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BACKGROUND: Prospective genetic evaluation of patients at our referral research hospital presents clinical research challenges. OBJECTIVE: This study sought not only a single-gene explanation for participants’ immune-related presentations, but viewed each participant holistically, with the potential to have multiple genetic contributions to their immune-phenotype and other heritable comorbidities relevant to their presentation and health. METHODS: We developed a program integrating exome sequencing, chromosomal microarray, phenotyping, results return with genetic counseling, and reanalysis in 1505 individuals from 1000 families with suspected or known inborn errors of immunity. RESULTS: Probands were 50.8% female, 71.5% ≥18 years, and had diverse immune presentations. Overall, 327/1000 probands (32.7%) received 361 molecular diagnoses. These included 17 probands with diagnostic copy number variants, 32 probands with secondary findings, and 31 probands with multiple molecular diagnoses. Reanalysis added 22 molecular diagnoses, predominantly due to new disease-gene associations (9/22, 40.9%). One-quarter of the molecular diagnoses (92/361) did not involve immune-associated genes. Molecular diagnosis was correlated with younger age, male sex, and a higher number of organ systems involved. This program also facilitated the discovery of new gene-disease associations such as SASH3-related immunodeficiency. A review of treatment options and ClinGen actionability curations suggest that at least 251/361 (69.5%) of these molecular diagnoses could translate into ≥1 management option. CONCLUSION: This program contributes to our understanding of the diagnostic and clinical utility whole exome analysis on a large scale.

Ribavirin (RBV) is an antiviral drug used for treating COVID-19 infection. Its release into natural waters would threaten the health of aquatic ecosystem. This study reports an effective approach to degrade RBV by the trace N-oxyl compounds (2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) and N-Hydroxyphthalimide (NHPI)) enhanced UV activated free chlorine (UV/Chlorine) process. The results indicated that TEMPO and NHPI at low concentrations (0.1 μM and 1 μM, respectively) could strongly enhance RBV degradation in both deionized water with different pHs and practical surface water. The enhancement was verified to be attributed to the transformation of TEMPO and NHPI into their reactive forms (i.e., TEMPO

Chloroquine Phosphate (CP) is an antiviral drug used for treatment of COVID-19. It is released into wastewater and eventually contaminates natural water. This study reports an effective homogeneous catalysis way for CP degradation by the 2,2,6,6-Tetramethylpiperidine-N-oxyl (TEMPO) enhanced persulfate (PDS) activation under UVB-LEDs irradiation at 305 nm. TEMPO at a low concentration (0.1 μM) enhanced CP degradation in UV

Natural ventilation by shafts is widely applied in urban shallow tunnels due to its simple structure, steady smoke extraction efficiency and environment-friendly means. In order to investigate the influence of vehicle blockage on the smoke extraction efficiency of the shaft in tunnel fires, a series of n-heptane fire experiments were conducted in a 1:15 small-scale tunnel model with seven blockage ratios (0, 0.16, 0.24, 0.32, 0.40, 0.48, 0.56). The smoke extraction efficiency is calculated by the measured smoke temperature and CO volume fraction in the shaft and in the tunnel near the exhaust vent. Results show that the smoke extraction efficiency of the tunnel with shafts decreases firstly, then increases and drops lastly with the increasing blockage ratio. The smoke temperature in the shaft and at the downstream tunnel change similarly, which indicates that the vehicle blockage can affect the thermal energy discharged by a shaft. The main influence factors are the blocking effect, the necking effect caused by the blockage and the stack effect of the shaft, resulting in the variability of the smoke extraction efficiency. The smoke extraction efficiency reaches the maximum around the blockage 0.48 in the present tunnel, which can be referred to design the tunnel cross section in engineering applications.

Plasmonic Bi

We recently developed the Genomics Research Integration System (GRIS) to help NIAID investigators at the NIH leverage both phenotypic and genotypic patient data to identify causal variants for rare diseases. The project is a bioinformatics compliment to an initiative to sequence exomes for all NIAID patients visiting the NIH Clinical Center. The system is designed to serve as a valuable resource for clinical genomic data annotated with standardized phenotypic terms using the Human Phenotype Ontology \citeKohler2013. GRIS uses PhenoTips® \citeGirdea2013 to capture clinical records and family pedigrees which are linked to genomic records stored in a genetic analysis tool,seqr, developed at the Broad Institute (\urlseqr.broadinstitute.org ) to enable causal variant identification. We have customized both programs in novel ways to meet NIH encryption requirements, to link patient records across programs in a controlled manner, and to provide "tiers" of access so that individual research groups can customize users' ability to edit their patient records and view personally identifiable information (PII). A challenge faced by shared clinical data repositories is to facilitate maximal collective research value of data through open sharing, while respecting the needs of researchers to adjust access to patient data in accordance with research goals and subject to clinical sharing guidelines. We devised a technical approach to meet the needs of sharing policies, formulated collectively by researchers and clinicians, to promote wider acceptance and usage of the system. Accordingly, we implemented a patient identifier mapping system in conjunction with automated notifications to enable transparent sharing. Our approach may prove helpful to other hospital or clinical support systems seeking to respect the confidentiality of patient PII and early findings of individual researchers, while recognizing that data repositories are most primed for discovery (and can significantly increase return on investment) if they are open and accessible to a larger research community.

In this paper, a QoS multipath source routing protocol (QoS-MSR) is proposed for ad hoc networks. It can collect QoS information through route discovery mechanism of multipath source routing (MSR) and establish QoS route with reserved bandwidth. In order to reserve bandwidth efficiently, a bandwidth reservation approach called the multipath bandwidth splitting reservation (MBSR) is presented, under which the overall bandwidth request is split into several smaller bandwidth requests among multiple paths. In simulations, the anthors introduce Insignia, an in-bind signaling system that supports QoS in ad hoc networks, and extend it to multipath Insignia (M-Insignia) with QoS-MSR and MBSR. The results show that QoS-MSR routing protocol with the MBSR algorithm can improve the call admission ratio of QoS traffic, the packet delivery ratio, and the end-to-end delay of both best-effort traffic and QoS traffic. Therefore, QoS-MSR with MBSR is an efficient mechanism that supports QoS for ad hoc networks.

To explore the repairing effect of combination of adipose stem cells (ASCs) and composite scaffolds on CWR, the electrospun Poly 1, 8-octanediol-co-citric acid (POC)-poly-L-lactide acid (PLA) composite scaffolds were prepared, followed by in vitro and in vivo biocompatibility evaluation of the scaffolds. Afterwards, ASCs were seeded on POC-PLA to construct the POC-PLA-ASCs scaffolds, and the POC-PLA, POC-PLA-ASCs, and traditional materials expanded polytetrafluoroethylene (ePTFE) were adopt for CWR in New Zealand white (NZW) rabbit models. As results, the POC-PLA-ASCs patches possessed good biocompatibility as the high proliferation ability of cells surrounding the patches. Rabbits in POC-PLA-ASCs groups showed better pulmonary function, less pleural adhesion, higher degradation rate and more neovascularization when compared with that in other two groups. The results of western blot indicated that POC-PLA-ASCs patches accelerated the expression of VEGF and Collagen I in rabbit models. From the above, our present study demonstrated that POC-PLA material was applied for CWR successfully, and ASCs seeded on the sheets could improve the pleural adhesions and promote the reparation of chest wall defects.

/spl mu/TESLA is a symmetric-key based broadcast authentication algorithm that periodically broadcasts key authentication packets in sensor networks with a key disclosure delay interval, T. Determining appropriate values for T is important to both performance and security. We analyze how to structure /spl mu/TESLA to satisfy application imposed security and performance requirements while minimizing the network cost. The main contribution of the paper is a quantitative analysis of the optimal value of T such that the authentication broadcast cost is minimized while satisfying application imposed constraints on data authentication delay and packet rejection probability. We model the system using stochastic Petri nets. Our analysis results show that an optimal value of T exists and can be determined as a function of model parameter values characterizing the operating conditions.

This paper proposes a novel bandwidth reservation mechanism called the multipath bandwidth splitting reservation (MBSR) for ad hoc networks. In MBSR, an overall bandwidth B-quest is split into several smaller bandwidth requests, and these requests will be reserved on multiple disjoint paths respectively. Both theoretical analysis and simulation results prove that the probability of successful reservation of MBSR is higher than that of single-path reservation, In addition, simulation results show that the MBSR can improve the reserved packet ratio of QoS traffic, the packet delivery ratio and the end-to-end delay of both best-effort traffic and QoS traffic.

In this paper, we propose an efficient resource reservation mechanism called the neighborhood reservation (NR) for ad hoc networks. When a node reserves bandwidth for a QoS flow, corresponding bandwidth reservation must be done in all its neighborhood nodes simultaneously to eliminate the impact on reserved bandwidth caused by channel contention. Thus the reserved bandwidth for the QoS flow can be guaranteed with certainty. The simulation results show that the effectiveness of QoS reservation can be improved remarkably by using neighborhood reservation.