A non-interleaving process calculus for multi-party synchronisation

We introduce the wire calculus. Its dynamic features are inspired by Milner's CCS: a unary prefix operation, binary choice and a standard recursion construct. Instead of an interleaving parallel composition operator there are operators for synchronisation along a common boundary and non-communicating parallel composition. The (operational) semantics is a labelled transition system obtained with SOS rules. Bisimilarity is a congruence with respect to the operators of the language. Quotienting terms by bisimilarity results in a compact closed category

Varying numbers of players in small-sided soccer games modifies action opportunities during training

This study examined the effects of the numbers of players involved in small-sided team games (underloading and overloading) on opportunities for maintaining ball possession, shooting at goal and passing to teammates during training. These practice constraint manipulations were assumed to alter values of key performance variables identified in previous research, such as interpersonal distances between players and time to intercept shots and passes. Fifteen male soccer players (age: 19.60±1.99 years) were grouped into three teams and played against each other in different versions of small-sided soccer games, in which the number of players was manipulated in three different conditions: 5 vs. 5, 5 vs. 4 and 5 vs. 3. Dependent variables were the values of interpersonal distance between an outfield attacker and nearest defender (ID), and the relative distance of a defender needed to intercept the trajectory of a shot (RDishot) or pass (RDipass). Statistical analyses revealed that mean ID values were significantly lower in 5 vs. 5 than in 5 vs. 4 and 5 vs. 3 conditions, and significantly lower in 5 vs. 4 than 5 vs. 3. They also revealed that mean values of RDishot were significantly higher in 5 vs. 3 than in 5 vs. 5 conditions. Finally, results showed that the mean values of RDipass were significantly higher in 5 vs. 3 than in 5 vs. 5. Findings revealed how task constraints in SSGs can be manipulated to vary values of key spatial and temporal performance variables (interpersonal distance and time to intercept) to influence the nature of interpersonal interactions between competing players during practice. We observed that these manipulations tended to decrease opportunities for maintaining ball possession during training when equal numbers of attackers and defenders existed in SSGs, and led to more shots and passes emerging when the number of defenders was decreased relative to attackers

Principal maize viruses in Mediterranean countries

Maize plants with virus-like symptoms were sampled in fields in Greece, Yugoslavia and Italy in 1994. Disease incidence (%) and disease severity (1-6) were assessed. Leaf samples were tested by enzyme-linked immunosorbent assay (ELISA) and electroblot immunoassay (EBIA). Antisera against maize dwarf mosaic virus (MDMV), sugarcane mosaic virus (SCMV) and barley yellow dwarf viruses (BYDVs) (PAV- and RPV-like) were used in these tests. A higher disease incidence occurred in Italy and Greece than in Yugoslavia. MDMV was proved by both ELISA and EBIA in all maize genotypes in Greece, Yugoslavia and Italy. None of the samples reacted with SCMV antibodies. A total of 13.7 and 11% of individual Greek samples were positive for PAV- and RPV- respectively, while, 17.5 and 5% of Yugoslav samples were positive for PAV- and RPV- respectively. Phragmites sp, a perennial maize weed, was also positive for PAV- and RPV- by ELISA

Nanofabrication technologies: high-throughput for tomorrow's metadevices

Fabrication fundamentals1. Serial versus parallel? Most are currently fabricated by serial writing….2. Additive or subtractive?3. Feature size required.4. One-off demonstration (journal paper) or volume production (in the shops by next Christmas…)5. What material?6. Cost….(+ normalise to 150mm diameter wafer)7. Time to fabricat

Front-line paclitaxel and irinotecan combination chemotherapy in advanced non-small-cell lung cancer: a phase I–II trial

Our purpose was to determine the efficacy of irinotecan plus paclitaxel administered on day 1, repeated every 2 weeks, in untreated patients with advanced or metastatic non-small-cell lung cancer (NSCLC). In total, 56 patients with inoperable or metastatic stage III and IV NSCLC with a histologically or cytologically confirmed diagnosis were enrolled. None of the patients had undergone prior chemotherapy or radiation therapy. Treatment involved irinotecan 125 mg m−2 and paclitaxel 135 mg m−2 administered on day 1 and repeated every 2 weeks for a planned number of nine cycles. With a standard dose of paclitaxel at 135 mg m−2, the dosage of irinotecan was escalated at four levels: 75, 100, 125 and 150 mg m−2; 125 mg m−2 was established as the maximum tolerated dose; this dosage was administered to 46 patients. A total of 52 patients (median age 65 years, range 38–77 years) were assessable for toxicity and survival and 46 for response rate. Out of 46 evaluable patients, 19 achieved partial response (41.3%), 17 had stable disease (37%) and 10 (21.7%) experienced disease progression. The median duration of response was 6 months (range 2–9+ months). The main adverse reactions were myelotoxicity (grades 3 and 4) in 10 (19.2%) patients and diarrhoea (grade 3) in four (7.7%) patients. Irinotecan combined with paclitaxel, administered every 2 weeks, appears to be an effective treatment for advanced-stage NSCLC

Development of SYK NanoBRET cellular target engagement assays for gain–of–function variants

Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase that is activated by phosphorylation events downstream of FcR, B-cell and T-cell receptors, integrins, and C-type lectin receptors. When the tandem Src homology 2 (SH2) domains of SYK bind to phosphorylated immunoreceptor tyrosine-based activation motifs (pITAMs) contained within these immunoreceptors, or when SYK is phosphorylated in interdomain regions A and B, SYK is activated. SYK gain-of-function (GoF) variants were previously identified in six patients that had higher levels of phosphorylated SYK and phosphorylated downstream proteins JNK and ERK. Furthermore, the increased SYK activation resulted in the clinical manifestation of immune dysregulation, organ inflammation, and a predisposition for lymphoma. The knowledge that the SYK GoF variants have enhanced activity was leveraged to develop a SYK NanoBRET cellular target engagement assay in intact live cells with constructs for the SYK GoF variants. Herein, we developed a potent SYK-targeted NanoBRET tracer using a SYK donated chemical probe, MRL-SYKi, that enabled a NanoBRET cellular target engagement assay for SYK GoF variants, SYK(S550Y), SYK(S550F), and SYK(P342T). We determined that ATP-competitive SYK inhibitors bind potently to these SYK variants in intact live cells. Additionally, we demonstrated that MRL-SYKi can effectively reduce the catalytic activity of SYK variants, and the phosphorylation levels of SYK(S550Y) in an epithelial cell line (SW480) stably expressing SYK(S550Y)

Parameterized Synthesis with Safety Properties

Parameterized synthesis offers a solution to the problem of constructing correct and verified controllers for parameterized systems. Such systems occur naturally in practice (e.g., in the form of distributed protocols where the amount of processes is often unknown at design time and the protocol must work regardless of the number of processes). In this paper, we present a novel learning based approach to the synthesis of reactive controllers for parameterized systems from safety specifications. We use the framework of regular model checking to model the synthesis problem as an infinite-duration two-player game and show how one can utilize Angluin's well-known L* algorithm to learn correct-by-design controllers. This approach results in a synthesis procedure that is conceptually simpler than existing synthesis methods with a completeness guarantee, whenever a winning strategy can be expressed by a regular set. We have implemented our algorithm in a tool called L*-PSynth and have demonstrated its performance on a range of benchmarks, including robotic motion planning and distributed protocols. Despite the simplicity of L*-PSynth it competes well against (and in many cases even outperforms) the state-of-the-art tools for synthesizing parameterized systems.Comment: 18 page

Discovery of FERM domain protein-protein interaction inhibitors for MSN and CD44 as a potential therapeutic approach for Alzheimer\u27s disease.

Proteomic studies have identified moesin (MSN), a protein containing a four-point-one, ezrin, radixin, moesin (FERM) domain, and the receptor CD44 as hub proteins found within a coexpression module strongly linked to Alzheimer\u27s disease (AD) traits and microglia. These proteins are more abundant in Alzheimer\u27s patient brains, and their levels are positively correlated with cognitive decline, amyloid plaque deposition, and neurofibrillary tangle burden. The MSN FERM domain interacts with the phospholipid phosphatidylinositol 4,5-bisphosphate (PI

Novel Role of Phosphorylation-Dependent Interaction between FtsZ and FipA in Mycobacterial Cell Division

The bacterial divisome is a multiprotein complex. Specific protein-protein interactions specify whether cell division occurs optimally, or whether division is arrested. Little is known about these protein-protein interactions and their regulation in mycobacteria. We have investigated the interrelationship between the products of the Mycobacterium tuberculosis gene cluster Rv0014c-Rv0019c, namely PknA (encoded by Rv0014c) and FtsZ-interacting protein A, FipA (encoded by Rv0019c) and the products of the division cell wall (dcw) cluster, namely FtsZ and FtsQ. M. smegmatis strains depleted in components of the two gene clusters have been complemented with orthologs of the respective genes of M. tuberculosis. Here we identify FipA as an interacting partner of FtsZ and FtsQ and establish that PknA-dependent phosphorylation of FipA on T77 and FtsZ on T343 is required for cell division under oxidative stress. A fipA knockout strain of M. smegmatis is less capable of withstanding oxidative stress than the wild type and showed elongation of cells due to a defect in septum formation. Localization of FtsQ, FtsZ and FipA at mid-cell was also compromised. Growth and survival defects under oxidative stress could be functionally complemented by fipA of M. tuberculosis but not its T77A mutant. Merodiploid strains of M. smegmatis expressing the FtsZ(T343A) showed inhibition of FtsZ-FipA interaction and Z ring formation under oxidative stress. Knockdown of FipA led to elongation of M. tuberculosis cells grown in macrophages and reduced intramacrophage growth. These data reveal a novel role of phosphorylation-dependent protein-protein interactions involving FipA, in the sustenance of mycobacterial cell division under oxidative stress