Numerical investigation on the effects of bore reduction in a high performance turbocharged GDI engine. 3D investigation of knock tendency

Abstract Downsizing is a must for current high performance turbocharged SI engines. This is often achieved through the reduction of cylinder number, while keeping constant unit displacement and increasing boost pressure. However, the ensuing higher loads strongly increases the risk of abnormal combustion and thermo-mechanical failures. An alternative path to downsizing is the reduction of cylinder bore: this approach is more expensive, requiring a brand new design of the combustion system, but it also provides some advantages. The goal of the present paper is to explore the potential of bore reduction for achieving a challenging downsizing target, while preserving the engine knock safety margins. A current V8 GDI turbocharged sporting engine is taken as a reference, and a preliminary CFD-3D analysis is carried out in order to define the most suitable bore-to-stroke ratio. On this basis, bore is reduced by 11% at constant stroke, thus obtaining a reduction of about 20% on the engine displacement. In order to achieve the same peak power target, both engine boost and spark advance are adjusted until the knock safety margin of the original engine is met. 3D CFD tools, accurately calibrated on the reference engine, are used to address engine design and the calibration of the operating parameters

Length and clinical effectiveness of pulmonary rehabilitation in outpatients with chronic airway obstruction

Study objective: To assess the clinical effectiveness of pulmonary rehabilitation (PR) after 10 or 20 consecutive sessions in outpatients with chronic airway obstruction (CAO). Design: Observational prospective cohort trial. Setting: Outpatient clinic of a rehabilitation center. Patients and interventions: Twenty-five outpatients (mean age, 65 +/- 9 years [+/- SD]; FEV1, 64 +/- 12% predicted) admitted to a comprehensive PR program, including exercise training. Measurements and results: The load reached on a cycloergometer (maximal achieved load [W-max]), the maximal and isoload dyspnea and leg fatigue on a Borg scale, 6-min walk distance (6MWD), and the health-related quality of life as assessed using the St. George's Respiratory Questionnaire (SGRQ) [total and components score] have been recorded as outcome measures at baseline, after 10 sessions (T10), and after 20 sessions (T20). The predefined criteria of the clinically significant improvement were as follows: + 15% W-max, + 54 m at 6MWD, - 1 point at isoload dyspnea and leg fatigue, and - 4% at SGRQ scores. There was a mean significant difference between changes at T20 and T10 for 6MWD (- 42.96 m; 95% confidence interval [0], - 57.79 to - 28.12 m; p = 0.001), total SGRQ (4.80; 95% CI, 2.29 to 7.31; p = 0.001), activity SGRQ (3.60; 95% CI, 0.48 to 6.71; p = 0.025), and symptoms SGRQ (5.96; 95% CI, 2.72 to 9.2; p = 0.001). The percentage of patients who improved was different at T20 as compared with T 10 for W-max (68% and 48%, respectively; p = 0.025), 6MWD (76% and 20%, p = 0.001), and total SGRQ (64% and 36%, p = 0.008). Conclusions: A 10-session course of PR provides only limited clinically significant changes of outcome measures when compared with a 20-session course in outpatients with CAO of mild-to-moderate severity

Interdisciplinary rehabilitation in morbidly obese subjects: an observational pilot study.

BACKGROUND AND AIM: To assess the clinical effectiveness of a interdisciplinary rehabilitation programme (CR), in a population of morbidly obese subjects we have undertaken a observational study. METHODS: The study included fifty-nine adult subjects (18 M, 60+/-10 years, BMI 47+/-8) with sleep-disturbance related symptoms and disabilities. Assessment and correction of sleep disordered breathing (SDB) abnormalities, improvement of exercise tolerance, body weight and associated psychological features were the aims of this CR, which has been carried out over a 1 month period.Lung functions, apnea/hypopnea index (AHI), 6-minute walking distance (6MWD), body weight (BW), quality of life by means of Sat-P questionnaire and serum metabolic data has been recorded at baseline (TO), at the end (Ti) and 6 months after (T2) the CR. RESULTS: The percentage of patients with AHI > 10 declined from 65% (at TO) to 20% (at both T1 and T2). 6MWD and BW significantly improved (p < 0.005) at T1 and still maintained at T2; a significant relationship (r = 0.379, p < 0.01) has been found between changes of BW and 6MWD recorded in between TO and T2. Sat-P item scores dealing with sleep efficiency, problem solving, and social interactions improved (p < 0.01) at T1 and still maintained at T2. CONCLUSIONS: This hospital-based CR provides indication for effectiveness in advanced morbidly obese subjects and warrants further controlled trials to confirm the results

Respiratory muscle training in patients recovering recent open cardio-thoracic surgery: a randomized-controlled trial.

Objectives- To evaluate the clinical efficacy and feasibility of an expiratory muscle training (EMT) device (Respilift™) applied to patients recovering from recent open cardio-thoracic surgery (CTS). Design- Prospective, double-blind, 14-day randomised-controlled trial. Participants and setting- 60 inpatients recovering from recent CTS and early admitted to a pulmonary rehabilitation program. Interventions- Chest physiotherapy plus EMT with a resistive load of 30 cm H2O for active group and chest physiotherapy plus EMT with a sham load for control group. Measures- Changes in maximal expiratory pressure (MEP) was considered as primary outcome, while maximal inspiratory pressures (MIP), dynamic and static lung volumes, oxygenation, perceived symptoms of dyspnoea, thoracic pain and well being (evaluated by visual analogic scale-VAS) and general health status were considered secondary outcomes. Results- All outcomes recorded showed significant improvements in both groups; however, the change of MEP (+34.2 mmHg, p<0.001 and +26.1%, p<0.001 for absolute and % of predicted, respectively) was significantly higher in Active group. Also VAS-dyspnoea improved faster and more significantly (p<0.05) at day 12 and 14 in Active group when compared with Control. The drop out rate was 6%, without differences between groups. Conclusions- In patients recovering from recent CTS specific EMT by Respilift™ is feasible and effective

Identification, isolation and in vitro expansion of human and nonhuman primate T stem cell memory cell

The T cell compartment is phenotypically and functionally heterogeneous; subsets of naive and memory cells have different functional properties, and also differ with respect to homeostatic potential and the ability to persist in vivo. Human stem cell memory T (TSCM) cells, which possess superior immune reconstitution and antitumor response capabilities, can be identified by polychromatic flow cytometry on the basis of the simultaneous expression of several naive markers together with the memory marker CD95. We describe here a protocol based on the minimum set of markers required for optimal identification of human and nonhuman primate (NHP) TSCM cells with commonly available flow cytometers. By using flow sorters, TSCM cells can thereby be isolated efficiently at high yield and purity. With the use of the 5.5-h isolation procedure, depending on the number of cells needed, the sorting procedure can last for 2-15 h. We also indicate multiple strategies for their efficient expansion in vitro at consistent numbers for functional characterization or adoptive transfer experiments

InteractomeSeq: a web server for the identification and profiling of domains and epitopes from phage display and next generation sequencing data

High-Throughput Sequencing technologies are transforming many research fields, including the analysis of phage display libraries. The phage display technology coupled with deep sequencing was introduced more than a decade ago and holds the potential to circumvent the traditional laborious picking and testing of individual phage rescued clones. However, from a bioinformatics point of view, the analysis of this kind of data was always performed by adapting tools designed for other purposes, thus not considering the noise background typical of the 'interactome sequencing' approach and the heterogeneity of the data. InteractomeSeq is a web server allowing data analysis of protein domains ('domainome') or epitopes ('epitome') from either Eukaryotic or Prokaryotic genomic phage libraries generated and selected by following an Interactome sequencing approach. InteractomeSeq allows users to upload raw sequencing data and to obtain an accurate characterization of domainome/epitome profiles after setting the parameters required to tune the analysis. The release of this tool is relevant for the scientific and clinical community, because InteractomeSeq will fill an existing gap in the field of large-scale biomarkers profiling, reverse vaccinology, and structural/functional studies, thus contributing essential information for gene annotation or antigen identification. InteractomeSeq is freely available at https://InteractomeSeq.ba.itb.cnr.it/

Clinical Study Respiratory Muscle Training in Patients Recovering Recent Open Cardiothoracic Surgery: A Randomized-Controlled Trial

Objectives. To evaluate the clinical efficacy and feasibility of an expiratory muscle training (EMT) device (Respilift) applied to patients recovering from recent open cardiothoracic surgery (CTS). Design. Prospective, double-blind, 14-day randomisedcontrolled trial. Participants and Setting. A total of 60 inpatients recovering from recent CTS and early admitted to a pulmonary rehabilitation program. Interventions. Chest physiotherapy plus EMT with a resistive load of 30 cm H 2 O for active group and chest physiotherapy plus EMT with a sham load for control group. Measures. Changes in maximal expiratory pressure (MEP) were considered as primary outcome, while maximal inspiratory pressures (MIP), dynamic and static lung volumes, oxygenation, perceived symptoms of dyspnoea, thoracic pain, and well being (evaluated by visual analogic scale-VAS) and general health status were considered secondary outcomes. Results. All outcomes recorded showed significant improvements in both groups; however, the change of MEP (+34.2 mmHg, &lt; 0.001 and +26.1%, &lt; 0.001 for absolute and % of predicted, resp.) was significantly higher in active group. Also VAS dyspnoea improved faster and more significantly ( &lt; 0.05) at day 12, and 14 in active group when compared with control. The drop-out rate was 6%, without differences between groups. Conclusions. In patients recovering from recent CTS, specific EMT by Respilift is feasible and effective. This trial is registered with ClinicalTrials.gov NCT01510275

The early expansion of anergic NKG2Apos/CD56dim/CD16neg natural killer cells represents a therapeutic target in haploidentical haematopoietic stem cell transplantation

Natural Killer cells are the first lymphocyte population to reconstitute early after non myelo-ablative and T cell-replete haploidentical hematopoietic stem cell transplantation with post-transplant infusion of cyclophosphamide. The present study characterizes the transient and predominant expansion starting from the 2nd week after haploidentical hematopoietic stem cell transplantation of a donor-derived unconventional subset of NKp46neg-low/CD56dim/CD16neg natural killer cells expressing remarkable high levels of CD94/NKG2A. Both transcription and phenotypic profiles indicated that unconventional NKp46neg-low/CD56dim/CD16neg natural killer cells are a distinct natural killer cell subpopulation with features of late stage differentiation, yet retaining proliferative capability and functional plasticity to generate conventional NKp46pos/CD56bright/CD16pos natural killer cells in response to interleukin-15 plus interleukin-18. While present at low frequency in healthy donors, unconventional NKp46neg-low/CD56dim/CD16neg natural killer cells are greatly expanded in the following 7 weeks after haploidentical hematopoietic stem cell transplantation and express high levels of the activating receptors NKGD and NKp30 as well as of the lytic granules Granzyme-B and Perforin. Nonetheless, NKp46neg-low/CD56dim/CD16neg natural killer cells displayed a markedly defective cytotoxicity that could be reversed by blocking the inhibitory receptor CD94/NKG2A. These data open new important perspectives to better understand the ontogenesis/homeostasis of human natural killer cells and to develop a novel immune-therapeutic approach that targets the inhibitory NKG2A check point, thus unleashing natural killer cell alloreactivity early after haploidentical hematopoietic stem cell transplantation

Minipuberty in Male Full-term Neonates Appropriate and Small for Gestational Age and in Preterm Babies: Data from a Single Centre

INTRODUCTION: The postnatal activation of the hypothalamic-pituitary-gonadal (HPG) axis is usually known as 'minipuberty'. There are still open questions about its biological function and significance depending on sex, gestational age (GA) and birth weight (BW) with few available longitudinal data. METHODS: A single-centre, longitudinal study to quantify urinary follicle stimulating hormone (uFSH), luteinizing hormone (uLH) and testosterone (uTs) in male neonates. Neonates were enrolled and stratified into three subgroups: full-term boys appropriate for GA (FT AGA); FT boys with BW ≤3rd centile [FT small for gestational age (SGA)]; and preterm (PT) boys ≤33 weeks of GA. Urinary hormones were correlated to simultaneous auxological parameters, linear growth and external genitalia at scheduled time-points. RESULTS: Forty-six boys were recruited, with subgroup sizes FT AGA n=23, FT SGA n=11 and PT n=12. PT boys display a pulsatile pattern of urinary gonadotropins (uGns) with higher levels of uLH and a gradual increase of uTs. Testicular descent started from 29-32 weeks with the peak of uTs. During the first 12-months post-term age (PTA), FT AGA boys displayed a better linear growth (p<0.05). PT showed higher uGns levels until 3-months PTA. PT babies had higher uLH levels than FT AGA, with a peak at 7 and 30 days, during the first 90 days of life (p<0.001) and higher uTs levels. Correlation analysis between penile growth of all neonates and uTs was significant (p=0.04) but not within subgroups. DISCUSSION AND CONCLUSION: This study investigated postnatal HPG axis activation in term and PT infants. Minipuberty may involve an early window of opportunity to evaluate the functionality of the HPG axis. Further studies with a long-term follow-up are needed with a special focus on possible consequences of GA and BW

Direct analysis of thymic function in children with Down's syndrome

BACKGROUND: Down's syndrome (DS) is characterized by several immunological defects, especially regarding T cell compartment. DS is considered the best example of accelerated ageing in humans. Direct observations of the thymus have shown that in DS this organ undergoes severe histological and morphological changes. However, no data on its capacity to generate T cells are present in the literature. Here, using a new technology based upon real time PCR, we have investigated the capacity of the thymus to produce and release newly generated T lymphocytes (the so called "recent thymic emigrants", RTE) in children with DS. METHODS: We studied 8 children affected by DS, aged 2–7 years, compared with 8 age- and sex-matched healthy controls. Flow cytometry was used to determine different lymphocytes subsets. Real time PCR with the Taqman system was used to quantify the amount of RTE, i.e. peripheral blood lymphocytes that express the T cell receptor rearrangement excision circles (TREC). RESULTS: In comparison with control children, those with DS had a significant lower number of TREC+ peripheral blood cells. Moreover, in DS children but not in controls, a strong negative correlation between age and the levels of TREC+ cells was found. CONCLUSIONS: The direct measure of thymic output indicates that the impairment of the organ results in a reduced production of newly generated T cells. This observation could suggest that cytokines able to modulate thymic function, such as interleukins, could be useful to improve the functionality of the organ and to treat the immunodeficiency present in DS subjects