Homozygous Cys542-->Arg substitution in GPIIIa in a Swiss patient with type I Glanzmann's thrombasthenia

Glanzmann's thrombasthenia (GT) arises from a qualitative or quantitative defect in the GPIIb-IIIa complex (integrin alphaIIbbeta3), the mediator of platelet aggregation. We describe a patient in whom clinical and laboratory findings typical of type I GT were found together with a second pathology involving neurological and other complications symptomatic of tuberous sclerosis. Analysis of platelet proteins by Western blotting revealed trace amounts of normally migrating GPIIb and equally small amounts of GPIIIa of slightly slower than normal migration. Flow cytometry confirmed a much decreased binding to platelets of monoclonal antibodies to GPIIb, GPIIIa or GPIIb-IIIa, and an antibody to the alphav subunit also showed decreased binding. Nonradioactive PCR single-strand conformation polymorphism analysis followed by direct sequencing of PCR-amplified DNA fragments showed a homozygous point mutation (T to C) at nucleotide 1722 of GPIIIa cDNA and which led to a Cys542-->Arg substitution in the GPIIIa protein. The mutation gave rise to a HinP1 I restriction site in exon 11 of the GPIIIa gene and allele-specific restriction enzyme analysis of family members confirmed that a single mutated allele was inherited from each parent. This amino acid substitution presumably changes the capacity for disulphide bond formation within the cysteine-rich core region of GPIIIa and its study will provide new information on GPIIb-IIIa and alphavbeta3 structure and biosynthesis.

Phenotype-genotype correlation in eight Polish patients with inherited Factor XIII deficiency: identification of three novel mutations

Inherited factor XIII (FXIII) deficiency is known as one of the most rare blood coagulation disorder in humans. In the present study, phenotype and genotype of eight FXIII deficient Polish patients from five unrelated families were compared. The patients presented with a severe phenotype demonstrated by a high incidence of intracerebral haemorrhages (seven of eight patients), haemarthrosis (six patients) and bleeding due to trauma (five patients). Introduction of regular substitution with FXIII concentrate prevented spontaneous bleeding in seven patients. In all patients, mutations within the F13A gene have been identified revealing four missense mutations (Arg77Cys, Arg260Cys, Ala378Pro, Gly420Ser), one nonsense mutation (Arg661X), one splice site mutation (IVS5-1 G>A) and one small deletion (c.499-512del). One homozygous large deletion involving exon 15 was detected by failure of PCR product. The corresponding mutations resulted in severely reduced FXIII activity and FXIII A-subunit antigen concentration, while FXIII B-subunit antigen remained normal or mildly decreased. Structural analysis demonstrated that the novel Ala378Pro mutation may cause a disruption of the FXIII catalytic triad leading to a non-functional protein which presumably undergoes premature degradation. In conclusion, the severe phenotype with high incidence of intracranial bleeding and haemarthrosis was in accordance with laboratory findings on FXIII and with severe molecular defects of the F13A gene.

Dynamic Languages and Applications. Report on the Workshop Dyla 07 at ECOOP 2007

Following last two years’ workshop on dynamic languages at the ECOOP conference, the Dyla 2007 workshop was a successful and popular event. As its name implies, the workshop’s focus was on dynamic languages and their applications. Topics and discussions at the workshop included macro expansion mechanisms, extension of the method lookup algorithm, language interpretation, reflexivity and languages for mobile ad hoc networks. The main goal of this workshop was to bring together different dynamic language communities and favouring cross communities interaction. Dyla 2007 was organised as a full day meeting, partly devoted to presentation of submitted position papers and partly devoted to tool demonstration. All accepted papers can be downloaded from the workshop’s web site. In this report, we provide an overview of the presentations and a summary of discussions.

Fixed block configuration GDDs with block size 6 and (3, r)-regular graphs

Chapter 1 is used to introduce the basic tools and mechanics used within this thesis. Most of the definitions used in the thesis will be defined, and we provide a basic survey of topics in graph theory and design theory pertinent to the topics studied in this thesis. In Chapter 2, we are concerned with the study of fixed block configuration group divisible designs, GDD(n; m; k; λ1; λ2). We study those GDDs in which each block has configuration (s; t), that is, GDDs in which each block has exactly s points from one of the two groups and t points from the other. Chapter 2 begins with an overview of previous results and constructions for small group size and block sizes 3, 4 and 5. Chapter 2 is largely devoted to presenting constructions and results about GDDs with two groups and block size 6. We show the necessary conditions are sufficient for the existence of GDD(n, 2, 6; λ1, λ2) with fixed block configuration (3; 3). For configuration (1; 5), we give minimal or nearminimal index constructions for all group sizes n ≥ 5 except n = 10, 15, 160, or 190. For configuration (2, 4), we provide constructions for several families ofGDD(n, 2, 6; λ1, λ2)s. Chapter 3 addresses characterizing (3, r)-regular graphs. We begin with providing previous results on the well studied class of (2, r)-regular graphs and some results on the structure of large (t; r)-regular graphs. In Chapter 3, we completely characterize all (3, 1)-regular and (3, 2)-regular graphs, as well has sharpen existing bounds on the order of large (3, r)- regular graphs of a certain form for r ≥ 3. Finally, the appendix gives computational data resulting from Sage and C programs used to generate (3, 3)-regular graphs on less than 10 vertices.

Hamilton decompositions of 6-regular abelian Cayley graphs

In 1969, Lovasz asked whether every connected, vertex-transitive graph has a Hamilton path. This question has generated a considerable amount of interest, yet remains vastly open. To date, there exist no known connected, vertex-transitive graph that does not possess a Hamilton path. For the Cayley graphs, a subclass of vertex-transitive graphs, the following conjecture was made: Weak Lovász Conjecture: Every nontrivial, finite, connected Cayley graph is hamiltonian. The Chen-Quimpo Theorem proves that Cayley graphs on abelian groups flourish with Hamilton cycles, thus prompting Alspach to make the following conjecture: Alspach Conjecture: Every 2k-regular, connected Cayley graph on a finite abelian group has a Hamilton decomposition. Alspach’s conjecture is true for k = 1 and 2, but even the case k = 3 is still open. It is this case that this thesis addresses. Chapters 1–3 give introductory material and past work on the conjecture. Chapter 3 investigates the relationship between 6-regular Cayley graphs and associated quotient graphs. A proof of Alspach’s conjecture is given for the odd order case when k = 3. Chapter 4 provides a proof of the conjecture for even order graphs with 3-element connection sets that have an element generating a subgroup of index 2, and having a linear dependency among the other generators. Chapter 5 shows that if Γ = Cay(A, {s1, s2, s3}) is a connected, 6-regular, abelian Cayley graph of even order, and for some1 ≤ i ≤ 3, Δi = Cay(A/(si), {sj1 , sj2}) is 4-regular, and Δi ≄ Cay(ℤ3, {1, 1}), then Γ has a Hamilton decomposition. Alternatively stated, if Γ = Cay(A, S) is a connected, 6-regular, abelian Cayley graph of even order, then Γ has a Hamilton decomposition if S has no involutions, and for some s ∈ S, Cay(A/(s), S) is 4-regular, and of order at least 4. Finally, the Appendices give computational data resulting from C and MAGMA programs used to generate Hamilton decompositions of certain non-isomorphic Cayley graphs on low order abelian groups.

How to avoid clean intermittent catheterization in men with ileal bladder substitution

PURPOSE: In male patients with ileal bladder substitute we ascertained the likelihood of spontaneous voiding failure, the corrective procedures required and the eventual outcomes. MATERIALS AND METHODS: Following cystectomy and ileal bladder substitution for urothelial cancer between April 1985 and September 2002 male patients were identified and analyzed from the prospective departmental database. Four patients underwent ileum conduit conversion following urethral recurrence or pouch necrosis and were excluded from study. Funnel-shaped outlets were avoided during bladder substitute surgery after the first 4 patients with this configuration experienced voiding failure and required corrective procedures. Only patients with a minimum 5-year followup were assessed for voiding failure, corrective procedures and final outcomes. RESULTS: Of 354 patients with a median age of 65 years (range 36 to 84) treated with bladder substitute 180 (51%) were alive at 5 years. All 180 of these patients spontaneously voided within 3 months of surgery. During this 5-year observation period 22 (12%) patients experienced voiding problems requiring de-obstructive procedures. Following intervention 177 (98%) patients were spontaneously voiding by 5 years. Of 237 patients 77 (32%) were alive at 10 years. Of these 77 patients followed for another 5 years 10 (13%) had similar voiding problems requiring de-obstructive procedures. Subsequently 74 (96%) were voiding spontaneously by 10 years. CONCLUSIONS: Patients often fail to void spontaneously after ileal bladder substitution. However, if a funnel-shaped outlet is avoided and de-obstructive surgery is appropriately implemented, excellent long-term results are seen with spontaneous voiding and clean intermittent catheterization can be avoided.

Experimental investigation of regular fluids and nanofluids during flow boiling in a single microchannel at different heat fluxes and mass fluxes

The dissipation of high heat flux from integrated circuit chips and the maintenance of acceptable junction temperatures in high powered electronics require advanced cooling technologies. One such technology is two-phase cooling in microchannels under confined flow boiling conditions. In macroscale flow boiling bubbles will nucleate on the channel walls, grow, and depart from the surface. In microscale flow boiling bubbles can fill the channel diameter before the liquid drag force has a chance to sweep them off the channel wall. As a confined bubble elongates in a microchannel, it traps thin liquid films between the heated wall and the vapor core that are subject to large temperature gradients. The thin films evaporate rapidly, sometimes faster than the incoming mass flux can replenish bulk fluid in the microchannel. When the local vapor pressure spike exceeds the inlet pressure, it forces the upstream interface to travel back into the inlet plenum and create flow boiling instabilities. Flow boiling instabilities reduce the temperature at which critical heat flux occurs and create channel dryout. Dryout causes high surface temperatures that can destroy the electronic circuits that use two-phase micro heat exchangers for cooling. Flow boiling instability is characterized by periodic oscillation of flow regimes which induce oscillations in fluid temperature, wall temperatures, pressure drop, and mass flux. When nanofluids are used in flow boiling, the nanoparticles become deposited on the heated surface and change its thermal conductivity, roughness, capillarity, wettability, and nucleation site density. It also affects heat transfer by changing bubble departure diameter, bubble departure frequency, and the evaporation of the micro and macrolayer beneath the growing bubbles. Flow boiling was investigated in this study using degassed, deionized water, and 0.001 vol% aluminum oxide nanofluids in a single rectangular brass microchannel with a hydraulic diameter of 229 µm for one inlet fluid temperature of 63°C and two constant flow rates of 0.41 ml/min and 0.82 ml/min. The power input was adjusted for two average surface temperatures of 103°C and 119°C at each flow rate. High speed images were taken periodically for water and nanofluid flow boiling after durations of 25, 75, and 125 minutes from the start of flow. The change in regime timing revealed the effect of nanoparticle suspension and deposition on the Onset of Nucelate Boiling (ONB) and the Onset of Bubble Elongation (OBE). Cycle duration and bubble frequencies are reported for different nanofluid flow boiling durations. The addition of nanoparticles was found to stabilize bubble nucleation and growth and limit the recession rate of the upstream and downstream interfaces, mitigating the spreading of dry spots and elongating the thin film regions to increase thin film evaporation.

Uptake of and virological response to antiretroviral therapy among HIV-infected former and current injecting drug users and persons in an opiate substitution treatment programme: the Swiss HIV Cohort Study

OBJECTIVES: The aim of the study was to investigate the influence of continued injecting drug use, enrolment in an opiate substitution treatment programme (OSTP), or cessation of injecting drug use on the uptake and course of antiretroviral therapy (ART). Design A prospective observational study of all participants in the Swiss HIV Cohort Study followed between 1997 and 2006 was carried out. METHODS: We distinguished four groups of former or current injecting drug users (IDUs): (i) abstinent former IDUs; (ii) persons in OSTPs without concomitant injecting drug use; (iii) persons in OSTPs with concomitant injecting drug use; (vi) current IDUs. These groups were compared with a group of patients who had never been IDUs. Factors related to ART uptake and virological endpoints were analysed using logistic generalized estimating equations. RESULTS: We followed 8660 participants for 48 477 person-years; 29.7% were in the IDU HIV transmission group. The likelihood of being on ART at biannual visits was lower among individuals in OSTPs with concomitant injecting drug use [odds ratio (OR) 0.79; 95% confidence interval (CI) 0.71-0.89] and current IDUs (OR 0.80; 95% CI 0.67-0.96), compared with those who had never been IDUs (reference), abstinent former IDUs (OR 1.13; 95% CI 1.02-1.25) and individuals in OSTPs without injecting drug use (OR 1.18; 95% CI 1.06-1.31). The likelihood of suppressed viral replication on ART was similar among those who had never been IDUs, abstinent former IDUs and individuals in an OSTP without injecting drug use, and lower among those in OSTPs with concomitant drug use (OR 0.82; 95% CI 0.72-0.93) and current IDUs (OR 0.81; 0.65-1.00). Adherence to ART was decreased among persons with continued injecting drug use, and correlated with virological outcome. CONCLUSIONS: Uptake of and virological response to ART were improved among abstinent former IDUs and persons in OSTPs without concomitant injecting drug use, compared with persons with continued injecting drug use.

Studies on Electrophilic Substitution Reactions of 3-Phenyl-cycl[3.2.2]azine

Acetylation and formylation of 3-phenyl-cycl[3.2.2]azine derivatives, in the presence of Lewis acids, have been Investigated. It has been found that the orientation of substitution in 2-carbomethoxy- 3-phenyl-cycl[3.2.2]azine for these two reactions, under Identical conditions, is different.