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SUMMARY: Bone mineral density screening prior to initiating aromatase inhibitor therapy was associated with lower incident bone fractures and healthcare resource utilization among postmenopausal breast cancer survivors. INTRODUCTION: Postmenopausal women with hormone receptor–positive breast cancer (BC) often receive aromatase inhibitor (AI) therapy. However, AIs induce bone loss and BC survivors are at an increased risk of bone fractures. This study determined whether receipt of baseline dual-energy x-ray absorptiometry (DXA) screening is associated with decreased incident fractures and lower healthcare resource utilization. METHODS: We retrospectively analyzed 22,713 stage 0–III primary BC survivors who received AI therapy ≤ 1 year prior to BC diagnosis from the Medicare-Linked Surveillance, Epidemiology, and End-Results database. We categorized DXA screening for those who had a procedural claim within 12 months prior through 6 months after first AI claim. We used propensity score methods to assess the association of DXA screening with bone fractures and health resource utilization. RESULTS: Of the study cohort, 62% received a DXA screening. Women with comorbid dementia, renal disease, and congestive heart failure were less likely to receive a DXA. After adjusting for confounders, BC survivors who received a DXA had a 32% decreased risk of any bone fracture compared to those who did not (hazard ratio (HR): 0.68, 95% confidence interval (CI): 0.60–0.76, p < 0.001). Similarly, those who received a DXA were less likely to be hospitalized (HR 0.73 (0.62–0.86)) or use outpatient services (HR 0.85 (0.74–0.97)). CONCLUSIONS: Bone density screening is associated with decreased incident bone fractures and a lower likelihood of utilizing healthcare resource for fracture-related events. Postmenopausal BC survivors treated with AIs should undergo appropriate bone density screening to reduce morbidity, mortality, and health care expenses.

Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease (ESKD) across the lifespan. While 10% to 15% of children and 3% of adults who develop ESKD have FSGS, it remains uncertain whether the natural history differs in pediatric vs adult patients, and this uncertainty contributes to the exclusion of children and adolescents in clinical trials.To examine whether there are differences in the kidney health outcomes among children, adolescents, and adults with FSGS.This cohort study used pooled and parallel analyses, completed July 5, 2022, from 3 complimentary data sources: (1) Nephrotic Syndrome Rare Disease Clinical Research Network (NEPTUNE); (2) FSGS clinical trial (FSGS-CT); and (3) Kidney Research Network (KRN). NEPTUNE is a multicenter US/Canada cohort study; FSGS-CT is a multicenter US/Canada clinical trial; and KRN is a multicenter US electronic health record-based registry from academic and community nephrology practices. NEPTUNE included 166 patients with incident FSGS enrolled at first kidney biopsy; FSGS-CT included 132 patients with steroid-resistant FSGS randomized to cyclosporine vs dexamethasone with mycophenolate; and KRN included 184 patients with prevalent FSGS. Data were collected from November 2004 to October 2019 and analyzed from October 2020 to July 2022.Age: children (age13 years) vs adolescents (13-17 years) vs adults (≥18 years). Covariates of interest included sex, disease duration, APOL1 genotype, urine protein-to-creatinine ratio, estimated glomerular filtration rate (eGFR), edema, serum albumin, and immunosuppressive therapy.ESKD, composite outcome of ESKD or 40% decline in eGFR, and complete and/or partial remission of proteinuria.The study included 127 (26%) children, 102 (21%) adolescents, and 253 (52%) adults, including 215 (45%) female participants and 138 (29%) who identified as Black, 98 (20%) who identified as Hispanic, and 275 (57%) who identified as White. Overall, the median time to ESKD was 11.9 years (IQR, 5.2-19.1 years). There was no difference in ESKD risk among children vs adults (hazard ratio [HR], 0.67; 95% CI, 0.43-1.03) or adolescents vs adults (HR, 0.85; 95% CI, 0.52-1.36). The median time to the composite end point was 5.7 years (IQR 1.6-15.2 years), with hazard ratio estimates for children vs adults of 1.12 (95% CI, 0.83-1.52) and adolescents vs adults of 1.06 (95% CI, 0.75-1.50).In this study, the association of FSGS with kidney survival and functional outcomes was comparable at all ages.

Transjugular intrahepatic portosystemic shunt (TIPS) can effectively reduce the portal venous pressure and relieve the clinical complications related to portal hypertension. However, hepatic encephalopathy (HE) is still the main complication post TIPS. Studies have shown that patients over 65 years old with liver function reserve in Child-Pugh grade C are the high-HE-risk group post TIPS, and early TIPS treatment can benefit the survival of these high-risk patients. In this study, TIPS was used to treat 60 cases aged65 years old and liver function reserve in Child-Pugh grade C (decompensated liver cirrhosis) with esophagogastric variceal bleeding. The clinical results of 1-year was observed and the porto systemic gradient (PSG) was evaluated. The relationship between the incidence of HE and the PSG of patients with and without HE were compared to evaluate the effect of PSG on the incidence of HE.经颈静脉肝内门-体分流术（TIPS）能有效地降低门静脉压力以及缓解门静脉高压相关的临床并发症。但是肝性脑病（HE）仍是TIPS术后主要并发症。有研究表明年龄65岁、肝功能Child-Pugh C级患者是发生TIPS术后HE的高危人群，且早期TIPS治疗能使这部分高危患者生存获益。对60例年龄65岁和肝功能Child-Pugh C级失代偿期肝硬化合并食管胃底静脉曲张破裂出血患者行TIPS治疗，观察1年的临床结果，评价门静脉压力梯度（PSG）与HE发生率的关系，再将无HE患者的PSG与有HE患者的PSG进行对比分析，评价PSG对HE发生率的影响。.

大动脉炎（Takayasu′s arteritis, TA）肺动脉受累（pulmonary artery involvement, PAI）有别于主动脉系统受累的大动脉炎，其临床症状、受累血管及预后与传统的大动脉炎有较大差异。近年来，有关单纯肺动脉受累的大动脉炎（isolated PAI）或以肺动脉受累为首发表现的大动脉炎的报道逐渐增多，然而由于临床经验不足以及诊断标准的局限，大动脉炎肺动脉受累的漏诊和误诊率仍然较高，应引起更多重视。本文对以肺动脉受累为主要表现的大动脉炎的临床特点及研究进展进行总结，综述如下。.

We aim to uncover the expression pattern and biological functions of PAG1 in the progression of nasopharyngeal carcinoma (NPC).PAG1 levels in 28 paired NPC tissues and paracancerous tissues were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Then, the potential influences of PAG1 on proliferative, migratory and invasive abilities of SUNE2 and CNE2 cells were assessed by cell counting kit-8 (CCK-8) and transwell assay, respectively. Next, the interaction between PAG1 and its direct target gene of phosphate and tension homology deleted on chromosome ten (PTEN) was verified by Dual-Luciferase reporter gene assay. At last, rescue experiments were conducted to uncover the role of PAG1/PTEN axis in the malignant progression of NPC.PAG1 was highly expressed in NPC tissues and cell lines. Knockdown of PAG1 blocked NPC cells to proliferate, migrate, and invade. Dual-Luciferase reporter gene assay indicated the binding relationship between PAG1 and PTEN. In addition, both mRNA and protein levels of PTEN were negatively regulated by PAG1 in NPC cells. Notably, PTEN was responsible for PAG1-regulated malignant progression of NPC.PAG1 is upregulated in NPC tissues and cells and stimulates the proliferative and metastatic abilities in NPC by targeting PTEN, thus aggravating the malignant progression of NPC.

The purpose of this study was to explore the mitigating effect of morphine on the myocardial ischemia-reperfusion injury (MIRI) in rats through the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway. A total of 30 male Wistar rats were assigned into sham group, MIRI group and morphine group using a random number table. The model of MIRI was routinely established. Then, the pathological changes in the morphology of myocardial tissues were observed via hematoxylin-eosin (HE) staining. The levels of the oxidative stress indicators superoxide dismutase (SOD) and malondialdehyde (MDA), the content of the inflammatory cytokine tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6 and the quantity of glutathione peroxidase (GSH-Px), lactate dehydrogenase (LDH), creatine kinase (CK), CK-MB and cardiac troponin I (cTnI) in the myocardial enzyme spectrum were determined and analyzed through enzyme-linked immunosorbent assay (ELISA). Moreover, the messenger ribonucleic acid (mRNA) and protein expressions of cAMP, PKA, cAMP-response element binding protein (CREB) and phosphorylated CREB (p-CREB) in the cAMP/PKA signaling pathway in the myocardial tissues were measured using real-time polymerase chain reaction (PCR) and Western blotting, respectively. The results manifested that compared with those in MIRI group, the levels of myocardial infarct size, LDH, CK, CK-MB, cTnI, MDA, TNF-α, IL-1β, IL-6 and p-CREB were decreased, while the levels of GSH-Px, SOD, PKA and CREB were increased in the morphine group. In conclusion, morphine may mitigate MIRI in rats through the cAMP/PKA signaling pathway.

The aim of this work was to investigate the mechanism by which long non-coding RNA (lncRNA) WTAPP1 promotes the malignant progression of laryngeal cancer.In this study, quantitative real-time polymerase chain reaction (qRT-PCR) examined the expression of lncRNA WTAPP1 in 49 pairs of tumor tissue specimens and paracancerous normal ones collected from laryngeal cancer patients. Subsequently, in the laryngeal squamous cell carcinoma cell lines AMC-HN-8 and Hep-2, WTAPP1 overexpression and knockdown vectors were constructed using lentivirus, and cell counting kit-8 (CCK-8), cell colony formation and 5-ethynyl-2'-deoxyuridine (EdU) assays were carried out to analyze the impact of lncRNA WTAPP1 on the function of laryngeal cancer cells. Finally, Luciferase reporting assay and recovery experiments were carried out to further explore whether lncRNA WTAPP1 has an impact on the malignant progression of laryngeal cancer via modulating microRNA-592.QRT-PCR results revealed a significantly higher expression of lncRNA WTAPP1 in tumor tissues of patients with laryngeal cancer than that in adjacent normal ones. Compared with patients with low expression of WTAPP1, those with higher expression had a more advanced pathological stage. Meanwhile, the proliferation ability of cells in sh-WTAPP1 group was remarkably attenuated when compared with that in sh-NC group. In addition, microRNA-592 and WTAPP1 mRNA levels were found negatively correlated in laryngeal carcinoma tissue specimens. Luciferase reporter gene assay indicated that WTAPP1 can be targeted by microRNA-592 through certain binding sites. Moreover, we demonstrated through some recovery experiments that WTAPP1 can indeed serve as an oncogene accelerating the malignant progression of laryngeal cancer through the modulation of microRNA-592.LncRNA WTAPP was markedly highly expressed both in laryngeal carcinoma tissues and cell lines, which was also found to be closely relevant to the pathological stage of laryngeal cancer patients. Additionally, lncRNA WTAPP1 is able to enhance the proliferation capacity of laryngeal carcinoma cells via regulating microRNA-592.

We investigate the Landau-Zener-St\"uckelberg-Majorana interferometry of a superconducting qubit in a semi-infinite transmission line terminated by a mirror. The transmon-type qubit is at the node of the resonant electromagnetic (EM) field, ``hiding'' from the EM field. We modulate the resonant frequency of the qubit by applying a sinusoidal flux pump. We perform spectroscopy by measuring the reflection coefficient of a weak probe in the system. Remarkable interference patterns emerge in the spectrum, which can be interpreted as multiphoton resonances in the dressed qubit. Our calculations agree well with the experiments.

In recent years, the research of spatiotemporal clustering of disease is attracting more and more attention, which plays an important role in understanding the temporal and spatial distribution characteristics of diseases, and can provide references for the etiology exploration and prevention and control of diseases. In order to better understand the research methods of spatiotemporal clustering of diseases and its application progress, this paper summarizes the statistical methods commonly used in relevant researches at demestic and abroad from three aspects of temporal clustering, spatial clustering and spatiotemporal clustering of diseases.近年来，疾病的时空聚集分析受到越来越多的关注，其在了解疾病在时间和空间上的分布特征方面发挥着重要的作用，可为探索病因和疾病防控提供参考依据。为了更好地理解疾病时空聚集性研究的方法及其应用进展，本文从疾病的时间聚集性、空间聚集性和时空聚集性3个方面对国内外相关研究中常用的统计学方法进行深入探讨。.

AIMS To evaluate the effect of a DNA priming and protein boosting immunization scheme in ducks. METHODS AND RESULTS Pekin ducks were immunized with pTCY/VP2 DNA vaccine; on day 14 (D14) after primary immunization, the ducks were boosted with either the same vaccine (DNA + DNA) or the rVP2 vaccine (DNA + rVP2). CpG oligodeoxynucleotides containing three copies of GACGTT motifs were used as the adjuvant in the vaccines. Compared with unimmunized controls, both immunization schemes significantly increased the titre of antigen-specific antibodies, lymphocyte proliferation index, percentage of CD4+ and CD8+ cells in peripheral blood mononuclear cells (PBMCs) and mRNA expression of interferon (IFN)-α, IFN-γ, interleukin (IL)-6 and IL-12 in antigen-stimulated PBMCs. Furthermore, compared with the DNA + DNA homologous scheme, the DNA + rVP2 heterologous scheme significantly increased lymphocyte proliferation, percentage of CD4+ and CD8+ cells in PBMCs and upregulation of mRNA expression of cytokines 2 weeks after the boost (D28). CONCLUSIONS The DNA + rVP2 immunization scheme enhanced immune responses, mainly Th1 type, against parvovirus in ducks. SIGNIFICANCE AND IMPACT OF THE STUDY The DNA priming and protein boosting heterologous immunization strategy can be applied to develop vaccines against viral infections in ducks. It can potentially be used in breeding ducks because of long-term immunity may confer protection for ducklings.

Background Alectinib, a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), is highly effective in advanced ALK-rearranged non-small-cell lung cancer and represents a standard first-line therapy. New strategies are needed, however, to delay resistance. We conducted a phase I/II study to assess the safety and efficacy of combining alectinib with bevacizumab, a monoclonal antibody against vascular endothelial growth factor. Patients and methods Patients with advanced ALK-rearranged non-squamous non-small-cell lung cancer were enrolled. The phase I portion employed a dose de-escalation strategy with alectinib and bevacizumab starting at the individual standard doses. The primary objective was to determine the recommended phase II dose (RP2D). In phase II, the primary objective was to evaluate the safety of the combination at the RP2D; the secondary objective was to determine extracranial and intracranial efficacy. Results Eleven patients were enrolled between September 2015 and February 2020. Most patients (82%) had baseline brain metastases. Six patients (55%) were treatment-naive; five (46%) had received prior ALK TKIs (crizotinib, n = 3; ceritinib, n = 1; crizotinib then brigatinib, n = 1). No dose-limiting toxicities occurred. RP2D was determined as alectinib 600 mg orally twice daily plus bevacizumab 15 mg/kg intravenously every 3 weeks. Three patients experienced grade 3 treatment-related adverse events: pneumonitis related to alectinib, proteinuria related to bevacizumab, and hypertension related to bevacizumab. Treatment-related intracranial hemorrhage was not observed. Six (100%) of six treatment-naive patients and three (60%) of five ALK TKI-pretreated patients had objective responses; median progression-free survival was not reached (95% confidence interval, 9.0 months-not reached) and 9.5 months (95% confidence interval, 4.3 months-not reached), respectively. Intracranial responses occurred in four (100%) of four treatment-naive and three (60%) of five TKI-pretreated patients with baseline brain metastases. The study was stopped prematurely because of slow accrual. Conclusions Alectinib plus bevacizumab was well tolerated without unanticipated toxicities or dose-limiting toxicities., Highlights • Alectinib plus bevacizumab is safe in patients with advanced ALK-rearranged non-small-cell lung cancer. • Bevacizumab combined with alectinib does not increase risk of intracranial hemorrhage in patients with brain metastases. • Enrollment challenges with this trial highlight important considerations for future studies of ALK inhibitor combinations.

Thiazide diuretics are still widely used as an initial therapy in essential hypertension, sometimes in both hypertensive and diabetic patients. However, the metabolic effects in type 2 diabetes treated with a thiazide diuretic have not been fully elucidated.Randomized controlled trials (RCTs) were identified from the electronic databases: the Cochrane Library, MEDLINE, and PubMed web of knowledge. The trials compared the metabolic effects of hydrochlorothiazide (HCTZ) versus no- HCTZ hypertension treatment in type 2 diabetes.A total of 368 papers showed a match, in the keyword search. Upon screening the title, reading the abstract and the entire article, 13 parallel-design RCTs, described in 7 reports, involving 720 patients, showed fasting glucose (FG) (SMD = 0.27, 95% CI 0.11-0.43) and HbA1c (SMD = 1.09, 95% CI 0.47-1.72)significantly increased in the patients treated with HCTZ groups and high-density lipoprotein-cholesterol (HDL-C) (SMD = -0.44, 95% CI -0.81- -0.08) decreased in the patients treated with low-dose HCTZ groups. Our study showed FG, HbA1c and HDL-C significantly affected in the patients treated with low-dose HCTZ groups.Our study showed FG and HbA1c increased in the patients treated with the low-dose HCTZ groups, and HDL-C decreased in the patients. While thiazide diuretics are still a recommended medication of hypertension therapy for type 2 diabetes, treatment with low-dose HCTZ should be attempted to evaluate the effectiveness and adverse metabolic effects.

AIM Peroxisome proliferator activated receptors (PPARs) are nuclear receptors involved in glucose and lipid metabolism. Three isoforms of PPARs have been identified with different tissue distribution and biological functions. Although the pharmacology of each receptor is well studied, the physiological effect of simultaneous activation of PPARalpha, gamma and delta is only starting to emerge. We sought to determine the biological effects of a novel PPAR pan activator and elucidate the physiological mechanisms involved. METHODS Ob/ob, diet-induced obese (DIO) or PPARalpha knockout mice were administered a novel agonist that activates all PPARs to various degrees to determine the effect on body weight, body composition, food intake and energy expenditure. In addition, serum parameters including glucose, insulin, triglycerides and ketone bodies as well as tissue acylcarnitine were evaluated. The effect of the novel agonist on liver and skeletal muscle histopathology was also studied. RESULTS We report that simultaneous activation of all PPARs resulted in substantial weight loss in ob/ob and DIO mice. Consistent with known PPAR pharmacology, we observed that agonist treatment increased lipid oxidation, although appetite suppression was mainly responsible for the weight loss. Agonist-induced weight loss was completely absent in PPARalpha knockout mice suggesting that PPARalpha pharmacology was the major contributor to weight regulation in mice. CONCLUSIONS Our work provides evidence that simultaneous activation of PPARalpha, gamma and delta decreases body weight by regulating appetite. These effects of the pan agonist were completely absent in PPARalpha knockout mice, suggesting that PPARalpha pharmacology was the major contributor to weight loss.

The one-dimensional t-J model Hamiltonian is realized by using hard-core boson operators. A simple algorithm written in Mathematica based on a differential realization of the hard-core bosons for finding exact solutions of the model is proposed. As a simple example, some low-lying excitation energies, the inverse compressibility, and the superconducting structure factors, as well as the particle and spin entanglement of a system with 8 sites are calculated. The results not only confirm the validity of the hard-core boson picture, but also indicate that a quantum phase transition near phase-separation at zero temperature can also be recognized by the particle and spin entanglement.

The equilibrium geometry, electronic structure and optical properties of thiourea S, S-dioxide crystal have been studied using DFT within generalized gradient approximation (GGA) and the local density approximation (LDA), implemented using ultrasoft pseudo-potentials. The optimum bulk geometry is in good agreement with crystallographic data. An analysis of electronic structure, charge and bond order is presented. The energy gap of thiourea dioxide with GGA and LDA calculation is 3.217 or 3.210 eV, respectively, indicating that the compound is an insulator. The calculated absorption spectrum shows a number of absorption peaks, which are believed to be associated with different exciton states, in the fundamental absorption region.

Background To reduce the incidence of early arteriovenous fistula failure (AVF) due to thrombosis in pediatric hemodialysis (HD) patients, a primary thromboprophylaxis (PTP) protocol was initiated at author's institution in June 2005. The goal of this study is to report author's experience with this protocol one year later. Methods and Results 19 AVFs (14 patients, Historical group) and 8 AVFs (7 patients, PTP group) were created prior to and after initiation of PTP respectively. PTP consisted of unfractionated heparin (5–10 units/kg/hr) infusion postoperatively, followed by subcutaneous low molecular weigh heparin (LMWH) until AVF was matured. LMWH dosing was “Prophylactic” (0.5 mg/kg/d, anti-factor Xa levels: peak 0.25–0.5 and trough < 0.3 units/mL) and “Therapeutic” (1 mg/kg/d, anti-factor Xa level: peak 0.5-1 and trough < 0.5 units/mL) based on thrombosis predisposition. In Historical group, 12 AVFs did not receive thromboprophylaxis (No-treatment group), 5 received 81 mg aspirin/day (Aspirin group), and 2 received LMWH. In No-treatment group 10/12 AVFs failed: 9 thromboses and 1 stenosis. In Aspirin group 1/5 AVFs failed due to thrombosis. In PTP group 1/8 AVFs failed due to stenosis; the first 2 AVFs developed hematoma prompting a reduction in LMWH dose and monitoring trough anti-factor Xa levels, one AVF required thrombectomy after LMWH was transiently held. The incidence of thrombosis was less in PTP group (12.5%) when comparing to No-treatment group (83%) (p < 0.05). Conclusion PTP is a feasible option to prevent early thrombosis at AVF. Close clinical and laboratory monitoring including trough anti-factor Xa levels is required to adjust optimum anticoagulation. Larger studies are needed to clarify safety and efficacy of our PTP protocol.

We determined the prevalence and seasonality of infections by Fasciola of goats and bovine species (cattle and water buffalo) in Hubei and Anhui provinces of China. Faecal samples were collected at 2- to 3-month intervals from 200 goats in Hubei province and from 152 bovine species in Anhui province. All faecal samples were examined for the presence of parasites. We determined the nucleotide sequences of the first and second internal transcribed spacers (ITS-1 and ITS-2) of the nuclear ribosomal DNA (rDNA) of 39 Fasciola worms from Anhui province. The prevalence of Fasciola infection in goats ranged between 3.5 and 37.0%, with mean eggs per gram (EPG) ranging between 29.0 and 166.0. Prevalence and EPG exhibited downward trends over time with significant differences. The prevalence of Fasciola infection in cattle ranged between 13.3 and 46.2% (mean EPG, 36.4–100.0), and that of water buffalo ranged between 10.3 and 35.4% (mean EPG, 25.0–89.6), with a higher prevalence of infection and EPG from June to October compared with December to March. Analysis of ITS-1 and ITS-2 sequences revealed that F. hepatica and F. gigantica were present in all bovine species of Anhui province and that F. gigantica mainly infected water buffalo. This is the first demonstration of Fasciola infection in Hubei province and detection of F. hepatica and F. gigantica in Anhui province. The present study of Hubei province shows that mass treatment of livestock with closantel sodium injections in April and August/September controlled Fasciola infection effectively.

Research is underway to explore the feasibility of implementing complete RF subsystems in standard mainstream CMOS processes without a need for any off-chip components. Progress to date has verified that RF circuits and on-chip antennas adequate for chip to chip communication can be realized, and it can be stated with some certainty that feasibility has been established. Radio architecture, signaling methodology, and individual circuit blocks have been devised and confirmed. It remains to demonstrate an on-chip reference with +/-150 ppm stability, optimize the individual circuit blocks, and demonstrate the overall concept in a single integrated chip

Recent studies suggest that inflammation may play an important role in the pathogenesis of Parkinson's disease (PD). Because the C(−260)→T polymorphism in the promoter of the CD14 monocyte receptor gene ( pCD14 ) could affect the predisposition to the inflammatory response, we conducted a case-control study to investigate a possible genetic susceptibility of the pCD14 polymorphism in patients with PD. This study included 200 sporadic PD patients and 200 controls, matched by sex and case-control pairs for age at onset in the case. All observed genotype frequencies were in Hardy-Weinberg equilibrium. Results revealed that the CD14-T allele of the pCD14 polymorphism in the female PD patients existed statistically significant difference from that of the female controls (OR=1.262, P =0.038), but not for male. Female individuals with homozygote CD14-TT genotype were significantly increased risk of PD by 1.28 time ( P =0.027). Furthermore, a logistic regression analysis confirmed that the homozygote CD14-TT genotype was an independent risk factor for PD (OR=1.576, P =0.030). In conclusion, results of this study indicate the pCD14 polymorphism to be a genetic risk factor for PD in females.

Effects of tacrolimus, a protein phosphatase 2B inhibitor, on the reflex plasticity between the pelvic afferent nerve fibers and the urethra were examined in urethane-anesthetized rats. Repetitive stimulation (1 Hz) induced a potentiation (0.9+/-0.2 and 10.5+/-1.6 spikes in control and repetitive stimulation groups, respectively, P0.01, N=10) in the activities of the pelvic-urethral reflex. Intrathecal tacrolimus (0.1 mM, 10 microl, bolus) blocked repetitive stimulation-induced potentiation in pelvic-urethral reflex activities (3.2+/-0.9 spikes in tacrolimus group versus 10.5+/-1.6 spikes in repetitive stimulation group, P0.01, N=10). Glutamate (intrathecal, 0.1 mM, 10 microl, bolus) and N-methyl-D-aspartic acid (intrathecal, 0.1 mM, 10 microl, bolus) both reversed the blocking effects exerted by tacrolimus on repetitive stimulation-induced pelvic-urethral reflex potentiation (15.0+/-1.4 spikes in glutamate group and 11.4+/-1.4 spikes in N-methyl-D-aspartic acid group versus 3.2+/-0.9 spikes in tacrolimus-treated repetitive stimulation group, P0.01, N=7). In addition, the reversal effect elicited by these two agonists of glutamate receptors showed no statistical difference (P=NS, N=7). All these results demonstrated that tacrolimus could block glutamatergic N-methyl-D-aspartic acid receptor-mediated potentiation in pelvic-urethral reflex activities. This finding may be pathologically relevant in patients who take tacrolimus as immunosuppressant therapy. Whether tacrolimus will induce urine incontinence in such patients or not needs further investigation.

The strength of a composite propeller blade is evaluated by performing a nonlinear hydroelastic analysis. The finite element method, lifting surface theory, least square method, equilibrium equation, and Hashin failure criteria are employed for the structural analysis, fluid analysis, stress smoothing, three-dimensional stress calculation, and strength assessment, respectively. Additionally, the strength of the blades with balanced and unbalanced stacking sequences are evaluated and discussed. Five failure modes, fiber tension and compression, matrix tension and compression, and delamination are considered. The strength is shown to be insufficient for the blades with [.../452/90/0]S. Meanwhile, the blades with [.../2/90/0]S and [.../15/15/90/0]S are shown to have sufficient structural strength. However, attention shall be paid to the delamination failure at the leading and trailing edges of the blade.

The concept of overall connectivity of a graph G was extended here to the definition of the overall hyper-Wiener index OWW(G) of a graph G, defined as the sum of the hyper-Wiener indexes in all subgraphs of G, as well as the sum of eth-order terms, eOWW(G), with e being the number of edges in the subgraph. The potential usefulness of the overall hyper-Wiener index in QSAR/QSPR is evaluated by its correlation with a number of properties of C3-C8 alkanes and cycloalkanes.

A new dynamic scheduling strategy, Parts-Machines Matching (PMM), is developed and tested in simulated flexible manufacturing systems. This strategy is aimed to achieve globally optimal matching between parts and machines by a semi-qualitative optimization algorithm, originally developed for the Stable Marriage Problem. Global and Partial implementations of PMM are presented and compared with other conventional part-flow rules. They are found to achieve better shop performance than conventional rules, in terms of system throughput, robustness against travel time uncertainties, and recovery from machine breakdowns. The prospect of bringing about system-wide optimization-based performance improvements into bidding schemes makes the proposed framework very significant.

Correction to: Oncogene (2017) 36, 4243–4252; doi: 10.1038/onc.2017.8; published online 6 March 2017 The authors noted an error in the bottom panel of Figure 2c. A revised version is shown below and the text of the manuscript remains unchanged. The authors would like to apologize for any inconvenience caused and confirm that the conclusions drawn from this research are not affected by this error.

PpLSU3, a mobile group I intron found in the ribo-somal RNA genes of Physarum polycephalum, encodes the I-PpoI homing endonuclease. This enzyme represents one of the rare cases in nature where a protein is expressed from an RNA polymerase I transcript. Our previous results showed that the full length intron, but not a further processed species, is the messenger for I-PpoI, implying a role of the untranslated region (UTR) in gene expression. To study the function of the 3'-UTR in expression of the endonuclease and in splicing of the intron, we replaced the I-PpoI gene in PpLSU3 with the gene for the alpha-fragment of Escherichia coli beta-galactosidase, and then integrated this chimeric intron into all the chromosomal rDNA repeats of yeast. The resulting cells synthesized functional alpha-fragment, as evidenced by a complementation assay analogous to that used in E.coli. The beta-galactosidase activity thus provides an unusual and potentially valuable readout for Pol I transcription from chromosomal rDNA. This is the first example in which a eucaryotic homing endonuclease gene has been successfully replaced by a heterologous gene. Using deletion mutagenesis and a novel randomization approach with the alpha-fragment as a reporter, we found that a small segment of the 3'-UTR dramatically influences both splicing and protein expression.

The O(1D)+CH4 reaction has been investigated using a new universal crossed molecular beam apparatus. Both the atomic hydrogen channel (CH3O/CH2OH+H) and the molecular hydrogen channel (H2CO/HCOH+H2) have been experimentally observed in this reaction. The experimental results suggest that the main atomic hydrogen channel in the O(1D)+CH4 reaction should be CH2OH (hydroxymethyl)+H, while the CH3O (methoxy)+H channel is at most a minor process. From the product angular distribution measurements, it is clear that the radical products (CH2OH and/or CH3O) in the hydrogen atom channel are only slightly backward scattered relative to the O(1D) beam direction, indicating that this product channel mainly goes through a long-lived intermediate pathway. The slightly backward scattered products are possibly due to other reaction mechanisms. For the molecular hydrogen channel, the product angular distribution obtained from simulation also seems isotropic, implying that this channel also likely goes through a long-lived...

Amplified restriction fragment length polymorphism (AFLP) was used to assess the levels of genomic variations among species and isolates of the genus Colletotrichum. Our objective was to characterize at the molecular level two alfalfa pathogens, isolates Arl-NW and 57RR, which are unusually aggressive to anthracnose-resistant alfalfa cultivars and whose taxa has been uncertain based on morphological criteria. The fingerprint patterns obtained were complex but did enable us to place these two isolates within the species C. trifolii and C. gloeosporioides, respectively. The diversity detected with AFLP among and within Colletotrichum species from alfalfa and other crops corroborated their published taxonomy based on morphology, ribosomal DNA sequence, and random amplified polymorphic DNA analyses. Similarity matrices generated with three primer pairs were highly correlated and, thus, were combined to determine the similarity among the fungal species and isolates that were analyzed. Analysis of the data generated with each of the primer pairs individually and application of either distance or parsimony methods supported the placement of these two isolates. The parsimony method of data analysis was more confirmatory in the placement of Phoma medicaginis as an out-group than the distance method, using either simple matching or Jaccard's coefficients to generate the similarity matrices. Our conclusion is that the AFLP technique will be useful for identification of individual isolates within complex genera such as Colletotrichum because of its ability to generate large numbers of polymorphisms and the consistency of polymerase chain reaction amplification.