A hybrid boundary for the prediction of intake wave dynamics in IC engines

This paper concerns the calculation of wave dynamics in the intake systems of naturally aspirated internal combustion (I.C.) engines. In particular it presents a method for improving the boundary conditions required to solve the one-dimensional Euler equations that are commonly used to describe the wave dynamics in time and space. A number of conclusions are reached in this work. The first relates to the quasi-steady state inflow boundary specified in terms of ingoing and outgoing characteristics that is commonly adopted for engine simulation. This is correctly specified by using the pair of primitive variables pressure (p) and density (ρ) but will be unrealistic at frequencies above a Hemholtz number of 0.1 as only stagnation values po, ρo are used. For the case of I.C. engine intake simulations this sets a maximum frequency of around 300Hz. Above that frequency the results obtained will become increasingly unrealistic. Secondly, a hybrid time and frequency domain boundary has been developed and tested against linear acoustic theory. This agrees well with results obtained using a quasi-steady state boundary at low frequencies (Helmholtz number less than 0.1) and should remain realistic at higher frequencies in the range of Helmholtz number 0.1 - 1.84. Thirdly, the cyclic nature of the operation of the IC engine has been exploited to make use of the inverse Fourier transform to develop an analytical hybrid boundary that functions for non-sinusoidal waves in ducts. The method is self starting, does not rely on iterations over complete cycles and is entirely analytical and therefore is an improvement over earlier hybrid boundaries

Use of deoxycorticosterone pivalate by veterinarians: A western european survey

open9siThis research was supported by FCT—Fundação para a Ciência e Tecnologia IP, grant UIDB/00276/2020This study aims to gather knowledge about the use of deoxycorticosterone pivalate (DOCP) by Western European Veterinarians (WEV) in dogs with typical hypoadrenocorticism. An observa-tional cross-sectional study was conducted using an online survey, translated into four languages and disseminated to veterinary affiliates and mailing lists in six countries of Western Continental Europe. Respondents were tasked to share their therapeutic approach to hypoadrenocorticism, whether they preferred DOCP or fludrocortisone and the specific practical use of DOCP. One-hundred and eighty-four responses were included. Of these, 79.9% indicated that they preferred prescribing DOCP over fludrocortisone as a first-line treatment for mineralocorticoid supplementation. A total of 154 respondents had used DOCP at least once. Eighty percent of those who reported their initial dosage prescribed 2.2 mg/kg. After starting DOCP, 68.2% of the respondents assess electrolytes 10 and 25 days after administration following manufacturer instructions. In stable dogs, electrolytes are monitored quarterly, monthly, semi-annually, and annually by 44.2%, 34.4%, 16.9%, and 4.6% of respondents respectively. When treatment adjustment is required, 53% prefer to reduce dosage while 47% increase the interval between doses. Overall, DOCP is the preferred mineralocorticoid supple-mentation among WEV. Reported variability underlies the need to investigate the best strategies for DOCP use and therapeutic adjustments.openRebocho R.; Dominguez-Ruiz M.; Englar R.E.; Arenas C.; Perez-Alenza M.D.; Corsini A.; Fracassi F.; Bennaim M.; Leal R.O.Rebocho R.; Dominguez-Ruiz M.; Englar R.E.; Arenas C.; Perez-Alenza M.D.; Corsini A.; Fracassi F.; Bennaim M.; Leal R.O

Laparoscopic management of a cavitated noncommunicating rudimentary uterine horn of a unicornuate uterus: a case report

<p>Abstract</p> <p>Introduction</p> <p>A unicornuate uterus with a rudimentary horn is the most uncommon uterine anomaly of the female genital tract. It has an estimated frequency of one in 100,000 among the fertile female population. This anomaly results from the abnormal maturation of one Müllerian duct with the normal development of the contralateral one.</p> <p>Case presentation</p> <p>We report here the case of a 14-year-old Caucasian girl who came to our hospital with intense dysmenorrhea. Imaging techniques revealed a unicornuate uterus with a rudimentary horn and a large hematosalpinx. We performed a laparoscopic removal of this uterine anomaly without any complication in the postoperative period.</p> <p>Conclusion</p> <p>In our case report, we demonstrate that laparoscopy is the best approach for the treatment of IIb Müllerian abnormalities. Laparoscopy resulted in anatomical and reproductive results equivalent to those offered by a laparotomic approach, but with the additional advantages of minimally invasive surgery, such as better cosmetic results and postoperative period, which are essential for very young patients.</p

Acceleration effect of coupled oscillator systems

We have developed a curved isochron clock (CIC) by modifying the radial isochron clock to provide a clean example of the acceleration (deceleration) effect. By analyzing a two-body system of coupled CICs, we determined that an unbalanced mutual interaction caused by curved isochron sets is the minimum mechanism needed for generating the acceleration (deceleration) effect in coupled oscillator systems. From this we can see that the Sakaguchi and Kuramoto (SK) model which is a class of non-frustrated mean feild model has an acceleration (deceleration) effect mechanism. To study frustrated coupled oscillator systems, we extended the SK model to two oscillator associative memory models, one with symmetric and one with asymmetric dilution of coupling, which also have the minimum mechanism of the acceleration (deceleration) effect. We theoretically found that the {\it Onsager reaction term} (ORT), which is unique to frustrated systems, plays an important role in the acceleration (de! celeration) effect. These two models are ideal for evaluating the effect of the ORT because, with the exception of the ORT, they have the same order parameter equations. We found that the two models have identical macroscopic properties, except for the acceleration effect caused by the ORT. By comparing the results of the two models, we can extract the effect of the ORT from only the rotation speeds of the oscillators.Comment: 35 pages, 10 figure

Mesoscopic organization reveals the constraints governing C. elegans nervous system

One of the biggest challenges in biology is to understand how activity at the cellular level of neurons, as a result of their mutual interactions, leads to the observed behavior of an organism responding to a variety of environmental stimuli. Investigating the intermediate or mesoscopic level of organization in the nervous system is a vital step towards understanding how the integration of micro-level dynamics results in macro-level functioning. In this paper, we have considered the somatic nervous system of the nematode Caenorhabditis elegans, for which the entire neuronal connectivity diagram is known. We focus on the organization of the system into modules, i.e., neuronal groups having relatively higher connection density compared to that of the overall network. We show that this mesoscopic feature cannot be explained exclusively in terms of considerations, such as optimizing for resource constraints (viz., total wiring cost) and communication efficiency (i.e., network path length). Comparison with other complex networks designed for efficient transport (of signals or resources) implies that neuronal networks form a distinct class. This suggests that the principal function of the network, viz., processing of sensory information resulting in appropriate motor response, may be playing a vital role in determining the connection topology. Using modular spectral analysis, we make explicit the intimate relation between function and structure in the nervous system. This is further brought out by identifying functionally critical neurons purely on the basis of patterns of intra- and inter-modular connections. Our study reveals how the design of the nervous system reflects several constraints, including its key functional role as a processor of information.Comment: Published version, Minor modifications, 16 pages, 9 figure

EFFICACY AND SAFETY OF BOCEPREVIR-BASED THERAPY IN HCVG1 TREATMENT-EXPERIENCED PATIENTS WITH ADVANCED FIBROSIS/CIRRHOSIS: THE ITALIAN AND SPANISH NPP EARLY ACCESS PROGRAM

Background and Aims: To maximize cost/efficay of boceprevirbased triple therapy (BOC) in patients with HCV-related advanced fibrosis/cirrhosis. Methods: ITT SVR12, safety and futility rules value were evaluated in the multicenter national Italian and Spanish early access Name- Patient-Program which includes treatment-experienced patients with HCVG1-related advanced fibrosis/cirrhosis (Metavir F3/4) treated with BOC in both countries. Results: 402 patients (mean age 55 years; range 22–75), 316 (78.6%) G1b, 255 (63.4%) F4, 60 (30.9%) with oesophageal varices, 137 (34.1%) relapsers, 95 (23.6%) partial and 168 (41.8%) null responders were enrolled. Platelets count <100,000 and albumin levels <3.5 g/dl were present in 49 (12.2%) and 22 (6.3%) patients, respectively. 369 (91.8%) received at least 1 dose of BOC. Overall ITT SVR12 rates and according to prior response to P/R, fibrosis stage and TW8 HCV-RNA value to P/R/BOC are reported in the table. At multivariate analysis, the strongest predictors of SVR12 were TW8 HCV-RNA undetectability (RR, 30.8; 95% CI, 8.7–108.7) and HCV-RNA detectable but <1000 IU/mL (RR, 9.1; 95% CI, 2.6–31.8) compared to those with HCV-RNA ≥1000 IU/mL. Two patients (0.5%) died from multi-organ failure, 13 (3.2%) developed hepatic decompensation, 41 (10.2%) had severe anemia (<8.5 g/dl) and 31 (7.7%) required at least one blood transfusion. Conclusions: In treatment-experienced patients with advanced fibrosis/cirrhosis, SVR12 attained by BOC was satisfactory. Mortality, life-threatening adverse events and severe anemia rates were similar to those reported in other real-practice studies. A TW8 futility rule enables a safely discontinuation of BOC in patients who are extremely unlikely to achieve SVR, thus optimizing the effectiveness of treatment in this difficult-to-cure population

Impact of the Mitochondrial Genetic Background in Complex III Deficiency

BACKGROUND: In recent years clinical evidence has emphasized the importance of the mtDNA genetic background that hosts a primary pathogenic mutation in the clinical expression of mitochondrial disorders, but little experimental confirmation has been provided. We have analyzed the pathogenic role of a novel homoplasmic mutation (m.15533 A>G) in the cytochrome b (MT-CYB) gene in a patient presenting with lactic acidosis, seizures, mild mental delay, and behaviour abnormalities. METHODOLOGY: Spectrophotometric analyses of the respiratory chain enzyme activities were performed in different tissues, the whole muscle mitochondrial DNA of the patient was sequenced, and the novel mutation was confirmed by PCR-RFLP. Transmitochondrial cybrids were constructed to confirm the pathogenicity of the mutation, and assembly/stability studies were carried out in fibroblasts and cybrids by means of mitochondrial translation inhibition in combination with blue native gel electrophoresis. PRINCIPAL FINDINGS: Biochemical analyses revealed a decrease in respiratory chain complex III activity in patient's skeletal muscle, and a combined enzyme defect of complexes III and IV in fibroblasts. Mutant transmitochondrial cybrids restored normal enzyme activities and steady-state protein levels, the mutation was mildly conserved along evolution, and the proband's mother and maternal aunt, both clinically unaffected, also harboured the homoplasmic mutation. These data suggested a nuclear genetic origin of the disease. However, by forcing the de novo functioning of the OXPHOS system, a severe delay in the biogenesis of the respiratory chain complexes was observed in the mutants, which demonstrated a direct functional effect of the mitochondrial genetic background. CONCLUSIONS: Our results point to possible pitfalls in the detection of pathogenic mitochondrial mutations, and highlight the role of the genetic mtDNA background in the development of mitochondrial disorders

The Opportunistic Pathogen Propionibacterium acnes: Insights into Typing, Human Disease, Clonal Diversification and CAMP Factor Evolution

We previously described a Multilocus Sequence Typing (MLST) scheme based on eight genes that facilitates population genetic and evolutionary analysis of P. acnes. While MLST is a portable method for unambiguous typing of bacteria, it is expensive and labour intensive. Against this background, we now describe a refined version of this scheme based on two housekeeping (aroE; guaA) and two putative virulence (tly; camp2) genes (MLST4) that correctly predicted the phylogroup (IA1, IA2, IB, IC, II, III), clonal complex (CC) and sequence type (ST) (novel or described) status for 91% isolates (n = 372) via cross-referencing of the four gene allelic profiles to the full eight gene versions available in the MLST database (http:// pubmlst.org/pacnes/). Even in the small number of cases where specific STs were not completely resolved, the MLST4 method still correctly determined phylogroup and CC membership. Examination of nucleotide changes within all the MLST loci provides evidence that point mutations generate new alleles approximately 1.5 times as frequently as recombination; although the latter still plays an important role in the bacterium’s evolution. The secreted/cell-associated ‘virulence’ factors tly and camp2 show no clear evidence of episodic or pervasive positive selection and have diversified at a rate similar to housekeeping loci. The co-evolution of these genes with the core genome might also indicate a role in commensal/normal existence constraining their diversity and preventing their loss from the P. acnes population. The possibility that members of the expanded CAMP factor protein family, including camp2, may have been lost from other propionibacteria, but not P. acnes, would further argue for a possible role in niche/host adaption leading to their retention within the genome. These evolutionary insights may prove important for discussions surrounding camp2 as an immunotherapy target for acne, and the effect such treatments may have on commensal lineages

Identification of Plasmodium vivax Proteins with Potential Role in Invasion Using Sequence Redundancy Reduction and Profile Hidden Markov Models

BACKGROUND: This study describes a bioinformatics approach designed to identify Plasmodium vivax proteins potentially involved in reticulocyte invasion. Specifically, different protein training sets were built and tuned based on different biological parameters, such as experimental evidence of secretion and/or involvement in invasion-related processes. A profile-based sequence method supported by hidden Markov models (HMMs) was then used to build classifiers to search for biologically-related proteins. The transcriptional profile of the P. vivax intra-erythrocyte developmental cycle was then screened using these classifiers. RESULTS: A bioinformatics methodology for identifying potentially secreted P. vivax proteins was designed using sequence redundancy reduction and probabilistic profiles. This methodology led to identifying a set of 45 proteins that are potentially secreted during the P. vivax intra-erythrocyte development cycle and could be involved in cell invasion. Thirteen of the 45 proteins have already been described as vaccine candidates; there is experimental evidence of protein expression for 7 of the 32 remaining ones, while no previous studies of expression, function or immunology have been carried out for the additional 25. CONCLUSIONS: The results support the idea that probabilistic techniques like profile HMMs improve similarity searches. Also, different adjustments such as sequence redundancy reduction using Pisces or Cd-Hit allowed data clustering based on rational reproducible measurements. This kind of approach for selecting proteins with specific functions is highly important for supporting large-scale analyses that could aid in the identification of genes encoding potential new target antigens for vaccine development and drug design. The present study has led to targeting 32 proteins for further testing regarding their ability to induce protective immune responses against P. vivax malaria