This work presents a novel electromagnetic clutch installed on the crankshaft pulley to decouple the internal combustion engine from the front-end accessory drive of a P0 hybrid electric vehicle. The ...objective is to supply the air conditioning compressor directly with the belt starter–generator electric machine without dragging the inertia of the engine during engine fuel cut-off phases. This operation yields an improved vehicle energetic efficiency and allows for uninterrupted air conditioning also when the start–stop function is activated. This paper focuses on the mechanical assembly and electromagnetic behavior of the device. Furthermore, two position-sensorless techniques are proposed to estimate the clutch state. The effectiveness of the proposed solution is experimentally validated on a dedicated test bench. Experimental tests demonstrated that the opening and closing phases required 50 and 25ms, respectively, thereby satisfying the time constraints for switching different operating modes in a vehicle (∼100ms).
Alternative splicing is the process of producing variably spliced mRNAs by choosing distinct combinations of splice sites within a messenger RNA precursor. This splicing enables mRNA from a single ...gene to synthesize different proteins, which have different cellular properties and functions and yet arise from the same single gene. A family of splicing factors, Serine-arginine rich proteins, are needed to initiate the assembly and activation of the spliceosome. Serine and arginine rich splicing factor 1, part of the arginine/serine-rich splicing factor protein family, can either activate or inhibit the splicing of mRNAs, depending on the phosphorylation status of the protein and its interaction partners. Considering that serine and arginine rich splicing factor 1 is either an activator or an inhibitor, this protein has been studied widely to identify its various roles in different diseases. Research has found that serine and arginine rich splicing factor 1 is a key target for neuroprotection, showing its promising potential use in therapeutics for neurodegenerative disorders. Furthermore, serine and arginine rich splicing factor 1 might be used to regulate cancer development and autoimmune diseases. In this review, we highlight how serine and arginine rich splicing factor 1 has been studied concerning neuroprotection. In addition, we draw attention to how serine and arginine rich splicing factor 1 is being studied in cancer and immunological disorders, as well as how serine and arginine rich splicing factor 1 acts outside the central or peripheral nervous system.
We perform state tomography of an itinerant squeezed state of the microwave field prepared by a Josephson parametric amplifier (JPA). We use a second JPA as a preamplifier to improve the quantum ...efficiency of the field quadrature measurement from 2% to 36%±4%. Without correcting for the detection inefficiency we observe a minimum quadrature variance which is 68(-7)(+9)% of the variance of the vacuum. We reconstruct the state's density matrix by a maximum likelihood method and infer that the squeezed state has a minimum variance less than 40% of the vacuum, with uncertainty mostly caused by calibration systematics.
Programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors have had a major impact on the approach to care of patients with lung cancer. An important issue ...that is not known is whether they benefit men and women the same. We conducted a meta-analysis of all randomised controlled trials evaluating PD-1/PD-L1 inhibition in patients with non-small cell lung cancer (NSCLC) to determine if clinical response and survival are influenced by gender.
A PubMed search was carried out to identify all randomised controlled trials evaluating PD-1/PD-L1 inhibitors compared with conventional chemotherapy in NSCLC. Random-effects meta-analysis and meta-regression were performed to assess overall survival and progression-free survival (PFS) and whether there were differences in these outcomes between men and women.
In total, 12 studies with data for overall survival and 11 studies with data for PFS were included. Immunotherapy showed a statistically significant benefit over chemotherapy for overall survival (pooled hazard ratio = 0.72, 95% confidence interval = 0.65–0.81, P < 0.001) and progression-free survival (pooled hazard ratio = 0.62, 95% confidence interval = 0.54–0.72, P < 0.001). We did not find a statistically significant difference between men and women in terms of overall survival (males versus females: pooled hazard ratio = 0.74, 95% confidence interval = 0.66–0.83 versus pooled hazard ratio = 0.72, 95% confidence interval = 0.63–0.82, P = 0.709) or progression-free survival (males versus females: pooled hazard ratio = 0.63, 95% confidence interval = 0.53–0.75 versus pooled hazard ratio = 0.72, 95% confidence interval = 0.58–0.88, P = 0.372).
This is the first systematic review and meta-analysis investigating the effect of gender and response to PD-1/PD-L1 checkpoint inhibitors in patients solely with NSCLC. We examined 9270 and 6193 patients in terms of overall survival and PFS, respectively. Although there are significant biological differences between men's and women's immune responses, we have shown that these drugs offer the same survival benefit in patients with NSCLC regardless of gender.
•PD1/PDL-1 inhibitors have proved as game changers in treatment of stage III and IV NSCLC treatment in recent decades.•Women historically have been underrepresented in cancer clinical trials.•Sex-based differences result from a complex interaction between gender-specific genes, environment, and hormonal milieu.•Immune checkpoint inhibitors showed improved overall and progression free survival in both genders.
Influence of the dissolution medium on the in vitro theophylline release profiles from matrices based on starch–methyl methacrylate copolymers. Tablets are compacted at a crushing force of 90–100N ...and tested in a pH-changing medium (1.2–7.5) at a basket rotation speed of 50r.p.m. Theo-Dur® and Theolair® are included as reference products. The type of copolymer, the tablet crushing force and the agitation rate affected the drug release kinetics.
Direct-compressed matrix tablets were obtained from a variety of potato starch–methyl methacrylate copolymers11OD-HSMMA, oven-dried hydroxypropylstarch methyl methacrylate; FD-HSMMA, freeze-dried hydroxypropylstarch methyl methacrylate; OD-CSMMA, oven-dried carboxymethylstarch methyl methacrylate; FD-CSMMA, freeze-dried carboxymethylstarch methyl methacrylate. as sustained-release agents, using anhydrous theophylline as a model drug. The aim of this work was to investigate the influence of the copolymer type, the tablet crushing force and dissolution variables such as the pH of the dissolution medium and the agitation intensity on the in vitro drug release behaviour of such matrices. Commercial sustained-release theophylline products (Theo-Dur® 100mg, Theolair® 175mg) were used as standards. Test formulations were compacted into tablets at three different crushing force ranges (70–80, 90–100 and 110–120N) to examine the effect of this factor on the porous network and drug release kinetics. In vitro release experiments were conducted in a pH-changing medium (1.2–7.5) with basket rotation speeds in the range 25–100r.p.m. to simulate the physiological conditions of the gastrointestinal tract. The release rate of theophylline was practically not affected by pH in the case of Theo-Dur® and HSMMA matrices. In contrast, Theolair® and CSMMA tablets demonstrated a biphasic drug release pattern, which appeared to be sensitive to the pH of the dissolution medium. An increase in the crushing force of the copolymer matrices was accompanied by a reduction of the matrix porosity, although the porous network depends markedly on the type of copolymer, having a strong influence on the drug release kinetics. Mathematical modelling of release data shows a Fickian diffusion or anomalous transport mechanism. Based on the similarity factor f2, FD-HSMMA, OD-CSMMA and FD-CSMMA at 90–100N were selected for agitation studies. In general, all formulations showed an agitation speed-dependent release, with Theo-Dur® and FD-CSMMA matrices being the less susceptible to this factor.
•A novel thiolated chitosan (CTS) useful as topical drug delivery systems is studied.•Theophylline (Th) and Diltiazem (Dt) were chosen as chemically diverse model drugs.•Aqueous dispersions were ...prepared with 1% or 3% w/v CTS and 0.5% w/v drug.•All flow curves fit the Herschel-Bulkley model with negative yields stress values.•Concentration of CTS and chemical nature of drugs are key factors in drug release.
The use of a novel cross-linked thiolated chitosan (CTS) was investigated as the main component of aqueous dispersions (at 1% and 3% w/v) for topical drug delivery systems. The nonionic theophiline (Th) and the cationic diltiazem.HCl (Dt) (at 0.5% w/v concentration) were used as model drugs. All aqueous dispersions behaved as viscoelastic fluids. The CTS 1% dispersions showed predominance of viscous component and low viscosity. However, in the CTS 3% dispersions, both the elastic component and high viscosities prevailed. So, texture parameters improved from CTS 1% to 3% dispersions and CTS 3%-Dt showed greater cohesion and adhesion than CTS 3%-Th, but always below CTS alone. All dispersions showed a Fickian diffusion mechanism. Despite release profiles of both drugs almost fully overlapped at 1% CTS, diffusion coefficients confirmed Dt released faster than Th at 3% CTS. The rheological behavior and the chemical nature of the drugs explained these results.
A P0 system is used in hybrid automobiles to improve engine economy and performance. An essential element of the P0 system for effectively transmitting power to the drive train is the belt drive ...system (BDS). The features of electric machine (EM) and internal combustion engines (ICE) are taken into account by standard energy management systems, such as the equivalent consumption minimization strategy (ECMS). In order to maximize the effectiveness of the P0 system, this work provides a novel formulation of the ECMS, which considers the power loss map of the BDS in addition to the characteristic maps of EM and ICE. A test bench is built up to characterize the BDS, and it is verified using an open-loop Hardware in the Loop (HIL) in the WLTP driving cycle. To find the most appropriate equivalence factors for the ECMS, which would ordinarily be tuned through trial and error, a genetic algorithm (GA) is used. With regard to the standard ECMS, the proposed methodology intends to reduce fuel usage and CO2 emissions. Two belts in BDS were tested in the WLTP to achieve CO2 savings of 1.1 and 0.9 g/km, indicating the enhancement of system performance by using the BDS power loss maps in ECMS.
Aims
Small invasive carcinomas arising in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can present as multiple, small foci. In such cases, there is no clear optimal measurement ...method for determining the invasive size for tumour staging and prognostication.
Methods
In all, 117 small invasive IPMNs (size of largest invasive component ≤2 cm) from seven institutions (2000–2016) were reviewed, and all individual foci of invasive carcinoma were measured. T stages (AJCC 8th edition) based on the largest single focus size (LS), average size of all foci (AS), and total sum of all foci (TS) were examined in association with clinicopathologic parameters and patient outcomes.
Results
The cohort comprised IPMNs with invasive tubular‐type (n = 82, 70%) and colloid‐type (n = 35, 30%) carcinomas. The mean LS, AS, and TS were 0.86, 0.71, and 1.32 cm, respectively. Based on the LS, AS, and TS, respectively, 48, 65, and 39 cases were classified as pT1a; 22, 18, and 11 cases as pT1b; and 47, 34, and 50 cases as pT1c. Higher pT stages based on all measurements were significantly associated with small vessel, large vessel, and perineural invasion (P < 0.05). LS‐, AS‐, and TS‐based pT stages were not significantly associated with recurrence‐free survival (RFS) or overall survival (OS) by univariate or multivariate analyses. However, among tubular‐type carcinomas, higher LS‐, AS‐, and TS‐based pT stages trended with lower RFS (based on 1‐, 3‐, and 5‐year survival rates). All microscopic measurement methods were most predictive of RFS and OS using a 1.5‐cm cutoff, with LS significantly associated with both RFS and OS by univariate and multivariate analysis.
Conclusions
For invasive tubular‐type carcinomas arising in IPMN, microscopic size‐based AJCC pT stages were not significant predictors of patient outcomes. However, for LS, a size threshold of 1.5 cm was optimal for stratifying both RFS and OS. The AJCC 8th ed. may not be applicable for stratifying small invasive IPMNs with colloid‐type histology that generally portend a more favourable prognosis.
For small invasive carcinomas arising from intraductal papillary mucinous neoplasms (IPMNs), the microscopic size of the largest invasive focus (LS) optimally stratifies recurrence‐free and overall survival at a threshold of 1.5 cm.
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