Concentration Distribution of Particles in Solid-Liquid Two-Phase Flow Through Vertical Pipe

The concentration distributions of particles were measured in a vertical pipe for both an upward and a doward flow. When the stream Reynolds number was low, the profile for the upward flow was opposite to that for the downward flow. The profiles of the concentration distributions under various conditions were classified into several kinds of modes. They were summarized into a figure by means of the stream Reynolds number and the particle Reynolds number. Two possible forces were suggested in order to explain the general distribution of partices

Transcriptional regulation of connective tissue growth factor by sphingosine 1-phosphate in rat cultured mesangial cells

AbstractConnective tissue growth factor (CTGF) is induced by transforming growth factor-β (TGF-β) via Smad activation in mesangial cells. We recently reported that sphingosine 1-phosphate (S1P) induces CTGF expression in rat cultured mesangial cells. However, the mechanism by which S1P induces CTGF expression is unknown. The present study revealed that S1P-induced CTGF expression is mediated via pertussis toxin-insensitive pathways, which are involved in the activation of small GTPases of the Rho family and protein kinase C. We also showed by luciferase reporter assays and chromatin immunoprecipitation that S1P induces CTGF expression via Smad activation as TGF-β does

Non–contact real–time detection of trace nitro-explosives by MOF composites visible–light chemiresistor

To create an artificial structure to remarkably surpass the sensitivity, selectivity and speed of the olfaction system of animals is still a daunting challenge. Herein, we propose a core-sheath pillar (CSP) architecture with a perfect synergistic interface that effectively integrates the advantages of metal–organic frameworks and metal oxides to tackle the above-mentioned challenge. The sheath material, NH₂-MIL-125, can concentrate target analyte, nitro-explosives, by 10¹² times from its vapour. The perfect band-matched synergistic interface enables the TiO₂ core to effectively harvest and utilize visible light. At room temperature and under visible light, CSP (TiO₂, NH₂-MIL-125) shows an unexpected self-promoting analyte-sensing behaviour. Its experimentally reached limit of detection (～0.8 ppq, hexogeon) is 10³ times lower than the lowest one achieved by a sniffer dog or all sensing techniques without analyte pre-concentration. Moreover, the sensor exhibits excellent selectivity against commonly existing interferences, with a short response time of 0.14 min

The usefulness of re-attachability of anti-adhesive cross-linked gelatin film and the required physical and biological properties.

Background:To overcome the unfavorable issues associated with conventional anti-adhesive HA/CMC film, we developed an anti-adhesive thermally cross-linked gelatin film.Objective:We tried to clarify the re-attachability of the film and the required properties concerning the film thickness, stiffness and anti-adhesion effect.Methods:To determine the optimal thickness, 5 kinds of the thickness of gelatin film and the conventional film were analyzed by the tensile test, shearing test, buckling test and tissue injury test. Finally, using the optimal film thickness, we tried to clarify the anti-adhesion effect of the reattached film.Results:The tensile and shearing test showed gelatin films ≥30 μm thick had greater tensile strength and a smaller number of film fractures, than the conventional film. The buckling and tissue injury test showed gelatin films ≥60 μm thick had higher buckling strength and worse injury scores than the conventional film. The anti-adhesive effect of re-attached gelatin film using optimal thickness (30-40 μm) found the anti-adhesion score was significantly better than that of the control.Conclusions:Provided it has an optimal thickness, gelatin film can be reattached with enough physical strength not to tear, safety stiffness not to induce tissue injury, and a sufficient anti-adhesion effect

Effects of Fiber Diameter and Spacing Size of an Artificial Scaffold on the In Vivo Cellular Response and Tissue Remodeling.

By mimicking the extracellular matrix, nonwoven fabrics can function as scaffolds for tissue engineering application ideally, and they have been characterized regarding their fiber diameter and fiber spacing (spacing size) in vitro. We chronologically examined the in vivo effects of these fabrics on the cellular response and tissue remodeling. Four types of nonwoven polyglycolic acid fabrics (Fabric-0.7, Fabric-0.9, Fabric-3, and Fabric-16 with fiber diameters of 0.7, 0.9, 3.0, and 16.2 μm and spacing sizes of 2.0, 19.3, 19.0, and 825.4 μm, respectively) were implanted into the rat dorsum and subjected to histologic and immunohistochemical analyses from day 3 to 70. With Fabric-0.7, inflammatory cells (mainly M1 macrophages) and myofibroblasts with collagen type III accumulated mainly on the surface of the fabric and did not infiltrate inside the fabric initially, likely due to the narrow fiber space. Massive formation of collagen type I then appeared with the degradation of the fabrics, and finally, the remodeled tissue turned into a dense scar. With Fabric-0.9 and Fabric-3, inflammatory cells (predominantly M2 macrophages) were seen in all layers of the fabric initially. A mild increase in collagen type I was then seen, with few myofibroblasts, and the remodeled tissue ultimately showed a relatively little scar with an adequate thickness of the tissue induced by the fabrics. With Fabric-16, inflammatory cells (predominantly M1 macrophages) infiltrated into all layers of the fabric initially along with many myofibroblasts, especially in the hole. Lately, massive formation of collagen type I was noted due to the slow degradation of the fabric, with the shrinking of the fabric substantially, and the remodeled tissue finally turned to a dense scar. These findings suggest that optimizing the spacing size as well as the fiber diameter of artificial scaffolds may control the cellular response and tissue remodeling and facilitate favorable tissue regeneration without scar formation

Incidence of orthostatic hypotension and cardiovascular response to postoperative early mobilization in patients undergoing cardiothoracic and abdominal surgery

Background: In cardiothoracic and abdominal surgery, postoperative complications remain major clinical problems. Early mobilization has been widely practiced and is an important component in preventing complications, including orthostatic hypotension (OH) during postoperative management. We investigated cardiovascular response during early mobilization and the incidence of OH after cardiothoracic and abdominal surgery. Methods: In this prospective observational study, we consecutively analyzed data from 495 patients who underwent elective cardiothoracic and abdominal surgery. We examined the incidence of OH, and the independent risk factors associated with OH during early mobilization after major surgery. Multivariate logistic regression was performed using various characteristics of patients to identify OH-related independent factors. Results: OH was observed in 191 (39%) of 495 patients. The incidence of OH in cardiac, thoracic, and abdominal groups was 39 (33%) of 119, 95 (46%) of 208, and 57 (34%) of 168 patients, respectively. Male sex (OR 1.538; p = 0.03) and epidural anesthesia (OR 2.906; p < 0.001) were independently associated with OH on multivariate analysis. Conclusions: These results demonstrate that approximately 40% patients experience OH during early mobilization aftercardiothoracic and abdominal surgery. Sex was identified as an independent factor for OH during early mobilization after all three types of surgeries, while epidural anesthesia was only identified after thoracic surgery. Therefore, the frequent occurrence of OH during postoperative early mobilization should be recognized

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction &gt;0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead