Polylogarithmic Approximation Algorithm for k-Connected Directed Steiner Tree on Quasi-Bipartite Graphs

In the k-Connected Directed Steiner Tree problem (k-DST), we are given a directed graph G = (V,E) with edge (or vertex) costs, a root vertex r, a set of q terminals T, and a connectivity requirement k > 0; the goal is to find a minimum-cost subgraph H of G such that H has k edge-disjoint paths from the root r to each terminal in T. The k-DST problem is a natural generalization of the classical Directed Steiner Tree problem (DST) in the fault-tolerant setting in which the solution subgraph is required to have an r,t-path, for every terminal t, even after removing k-1 vertices or edges. Despite being a classical problem, there are not many positive results on the problem, especially for the case k ? 3. In this paper, we present an O(log k log q)-approximation algorithm for k-DST when an input graph is quasi-bipartite, i.e., when there is no edge joining two non-terminal vertices. To the best of our knowledge, our algorithm is the only known non-trivial approximation algorithm for k-DST, for k ? 3, that runs in polynomial-time Our algorithm is tight for every constant k, due to the hardness result inherited from the Set Cover problem

以坡地土壤厚度及垂直結構探討淺層崩塌潛勢區位

The factors related to shallow slope failures include soil depth, vertical soil structure, and bedrock topography. In this study, we surveyed spatial variations of soil depth and vertical soil structure by conducting simplified penetration tests, and then estimated bedrock topography in a newly-planted hillslope. We analyze the ability of these three factors to detect potential slope failure locations (PSFL) on the basis of information from a shallow slope failure which occurred at the study site during the survey period. The results show that soil depth varies spatially on the hillslope. However, there are no obvious correlations between soil depth and any topographic factor. This finding differs from the results suggesting an inverse correlation between soil depth and slope in some previous studies. Comparing the three factors, the area of PSFL determined by soil depth is the smallest. This implies that soil depth plays an important role in predicting the potential of a shallow slope failure. According to information about vertical soil structure, we presume that vertical rainwater infiltration is impeded by local hard soil layers, rocks, and the soil-bedrock interface, and following increase of pore water pressure might trigger shallow slope failure. This indicates that vertical soil structure has implications for vertical soil water movement and PSFL. Consequently, we suggest that the spatial variations of soil depth and vertical soil structure should be carefully considered when assessing potential locations for shallow slope failures in Taiwan.判斷淺層崩塌潛勢的因子中，地表下不可視的土壤厚度、土壤垂直結構和基岩面地形等因子各別有不同的促崩機制和影響力。本研究利用簡易貫入試驗調查坡地的土壤垂直結構、土壤厚度及推估基岩面地形，瞭解這些因子的空間變異，並以樣區中發生的小崩塌為基礎探討各個因子對淺層崩塌潛勢區位的判釋能力。結果顯示土壤厚度具有空間變異，說明土壤厚度調查的重要性。在崩塌單一因子的分析中，以土壤厚度評估高崩塌潛勢區域 (PSFL) 所得的分布面積最小，且皆分布於崩塌位置附近，說明土壤厚度在崩塌潛勢的預測中佔有相當重要的角色。由崩塌地的貫入試驗和崩塌剖面觀察所得土壤垂直結構資訊，推測水分垂直移動受硬度較高的土壤層、塊石、基岩面阻擋，使得局部孔隙水壓上升進而引發淺層崩塌。這顯示土壤結構的影響力，也說明了相同的崩塌機制亦可能發生在具有同類土壤垂直結構的區域。根據本研究結果，建議就評估臺灣坡地水文過程及坡地穩定而言，應重視土壤厚度及土壤結構異質性在評估淺層崩塌潛勢區位的影響力

An increase in adenosine-5’-triphosphate (ATP) content in rostral ventrolateral medulla is engaged in the high fructose diet-induced hypertension

BACKGROUND: The increase in fructose ingestion has been linked to overdrive of sympathetic activity and hypertension associated with the metabolic syndrome. The premotor neurons for generation of sympathetic vasomotor activity reside in the rostral ventrolateral medulla (RVLM). Activation of RVLM results in sympathoexcitation and hypertension. Neurons in the central nervous system are able to utilize fructose as a carbon source of ATP production. We examined in this study whether fructose affects ATP content in RVLM and its significance in the increase in central sympathetic outflow and hypertension induced by the high fructose diet (HFD). RESULTS: In normotensive rats fed with high fructose diet (HFD) for 12 weeks, there was a significant increase in tissue ATP content in RVLM, accompanied by the increases in the sympathetic vasomotor activity and blood pressure. These changes were blunted by intracisternal infusion of an ATP synthase inhibitor, oligomycin, to the HFD-fed animals. In the catecholaminergic-containing N2a cells, fructose dose-dependently upregulated the expressions of glucose transporter 2 and 5 (GluT2, 5) and the rate-limiting enzyme of fructolysis, ketohexokinase (KHK), leading to the increases in pyruvate and ATP production, as well as the release of the neurotransmitter, dopamine. These cellular events were significantly prevented after the gene knocking down by lentiviral transfection of small hairpin RNA against KHK. CONCLUSION: These results suggest that increases in ATP content in RVLM may be engaged in the augmented sympathetic vasomotor activity and hypertension associated with the metabolic syndrome induced by the HFD. At cellular level, the increase in pyruvate levels via fructolysis is involved in the fructose-induced ATP production and the release of neurotransmitter

Toward Transparent Sequence Models with Model-Based Tree Markov Model

In this study, we address the interpretability issue in complex, black-box Machine Learning models applied to sequence data. We introduce the Model-Based tree Hidden Semi-Markov Model (MOB-HSMM), an inherently interpretable model aimed at detecting high mortality risk events and discovering hidden patterns associated with the mortality risk in Intensive Care Units (ICU). This model leverages knowledge distilled from Deep Neural Networks (DNN) to enhance predictive performance while offering clear explanations. Our experimental results indicate the improved performance of Model-Based trees (MOB trees) via employing LSTM for learning sequential patterns, which are then transferred to MOB trees. Integrating MOB trees with the Hidden Semi-Markov Model (HSMM) in the MOB-HSMM enables uncovering potential and explainable sequences using available information

Rewiring the Epigenetic Networks in MLL-Rearranged Leukemias: Epigenetic Dysregulation and Pharmacological Interventions

Leukemias driven by chromosomal translocation of the mixed-lineage leukemia gene (MLL or KMT2A) are highly prevalent in pediatric oncology. The poor survival rate and lack of an effective targeted therapy for patients with MLL-rearranged (MLL-r) leukemias emphasize an urgent need for improved knowledge and novel therapeutic approaches for these malignancies. The resulting chimeric products of MLL gene rearrangements, i.e., MLL-fusion proteins (MLL-FPs), are capable of transforming hematopoietic stem/progenitor cells (HSPCs) into leukemic blasts. The ability of MLL-FPs to reprogram HSPCs toward leukemia requires the involvement of multiple chromatin effectors, including the histone 3 lysine 79 methyltransferase DOT1L, the chromatin epigenetic reader BRD4, and the super elongation complex. These epigenetic regulators constitute a complicated network that dictates maintenance of the leukemia program, and therefore represent an important cluster of therapeutic opportunities. In this review, we will discuss the role of MLL and its fusion partners in normal HSPCs and hematopoiesis, including the links between chromatin effectors, epigenetic landscapes, and leukemia development, and summarize current approaches to therapeutic targeting of MLL-r leukemias

Influences of commuting mode, air conditioning mode and meteorological parameters on fine particle (PM2.5) exposure levels in traffic microenvironments

With the aim of determining the impacts of various factors on commuter exposure to fine particulate matter (PM2.5), a series of field studies were carried out to measure commuter exposure to PM2.5 on six major commuting modes (in-cabin mode: bus, taxi and metro; on-roadway mode: walking, bicycle and motorcycle) in a highly industrialized city in the Pearl River Delta, China. The results showed that the exposure level was greatly influenced by the commuter mode, with the on-roadway mode showing a higher PM2.5 concentration (76 μg/m3). An experiment with the taxi mode suggested that the use of air-conditioning can effectively reduce exposure levels in most cases (by at least 83%). Apart from traffic-related emissions, ambient PM2.5 concentration also had important impacts on exposure levels in most commuting modes, which was further ascertained by the seasonal variations in exposure levels and their significant correlations (p < 0.05) with meteorological parameters (temperature, relative humidity, wind speed and direction). The results of a General Linear Model analysis show that temperature, traffic mode and wind speed were significant factors that explained 27.3% of variability for the in-cabin mode, while relative humidity and wind speed were the significant determinants for the on-roadway mode, which contributed 14.1% of variability. In addition, wind direction was also an important determinant for both in-cabin and on-roadway modes. This study has some valuable implications that can help commuters to adopt appropriate travel behavior to reduce their personal exposure to such pollutants

Optimizing Vancomycin Dosing in Chronic Kidney Disease by Deriving and Implementing a Web-Based Tool Using a Population Pharmacokinetics Analysis.

Background: Chronic kidney disease (CKD) patients requiring intravenous vancomycin bear considerable risks of adverse outcomes both from the infection and vancomycin therapy itself, necessitating especially precise dosing to avoid sub- and supratherapeutic vancomycin exposure. Methods: In this retrospective study, we performed a population pharmacokinetic analysis to construct a vancomycin dose prediction model for CKD patients who do not require renal replacement therapy. The model was externally validated on an independent cohort of patients to assess its prediction accuracy. The pharmacokinetic parameter estimates and the equations were productized into a Web application (VancApp) subsequently implemented in routine care. The association between VancApp-based dosing and time-to-target concentration attainment, 30-day mortality, and nephrotoxicity were assessed postimplementation. Results: The model constructed from an initial cohort (n = 80) revealed a population clearance and volume of distribution of 1.30 L/h and 1.23 L/kg, respectively. External model validation (n = 112) demonstrated a mean absolute prediction error of 1.25 mg/L. Following 4 months of clinical implementation of VancApp as an optional alternative to usual care [VancApp (n = 22) vs. usual care (n = 21)], patients who had received VancApp-based dosing took a shorter time to reach target concentrations (median: 66 vs. 102 h, p = 0.187) and had fewer 30-day mortalities (14% vs. 24%, p = 0.457) compared to usual care. While statistical significance was not achieved, the clinical significance of these findings appear promising. Conclusion: Clinical implementation of a population pharmacokinetic model for vancomycin in CKD can potentially improve dosing precision in CKD and could serve as a practical means to improve vital clinical outcomes

Neuroparsin 1 (MrNP1) and Neuroparsin 2 (MrNP2) Are Involved in the Regulation of Vitellogenesis in the Shrimp Macrobrachium rosenbergii

Neuroparsins (NP) are small-size cysteine-rich neuropeptides first discovered in insects. They are known to be involved in insect reproduction. In this study, we have cloned two neuroparsin cDNAs (i.e., MrNP1 and MrNP2) from the freshwater shrimp Macrobrachium rosenbergii. The two neuroparsins consist of 12 cysteines, which is characteristic of the neuroparsin family. These cysteines are arranged in identical relative positions that form 6-disulfide bonds. MrNP1 and MrNP2 are most similar to the corresponding neuroparsin counterparts of the shrimp Macrobrachium nipponense. Phylogenetic study results suggested that MrNP1 and MrNP2 are closely related to MnNP1 and MnNP3, respectively. Also, an additional MrNP gene similar to MnNP2 is expected to exist in M. rosenbergii. The MrNP1 expression level is the highest in the ovary, and MrNP2 expression is higher in the brain and heart of the females. In addition, during the ovary maturation cycle, MrNP1 expression in the hepatopancreas is highest in stage V; in the ovary it is variable. MrNP2 expression in the hepatopancreas and ovary is the highest in stage II and stage I, respectively. In vivo and in vitro bioassay experiment results indicate that MrNP1 and MrNP2 recombinant proteins can stimulate the expression of the MrVg gene. In contrast, silencing of MrNP1 and MrNP2 genes would suppress MrVg, VgR, and CyclinB gene expressions. The results indicate that the products of both genes can stimulate vitellogenesis by up-regulating the MrVg gene expression. Results from their difference in expression patterns indicate that they might have different regulatory roles in vitellogenin synthesis. Since gene silencing of either MrNP1 or MrNP2 affected the expression of the other NP, we have hypothesized that coordinated regulatory action between MrNP1 and MrNP2 may be necessary for the normal vitellogenesis in M. rosenbergii

Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality:a systematic review

Objectives: to determine the effect of drugs with anti-cholinergic properties on relevant health outcomes.Design: electronic published and unpublished literature/trial registries were systematically reviewed. Studies evaluating medications with anti-cholinergic activity on cognitive function, delirium, physical function or mortality were eligible.Results: forty-six studies including 60,944 participants were included. Seventy-seven percent of included studies evaluating cognitive function (n = 33) reported a significant decline in cognitive ability with increasing anti-cholinergic load (P 0.05). Five of the eight included studies reported a decline in physical function in users of anti-cholinergics (P < 0.05). Three of nine studies evaluating mortality reported that the use of drugs with anti-cholinergic properties was associated with a trend towards increased mortality, but this was not statistically significant. The methodological quality of the evidence-base ranged from poor to very good.Conclusion: medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function, but limited evidence exists for delirium or mortality outcomes. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved