Ultrasonographic semiology of biliary prostheses

Pigeon hemoglobin has eight reactive sulphydryl groups per (tetramer) molecule, as determined by Boyer titration with p-chloromercuribenzoate. However, only four of these are titratable with 5,5'-dithiobis(2-nitrobenzoate) under the same experimental conditions. The time course of the reaction of pigeon hemoglobin with 5,5'-dithiobis(2-nitrobenzoate) is biphasic. In the pH range 6-9, the fast phase is between one and two orders of magnitude faster than the slow phase. For the fast phase, kapp, the apparent second-order rate constant, increases monotonously with pH. Quantitative analysis reveals that the reaction of the sulphydryl group responsible for this phase is coupled to the ionization of two groups with pKa values of 6.15 +/- 0.1 and 8.5 +/- 0.1. These pKa values are assigned to HisHC3(146) beta and to the CysF9(93) beta sulphydryl group, respectively. For the slow phase the kapp vs. pH profiles are bowl-shaped. Analysis reveals that the reaction of the sulphydryl group to which this phase may be attributed is coupled to the ionization of two groups with mean pKa values of 6.53 +/- 0.1 and 8.25 +/- 0.1. Examination of the structure of hemoglobin allows us to assign these values to HisG19(117) beta and CysB5(23) beta, respectively. The CysB5(23) beta sulphydryl is in the region of the molecule where amino acid substitutions have been found to give rise to significant changes in the oxygen affinity of hemoglobin [Huang et al. (1990), Biochemistry 29, 7020-7023].     

The Role of TNF-α and Anti-TNF-α Agents during Preconception,Pregnancy, and Breastfeeding

Tumor necrosis factor-alpha (TNF-α) is a multifunctional Th1 cytokine and one of the most important inflammatory cytokines. In pregnancy, TNF-α influences hormone synthesis, placental architecture, and embryonic development. It was also shown that increased levels of TNF-α are associated with pregnancy loss and preeclampsia. Increased TNF-α levels in complicated pregnancy draw attention to trophoblast biology, especially migratory activity, syncytialisation, and endocrine function. Additionally, elevated TNF-α levels may affect the maternal-fetal relationship by altering the secretory profile of placental immunomodulatory factors, which in turn affects maternal immune cells. There is growing evidence that metabolic/pro-inflammatory cytokines can program early placental functions and growth in the first trimester of pregnancy. Furthermore, early pregnancy placenta has a direct impact on fetal development and maternal immune system diseases that release inflammatory (e.g., TNF-α) and immunomodulatory factors, such as chronic inflammatory rheumatic, gastroenterological, or dermatological diseases, and may result in an abnormal release of cytokines and chemokines in syncytiotrophoblasts. Pregnancy poses a challenge in the treatment of chronic disease in patients who plan to have children. The activity of the disease, the impact of pregnancy on the course of the disease, and the safety of pharmacotherapy, including anti-rheumatic agents, in pregnancy should be considered.     

The Potential Role of Small-Molecule PERK Inhibitor LDN-0060609 in Primary Open-Angle Glaucoma Treatment

Primary open-angle glaucoma (POAG) constitutes the most common type of glaucoma. Emerging evidence suggests that Endoplasmic Reticulum (ER) stress and the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-mediated Unfolded Protein Response (UPR) signaling pathway play a key role in POAG pathogenesis. Thus, the main aim of the study was to evaluate the effectiveness of the PERK inhibitor LDN-0060609 in cellular model of glaucoma using primary human trabecular meshwork (HTM) cells. To evaluate the level of the ER stress marker proteins, Western blotting and TaqMan gene expression assay were used. The cytotoxicity was measured by XTT, LDH assays and Giemsa staining, whereas genotoxicity via comet assay. Changes in cell morphology were assessed by phase-contrast microscopy. Analysis of apoptosis was performed by caspase-3 assay and flow cytometry (FC), whereas cell cycle progression by FC. The results obtained have demonstrated that LDN-0060609 triggered a significant decrease of ER stress marker proteins within HTM cells with induced ER stress conditions. Moreover, LDN-0060609 effectively increased viability, reduced DNA damage, increased proliferation, restored normal morphology, reduced apoptosis and restored normal cell cycle distribution of HTM cells with induced ER stress conditions. Thereby, PERK inhibitors, such as LDN-0060609, may provide an innovative, ground-breaking treatment strategy against POAG.     

Maximum throughput of multiple access channels in adversarial environments

We consider deterministic distributed broadcasting on multiple access channels in the framework of adversarial queuing. Packets are injected dynamically by an adversary that is constrained by the injection rate and the number of packets that may be injected simultaneously; the latter we call burstiness. A protocol is stable when the number of packets in queues at the stations stays bounded. The maximum injection rate that a protocol can handle in a stable manner is called the throughput of the protocol. We consider adversaries of injection rate 1, that is, of one packet per round, to address the question if the maximum throughput 1 can be achieved, and if so then with what quality of service. We develop a protocol that achieves throughput 1 for any number of stations against leaky-bucket adversaries. The protocol has O(n²+\textburstiness){\mathcal{O}(n^2+\text{burstiness})} packets queued simultaneously at any time, where n is the number of stations; this upper bound is proved to be best possible. A protocol is called fair when each packet is eventually broadcast. We show that no protocol can be both stable and fair for a system of at least two stations against leaky-bucket adversaries. We study in detail small systems of exactly two and three stations against window adversaries to exhibit differences in quality of broadcast among classes of protocols. A protocol is said to have fair latency if the waiting time of packets is O(\textburstiness){\mathcal{O}(\text{burstiness})}. For two stations, we show that fair latency can be achieved by a full sensing protocol, while there is no stable acknowledgment based protocol. For three stations, we show that fair latency can be achieved by a general protocol, while no full sensing protocol can be stable. Finally, we show that protocols that either are fair or do not have the queue sizes affect the order of transmissions cannot be stable in systems of at least four stations against window adversaries.     

The between-day and inter-rater reliability of a novel wireless system to analyse lumbar spine posture

Lumbar posture is commonly assessed in non-specific chronic low back pain (NSCLBP), although quantitative measures have mostly been limited to laboratory environments. The BodyGuard? is a spinal position monitoring device that can monitor posture in real time, both inside and outside the laboratory. The reliability of this wireless device was examined in 18 healthy participants during usual sitting and forward bending, two tasks that are commonly provocative in NSCLBP. Reliability was determined using intraclass correlation coefficients (ICC), the standard error of measurement (SEM), the mean difference and the minimal detectable change (MDC90). Between-day ICC values ranged from 0.84 to 0.87, with small SEM (5%), mean difference (<9%) and MDC90 (<14%) values. Inter-rater ICC values ranged from 0.91 to 0.94, with small SEM (4%), mean difference (6%) and MDC90 (9%) values. Between-day and inter-rater reliability are essential requirements for clinical utility and were excellent in this study. Further studies into the validity of this device and its application in clinical trials in occupational settings are required. STATEMENT OF RELEVANCE: A novel device that can analyse spinal posture exposure in occupational settings in a minimally invasive manner has been developed. This study established that the device has excellent between-day and inter-rater reliability in healthy pain-free subjects. Further studies in people with low back pain are planned.     

Optimal Deterministic Broadcasting in Known Topology Radio Networks

We consider deterministic broadcasting in radio networks whose nodes have full topological information about the network. The aim is to design a polynomial algorithm, which, given a graph G with source s, produces a fast broadcast scheme in the radio network represented by G. The problem of finding a fastest broadcast scheme for a given graph is NP-hard, hence it is only possible to get an approximation algorithm. We give a deterministic polynomial algorithm which produces a broadcast scheme of length , for every n-node graph of diameter D, thus improving a result of Gąsieniec et al. (PODC 2005) [17] and solving a problem stated there. Unless the inclusion NP BPTIME( holds, the length of a polynomially constructible deterministic broadcast scheme is optimal.A preliminary version of this paper (with a weaker result) appeared in the Proc. 7th International Workshop on Approximation Algorithms for Combinatorial Optimization Problems (APPROX’2004), August 2004, Harvard University, Cambridge, USA, LNCS 3122, 171–182. Research of the second author supported in part by NSERC discovery grant and by the Research Chair in Distributed Computing of the Université du Québec en Outaouais. Part of this work was done during the second author’s visit at the Max-Planck-Institut für Informatik.     

An efficient algorithm for finding ideal schedules

We study the problem of scheduling unit execution time jobs with release dates and precedence constraints on two identical processors. We say that a schedule is ideal if it minimizes both maximum and total completion time simultaneously. We give an instance of the problem where the min-max completion time is exceeded in every preemptive schedule that minimizes total completion time for that instance, even if the precedence constraints form an intree. This proves that ideal schedules do not exist in general when preemptions are allowed. On the other hand, we prove that, when preemptions are not allowed, then ideal schedules do exist for general precedence constraints, and we provide an algorithm for finding ideal schedules in O(n ³) time, where n is the number of jobs. In finding such ideal schedules we resolve a conjecture of Baptiste and Timkovsky (Math. Methods Oper. Res. 60(1):145–153, 2004) Further, our algorithm for finding min-max completion-time schedules requires only O(n ³) time, while the most efficient solution to date has required O(n ⁹) time.     

Agent-based guided local search

The main contribution of the paper is to propose and validate a new hybrid approach for solving combinatorial optimization problems in which guided local search metaheuristic is incorporated into a cooperative multi-agent framework based on the concept of asynchronous teams (A-Teams). Generally, an A-Team assumes that a collection of software agents, each representing a particular problem solving method, cooperate to solve a problem by dynamically evolving a population of solutions. In the suggested implementation each software agent carries out a guided local search. The proposed approach has been extensively validated experimentally on one of the best known combinatorial optimization problem – the vehicle routing problem. The promising results of experiments have confirmed the effectiveness of the suggested approach.     

The Histamine H4 Receptor Participates in the Neuropathic Pain-Relieving Activity of the Histamine H3 Receptor Antagonist GSK189254

Growing evidence points to the histamine system as a promising target for the management of neuropathic pain. Preclinical studies reported the efficacy of H₃R antagonists in reducing pain hypersensitivity in models of neuropathic pain through an increase of histamine release within the CNS. Recently, a promising efficacy of H₄R agonists as anti-neuropathic agents has been postulated. Since H₃R and H₄R are both localized in neuronal areas devoted to pain processing, the aim of the study is to investigate the role of H₄R in the mechanism of anti-hyperalgesic action of the H₃R antagonist GSK189254 in the spared nerve injury (SNI) model in mice. Oral (6 mg/kg), intrathecal (6 µg/mouse), or intra locus coeruleus (LC) (10 µg/µL) administration of GSK189254 reversed mechanical and thermal allodynia in the ipsilateral side of SNI mice. This effect was completely prevented by pretreatment with the H₄R antagonist JNJ 10191584 (6 µg/mouse i.t.; (10 µg/µL intraLC). Furthermore, GSK189254 was devoid of any anti-hyperalgesic effect in H₄R deficient mice, compared with wild type mice. Conversely, pretreatment with JNJ 10191584 was not able to prevent the hypophagic activity of GSK189254. In conclusion, we demonstrated the selective contribution of H₄R to the H₃R antagonist-induced attenuation of hypernociceptive behavior in SNI mice. These results might help identify innovative therapeutic interventions for neuropathic pain.