Quality of service routing on wide area networks.

Moore [20] introduced the quickest path problem and it has been studied extensively in recent times. The quickest path problem is to determine a routing path to minimize end-to-end delay from the source to the destination node taking into account message size, and propagation delay and bandwidth on the links of the network. Thus the quickest path is a path with minimum end-to-end delay time required to send sigma units of message from a source node to the destination node.The main theme of this dissertation is to investigate unicast and multicast routing algorithms in wide area networks. Towards this end, first we present a unifying quickest path algorithm for different message transfer modes at intermediate nodes. The source to destination path varies with message sizes. Quickest path algorithms build a table called the Path-Table that when searched with message size gives the minimum end-to-end delay path for that message size. Our second result deals with efficient construction of the Path-Table when a link or path bandwidth changes, where path bandwidth is defined as the minimum of the bandwidths on the links of the path. Third, we present efficient algorithms for all-to-all quickest path problems in the presence of unreliable links in the network. By assigning probability of link failure to each link we can cast two problems namely, quickest most reliable path and most reliable quickest path.Routing is the process of sending a message from a source node to the destination node and the routing algorithm is a method to determine links that a message should be transmitted in order to reach the destination. The routing algorithm can be classified into the following three categories: unicast, multicast, and broadcast. Unicast involves sending a message from a given source to a destination; multicasting is a mechanism to send a message from a given source to a chosen set of destinations; broadcasting is sending a message from a given source to all the nodes in the network. Clearly, unicast and broadcast are special cases of multicast. The path selected by a routing algorithm depends on the application's Quality-of-Service (QoS) demands such as, end-to-end delay time, cost, delay jitter, and other factors.Our fourth result deals with multicast routing in wide area networks. We have developed several heuristics for the construction of a multicast tree that minimizes end-to-end delay time taking into account message size, and propagation delay and bandwidths on links. We consider different modes of message transfers at intermediate nodes and for each type of intermediate node architecture we present heuristics for the multicast tree construction. The heuristics are simulated on large networks that are generated using different network generation models including Waxman I and II, Locality, and Transit-Stub. Our heuristics are shown to outperform existing heuristics that are based on shortest path and minimum spanning tree for multicast tree construction. Finally, we introduce a novel heuristic for the construction of a multicast tree with minimum cost in Internet like topologies. Our algorithm on directed asymmetric networks is shown to have a performance gain in terms of tree costs over existing algorithms

Construction and Application of a Korean Reference Panel for Imputing Classical Alleles and Amino Acids of Human Leukocyte Antigen Genes

Genetic variations of human leukocyte antigen (HLA) genes within the major histocompatibility complex (MHC) locus are strongly associated with disease susceptibility and prognosis for many diseases, including many autoimmune diseases. In this study, we developed a Korean HLA reference panel for imputing classical alleles and amino acid residues of several HLA genes. An HLA reference panel has potential for use in identifying and fine-mapping disease associations with the MHC locus in East Asian populations, including Koreans. A total of 413 unrelated Korean subjects were analyzed for single nucleotide polymorphisms (SNPs) at the MHC locus and six HLA genes, including HLA-A, -B, -C, -DRB1, -DPB1, and -DQB1. The HLA reference panel was constructed by phasing the 5,858 MHC SNPs, 233 classical HLA alleles, and 1,387 amino acid residue markers from 1,025 amino acid positions as binary variables. The imputation accuracy of the HLA reference panel was assessed by measuring concordance rates between imputed and genotyped alleles of the HLA genes from a subset of the study subjects and East Asian HapMap individuals. Average concordance rates were 95.6% and 91.1% at 2-digit and 4-digit allele resolutions, respectively. The imputation accuracy was minimally affected by SNP density of a test dataset for imputation. In conclusion, the Korean HLA reference panel we developed was highly suitable for imputing HLA alleles and amino acids from MHC SNPs in East Asians, including Koreans

Peptidyl arginine deiminase type IV (PADI4) haplotypes interact with shared epitope regardless of anti-cyclic citrullinated peptide antibody or erosive joint status in rheumatoid arthritis: a case control study

Introduction: Anti-cyclic citrullinated peptide autoantibodies (anti-CCP) are the most specific serologic marker for rheumatoid arthritis (RA). Genetic polymorphisms in a citrullinating (or deiminating) enzyme, peptidyl arginine deiminase type IV (PADI4) have been reproducibly associated with RA susceptibility in several populations. We investigated whether PADI4 polymorphisms contribute to anti-CCP-negative as well as -positive RA, whether they influence disease severity (erosive joint status), and whether they interact with two major risk factors for RA, Human Leukocyte Antigen-DRB1 (HLA-DRB1) shared epitope (SE) alleles and smoking, depending on anti-CCP and erosive joint status.Methods: All 2,317 unrelated Korean subjects including 1,313 patients with RA and 1,004 unaffected controls were genotyped for three nonsynonymous (padi4_89, padi4_90, and padi4_92) and one synonymous (padi4_104) singlenucleotide polymorphisms (SNPs) in PADI4 and for HLA-DRB1 by direct DNA sequence analysis. Odds ratios (OR) were calculated by multivariate logistic regression. Interaction was evaluated by attributable proportions (AP), with 95% confidence intervals (CI).Results: A functional haplotype of the three fully correlated nonsynonymous SNPs in PADI4 was significantly associated with susceptibility to not only anti-CCP-positive (adjusted OR 1.73, 95% CI 1.34 to 2.23) but also -negative RA (adjusted OR 1.75, 95% CI 1.15 to 2.68). A strong association with both non-erosive (adjusted OR 1.62, 95% CI 1.29 to 2.05) and erosive RA (adjusted OR 1.62, 95% CI 1.14 to 2.31) was observed for PADI4 haplotype. Gene-gene interactions between the homozygous RA-risk PADI4 haplotype and SE alleles were significant in both anti-CCP-positive (AP 0.45, 95% CI 0.20 to 0.71) and -negative RA (AP 0.61, 95% CI 0.29 to 0.92). Theses interactions were also observed for both non-erosive (AP 0.48, 95% CI 0.25 to 0.72) and erosive RA (AP 0.46, 95% CI 0.14 to 0.78). In contrast, no interaction was observed between smoking and PADI4 polymorphisms.Conclusions: A haplotype of nonsynonymous SNPs in PADI4 contributes to development of RA regardless of anti-CCP or erosive joint status. The homozygous PADI4 haplotype contri bution is affected by gene-gene interactions with HLADRB1 SE alleles.We are grateful to many research workers for assistance with sample preparation, data collection, and technical study. Dr. Bang's work was supported by a grant from the Korea Healthcare Technology R&D Project (A090706). Dr. Bae's work was supported by a grant from the Korea Healthcare Technology R&D Project (A084794 and A010252). Dr. Kang's work was supported by a grant from the Research Program for New Drug Target Discovery (M10748000231-08N4800-23110)

Effect of Diabetes Mellitus on Symptomatic Improvement After Surgery for Benign Prostatic Hyperplasia in Patients With Lower Urinary Tract Symptom and its Relations With Prostatic Urethral Angulation

Purpose To compare improvement of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia in diabetic versus nondiabetic patients after transurethral resection of the prostate (TURP) or holmium laser enucleation of the prostate (HoLEP). Methods The medical records of 437 patients who underwent TURP or HoLEP at a tertiary referral center from January 2006 to January 2022 were retrospectively analyzed. Among them, 71 patients had type 2 diabetes. Patients in the diabetic mellitus (DM) and non-DM groups were matched 1:1 according to age, baseline International Prostate Symptom Score (IPSS), and ultrasound measured prostate volume. Changes in LUTS were assessed at 3 months after surgery using IPSS and evaluated by categorizing patients according to prostatic urethral angulation (PUA; <50° vs. ≥50°). Medication-free survival after surgery was also investigated. Results No significant differences were noted between the DM and non-DM groups in baseline characteristics except for comorbidities (i.e., hypertension, cerebrovascular disease, and ischemic heart disease, P=0.021, P=0.002, and P=0.017, respectively) and postvoid residual urine volume (115±98 mL vs. 76±105 mL, P=0.028). Non-DM patients showed significant symptomatic improvement regardless of PUA, while DM patients demonstrated improvement in obstructive symptoms only in those with large PUA (≥51°). Among patients with small PUA, DM patients had worse medication-free survival after surgery compared to controls (P=0.044) and DM was an independent predictor of medication reuse (hazard ratio, 1.422; 95% confidence interval, 1.285–2.373; P=0.038). Conclusions DM patients experienced symptomatic improvement after surgery only in those with large PUA. Among patients with small PUA, DM patients were more likely to reuse medication after surgery

ATLAS: A Traffic Load Aware Sensor MAC Design for Collaborative Body Area Sensor Networks

In collaborative body sensor networks, namely wireless body area networks (WBANs), each of the physical sensor applications is used to collaboratively monitor the health status of the human body. The applications of WBANs comprise diverse and dynamic traffic loads such as very low-rate periodic monitoring (i.e., observation) data and high-rate traffic including event-triggered bursts. Therefore, in designing a medium access control (MAC) protocol for WBANs, energy conservation should be the primary concern during low-traffic periods, whereas a balance between satisfying high-throughput demand and efficient energy usage is necessary during high-traffic times. In this paper, we design a traffic load-aware innovative MAC solution for WBANs, called ATLAS. The design exploits the superframe structure of the IEEE 802.15.4 standard, and it adaptively uses the contention access period (CAP), contention free period (CFP) and inactive period (IP) of the superframe based on estimated traffic load, by applying a dynamic “wh” (whenever which is required) approach. Unlike earlier work, the proposed MAC design includes load estimation for network load-status awareness and a multi-hop communication pattern in order to prevent energy loss associated with long range transmission. Finally, ATLAS is evaluated through extensive simulations in ns-2 and the results demonstrate the effectiveness of the protocol

Spinal epidural hematoma related to an epidural catheter in a cardiac surgery patient -A case report-

The addition of thoracic epidural anesthesia to general anesthesia during cardiac surgery may have a beneficial effect on clinical outcome. However, epidural catheter insertion in a patient anticoagulated with heparin may increase the risk of epidural hematoma. We report a case of epidural hematoma in a 55-year-old male patient who had a thoracic epidural placed under general anesthesia preceding uneventful mitral valve replacement and tricuspid valve annular plasty. During the immediate postoperative period and first postoperative day, prothrombin time (PT) and activate partial thromboplastin time (aPTT) were mildly prolonged. On the first postoperative day, he complained of motor weakness of the lower limbs and back pain. An immediate MRI of the spine was performed and it revealed an epidural hematoma at the T5-6 level. Rapid surgical decompression resulted in a recovery of his neurological abnormalities to near normal levels. Management and preventing strategies of epidural hematoma are discussed

Co-Immunization of Plasmid DNA Encoding IL-12 and IL-18 with Bacillus Calmette-Guérin Vaccine against Progressive Tuberculosis

∙ The authors have no financial conflicts of interest. Purpose: Bacillus Calmette-Guérin (BCG) vaccine has widely been used to immunize against tuberculosis, but its protective efficacy is variable in adult pulmonary tuberculosis, while it is not efficiently protective against progressive infection of virulent Mycobacterium tuberculosis strains. In this study, the protective effects of plasmid DNA vaccine constructs encoding IL-12 or IL-18 with the BCG vaccine were evaluated against progressive infection of M. tuberculosis, using mouse aerosol challenge model. Materials and Methods: Plasmid DNA vaccine constructs encoding IL-12 or IL-18 were constructed and mice were immunized with the BCG vaccine or with IL-12 DNA or IL-18 DNA vaccine constructs together with the BCG vaccine. Results: The BCG vaccine induced high level of interferon gamma (IFN-γ) but co-immunization of IL-12 or IL-18 DNA vaccine constructs with the BCG vaccine induced significantly higher level of IFN-γ than a single BCG vaccine. The BCG vaccine was highly protective at early stage of M. tuberculosi

The Impact of Intima-media Thickness of Radial Artery on Early Failure of Radiocephalic Arteriovenous Fistula in Hemodialysis Patients

This study was performed to investigate the impact of intima-media thickness (IMT) of radial artery on early failure of radiocephalic arteriovenous fistula (AVF) in hemodialysis (HD) patients. Ninety uremic patients undergoing radiocephalic AVF operation were included in this study. During the operation, 10-mm long partial arterial walls were removed with elliptical form for microscopic analysis. Specimens were stained with trichrome and examined by a pathologist blinded to the clinical data. And then AVF patency was followed up for 1 yr after the operation. Of the total 90 patients, 31 patients (34%) had AVF failure within 1 yr after the operation. Mean IMT was thicker in failed group (n=31) than in patent group (n=59) (486±130 µm vs. 398±130 µm, p=0.004). The AVF patency rate within 1 yr after the operation was lower in patients with IMT ≥500 µm (n=26) than in patients with IMT <500 µm (n=64) (p=0.017). Age was an independent risk factor of IMT. Diabetes mellitus tended to be independent risk factor but not statistically significant. Our data suggest that increased radial artery IMT is closely associated with early failure of radiocephalic AVF in HD patients

Ethanol extract of Scutellaria baicalensis Georgi prevents oxidative damage and neuroinflammation and memorial impairments in artificial senescense mice

Aging is a progressive process related to the accumulation of oxidative damage and neuroinflammation. We tried to find the anti-amnesic effect of the Scutellaria baicalens Georgia (SBG) ethanol extract and its major ingredients. The antioxidative effect of SBG on the mice model with memory impairment induced by chronic injection of D-galactose and sodium nitrate was studied. The Y-maze test was used to evaluate the learning and memory function of mice. The activities of superoxide dismutase, catalase and the content of malondialdehyde in brain tissue were used for the antioxidation activities. Neuropathological alteration and expression of bcl-2 protein were investigated in the hippocampus by immunohistochemical staining. ROS, neuroinflammation and apoptosis related molecules expression such as Cox-2, iNOS, procaspase-3, cleaved caspase-3, 8 and 9, bcl-2 and bax protein and the products of iNOS and Cox-2, NO, PGE2, were studied using LPS-activated Raw 264.7 cells and microglia BV2 cells. The cognition of mice was significantly improved by the treatment of baicalein and 50 and 100 mg/kg of SBG in Y-maze test. Both SBG groups showed strong antioxidation, antiinflammation effects with significantly decreased iNOS and Cox-2 expression, NO and PGE2 production, increased bcl-2 and decreased bax and cleaved caspase-3 protein expression in LPS induced Raw 264.7 and BV2 cells. We also found that apoptotic pathway was caused by the intrinsic mitochondrial pathway with the decreased cleaved caspase-9 and unchanged cleaved caspase-8 expression. These findings suggest that SBG, especially high dose, 100 mg/kg, improved the memory impairments significantly and showed antioxidation, antiinflammation and intrinsic caspase-mediated apoptosis effects

Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility

Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the CFH-CFHRs region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic CFH SNP (rs6677604, in intron 11, Pmeta = 6.6×10-8, OR = 1.18) and an intergenic SNP between CFHR1 and CFHR4 (rs16840639, Pmeta = 2.9×10-7, OR = 1.17) rather than to previously identified disease-associated CFH exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a ~146 kb block extending from intron 9 of CFH to downstream of CFHR1. Within this block, the deletion of CFHR3 and CFHR1 (CFHR3-1Δ), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of CFHR3-1Δ (Pmeta = 3.2×10-7, OR = 1.47) conferred a higher risk of SLE than heterozygous deletion (Pmeta = 3.5×10-4, OR = 1.14). These results suggested that the CFHR3-1Δ deletion within the SLE-associated block, but not the previously described exonic SNPs of CFH, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE