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The goal of the 8th edition of the Clinical Practice Guidelines for Obesity is to help primary care physician provide safe, effective care to patients with obesity by offering evidence-based recommendations to improve the quality of treatment. The Committee for Clinical Practice Guidelines comprised individuals with multidisciplinary expertise in obesity management. A steering board of seven experts oversaw the entire project. Recommendations were developed as the answers to key questions formulated in patient/problem, intervention, comparison, outcomes (PICO) format. Guidelines underwent multi-level review and cross-checking and received endorsement from relevant scientific societies. This edition of the guidelines includes criteria for diagnosing obesity, abdominal obesity, and metabolic syndrome; evaluation of obesity and its complications; weight loss goals; and treatment options such as diet, exercise, behavioral therapy, pharmacotherapy, and bariatric and metabolic surgery for Korean people with obesity. Compared to the previous edition of the guidelines, the current edition includes five new topics to keep up with the constantly evolving field of obesity: diagnosis of obesity, obesity in women, obesity in patients with mental illness, weight maintenance after weight loss, and the use of information and communication technology-based interventions for obesity treatment. This edition of the guidelines features has improved organization, more clearly linking key questions in PICO format to recommendations and key references. We are confident that these new Clinical Practice Guidelines for Obesity will be a valuable resource for all healthcare professionals as they describe the most current and evidence-based treatment options for obesity in a well-organized format. [ABSTRACT FROM AUTHOR]

Background/Aims: There have been few studies regarding the prognosis of intestinal Behçet’s disease (iBD) patients according to consensus-based diagnostic categories, which reflects the typicality of intestinal ulcers, the presence of oral ulcers, and the accompanying systemic manifestations. Methods: The medical records of patients who had ileocolonic ulcers with a clinical impression of iBD were reviewed. The patients were categorized according to the diagnostic algorithm at the time of diagnosis. Adverse events were defined as major surgery or admission related to iBD deterioration. Results: A total of 163 patients were included in the study. The male-to-female ratio was 1:1.2, and the mean age at the time of diagnosis was 48.9±15.9 years. The numbers of patients who met the definite, probable, suspected, and nondiagnostic iBD criteria were 19 (11.7%), 61 (37.4%), 38 (23.3%), and 45 (27.6%), respectively. The event-free survival of patients with definite, probable, and suspected iBD was significantly shorter than that of patients with nondiagnostic iBD (p=0.026), while there was no significant difference among the definite iBD, probable iBD, and suspected iBD groups (p=0.596). After excluding patients with nondiagnostic iBD, multivariate analysis showed that anemia, fever, colonic involvement other than the ileocecum, and accompanying hematologic disorders at the time of diagnosis were significantly associated with the development of adverse events. Conclusions: The clinical course of patients with definite, probable, and suspected iBD is distinguished from that of patients with nondiagnostic iBD, but patients with definite, probable, and suspected iBD share similar clinical courses. [ABSTRACT FROM AUTHOR]

Obesity is a prevalent and complex disease. The prevalence of obesity in Korea increased from 29.7% in 2010 to 35.7% in 2018, with the prevalence of abdominal obesity being 23.8% in 2018. Obesity contributes to medical costs and socioeconomic burden due to associated comorbidities. The treatment and management of obesity is changing based on new clinical evidence. The 2020 Korean Society for the Study of Obesity Guideline for the Management of Obesity in Korea summarizes evidence-based recommendations and treatment guidelines. [ABSTRACT FROM AUTHOR]

The underlying mechanism of necroptosis in relation to cancer is still unclear. Here, MYC, a potent oncogene, is an antinecroptotic factor that directly suppresses the formation of the RIPK1–RIPK3 complex. Gene set enrichment analyses reveal that the MYC path-way is the most prominently down-regulated signaling pathway during necroptosis. Depletion or deletion of MYC promotes the RIPK1–RIPK3 interaction, thereby stabilizing the RIPK1 and RIPK3 proteins and facilitating necroptosis. Interestingly, MYC binds to RIPK3 in the cytoplasm and inhibits the interaction between RIPK1 and RIPK3 in vitro. Furthermore, MYC-nick, a truncated form that is mainly localized in the cytoplasm, prevented TNF-induced necroptosis. Finally, down-regulation of MYC enhances necroptosis in leukemia cells and suppresses tumor growth in a xenograft model upon treatment with birinapant and emricasan. MYC-mediated suppression of necroptosis is a mechanism of necroptosis resistance in cancer, and approaches targeting MYC to induce necroptosis represent an attractive therapeutic strategy for cancer. [ABSTRACT FROM AUTHOR]

Obesity is a serious and growing worldwide health challenge associated with type 2 diabetes mellitus, cardiovascular disease, osteoarthritis, some cancers, sleep apnea, asthma, and nonalcoholic fatty liver. The Korean Society for the Study of Obesity recommends that pharmacotherapy should be considered when intensive lifestyle modifications fail to achieve a weight reduction in obese patients with a body mass index ≥25 kg/m². Long-term medications for obesity have traditionally fallen into two major categories: centrally acting anorexiant medications and peripherally acting medications, such as orlistat. In this paper, we provide an overview of the anti-obesity medications currently available for the long-term and individualized treatment of obesity. [ABSTRACT FROM AUTHOR]

Cep57 has been characterized as a component of a pericentriolar complex containing Cep63 and Cep152. Interestingly, Cep63 and Cep152 self-assemble into a pericentriolar cylindrical architecture, and this event is critical for the orderly recruitment of Plk4, a key regulator of centriole duplication. However, the way in which Cep57 interacts with the Cep63-Cep152 complex and contributes to the structure and function of Cep63-Cep152 self-assembly remains unknown. We demonstrate that Cep57 interacts with Cep63 through N-terminal motifs and associates with Cep152 via Cep63. Three-dimensional structured illumination microscopy (3DSIM) analyses suggested that the Cep57-Cep63-Cep152 complex is concentrically arranged around a centriole in a Cep57-in and Cep152-out manner. Cep57 mutant cells defective in Cep63 binding exhibited improper Cep63 and Cep152 localization and impaired Sas6 recruitment for procentriole assembly, proving the significance of the Cep57-Cep63 interaction. Intriguingly, Cep63 fused to a microtubule (MT)-binding domain of Cep57 functioned in concert with Cep152 to assemble around stabilized MTs in vitro. Thus, Cep57 plays a key role in architecting the Cep63-Cep152 assembly around centriolar MTs and promoting centriole biogenesis. This study may offer a platform to investigate how the organization and function of the pericentriolar architecture are altered by disease-associated mutations found in the Cep57-Cep63-Cep152 complex. [ABSTRACT FROM AUTHOR]

Patients receiving hemodialysis are vulnerable to infectious diseases due to their impaired immunity and high risk of exposure to pathogens. To protect patients, staff, and visitors from potential infections, each hemodialysis unit should establish and follow standard infection control and prevention measures. Therefore, clinical practice guidelines were developed by a working group of nephrologists and infection control specialists to provide evidence-based guidance for dialysis physicians and nurses, with the aim of preventing infection transmission and controlling infection sources in hemodialysis facilities. The areas of infection control covered by these guidelines include standard precautions, isolation strategies, vascular access, water treatment, cleaning/disinfecting/sterilizing, and vaccination. This special report summarizes the key recommendations from the Korean clinical practice guidelines for preventing the transmission of infections in hemodialysis facilities. [ABSTRACT FROM AUTHOR]

Macroautophagy mediates the selective degradation of proteins and non-proteinaceous cellular constituents. Here, we show that the N-end rule pathway modulates macroautophagy. In this mechanism, the autophagic adapter p62/SQSTM1/Sequestosome-1 is an N-recognin that binds type-1 and type-2 N-terminal degrons (N-degrons), including arginine (Nt-Arg). Both types of N-degrons bind its ZZ domain. By employing three-dimensional modeling, we developed synthetic ligands to p62 ZZ domain. The binding of Nt-Arg and synthetic ligands to ZZ domain facilitates disulfide bond-linked aggregation of p62 and p62 interaction with LC3, leading to the delivery of p62 and its cargoes to the autophagosome. Upon binding to its ligand, p62 acts as a modulator of macroautophagy, inducing autophagosome biogenesis. Through these dual functions, cells can activate p62 and induce selective autophagy upon the accumulation of autophagic cargoes. We also propose that p62 mediates the crosstalk between the ubiquitin-proteasome system and autophagy through its binding Nt-Arg and other N-degrons. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the prevalence and prognostic significance of psychological distress in gastric cancer patients.Methods: The study population included 229 gastric cancer patients visiting Yonsei Cancer Center between November 2009 and March 2011. The distress was measured by available tools including the Modified Distress Thermometer (MDT), Hospital Anxiety and Depression Scale (HADS), and Center for Epidemiologic Studies-Depression Scale (CES-D). Patients with psychological distress were defined as those who scored above the cut-off values in both the MDT and either one of the HADS or CES-D.Results: The median age of patients was 56 (range, 20 to 86) and 97 (42.4%) patients were with stage IV disease status at enrollment. The overall prevalence of psychological distress was 33.6% (95% CI: 27.5-39.8%) in 229 gastric cancer patients. In multiple logistic regression analysis, lower education level (odds ratio [OR] 2.39; 95% confidence interval [CI] 1.11-5.17, P = 0.026) and higher disease stage (OR 2.72; 95% CI 1.47-5.03, P = 0.001) were associated with psychological distress. In stage I-III disease, patients with psychological distress had worse disease-free survival (DFS) (5-year DFS rate: 60% vs 76%, P = 0.49) compared with those without psychological distress. In stage IV disease (n = 97), patients with psychological distress showed poorer overall survival than those without psychological distress (median OS (Overall Survival): 12.2 vs. 13.8 months, P = 0.019).Conclusion: Psychological distress is common in patients with all stages of gastric cancer and is associated with worse outcomes. [ABSTRACT FROM AUTHOR]

Background: Loss-of-function mutations in methyl-CpG-binding protein 2 (MECP2; MIM *300005) results in the Rett syndrome, whereas gain-of-function mutations are associated with the MECP2 duplication syndrome. Methods: We did research on a family with two brothers showing Xq28 duplication syndrome using various molecular cytogenetic techniques such as multiplex ligation-dependent probe amplification and array-based genomic hybridization. Results: The duplicated region had several genes including MECP2 and interleukin-1 receptor associated kinase 1 (IRAK1; MIM *300283). MECP2 and IRAK1 were associated with the neurological phenotypes in dose-sensitive and dose-critical manner. The brothers demonstrated severe intellectual disability, autistic features, generalized hypotonia, recurrent infections, epilepsy, choreiform movements such as hand-wringing movement, and moderate increased spasticity with the lower limbs. The X-inactivation test showed a complete skewed X inactivation pattern of mother. In this reason, the mother had the same loci duplication but showed significantly little neurological manifestation compared to the two sons. Conclusions: MECP2/IRAK1 duplication at Xq28 is inherited as an X-linked recessive trait and male-specific disorder associated with severe intellectual disability. We tried to analyze the information of the relationship between neuropsychiatric phenotype and the extent of duplication at Xq28 by comparing with previous reports. [ABSTRACT FROM AUTHOR]

Motivation: Identification of altered pathways that are clinically relevant across human cancers is a key challenge in cancer genomics. Precise identification and understanding of these altered pathways may provide novel insights into patient stratification, therapeutic strategies and the development of new drugs. However, a challenge remains in accurately identifying pathways altered by somatic mutations across human cancers, due to the diverse mutation spectrum. We developed an innovative approach to integrate somatic mutation data with gene networks and pathways, in order to identify pathways altered by somatic mutations across cancers. Results: We applied our approach to The Cancer Genome Atlas (TCGA) dataset of somatic mutations in 4790 cancer patients with 19 different types of tumors. Our analysis identified cancer-typespecific altered pathways enriched with known cancer-relevant genes and targets of currently available drugs. To investigate the clinical significance of these altered pathways, we performed consensus clustering for patient stratification using member genes in the altered pathways coupled with gene expression datasets from 4870 patients from TCGA, and multiple independent cohorts confirmed that the altered pathways could be used to stratify patients into subgroups with significantly different clinical outcomes. Of particular significance, certain patient subpopulations with poor prognosis were identified because they had specific altered pathways for which there are available targeted therapies. These findings could be used to tailor and intensify therapy in these patients, for whom current therapy is suboptimal. Availability and implementation: The code is available at: http://www.taehyunlab.org. [ABSTRACT FROM AUTHOR]

Dual specificity protein phosphatase 4 (DUSP4) has been considered a promising target for the development of therapeutics for various human cancers. Here, we report the first example for a successful application of the structure-based virtual screening to identify the novel small-molecule DUSP4 inhibitors. As a consequence of the virtual screening with the modified scoring function to include an effective molecular solvation free energy term, five micromolar DUSP4 inhibitors are found with the associated IC50 values ranging from 3.5 to 10.8 µM. Because these newly identified inhibitors were also screened for having desirable physicochemical properties as a drug candidate, they may serve as a starting point of the structure-activity relationship study to optimize the medical efficacy. Structural features relevant to the stabilization of the new inhibitors in the active site of DUSP4 are discussed in detail. [ABSTRACT FROM AUTHOR]

Protein tyrosine phosphatase receptor type Q (PTPRQ) is an unusual PTP that has intrinsic dephosphorylating activity for various phosphatidyl inositides instead of phospho-tyrosine substrates. Although PTPRQ was known to be involved in the pathogenesis of obesity, no small-molecule inhibitor has been reported so far. Here we report six novel PTPRQ inhibitors identified with computer-aided drug design protocol involving the virtual screening with docking simulations and enzyme inhibition assay. These inhibitors exhibit moderate potencies against PTPRQ with the associated IC50 values ranging from 29 to 86 μM. Because the newly discovered inhibitors were also computationally screened for having desirable physicochemical properties as a drug candidate, they deserve consideration for further development by structure-activity relationship studies to optimize the antiobestic activities. Structural features relevant to the stabilization of the inhibitors in the active site of PTPRQ are addressed in detail. [ABSTRACT FROM AUTHOR]

Backgrounds and Aims: The presence and progression of vascular calcification have been demonstrated as important risk factors for mortality in dialysis patients. However, since the majority of subjects included in most previous studies were hemodialysis patients, limited information was available in peritoneal dialysis (PD) patients. Therefore, the aim of this study was to investigate the prevalence of aortic arch calcification (Aplusmn;AC) and prognostic value of Aplusmn; AC progression in PD patients. Methods: We prospectively determined Aplusmn;AC by chest X-ray at PD start and after 12 months, and evaluated the impact of Aplusmn; AC progression on mortality in 415 incident PD patients. Results: Of 415 patients, 169 patients (40.7%) had Aplusmn;AC at baseline with a mean of 18.1611.2%. The presence of baseline Aplusmn;AC was an independent predictor of all-cause [Hazard ratio (HR): 2.181, 95% confidence interval (CI): 1.336-3.561, P = 0.002] and cardiovascular mortality (HR: 3.582, 95% CI: 1.577-8.132, P = 0.002). Among 363 patients with follow-up chest X-rays at 12 months after PD start, the proportion of patients with A±AC progression was significantly higher in patients with baseline A plusmn;AC (64.2 vs. 5.3%, P,0.001). Moreover, all-cause and cardiovascular death rates were significantly higher in the progression groups than in the non-progression group (P,0.001). Multivariate Cox analysis revealed that A plusmn;AC progression was an independent predictor for all-cause (HR: 2.625, 95% CI: 1.150-5.991, P = 0.022) and cardiovascular mortality (HR: 4.008, 95% CI: 1.079-14.890, P = 0.038) in patients with A plusmn;AC at baseline. Conclusions: The presence and progression of A plusmn;AC assessed by chest X-ray were independently associated with unfavorable outcomes in incident PD patients. Regular follow-up by chest X-ray could be a simple and useful method to stratify mortality risk in these patients. [ABSTRACT FROM AUTHOR]

Background and Aims: Mesangial C3 deposition is frequently observed in patients with IgA nephropathy (IgAN). However, the role of complement in the pathogenesis or progression of IgAN is uncertain. In this observational cohort study, we aimed to identify the clinical implications of circulating C3 levels and mesangial C3 deposition and to investigate their utility as predictors of renal outcomes in patients with IgAN. Methods: A total of 343 patients with biopsy-proven IgAN were enrolled between January 2000 and December 2008. Decreased serum C3 level (hypoC3) was defined as C3 <90 mg/dl. The study endpoint was end-stage renal disease (ESRD) and a doubling of the baseline serum creatinine (D-SCr). Results: Of the patients, there were 66 patients (19.2%) with hypoC3. During a mean follow-up of 53.7 months, ESRD occurred in 5 patients (7.6%) with hypoC3 compared with 9 patients (3.2%) with normal C3 levels (P = 0.11). However, 12 patients (18.2%) with hypoC3 reached D-SCr compared with 17 patients (6.1%) with normal C3 levels [Hazard ratio (HR), 3.59; 95% confidence interval (CI), 1.33-10.36; P = 0.018]. In a multivariable model in which serum C3 levels were treated as a continuous variable, hypoC3 significantly predicted renal outcome of D-SCr (per 1 mg/dl increase of C3; HR, 0.95; 95% CI, 0.92-0.99; P = 0.011). The risk of reaching renal outcome was significantly higher in patients with mesangial C3 deposition 2+ to 3+ than in patients without deposition (HR 9.37; 95% CI, 1.10-80.26; P = 0.04). Conclusions: This study showed that hypoC3 and mesangial C3 deposition were independent risk factors for progression, suggesting that complement activation may play a pathogenic role in patients with IgAN. [ABSTRACT FROM AUTHOR]

Background and Aims: Electrocardiography (ECG) is the most widely used initial screening test for the assessment of left ventricular hypertrophy (LVH), an independent predictor of cardiovascular mortality in patients with end-stage renal disease (ESRD). However, traditional ECG criteria based only on voltage to detect LVH have limited clinical utility for the detection of LVH because of their poor sensitivity. Methods: This prospective observational study was undertaken to compare the prognostic significance of commonly used ECG criteria for LVH, namely Sokolow-Lyon voltage (SV) or voltage-duration product (SP) and Cornell voltage (CV) or voltage-duration product (CP) criteria, and to investigate the association between echocardiographic LV mass index (LVMI) and ECG-LVH criteria in ESRD patients, who consecutively started maintenance hemodialysis (HD) between January 2006 and December 2008. Results: A total of 317 patients, who underwent both ECG and echocardiography, were included. Compared to SV and CV criteria, SP and CP criteria, respectively, correlated more closely with LVMI. In addition, CP criteria provided the highest positive predictive value for echocardiographic LVH. The 5-year cardiovascular survival rates were significantly lower in patients with ECG-LVH by each criterion. In multivariate analyses, echocardiographic LVH [adjusted hazard ratio (HR): 11.71; 95% confidence interval (CI): 1.57-87.18; P = 0.016] and ECG-LVH by SP (HR: 3.43; 95% CI: 1.32-8.92; P = 0.011) and CP (HR: 3.07; 95% CI: 1.16-8.11; P = 0.024) criteria, but not SV and CV criteria, were significantly associated with cardiovascular mortality. Conclusions: The product of QRS voltage and duration is helpful in identifying the presence of LVH and predicting cardiovascular mortality in incident HD patients. [ABSTRACT FROM AUTHOR]

Background: The effect of glycemic control after starting peritoneal dialysis (PD) on the survival of diabetic PD patients has largely been unexplored, especially in Asian population. Methods: We conducted a prospective observational study, in which 140 incident PD patients with diabetes were recruited. Patients were divided into tertiles according to the means of quarterly HbA1C levels measured during the first year after starting PD. We examined the association between HbA1C and all-cause mortality using Cox proportional hazards models. Results: The mean age was 58.7 years, 59.3% were male, and the mean follow-up duration was 3.5 years (range 0.4-9.5 years). The mean HbA1C levels were 6.3%, 7.1%, and 8.5% in the 1st, 2nd, and 3rd tertiles, respectively. Compared to the 1st tertile, the all-cause mortality rates were higher in the 2nd [hazard ratio (HR), 4.16; 95% confidence interval (CI), 0.91-18.94; p = 0.065] and significantly higher in the 3rd (HR, 13.16; 95% CI, 2.67-64.92; p = 0.002) tertiles (p for trend = 0.005), after adjusting for confounding factors. Cardiovascular mortality, however, did not differ significantly among the tertiles (p for trend = 0.682). In contrast, non-cardiovascular deaths, most of which were caused by infection, were more frequent in the 2nd (HR, 7.67; 95% CI, 0.68-86.37; p = 0.099) and the 3rd (HR, 51.24; 95% CI, 3.85-681.35; p = 0.003) tertiles than the 1st tertile (p for trend = 0.007). Conclusions: Poor glycemic control is associated with high mortality rates in diabetic PD patients, suggesting that better glycemic control may improve the outcomes of these patients. [ABSTRACT FROM AUTHOR]

A collaborative algorithm is developed to estimate the channel gains of wireless links in a geographical area. The spatiotemporal evolution of shadow fading is characterized by judiciously extending an experimentally verified spatial-loss field model. Kriged Kalman filtering (KKF), which is a tool with widely appreciated merits in spatial statistics and geosciences, is adopted and implemented in a distributed fashion to track the time-varying shadowing field using a network of radiometers. The novel distributed KKF requires only local message passing yet achieves a global view of the radio frequency environment through consensus iterations. Numerical tests demonstrate superior tracking accuracy of the collaborative algorithm compared with its noncollaborative counterpart. Furthermore, the efficacy of the global channel gain knowledge obtained is showcased in the context of cognitive radio resource allocation. [ABSTRACT FROM PUBLISHER]

The article discusses a research study on other binding sites in the crystal structure of map kinase phosphatase 4 (MKP-4) catalytic domain. Researchers cloned and subcloned the MKP-4C residues from human kidney that contain maltose-binding protein (MBP), collected the data on crystallization and proceeded with the molecular-replacement method and virtual screening. Results showed that one MKP-4C molecule was in the assymetric unit with no indication of oligometric interaction in the crystal.

Effective spectrum sensing is a critical prerequisite for multi-channel cognitive radio (CR) networks, where multiple spectrum bands are sensed to identify transmission opportunities, while preventing interference to the primary users. The present paper develops sequential spectrum sensing algorithms which explicitly take into account the sensing time overhead, and optimize a performance metric capturing the effective average data rate of CR transmitters. A constrained dynamic programming problem is formulated to obtain the policy that chooses the best time to stop taking measurements and the best set of channels to access for data transmission, while adhering to hard "collision" constraints imposed to protect primary links. Given the associated Lagrange multipliers, the optimal access policy is obtained in closed form, and the subsequent problem reduces to an optimal stopping problem. A basis expansion-based sub-optimal strategy is employed to mitigate the prohibitive computational complexity of the optimal stopping policy. A novel on-line implementation based on the recursive least-squares (RLS) algorithm along with a stochastic dual update procedure is then developed to obviate the lengthy training phase of the batch scheme. Cooperative sequential sensing generalizations are also provided with either raw or quantized measurements collected at a central processing unit. The numerical results presented verify the efficacy of the proposed algorithms. [ABSTRACT FROM AUTHOR]

Eya proteins are transcription factors that play pivotal roles in organ formation during development by mediating interactions between Sine Oculis (SO) and Dachshund (DAC). Remarkably, the transcriptional activity of Eya proteins is regulated by a dephosphorylating activity within its Eya domain (ED). However, the molecular basis for the link between catalytic and transcriptional activities remains unclear. Here we report the first description of the crystal structure of the ED of human Eya2 (ED-Eya2), determined at 2.4-Å resolution. In stark contrast to other members of the haloacid dehalogenase (HAD) family to which ED-Eya2 belongs, the helix-bundle motif (HBM) is elongated along the back of the catalytic site. This not only results in a structure that accommodates large protein substrates but also positions the catalytic and the SO-interacting sites on opposite faces, which suggests that SO binding is not directly affected by catalytic function. Based on the observation that the DAC-binding site is located between the catalytic core and SO binding sites within ED-Eya2, we propose that catalytic activity can be translated to SO binding through DAC, which acts as a transcriptional switch. We also captured at two stages of reaction cycles-acylphosphate intermediate and transition state of hydrolysis step, which provided a detailed view of reaction mechanism. The ED-Eya2 structure defined here serves as a model for other members of the Eya family and provides a framework for understanding the role of Eya phosphatase mutations in disease. [ABSTRACT FROM AUTHOR]

The receptor-type protein tyrosine phosphatases (RPTPs) have been linked to signal transduction, cell adhesion, and neurite extension. PTPRT/RPTPρ is exclusively expressed in the central nervous system and regulates synapse formation by interacting with cell adhesion molecules and Fyn protein tyrosine kinase. Overexpression of PTPRT in cultured neurons increased the number of excitatory and inhibitory synapses by recruiting neuroligins that interact with PTPRT through their ecto-domains. In contrast, knockdown of PTPRT inhibited synapse formation and withered dendrites. Incubation of cultured neurons with recombinant proteins containing the extracellular region of PTPRT reduced the number of synapses by inhibiting the interaction between ecto-domains. Synapse formation by PTPRT was inhibited by phosphorylation of tyrosine 912 within the membrane–proximal catalytic domain of PTPRT by Fyn. This tyrosine phosphorylation reduced phosphatase activity of PTPRT and reinforced homophilic interactions of PTPRT, thereby preventing the heterophilic interaction between PTPRT and neuroligins. These results suggest that brain-specific PTPRT regulates synapse formation through interaction with cell adhesion molecules, and this function and the phosphatase activity are attenuated through tyrosine phosphorylation by the synaptic tyrosine kinase Fyn. [ABSTRACT FROM AUTHOR]

Sequential sensing algorithms are developed for OFDM-based hierarchical cognitive radio (CR) systems. Secondary users sense multiple subbands simultaneously for possible spectrum availabilities under hard misdetection constraints to prevent interference to the primary users. Accounting for the fact that the sensing time overhead can often be significant, a novel performance metric is introduced based on the effective achievable data rate. An optimization problem is formulated in the framework of optimal stopping problems to maximize the average effective data rate by determining the best time to stop taking samples and proceed to data transmission. A basis expansion-based suboptimal algorithm is developed to reduce the prohibitive complexity of the optimal solution. The numerical results presented verify the efficacy of the proposed approach. [ABSTRACT FROM AUTHOR]

We consider an optimal resource allocation strategy for cooperative relaying-enabled OFDMA multi-hop wireless networks. A cross-layer optimization problem is formulated that maximizes the balanced end-to-end throughput under the routing and the PHY/MAC constraints. A dual method is employed to solve the problem efficiently and optimally. A cooperative relaying technique is incorporated into the framework by introducing virtual links and nodes. Half-duplex operation of the radios is assumed, and mutual interference between the links is explicitly modeled to allow maximal spatial reuse of the spectral resources. Numerical results are provided to demonstrate how the bottleneck phenomenon typical in multi-hop networks can be alleviated by the proposed technique to yield significant improvement in the throughput. [ABSTRACT FROM PUBLISHER]

A cross-layer design approach is considered for joint routing and resource allocation for the physical (PHY) and the medium access control (MAC) layers in multihop wireless backhaul networks. The access points (APs) are assumed to be equipped with multiple antennas capable of both transmit and receive beamforming. A nonlinear optimization problem is formulated, which maximizes the fair throughput of the APs in the network under the routing and the PHY/MAC constraints. Dual decomposition is employed to decouple the odginal problem into smaller subproblems in different layers, which are coordinated by the dual prices. The network layer subproblem can be solved in a distributed manner and the PHY layer subproblem in a semidistributed manner. To solve the PHY layer subproblem, an iterative minimum mean square error (IMMSE) algorithm is used with the target link signal-to-interference-and-noiseratio (SINR) set dynamically based on the price generated from the upper layers. A scheduling heuristic is also developed, which improves the choice of the transmission sets over time. Simulation results illustrate the efficacy of the proposed cross-layer design. [ABSTRACT FROM AUTHOR]

Abstract  The multi-input multi-output (MIMO) communication framework is adopted for wireless sensor networks by having multiple sensors equipped with single-element antennas cooperate in transmission. A power method-based iterative algorithm is developed that computes the optimal transmit and receive eigen-filters distributively among the sensors while transferring most of the computational burden to the central collector node. Since the proposed algorithm implicitly exploits the channel state information (CSI) both at the receiver and the transmitter, it is expected that the resulting spectral efficiency is higher than what can be achieved by receive CSI-only space-time coding. This intuition is confirmed by employing a variable-rate adaptive modulation scheme for the eigen-transmission and comparing its spectral efficiency with that of orthogonal space time block codes (OSTBCs) at specific target bit error rates. The performance is also evaluated using realistic channel estimation as well as the least mean square (LMS) and recursive least square (RLS) algorithms for iterative eigencoding. [ABSTRACT FROM AUTHOR]

The humanized monoclonal antibody HzKR127 recognizes the preS1 domain of the human hepatitis B virus surface proteins with a broadly neutralizing activity in vivo. We present the crystal structures of HzKR127 Fab and its complex with a major epitope peptide. In the complex structure, the bound peptide forms a type IV β-turn followed by 310 helical turn, the looped-out conformation of which provides a structural basis for broad neutralization. Upon peptide binding, the antibody undergoes a dramatic complementarity determining region H3 lid opening. To understand the structural implication of the virus neutralization, we carried out comprehensive alanine-scanning mutagenesis of all complementarity determining region residues in HzKR127 Fab. The functional mapping of the antigen-combining site demonstrates the specific roles of major binding determinants in antigen binding, contributing to the rational design for maximal humanization and affinity maturation of the antibody. [ABSTRACT FROM AUTHOR]

Multi-hop wireless backhual networks are emerging as a cost-effective solution to provide ubiquitous and broadband access to meet the rapidly increasing demands of multimedia applications. In this paper, we consider the joint optimal design of routing, medium access control (MAC) scheduling and physical layer resource allocation for such networks, where beamforming antenna arrays are equipped at the physical layer. The notion of transmission set (TS) is introduced to separate the physical layer operations from those at the upper layers; and a column generation approach is employed to efficiently identify the TSs. We then apply the dual decomposition method to decouple the routing and scheduling subproblems, which are performed at different layers and are coordinated by a pricing mechanism to achieve the optimal overall system objective. To efficiently support multimedia traffic, an admission control criterion is considered for the system objective. The performance of the proposed scheme is verified by simulation results, and the impact of the physical layer capabilities on the network performance is evaluated. We also discuss the implementation issues of the cross-layer scheme based on the IEEE 802.16 mesh mode. [ABSTRACT FROM AUTHOR]