Hypercube orientations with only two in-degrees

We consider the problem of orienting the edges of the n-dimensional hypercube so only two different in-degrees a and b occur. We show that this can be done, for two specified in-degrees, if and only if obvious necessary conditions hold. Namely, we need 0?a,b?n and also there exist non-negative integers s and t so that s+t=n² and as+bt=n²n−1. This is connected to a question arising from constructing a strategy for a “hat puzzle”.     

基于统一价格拍卖的初始排污权分配方法

针对初始排污权总量分配的实际问题,基于统一价格拍卖的思想提出了一种具有激励性的可变总量的分配方法,分别给出了排污企业对称和排污企业非对称两种情形下的线性均衡报价策略,并证明了该方法的可行性和有效性,从而为建设排污权分配和交易制度提供了理论依据和方法参考.     

Proteomic Insights into Cardiac Fibrosis: From Pathophysiological Mechanisms to Therapeutic Opportunities

Cardiac fibrosis is a common pathophysiologic process in nearly all forms of heart disease which refers to excessive deposition of extracellular matrix proteins by cardiac fibroblasts. Activated fibroblasts are the central cellular effectors in cardiac fibrosis, and fibrotic remodelling can cause several cardiac dysfunctions either by reducing the ejection fraction due to a stiffened myocardial matrix, or by impairing electric conductance. Recently, there is a rising focus on the proteomic studies of cardiac fibrosis for pathogenesis elucidation and potential biomarker mining. This paper summarizes the current knowledge of molecular mechanisms underlying cardiac fibrosis, discusses the potential of imaging and circulating biomarkers available to recognize different phenotypes of this lesion, reviews the currently available and potential future therapies that allow individualized management in reversing progressive fibrosis, as well as the recent progress on proteomic studies of cardiac fibrosis. Proteomic approaches using clinical specimens and animal models can provide the ability to track pathological changes and new insights into the mechanisms underlining cardiac fibrosis. Furthermore, spatial and cell-type resolved quantitative proteomic analysis may also serve as a minimally invasive method for diagnosing cardiac fibrosis and allowing for the initiation of prophylactic treatment.     

A Rapid Therapeutic Drug Monitoring Strategy of Carbamazepine in Serum by Using Coffee-Ring Effect Assisted Surface-Enhanced Raman Spectroscopy

Carbamazepine (CBZ) has a narrow therapeutic concentration range, and therapeutic drug monitoring (TDM) is necessary for its safe and effective individualized medication. This study aims to develop a procedure for CBZ detection in serum using coffee-ring effect assisted surface-enhanced Raman spectroscopy (SERS). Silver nanoparticles deposited onto silicon wafers were used as the SERS-active material. Surface treatment optimization of the silicon wafers and the liquid–liquid extraction method were conducted to eliminate the influence of impurities on the silicon wafer surface and the protein matrix. The proposed detection procedure allows for the fast determination of CBZ in artificially spiked serum samples within a concentration range of 2.5–40 μg·mL⁻¹, which matches the range of the drug concentrations in the serum after oral medication. The limit of detection for CBZ was found to be 0.01 μg·mL⁻¹. The developed method allowed CBZ and its metabolites to be ultimately distinguished from real serum samples. The developed method is anticipated to be a potential tool for monitoring other drug concentrations.     

Therapeutic Versus Preventative Use of Ginkgo biloba Extract (EGb 761) against Indomethacin-Induced Gastric Ulcer in Mice

The main bioactive constituents in the standardized Ginkgo biloba leaf extract (EGb 761) are the terpene lactones and flavonoid glycosides. EGb 761’s antioxidant and anti-inflammatory properties have previously been demonstrated. Indomethacin-induced gastric ulcers have a multifactorial etiology and represent a major restriction to its therapeutic utility. The underlying ulcerogenic process involves oxidative and inflammatory biomolecular insults. This study was performed to explore the curative and preventative benefits of EGb 761 in experimentally-induced ulcers. To develop gastric ulcers in mice, indomethacin (40 mg/kg) was administered orally. EGb 761 (200 mg/kg) was given by gavage for 7 days before (preventative) and after (therapeutic) indomethacin administration. The histological alterations and macroscopic mucosal lesions were assessed. In gastric tissue homogenates, malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), and inflammatory cytokines were measured. The expressions of cyclooxygenase-2 (COX-2), cytokines, and proliferating cell nuclear antigen (PCNA) in the stomach mucosa were also investigated. The ulcer index, histological alterations, gastric oxidants, and inflammatory biomarkers were all significantly increased by indomethacin. In stomach specimens, it increased COX-2 and PCNA expression. EGb 761 treatments, both prophylactic and therapeutic, resulted in significant reductions in ulcer lesions, nitrosative and oxidative damage, and inflammatory markers, along with the lowering of COX-2 and PCNA expressions. Furthermore, in the fight against stomach ulcers, EGb 761 treatment was found to be more efficient than prevention.     

Development and Validation of a UHPLC–MS/MS-Based Method to Quantify Cenobamate in Human Plasma Samples

Cenobamate (CNB) is the newest antiseizure medication (ASM) approved by the FDA in 2019 to reduce uncontrolled partial-onset seizures in adult patients. Marketed as Xcopri in the USA or Ontozry in the EU (tablets), its mechanism of action has not been fully understood yet; however, it is known that it inhibits voltage-gated sodium channels and positively modulates the aminobutyric acid (GABA) ion channel. CNB shows 88% of oral bioavailability and is responsible for modifying the plasma concentrations of other co-administered ASMs, such as lamotrigine, carbamazepine, phenytoin, phenobarbital and the active metabolite of clobazam. It also interferes with CYP2B6 and CYP3A substrates. Nowadays, few methods are reported in the literature to quantify CNB in human plasma. The aim of this study was to develop and validate, according to the most recent guidelines, an analytical method using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS) to evaluate CNB dosage in plasma samples. Furthermore, we provided a preliminary clinical application of our methodology by evaluating the pharmacokinetic parameters of CNB in two non-adult patients. Plasma levels were monitored for two months. Preliminary data showed a linear increase in plasma CNB concentrations, in both patients, in agreement with the increase in CNB dosage. A seizure-free state was reported for both patients at the dose of 150 mg per day.     

Pharmacological and Therapeutic Potential of Myristicin: A Literature Review

Natural products have been used by humanity for many centuries to treat various illnesses and with the advancement of technology, it became possible to isolate the substances responsible for the beneficial effects of these products, as well as to understand their mechanisms. In this context, myristicin, a substance of natural origin, has shown several promising activities in a large number of in vitro and in vivo studies carried out. This molecule is found in plants such as nutmeg, parsley, carrots, peppers, and several species endemic to the Asian continent. The purpose of this review article is to discuss data published in the last 10 years at Pubmed, Lilacs and Scielo databases, reporting beneficial effects, toxicity and promising data of myristicin for its future use in medicine. From 94 articles found in the literature, 68 were included. Exclusion criteria took into account articles whose tested extracts did not have myristicin as one of the major compounds.     

Dynamic routing in open queueing networks: Brownian models,cut constraints and resource pooling

We present an introductory review of recent work on the control of open queueing networks. We assume that customers of different types arrive at a network and pass through the system via one of several possible routes; the set of routes available to a customer depends on its type. A route through the network is an ordered set of service stations: a customer queues for service at each station on its route and then leaves the system. The two methods of control we consider are the routing of customers through the network, and the sequencing of service at the stations, and our aim is to minimize the number of customers in the system. We concentrate especially on the insights which can be obtained from heavy traffic analysis, and in particular from Harrison's Brownian network models. Our main conclusion is that in many respects dynamic routingsimplifies the behaviour of networks, and that under good control policies it may well be possible to model the aggregate behaviour of a network quite straightforwardly.Supported by SERC grant GR/F 94194.     

Markov games with incomplete information

We consider zero-sum Markov games with incomplete information. Here, the second player is never informed about the current state of the underlying Markov chain. The existence of a value and of optimal strategies for both players is shown. In particular, we present finite algorithms for computing optimal strategies for the informed and uninformed player. The algorithms are based on linear programming results.     

On a student-related optimal control problem

In a recent paper (Ref. 1), Cheng and Teo discussed some further extensions of a student-related optimal control problem which was originally proposed by Raggettet al. (Ref. 2) and later on modified by Parlar (Ref. 3). In this paper, we treat further extensions of the problem.This paper is a modified and improved version of Ref. 4. It is based, in part, on research sponsored by NSF.