Drag reduction induced by superhydrophobic surfaces in turbulent pipe flow

The drag reduction induced by superhydrophobic surfaces is investigated in a turbulent pipe flow. Wetted superhydrophobic surfaces are shown to trap gas bubbles in their asperities. This stops the liquid from coming in direct contact with the wall in that location, allowing the flow to slip over the air bubbles. We consider a well-defined texture with streamwise grooves at the walls in which the gas is expected to be entrapped. This configuration is modeled with alternating no-slip and shear-free boundary conditions at the wall. With respect to the classical turbulent pipe flow, a substantial drag reduction is observed which strongly depends on the grooves’ dimension and on the solid fraction, i.e., the ratio between the solid wall surface and the total surface of the pipe’s circumference. The drag reduction is due to the mean slip velocity at the wall which increases the flow rate at a fixed pressure drop. The enforced boundary conditions also produce peculiar turbulent structures which on the contrary decrease the flow rate. The two concurrent effects provide an overall flow rate increase as demonstrated by means of the mean axial momentum balance. This equation provides the balance between the mean pressure gradient, the Reynolds stress, the mean flow rate, and the mean slip velocity contribution

Characterization and kinetics studies of water buffalo (Bubalus bubalis) myoglobin

The colour of buffalo (Bubalus bubalis L.) meat is darker than bovine meat. Since meat colour depends on the concentration of myoglobin (Mb) and its oxidation state, we have determined the main structural and functional properties of buffalo Mb. Buffalo Mb was purified from longissimus dorsi muscles and its molecular mass determined by ESI Q-TOF mass spectrometry. The molecular mass 17,034.50 was 86.20 Da higher than the bovine Mb. This was confirmed by analysing its primary structure, using a combined approach based on Edman degradation and MALDI-TOF mass spectrometry. Comparing the amino acid sequences of both Mbs, we found three amino acid differences out of 153 amino acid residues. One is a conservative substitution (Dbov141Ebuf), and the other two (Abov19Tbuf and Abov117Dbuf) are nonconservative. These amino acid substitutions are unlikely to cause structural changes because they are located far from the heme binding pocket, as revealed by the 3D structure of buffalo Mb elaborated by homology modelling. Stability analyses show no difference with the bovine Mb for helix E and only minor differences in the stability values for helices A and G. Moreover, autoxidation rates of purified buffalo and bovine myoglobins at 37 °C, pH 7.2, were almost identical, 0.052 ± 0.001 h- 1 and 0.054 ± 0.002 h- 1, respectively, as were their oxygen-binding Kd values, 3.7 ± 0.1 μM and 3.5 ± 0.1 μM, respectively. The percent of MetMb values were almost identical. The results presented here suggest that the darker buffalo meat depends on factors other than the oxidation rate of its Mb, as, for example, the Mb content (0.393 ± 0.005 g/100 g of tissue) and consequently MetMb, which are almost twice as high as bovine meat (Mb: 0.209 ± 0.003 g/100 g of tissue). © 2006 Elsevier Inc. All rights reserved

The androgen receptor/filamin A complex as a target in prostate cancer microenvironment.

Prostate cancer represents the major cause of cancer-related death in men and patients frequently develop drug-resistance and metastatic disease. Most studies focus on hormone-resistance mechanisms related to androgen receptor mutations or to the acquired property of prostate cancer cells to over-activate signalling pathways. Tumour microenvironment plays a critical role in prostate cancer progression. However, the mechanism involving androgen/androgen receptor signaling in cancer associated fibroblasts and consequences for prostate cancer progression still remains elusive. We now report that prostate cancer associated fibroblasts express a transcriptional-incompetent androgen receptor. Upon androgen challenging, the receptor co-localizes with the scaffold protein filamin A in the extra-nuclear compartment of fibroblasts, thus mediating their migration and invasiveness. Cancer-associated fibroblasts move towards epithelial prostate cancer cells in 2D and 3D cultures, thereby inducing an increase of the prostate cancer organoid size. Androgen enhances both these effects through androgen receptor/filamin A complex assembly in cancer-associated fibroblasts. An androgen receptor-derived stapled peptide, which disrupts the androgen receptor/filamin A complex assembly, abolishes the androgen-dependent migration and invasiveness of cancer associated fibroblasts. Notably, the peptide impairs the androgen-induced invasiveness of CAFs in 2D models and reduces the overall tumour area in androgen-treated 3D co-culture. The androgen receptor in association with β1 integrin and membrane type-matrix metalloproteinase 1 activates a protease cascade triggering extracellular matrix remodeling. The peptide also impairs the androgen activation of this cascade. The present study offers a potential new marker, the androgen receptor/filamin A complex, and a new therapeutic approach targeting intracellular pathways activated by the androgen/androgen receptor axis in prostate cancer-associated fibroblasts. Such a strategy, alone or in combination with conventional therapies, may allow a more efficient treatment of prostate cancer

Haploidentical hematopoietic stem cell transplantation in a myelofibrosis patient with primary graft failure

The prognosis of patients affected by myelofibrosis (MF) is usually dismal and allogeneic hematopoietic stem cell transplantation (HSCT) remains the only cure. The number of HSCTs in MF patients has recently increased. However, a major obstacle is still represented by primary graft failure (PGF). Currently there are no definitive guidelines for the treatment of PGF and a second HSCT can be performed only when an allogeneic donor is rapidly available. Herein we report on a MF patient with PGF after an unrelated HSCT, who was rescued by a non-myeloablative, unmanipulated, haploidentical HSCT that resulted in persistent engraftment and bone-marrow fibrosis regression, but not in a long-term disease control. Based on this experience we briefly review the role of different conditioning regimens and hematopoietic stem cell sources in the setting of HSCT for MF patients with PGF. The role of haploidentical donors in MF patients lacking HLAmatched relatives is also discussed

Escherichia coli Is Overtaking Group B Streptococcus in Early-Onset Neonatal Sepsis

The widespread use of intrapartum antibiotic prophylaxis (IAP) to prevent group B streptococcus (GBS) early-onset sepsis (EOS) is changing the epidemiology of EOS. Italian prospective area-based surveillance data (from 1 January 2016 to 31 December 2020) were used, from which we identified 64 cases of culture-proven EOS (E. coli, n = 39; GBS, n = 25) among 159,898 live births (annual incidence rates of 0.24 and 0.16 per 1000, respectively). Approximately 10% of E. coli isolates were resistant to both gentamicin and ampicillin. Five neonates died; among them, four were born very pre-term (E. coli, n = 3; GBS, n = 1) and one was born full-term (E. coli, n = 1). After adjustment for gestational age, IAP-exposed neonates had ≥95% lower risk of death, as compared to IAP-unexposed neonates, both in the whole cohort (OR 0.04, 95% CI 0.00-0.70; p = 0.03) and in the E. coli EOS cohort (OR 0.05, 95% CI 0.00-0.88; p = 0.04). In multi-variable logistic regression analysis, IAP was inversely associated with severe disease (OR = 0.12, 95% CI 0.02-0.76; p = 0.03). E. coli is now the leading pathogen in neonatal EOS, and its incidence is close to that of GBS in full-term neonates. IAP reduces the risk of severe disease and death. Importantly, approximately 10% of E. coli isolates causing EOS were found to be resistant to typical first-line antibiotics

乳兒に於ける化膿性骨髄炎の統計的觀察

Additional file 3: Figure S1. Methylation percentages of the two genes (CASP8 and SCGB3A1) in P, C and PCa samples that were differentially methylated in C and P samples in the training set. The figure highlights a higher methylation percentage for PCa than for healthy samples, but also a higher methylation percentage for P than for C samples in both genes

Search for heavy neutral lepton production in K+ decays

A search for heavy neutral lepton production in K + decays using a data sample collected with a minimum bias trigger by the NA62 experiment at CERN in 2015 is reported. Upper limits at the 10−7 to 10−6 level are established on the elements of the extended neutrino mixing matrix |Ue4| 2 and |Uμ4| 2 for heavy neutral lepton mass in the ranges 170–448 MeV/c2 and 250–373 MeV/c2, respectively. This improves on the previous limits from HNL production searches over the whole mass range considered for |Ue4|2 and above 300 MeV/c2 for |Uμ4|2

Systematic versus on-demand early palliative care: results from a multicentre, randomised clinical trial

Background Early palliative care (EPC) in oncology has been shown to have a positive impact on clinical outcome, quality-of-care outcomes, and costs. However, the optimal way for activating EPC has yet to be defined. Methods This prospective, multicentre, randomised study was conducted on 207 outpatients with metastatic or locally advanced inoperable pancreatic cancer. Patients were randomised to receive ‘standard cancer care plus on-demand EPC’ (n = 100) or ‘standard cancer care plus systematic EPC’ (n = 107). Primary outcome was change in quality of life (QoL) evaluated through the Functional Assessment of Cancer Therapy – Hepatobiliary questionnaire between baseline (T0) and after 12 weeks (T1), in particular the integration of physical, functional, and Hepatic Cancer Subscale (HCS) combined in the Trial Outcome Index (TOI). Patient mood, survival, relatives' satisfaction with care, and indicators of aggressiveness of care were also evaluated. Findings The mean changes in TOI score and HCS score between T0 and T1 were −4.47 and −0.63, with a difference between groups of 3.83 (95% confidence interval [CI] 0.10–7.57) (p = 0.041), and −2.23 and 0.28 (difference between groups of 2.51, 95% CI 0.40–4.61, p = 0.013), in favour of interventional group. QoL scores at T1 of TOI scale and HCS were 84.4 versus 78.1 (p = 0.022) and 52.0 versus 48.2 (p = 0.008), respectively, for interventional and standard arm. Until February 2016, 143 (76.9%) of the 186 evaluable patients had died. There was no difference in overall survival between treatment arms. Interpretations Systematic EPC in advanced pancreatic cancer patients significantly improved QoL with respect to on-demand EPC

2-Deoxy-D-Glucose Treatment Induces Ketogenesis, Sustains Mitochondrial Function, and Reduces Pathology in Female Mouse Model of Alzheimer's Disease

Previously, we demonstrated that mitochondrial bioenergetic deficits preceded Alzheimer's disease (AD) pathology in the female triple-transgenic AD (3xTgAD) mouse model. In parallel, 3xTgAD mice exhibited elevated expression of ketogenic markers, indicating a compensatory mechanism for energy production in brain. This compensatory response to generate an alternative fuel source was temporary and diminished with disease progression. To determine whether this compensatory alternative fuel system could be sustained, we investigated the impact of 2-deoxy-D-glucose (2-DG), a compound known to induce ketogenesis, on bioenergetic function and AD pathology burden in brain. 6-month-old female 3xTgAD mice were fed either a regular diet (AIN-93G) or a diet containing 0.04% 2-DG for 7 weeks. 2-DG diet significantly increased serum ketone body level and brain expression of enzymes required for ketone body metabolism. The 2-DG-induced maintenance of mitochondrial bioenergetics was paralleled by simultaneous reduction in oxidative stress. Further, 2-DG treated mice exhibited a significant reduction of both amyloid precursor protein (APP) and amyloid beta (Aβ) oligomers, which was paralleled by significantly increased α-secretase and decreased γ-secretase expression, indicating that 2-DG induced a shift towards a non-amyloidogenic pathway. In addition, 2-DG increased expression of genes involved in Aβ clearance pathways, degradation, sequestering, and transport. Concomitant with increased bioenergetic capacity and reduced β-amyloid burden, 2-DG significantly increased expression of neurotrophic growth factors, BDNF and NGF. Results of these analyses demonstrate that dietary 2-DG treatment increased ketogenesis and ketone metabolism, enhanced mitochondrial bioenergetic capacity, reduced β-amyloid generation and increased mechanisms of β-amyloid clearance. Further, these data link bioenergetic capacity with β-amyloid generation and demonstrate that β-amyloid burden was dynamic and reversible, as 2-DG reduced activation of the amyloidogenic pathway and increased mechanisms of β-amyloid clearance. Collectively, these data provide preclinical evidence for dietary 2-DG as a disease-modifying intervention to delay progression of bioenergetic deficits in brain and associated β-amyloid burden