Regular spherical dust spacetimes

Physical (and weak) regularity conditions are used to determine and classify all the possible types of spherically symmetric dust spacetimes in general relativity. This work unifies and completes various earlier results. The junction conditions are described for general non-comoving (and non-null) surfaces, and the limits of kinematical quantities are given on all comoving surfaces where there is Darmois matching. We show that an inhomogeneous generalisation of the Kantowski-Sachs metric may be joined to the Lemaitre-Tolman-Bondi metric. All the possible spacetimes are explicitly divided into four groups according to topology, including a group in which the spatial sections have the topology of a 3-torus. The recollapse conjecture (for these spacetimes) follows naturally in this approach.Comment: Minor improvements, additional references. Accepted by GR

Differing predictive relationships between baseline LDL-C, systolic blood pressure, and cardiovascular outcomes

Funded by Pfizer

Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing:a population-based study

Background<p></p> Familial hypercholesterolaemia (FH) is a common Mendelian condition which, untreated, results in premature coronary heart disease. An estimated 88% of FH cases are undiagnosed in the UK. We previously validated a method for FH mutation detection in a lipid clinic population using next generation sequencing (NGS), but this did not address the challenge of identifying index cases in primary care where most undiagnosed patients receive healthcare. Here, we evaluate the targeted use of NGS as a potential route to diagnosis of FH in a primary care population subset selected for hypercholesterolaemia.<p></p> Methods<p></p> We used microfluidics-based PCR amplification coupled with NGS and multiplex ligation-dependent probe amplification (MLPA) to detect mutations in LDLR, APOB and PCSK9 in three phenotypic groups within the Generation Scotland: Scottish Family Health Study including 193 individuals with high total cholesterol, 232 with moderately high total cholesterol despite cholesterol-lowering therapy, and 192 normocholesterolaemic controls.<p></p> Results<p></p> Pathogenic mutations were found in 2.1% of hypercholesterolaemic individuals, in 2.2% of subjects on cholesterol-lowering therapy and in 42% of their available first-degree relatives. In addition, variants of uncertain clinical significance (VUCS) were detected in 1.4% of the hypercholesterolaemic and cholesterol-lowering therapy groups. No pathogenic variants or VUCS were detected in controls.<p></p> Conclusions<p></p> We demonstrated that population-based genetic testing using these protocols is able to deliver definitive molecular diagnoses of FH in individuals with high cholesterol or on cholesterol-lowering therapy. The lower cost and labour associated with NGS-based testing may increase the attractiveness of a population-based approach to FH detection compared to genetic testing with conventional sequencing. This could provide one route to increasing the present low percentage of FH cases with a genetic diagnosis

A knowledge-based design advisory system for collaborative design for micromanufacturing

The manufacture of microproducts differs from that of conventional products in many ways, not only in the sizes, but also in issues concerning the effects of material properties, tools, and manufacturing equipment. There was a need for a new design methodology and associated design tools to aid designers in assessing the design of their microproducts by considering new micromanufacturing capabilities and constraints. A knowledge-based design advisory system (DAS) was, therefore, developed in MASMICRO in which the knowledge-based system with dedicated assessment modules and knowledge representatives based on the ontology was created to implement the distributed design and manufacturing assessment for micromanufacturing. The modules address the assessment on geometrical features relating to manufacturability, manufacturing processes, selection of materials, tools, and machines, as well as manufacturing cost. The Microsoft C# programming language, ASP.NET web technology, Prolog, and Microsoft Access database were used to develop the DAS. The test on the DAS prototype system was found to provide an increase of design efficiency due to more efficient use of design and manufacturing knowledge and afforded a web-based collaborative design environment

A 15.65 solar mass black hole in an eclipsing binary in the nearby spiral galaxy Messier 33

Stellar-mass black holes are discovered in X-ray emitting binary systems, where their mass can be determined from the dynamics of their companion stars. Models of stellar evolution have difficulty producing black holes in close binaries with masses >10 solar masses, which is consistent with the fact that the most massive stellar black holes known so all have masses within 1 sigma of 10 solar masses. Here we report a mass of 15.65 +/- 1.45 solar masses for the black hole in the recently discovered system M33 X-7, which is located in the nearby galaxy Messier 33 (M33) and is the only known black hole that is in an eclipsing binary. In order to produce such a massive black hole, the progenitor star must have retained much of its outer envelope until after helium fusion in the core was completed. On the other hand, in order for the black hole to be in its present 3.45 day orbit about its 70.0 +/- 6.9 solar mass companion, there must have been a ``common envelope'' phase of evolution in which a significant amount of mass was lost from the system. We find the common envelope phase could not have occured in M33 X-7 unless the amount of mass lost from the progenitor during its evolution was an order of magnitude less than what is usually assumed in evolutionary models of massive stars.Comment: To appear in Nature October 18, 2007. Four figures (one color figure degraded). Differs slightly from published version. Supplementary Information follows in a separate postin

Tracheostomy reveals a rare aberrant right subclavian artery; a case report

BACKGROUND: Anomalies of vascular anatomy in the neck are well recognised. We present a case of a very rare aberrant artery discovered during tracheostomy. CASE PRESENTATION: Elective tracheostomy was performed in theatre for an elderly gentleman on long-term ventilation. Pre-operative examination of the neck revealed no obvious abnormality. During surgery, a large vessel was revealed overlying the tracheal fourth ring. This was found to be an anomalous right subclavian artery. The procedure was completed without complication. CONCLUSIONS: The vessel abnormality described has not been previously documented in this context. It illustrates the importance of thorough pre-operative assessment of the neck and a sound knowledge of the potential for vascular abnormalities. The increasing prevalence of percutaneous dilatational tracheostomy techniques makes this lesson increasingly relevant

Mtss1 promotes cell-cell junction assembly and stability through the small GTPase Rac1

Cell-cell junctions are an integral part of epithelia and are often disrupted in cancer cells during epithelial-to-mesenchymal transition (EMT), which is a main driver of metastatic spread. We show here that Metastasis suppressor-1 (Mtss1; Missing in Metastasis, MIM), a member of the IMD-family of proteins, inhibits cell-cell junction disassembly in wound healing or HGF-induced scatter assays by enhancing cell-cell junction strength. Mtss1 not only makes cells more resistant to cell-cell junction disassembly, but also accelerates the kinetics of adherens junction assembly. Mtss1 drives enhanced junction formation specifically by elevating Rac-GTP. Lastly, we show that Mtss1 depletion reduces recruitment of F-actin at cell-cell junctions. We thus propose that Mtss1 promotes Rac1 activation and actin recruitment driving junction maintenance. We suggest that the observed loss of Mtss1 in cancers may compromise junction stability and thus promote EMT and metastasis

Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature

The Ecm11-Gmc2 complex promotes synaptonemal complex formation through assembly of transverse filaments in budding yeast

During meiosis, homologous chromosomes pair at close proximity to form the synaptonemal complex (SC). This association is mediated by transverse filament proteins that hold the axes of homologous chromosomes together along their entire length. Transverse filament proteins are highly aggregative and can form an aberrant aggregate called the polycomplex that is unassociated with chromosomes. Here, we show that the Ecm11-Gmc2 complex is a novel SC component, functioning to facilitate assembly of the yeast transverse filament protein, Zip1. Ecm11 and Gmc2 initially localize to the synapsis initiation sites, then throughout the synapsed regions of paired homologous chromosomes. The absence of either Ecm11 or Gmc2 substantially compromises the chromosomal assembly of Zip1 as well as polycomplex formation, indicating that the complex is required for extensive Zip1 polymerization. We also show that Ecm11 is SUMOylated in a Gmc2-dependent manner. Remarkably, in the unSUMOylatable ecm11 mutant, assembly of chromosomal Zip1 remained compromised while polycomplex formation became frequent. We propose that the Ecm11-Gmc2 complex facilitates the assembly of Zip1 and that SUMOylation of Ecm11 is critical for ensuring chromosomal assembly of Zip1, thus suppressing polycomplex formation