures and raising the adequacy of smaller bed 3D printers.

Problem: Hallux sesamoid injuries can be a debilitating source of pain for patients. The mainstay of treatment is offloading to reduce symptoms, activity modification, injections, and other non-operative measures. When non-operative treatment fails, surgical resection is considered. This report describes a novel non-surgical treatment of chronic sesamoid injuries using focused extracorporeal shockwave therapy (F-SWT) combined with physical therapy (PT). Methods: Patients in this case series were identified through review of all cases during years 2018 to 2022 identified with hallux sesamoid mediated pain refractory to non-surgical management treated with F-SWT and foot intrinsic strengthening. Functional outcomes were compared at pretreatment and posttreatment using the foot and ankle ability measure (FAAM). Results: FAAM-ADL subscale scores improved pretreatment (median 63, IQR 53 to 74) to posttreatment (median 80.5, IQR 62.5 to 83), p = 0.0157. Similarly, FAAM-Sport subscale scores also increased pretreatment (median 13, IQR 5.25 to 14.75) to posttreatment (median 23, IQR 18.25 to 26), p = 0.0009. Eight of 11 (73%) patients met the minimally clinically important difference in FAAM-ADL or FAAM-Sport subscales. Discussion: This case series describes the use of F-SWT combined with foot intrinsic strengthening PT as a reasonable treatment strategy in athletes with hallux sesamoid injuries. Future prospective studies with long term outcomes are needed to compare the effectiveness of F-SWT and PT and clarify the optimal treatment protocol. [ABSTRACT FROM AUTHOR]

Recent development in modern wireless applications and services, such as augmented reality, image processing, and network gaming requires persistent computing on average commercial wireless devices to perform complex tasks with low latency. The traditional cloud systems are unable to meet those requirements solely. In the said perspective, Mobile Edge Computing (MEC) serves as a proxy between the things (devices) and the cloud, pushing the computations at the edge of the network. The MEC provides an effective solution to fulfill the demands of low-latency applications and services by executing most of the tasks within the proximity of users. The main challenge, however, is that too many simultaneous service requests created by wireless access produce severe interference, resulting in a decreased rate of data transmission. In this paper, we made an attempt to overcome the aforesaid limitation by proposing a user-centric QoS-aware multi-path service provisioning approach. A densely deployed base station MEC environment has overlapping coverage regions. We exploit such regions to distribute the service requests in a way that avoid hotspots and bottlenecks. Our approach is adaptive and can tune to different parameters based on service requirements. We performed several experiments to evaluate the effectiveness of our approach and compared it with the traditional Greedy approach. The results revealed that our approach improves the network state by 26.95% and average waiting time by 35.56% as compared to the Greedy approach. In addition, the QoS violations were also reduced by the fraction of 16.

Background: Approximately half of the reported laboratory-confirmed infections of Middle East respiratory syndrome coronavirus (MERS-CoV) have occurred in healthcare settings, and healthcare workers constitute over one third of all secondary infections. This study aimed to describe secondary cases of MERS-CoV infection among healthcare workers and to identify risk factors for death. Methods: A retrospective analysis was conducted on epidemiological data of laboratory-confirmed MERS-CoV cases reported to the World Health Organization from September 2012 to 2 June 2018. We compared all secondary cases among healthcare workers with secondary cases among non-healthcare workers. Multivariable logistic regression identified risk factors for death. Results: Of the 2223 laboratory-confirmed MERS-CoV cases reported to WHO, 415 were healthcare workers and 1783 were non-healthcare workers. Compared with non-healthcare workers cases, healthcare workers cases were younger (P

Understanding how nutrients accumulate and change throughout the developmental stages according to the BBCH scale can be a very effective technique for developing fertilization programmes for high-quality, marketable grape production. Accordingly, the macro- and micronutrient concentrations at different growth stages were analyzed for two commercial grape cultivars, viz., “Anab-e-Shahi” and “Perlette”, by using an extended BBCH scale. The results show nitrogen content was reduced during the sampling period (D1 to D6) from 1.76 percent to 1.09 percent. Potassium concentration in developing berries kept on increasing from 0.15%, at principal growth stage 7 with BBCH code 73 (D1), to 0.26% at principal growth stage 8 code 89 (D6). The lowest phosphorus content of 253.88 ppm and the highest of 338.43 ppm were found in growth stages D1 and D6, respectively. The berry Ca however showed an increase first and thereafter decreased to 225.18 ppm at harvest. Mg content also recorded a similar trend from stages D1 to D6 of the BBCH scale and decreased to 116.08 ppm at D6. B and Cu concentrations increased from D1 to D6, and Mn and Zn increased first and decreased thereafter until harvest. No specific trend was recorded in Fe concentration. The concentration of nutrients in berries at different developmental stages can be used as the standard reference for growing berries using proper fertilization.

Patients’ decisions regarding orthodontic treatment are influenced by a variety of factors, such as their subjective opinions of how their oral cavity looks, age, gender, educational level, and income. The present study aimed to measure the orthodontic treatments needs for the Saudi Arabian population, and also to report potential barriers towards it. It is an observational study with cross sectional design. Data was collected from nationals and residents living in Saudi Arabia and who are at least 18 years old. A total of 1184 adult patients (880 females and 304 males) were included in this study. The population for the study was reached and chosen using a non-probability snowball sampling method. A validated and reliable questionnaire was distributed to the participants electronically through google form. Inferential statistics was applied using Pearson Chi Square test. p value < 0.05 was considered significant. The majority of the sample (73.2%) exhibited a favorable attitude toward orthodontic treatment. Most participants including male and female gender wanted orthodontic treatment primarily to have their protruding teeth fixed. The proportion of persons who cited chewing difficulty as the reason they needed orthodontic treatment was strongly influenced by the monthly income variable (p = 0.005). Cost and time of orthodontic therapy were the biggest obstacles to undergoing treatment, accounting for 34.5% and 19.5%, respectively. There was highly significant difference between the underlying medical conditions and the age and monthly income variables (p = 0.000). Based on the findings of the present study, it can be concluded that protruding teeth are the most important treatment needs perceived by the Saudi population, followed by spacing in between teeth, crowding of teeth, and unaesthetic smile. Cost of the orthodontic treatment was identified as the most significant barrier to the treatment needs, followed by long duration of orthodontic treatment, and pain.

Abstract Due to their post-mitotic state, metabolic demands and often large polarised morphology, the function and survival of neurons is dependent on an efficient cellular waste clearance system both for generation of materials for metabolic processes and removal of toxic components. It is not surprising therefore that deficits in protein clearance can tip the balance between neuronal health and death. Here we discuss how autophagy and lysosome-mediated degradation pathways are disrupted in several neurological disorders. Both genetic and cell biological evidence show the diversity and complexity of vesicular clearance dysregulation in cells, and together may ultimately suggest a unified mechanism for neuronal demise in degenerative conditions. Causative and risk-associated mutations in Alzheimer’s disease, Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, Parkinson’s disease, Huntington’s disease and others have given the field a unique mechanistic insight into protein clearance processes in neurons. Through their broad implication in neurodegenerative diseases, molecules involved in these genetic pathways, in particular those involved in autophagy, are emerging as appealing therapeutic targets for intervention in neurodegeneration.

Abstract Recent years have seen a significant growth in Internet of Things (IoT) technology consisting of a large number of devices embedded with sensors and deployed to perform monitoring and actuation tasks. The IoT devices collect large volumes of data that is usually uploaded to cloud to perform analytics and predictions. One of the main challenges in IoT is the transportation of large-scale data collected over a period of time at a remote site. Cellular networks are already facing explosive growth of mobile data traffic due to the proliferation of smart devices and traffic-intensive applications. An alternate solution is to perform the data offloading, where a portion of data can be offloaded from primary links and transferred using opportunistic terminal-to-terminal (T2T) network that relies on direct communication between mobile users, without any need for an infrastructure backbone. However, such approach may lead to data loss and delay if dynamics of time-varying topology and mobility of nodes is not taken care of. To address this challenge, we propose three prediction-based offloading schemes that exploit the mobility patterns and temporal contacts of nodes to predict future data transfer opportunities. We have utilized the High-level Petri Nets to model and formally analyzed the communication processes of the proposed schemes. The new symbolic model verifier (NuSMV) has been employed for the verification of the three schemes against the identified constraints. The verification results affirm the correctness and scalability of the models. The protocols are evaluated with performance metrics, such as the delivery ratio, latency, and overhead. Our results indicate significant improvement in performance compared to existing approaches.

Abstract Introduction Rat mothers exhibit natural variations in care that propagate between generations of female offspring. However, there is limited information on genetic variation that could influence this propagation. Methods We assessed early‐life maternal care received by individual female rat offspring, later‐life maternal care provisioning, and dopaminergic activity in the maternal brain in relation to naturally occurring genetic polymorphisms linked to the dopaminergic system. We also conducted a systematic analysis of other genetic variants potentially related to maternal behavior in our Long‐Evans rat population. Results While we did not find a direct relationship between early‐life licking received and later‐life licking provisioning, this relationship was indirectly affected by dopamine levels in the nucleus accumbens and dependent on variation in the dopamine receptor 2 gene (rs107017253). More specifically, female rat offspring with the A/G genotype showed a positive relationship between average licking received and dopamine levels in the nucleus accumbens of the maternal brain; there was no relationship with female rat offspring with the A/A genotype. The higher dopamine levels in the nucleus accumbens corresponded with higher maternal licking provisioning from postnatal days 2–9. We also discovered and validated several new variants that were predicted by our systematic analysis. Conclusion Our findings suggest that genetic variation influences the relationship between early‐life maternal care received and the dopaminergic system of the maternal brain, which can indirectly influence later‐life maternal care provisioning.

Immune checkpoint inhibitors have opened a new era in treating advanced malignancies, resulting in a rapid increase in utilization, given the remarkable clinical outcomes. The incidence of immune-related adverse events increased due to the immunologic effects of these therapeutic agents. However, immune-related renal adverse events remain low, representing only a small incidence of reported cases. Common renal toxicity described includes acute interstitial nephritis, minimal change disease, and immune complex glomerulonephritis. Renal tubular acidosis has occasionally been reported but is highly uncommon. This report presents a case of a 68-year-old woman with a known history of metastatic melanoma undergoing treatment with ipilimumab+nivolumab, who developed distal renal tubular acidosis requiring stress dose steroids and sodium bicarbonate for treatment. We describe the clinical characteristics, potential mechanisms, and management of this case, highlighting the need among clinicians utilizing immune check inhibitors to be aware of this immune-related disease entity.

Protecting the privacy of individuals is of utmost concern in today’s society, as inscribed and governed by the prevailing privacy laws, such as GDPR. In serial data, bits of data are continuously released, but their combined effect may result in a privacy breach in the whole serial publication. Protecting serial data is crucial for preserving them from adversaries. Previous approaches provide privacy for relational data and serial data, but many loopholes exist when dealing with multiple sensitive values. We address these problems by introducing a novel privacy approach that limits the risk of privacy disclosure in republication and gives better privacy with much lower perturbation rates. Existing techniques provide a strong privacy guarantee against attacks on data privacy; however, in serial publication, the chances of attack still exist due to the continuous addition and deletion of data. In serial data, proper countermeasures for tackling attacks such as correlation attacks have not been taken, due to which serial publication is still at risk. Moreover, protecting privacy is a significant task due to the critical absence of sensitive values while dealing with multiple sensitive values. Due to this critical absence, signatures change in every release, which is a reason for attacks. In this paper, we introduce a novel approach in order to counter the composition attack and the transitive composition attack and we prove that the proposed approach is better than the existing state-of-the-art techniques. Our paper establishes the result with a systematic examination of the republication dilemma. Finally, we evaluate our work using benchmark datasets, and the results show the efficacy of the proposed technique.

BACKGROUND:Arboviruses are a cause of acute febrile illness and outbreaks worldwide. Recent outbreaks of Chikungunya virus (CHIKV) in dengue endemic areas have alarmed clinicians as unique clinical features differentiating CHIKV from Dengue virus (DENV) are limited. This has complicated diagnostic efforts especially in resource limited countries where lab testing is not easily available. Therefore, it is essential to analyse and compare clinical features of laboratory confirmed cases to assist clinicians in suspecting possible CHIKV infection at time of clinical presentation. METHODOLOGY:A prospective point prevalence study was conducted, with the hypothesis that not all patients presenting with clinical suspicion of dengue infections at local hospitals are suffering from dengue and that other arboviruses such as Chikungunya, West Nile viruses, Japanese Encephalitis virus and Zika virus are co-circulating in the Sindh region of Pakistan. Out-patients and hospitalized (in-patients) of selected district hospitals in different parts of Sindh province of Pakistan were recruited. Patients with presumptive dengue like illness (Syndromic diagnosis) by the treating physicians were enrolled between 2015 and 2017. Current study is a subset of larger study mentioned above. Here-in we compared laboratory confirmed cases of CHIKV and DENV to assess clinical features and laboratory findings that may help differentiate CHIKV from DENV infection at the time of clinical presentation. RESULTS:Ninety-eight (n = 98) cases tested positive for CHIKV, by IgM and PCR and these were selected for comparative analysis with DENV confirmed cases (n = 171). On multivariable analysis, presence of musculoskeletal [OR = 2.5 (95% CI:1.6-4.0)] and neurological symptoms [OR = 4.4 (95% CI:1.9-10.2)], and thrombocytosis [OR = 2.2 (95% CI:1.1-4.0)] were associated with CHIKV infection, while atypical lymphocytes [OR = 8.3 (95% CI:4.2-16.7)] and thrombocytopenia [OR = 8.1 (95% CI:1.7-38.8)] were associated with DENV cases at time of presentation. These findings may help clinicians in differentiating CHIKV from DENV infection. CONCLUSION:CHIKV is an important cause of illness amongst patients presenting with acute febrile illness in Sindh region of Pakistan. Arthralgia and encephalitis at time of presentation among patients with dengue-like illness should prompt suspicion of CHIKV infection, and laboratory confirmation must be sought.

Resolving the genetic architecture of painful neuropathy will lead to better disease management strategies. We aimed to develop a reliable method to re-sequence multiple genes in a large cohort of painful neuropathy patients at low cost. In this study, we compared sensitivity, specificity, targeting efficiency, performance and cost effectiveness of Molecular Inversion Probes-Next generation sequencing (MIPs-NGS) and TruSeq® Custom Amplicon-Next generation sequencing (TSCA-NGS). Capture probes were designed to target nine sodium channel genes (SCN3A, SCN8A-SCN11A, and SCN1B-SCN4B). One hundred sixty-six patients with diabetic and idiopathic neuropathy were tested by both methods, 70 patients were validated by Sanger sequencing. Sensitivity, specificity and performance of both techniques were comparable, and in agreement with Sanger sequencing. The average targeted regions coverage for MIPs-NGS was 97.3% versus 93.9% for TSCA-NGS. MIPs-NGS has a more versatile assay design and is more flexible than TSCA-NGS. The cost of MIPs-NGS is >5 times cheaper than TSCA-NGS when 500 or more samples are tested. In conclusion, MIPs-NGS is a reliable, flexible, and relatively inexpensive method to detect genetic variations in a large cohort of patients. In our centers, MIPs-NGS is currently implemented as a routine diagnostic tool for screening of sodium channel genes in painful neuropathy patients.

The problems associated with the fabrication of in situ metal matrix composites (MMC) by conventional methods can be avoided by using microwave sintering and friction stirring in combination. The current study investigates the mechanical and electrical properties of pure aluminum (Al-100 wt%) and Al-Cu MMC. The results showed that excellent ultimate tensile strength, toughness, and electrical conductivity can be acquired simultaneously. The obtained ultimate tensile strength in the case of Al-100wt% (184.5 MPa) has improved two-fold than that of a typical commercially pure aluminum AA1016 (90 MPa). Similarly, the electrical conductivity of developed pure aluminum (88.87% IACS) is 1.4 times higher compared to AA1016 alloy (62% IACS). For Al-Cu MMC the copper is added in steps of 5 wt% (5%, 10%, 15%, and 20%). The maximum ultimate tensile strength (205.2 MPa) and the electrical conductivity (71.53% IACS) obtained for Al-10wt%Cu are higher compared to the AA1016 alloy. The present investigation suggests a novel processing route and opens up new research avenues in the field of solid-state materials processing.

The traditional big-data analytical approaches use data clustering as small buckets while providing distributed computation among different child nodes. These approaches bring the issues especially concerning network capacity, specialized tools and applications not capable of being trained in a short period. Furthermore, raw data generated through IoT forming big data comes with the capability of producing highly unstructured and heterogeneous form of data. Such form of data grows into challenging task for the real-time analytics. It is highly valuable to have computational values available locally instead of through distributed resources to reduce real-time analytical challenges. This paper proposes a fusion of three different data models like relational, semantical, and big data based data and metadata involving their issues and enhanced capabilities. A case study is used to represent data fusion in action from RDB to Resource Description Framework. Whereas, issues and their feasible solutions are also being discussed in this paper.

Alzheimer’s disease (AD) is the most common form of dementia and is characterized by intracellular neurofibrillary tangles of hyperphosphorylated Tau, including the 0N4R isoform and accumulation of extracellular amyloid beta (Aβ) plaques. However, less than 5% of AD cases are familial, with many additional risk factors contributing to AD including aging, lifestyle, the environment and epigenetics. Recent epigenome-wide association studies (EWAS) of AD have identified a number of loci that are differentially methylated in the AD cortex. Indeed, hypermethylation and reduced expression of the Ankyrin 1 (ANK1) gene in AD has been reported in the cortex in numerous different post-mortem brain cohorts. Little is known about the normal function of ANK1 in the healthy brain, nor the role it may play in AD. We have generated Drosophila models to allow us to functionally characterize Drosophila Ank2, the ortholog of human ANK1 and to determine its interaction with human Tau and Aβ. We show expression of human Tau 0N4R or the oligomerizing Aβ 42 amino acid peptide caused shortened lifespan, degeneration, disrupted movement, memory loss, and decreased excitability of memory neurons with co-expression tending to make the pathology worse. We find that Drosophila with reduced neuronal Ank2 expression have shortened lifespan, reduced locomotion, reduced memory and reduced neuronal excitability similar to flies overexpressing either human Tau 0N4R or Aβ42. Therefore, we show that the mis-expression of Ank2 can drive disease relevant processes and phenocopy some features of AD. Therefore, we propose targeting human ANK1 may have therapeutic potential. This represents the first study to characterize an AD-relevant gene nominated from EWAS.

Summary: VPS10P domain receptors emerge as central regulators of intracellular protein sorting in neurons with relevance for various brain pathologies. Here, we identified a role for the family member SorCS2 in protection of neurons from oxidative stress and epilepsy-induced cell death. We show that SorCS2 acts as sorting receptor that sustains cell surface expression of the neuronal amino acid transporter EAAT3 to facilitate import of cysteine, required for synthesis of the reactive oxygen species scavenger glutathione. Lack of SorCS2 causes depletion of EAAT3 from the plasma membrane and impairs neuronal cysteine uptake. As a consequence, SorCS2-deficient mice exhibit oxidative brain damage that coincides with enhanced neuronal cell death and increased mortality during epilepsy. Our findings highlight a protective role for SorCS2 in neuronal stress response and provide a possible explanation for upregulation of this receptor seen in surviving neurons of the human epileptic brain. : Malik et al. uncover a mechanism crucial for neuronal oxidative stress defense. They show that sorting receptor SorCS2 facilitates cell surface expression of cysteine transporter EAAT3. Loss of Sorcs2 impairs neuronal cysteine import and glutathione production, increases vulnerability to oxidative damage, and aggravates epilepsy-induced brain pathology and death in mice. Keywords: VPS10P domain receptors, intracellular protein sorting, oxidative stress, EAAT3, EAAC1, epilepsy, glutathione