New perspectives on exploitation of incretin peptides for the treatment of diabetes and related disorders

The applicability of stable gut hormones for the treatment of obesity-related diabetes is now undisputable. This is based predominantly on prominent and sustained glucoselowering actions, plus evidence that these peptides can augment insulin secretion and pancreatic islet function over time. This review highlights the therapeutic potential of glucagon-like peptide-1(GLP-1), glucose-dependent insulinotropic polypeptide(GIP), oxyntomodulin(OXM) and cholecystokinin(CCK) for obesity-related diabetes.Stable GLP-1 mimetics have already been successfully adopted into the diabetic clinic, whereas GIP, CCK and OXM molecules offer promise as potential new classes of antidiabetic drugs. Moreover, recent studies have shown improved therapeutic effects following simultaneous modulation of multiple receptor signalling pathways by combination therapy or use of dual/triple agonist peptides. However, timing and composition of injections may be important to permit interludes of beta-cell rest. The review also addresses the possible perils of incretin based drugs for treatment of prediabetes. Finally, the unanticipated utility of stable gut peptides as effective treatments for complications of diabetes, bone disorders, cognitive impairment and cardiovascular dysfunction is considered.

Distinguishing normal brain aging from the development of Alzheimer＇s disease：inflammation,insulin signaling and cognition

As populations age, prevalence of Alzheimer＇s disease（AD） is rising. Over 100 years of research has provided valuable insights into the pathophysiology of the disease, for which age is the principal risk factor. However, in recent years, a multitude of clinical trial failures has led to pharmaceutical corporations becoming more and more unwilling to support drug development in AD. It is possible that dependence on the amyloid cascade hypothesis as a guide for preclinical research and drug discovery is part of the problem. Accumulating evidence suggests that amyloid plaques and tau tangles are evident in non-demented individuals and that reducing or clearing these lesions does not always result in clinical improvement. Normal aging is associated with pathologies and cognitive decline that are similar to those observed in AD, making differentiation of AD-related cognitive decline and neuropathology challenging. In this mini-review, we discuss the difficulties with discerning normal, age-related cognitive decline with that related to AD. We also discuss some neuropathological features of AD and aging, including amyloid and tau pathology, synapse loss, inflammation and insulin signaling in the brain, with a view to highlighting cognitive or neuropathological markers that distinguish AD from normal aging. It is hoped that this review will help to bolster future preclinical research and support the development of clinical tools and therapeutics for AD.

Effect of Air Plasma Processing on the Adsorption Behaviour of Bovine Serum Albumin on Spin-Coated PMMA Surfaces

This paper reports the adsorption of Bovine Serum Albumin （BSA） onto Dielectric Barrier Discharge （DBD） processed Poly（methyl methacrylate） （PMMA） surfaces by a Quartz Crystal Microbalance with Dissipation monitoring （QCM-D） technique. The purpose is to study the influence of DBD processing on the nature and scale of BSA adsorption on PMMA surface in vitro. It was observed that DBD processing improves the surface wettability of PMMA film, a fact attributable to the changes in surface chemistry and topography. Exposure of the PMMA to Phosphate Buffed Saline （PBS） solution in the QCM-D system resulted in surface adsorption which reaches an equilibrium after about 30 minutes for pristine PMMA, and 90 minutes for processed PMMA surface. Subsequent injection of BSA in PBS indicated that the protein is immediately adsorbed onto the PMMA surface. It was revealed that adsorption behaviour of BSA on pristine PMMA differs from that on processed PMMA surface. A slower adsorption kinetics was observed for pristine PMMA surface, whilst a quick adsorption kinetics for processed PMMA. Moreover, the dissipation shift of protein adsorption suggested that BSA forms a more rigid structure on pristine PMMA surface that on processed surface. These data suggest that changes in wettability and attendant chemical properties and surface texture of the PMMA surface may play a significant role in BSA adsorption process.

The influence of treatment modality on illness perception and secondary prevention outcomes among patients with acute myocardial infarction

Objectives:This study aims to determine if patients with acute myocardial infarction differ in illness perception and secondary prevention outcomes depending on the treatment they received.Methods:A repeated measures design was used to compare patients with acute myocardial infarction receiving three different treatment modalities:ST-elevation myocardial infarction treated by primary percutaneous coronary intervention,ST-elevation myocardial infarction treated by thrombolytic therapy,and non ST-elevation myocardial infarction treated by medication.A convenient sampling technique was used to recruit 206 patients with acute myocardial infarction who agreed to participate in the current study.Patients'illness perception,physical activity,and demographical and clinical data were collected during hospital admission and again at 6 months.Results:A total of 186 patients completed the study.Results showed that the primary percutaneous coronary intervention group perceived their illness as acute rather than chronic(P=0.034)and has lower personal control(P=0.032),higher treatment control(P=0.025),and higher perception of illness coherence(P=0.022)compared with patients receiving thrombolytic therapy and treated after non-ST segment infarction.Moreover,they report low control of their blood pressure(P=0.013)and less physical activity(P=0.001).Conclusion:The results of this study revealed that patients'treated with primary percutaneous coronary intervention had negative illness perception and limited behavioral changes 6 months after hospitalization in comparison with other treatment modalities such as percutaneous coronary intervention and thrombolytic treatment.Further research is recommended to confirm this association with longer follow-up study and among different cultures.

Theory of Approximate Reasoning in Two-Valued Predicate Logic Based on the Quasi-truth Degrees

Based on the theory of the quasi-truth degrees in two-valued predicate logic, some researches on approximate reasoning are studied in this paper. The relation of the pseudo-metric between first-order formulae and the quasi-truth degrees of first-order formulae is discussed, and it is proved that there is no isolated point in the logic metric space (F, ρ ). Thus the pseudo-metric between first-order formulae is well defined to develop the study about approximate reasoning in the logic metric space (F, ρ ). Then, three different types of approximate reasoning patterns are proposed, and their equivalence under some condition is proved. This work aims at filling in the blanks of approximate reasoning in quantitative predicate logic.

Reliability of Chinese web-based ocular surface disease index questionnaire in dry eye patients:a randomized,crossover study

AIM:To assess the reliability of web-based version of ocular surface disease index in Chinese(C-OSDI)on clinically diagnosed dry eye disease(DE)patients.METHODS:A total of 254 Chinese participants(51%male,129/254;mean age:27.90±9.06 y)with DED completed paper-and web-based versions of C-OSDI questionnaires in a randomized crossover design.Ophthalmology examination and DED diagnosis were performed prior to the participants being invited to join the study.Participants were randomly designated to either group A(paper-based first and webbased second)or group B(web-based first and paper-based second).Final data analysis included participants that had successfully completed both versions of the C-OSDI.Demographic characteristics,test-retest reliability,and agreement of individual items,subscales,and total score were evaluated with intraclass correlation coefficients(ICC),Spearman rank correlation,Wilcoxon test and Rasch analysis.RESULTS:Reliability indexes were adequate,Pearson correlation was greater than 0.8 and ICCs range was 0.827 to 0.982;total C-OSDI score was not statistically different between the two versions.The values of mean-squares fit statistics were very low compared to 1,indicating that the responses to the items by the model had a high degree of predictability.While comparing the favorability 72%(182/254)of the participants preferred web-based assessment.CONCLUSION:Web-based C-OSDI is reliable in assessing DED and correlation with the paper-based version is significant in all subscales and overall total score.Webbased C-OSDI can be administered to assess individuals with DED as participants predominantly favored online assessment.

Study of Human Serum Albumin Adsorption and Conformational Change on DLC and Silicon Doped DLC Using XPS and FTIR Spectroscopy

Diamond-like carbon (DLC) coatings are extremely useful for creating biocompatible surfaces on medical implants. DLC and silicon doped DLC synthesised on silicon wafer substrate by using plasma enhanced chemical vapour deposition (PECVD). The effects of surface morphology on the interaction of HSA with doped and undoped DLC films have been investigated. The chemical composition of the surface before and after adsorption was analysed using X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR). Results showed that silicon incorporation DLC tends to increase of sp3/sp2 hybridization ratio by decreasing sp2 hybridized carbon bonding configurations. Following exposure to solutions containing (0.250 μg/ml) HSA, the results indicated that significant changes in the C, N and O levels on the surfaces with reducing of the Si2p band at 100 eV. From FTIR spectrum, the peaks occur the following functional groups were assigned as amide I and II groups at 1650 cm-1 and 1580 cm-1. Both XPS and FTIR spectroscopy confirm that HSA was bound onto the surfaces of the DLC and Si-DLC films via interaction of ionized carboxyl groups and the amino group did not play a significant role in the adsorption of protein. These results from peak intensity show that an adsorbed layer of HSA is higher at high level (19%) silicon doping. Therefore doping of DLC may provide an approach to controlling the protein adsorption.

An implementation of cellular automaton model for single-line train working diagram

According to the railway transportation system＇s characteristics, a new cellular automaton model for the single- line railway system is presented in this paper. Based on this model, several simulations were done to imitate the train operation under three working diagrams. From a different angle the results show how the organization of train operation impacts on the railway carrying capacity. By using the non-parallel train working diagram the influence of fast-train on slow-train is found to be the strongest. Many slow-trains have to wait in-between neighbouring stations to let the fast-train（s） pass through first. So the slow-train will advance like a wave propagating from the departure station to the arrival station. This also resembles the situation of a highway jammed traffic flow. Furthermore, the nonuniformity of travel times between the sections also greatly limits the railway carrying capacity. After converting the nonuniform sections into the sections with uniform travel times while the total travel time is kept unchanged, all three carrying capacities are improved greatly as shown by simulation. It also shows that the cellular automaton model is an effective and feasible way to investigate the railway transportation system.

Research on the Changes of Celestial Tide-generating Force and the Outgoing Long-wave Radiation before the Lushan (China) M_S7.0 Earthquake

Calculation of tidal changes reveals that the MS 7. 0 Lushan County,Sichuan,China,earthquake of April 20,2013 occurred at the minimum phase point of tidal force. It indicates that the seismogenic fault on which the tidal force acts on is of thrust type. The outgoing long-wave radiation( OLR) is the energy radiating from the Earth as infrared radiation at low energy to space. According to the tidal cycle,abnormal OLR change is analyzed based on NOAA satellite data around the whole of China before and after the earthquake. The result shows that the OLR changed evidently with the tide force change.Temporally,the change went through the course: initial OLR rise → s trengthening →reaching abnormal peak → a ttenuation → r eturning to normal; in space,the abnormal area was distributed along the Longmenshan fault and evolved as: scattering→ c onvergent→ s cattering. The process is similar to the change process of rock breaking under stress loading. It indicates that the celestial tidal force can trigger earthquakes when the tectonic stress reaches the critical break point of an active fault and the OLR anomaly is proportional to the seismic tectonic stress change. It is of practical value to combine OLR and tidal force anomaly with earthquake precursor studies.

Study on Value Added Mechanism of Human Capital of Innovative Group

Innovation group is the subject of innovation activities,to promote the increment of human capital group innovation,contribute to more,better innovation,create more benefits and wealth for enterprises,organizations and the whole society.In the value-added mechanism,human capital value from an accretion and symbiotic value.Establish training mechanism and incentive mechanism to promote a health and value based human capital value,improve the communication mechanism and operation mechanism to promote symbiosis value-added based human capital value,is to strengthen the team effect,an important way to promote the increment of human capital group innovation.

Re-Thinking Biology—I. Maxwell’s Demon and the Spontaneous Origin of Life

A hypothesis is advanced in which life began from a Darwinian selection among a diversification of molecular species containing the phosphate moiety which broke the constraints implicit in the Second Law of Thermodynamics, discussed famously by Schrodinger, by obtaining energy from specific infrared frequencies located in the phosphorus-oxygen vibration at a frequency around 1000 cm-1. We propose the source of this energy was from the internal conversion of solar broadband energy by the phosphate mineral Apatite, present at the bottom of a primitive biogenesis pond. In this scenario, life is re-defined as being hotter than its environment and as using its excess energy, supplied by infra-red conversion, to react with its molecular environment and pump itself up the “entropy slope” thereby;replication is through breakages of increasingly large phosphate containing biopolymers. The idea has implications for modern explanations of living systems.

Obesity communication among patients by health professionals: Findings from the Weight Care Project

Obesity is on the increase worldwide and is a major global public health problem. In an increasingly obesogenic environment, it’s important that health professionals are equipped to identify and address obesity issues within their clinical practice. As part of the Weight Care Project, the aim of this study was to explore the obesity-related communication issues for primary care and community-based health professionals. The study design was a quantitative survey, which was completed by 382 primary care and community-based health professionals across Northern Ireland and Republic of Ireland working with adults and children. Key findings included that the majority of the health professionals (86%) recognized having a role in giving obesity advice, acknowledged that in clinical practice communication of obesity messages is both complex and challenging (81%), and reported difficulty in sensitively addressing obesity issues (27%). The health professionals surveyed stated that they communicate obesity messages to their patients using a range of different methods, mainly verbally to individuals, leaflets and factsheets. Numerous benefits of communicating obesity messages were reported;the main one was interacting with patients to build trust. Identified barriers to commu nication were: limited time in patient consultations, restricted access to appropriate information, and not sure where to access appropriate resources. Communication needed be reported by the health professionals included provision of greater resources, more information on obesity management and prevention, followed by health communication training, and clear and consistent messages. Significant differences were observed, including significantly much younger health professionals considered their role to provide obesity advice (P = 0.025). It is clear from this study that health professionals view as important the need to be given information on “what” and “how” to communicate with their patients on obesity. This study highlights that health professionals need continued support to enable them to effectively address weight-related issues in a sensitive manner that is acceptable to the patient.

Satellite detection of IR precursors using bi-angular advanced along-track scanning radiometer data:a case study of Yushu earthquake

The paper has developed and proposed a syn- thesis analysis method based on the robust satellite data analysis technique （RST） to detect seismic anomalies within the bi-angular advanced along-track scanning ra- diometer （AATSR） gridded brightness temperature （BT） data based on spatial/temporal continuity analysis. The proposed methods have been applied to analyze the Yushu （Qinghai, China） earthquake occurred on 14th April 2010, and a full AATSR data-set of 8 years data from March 2003 to May 2010 with longitude from 91~E to 101°E and latitude from 28°N to 38°N has been analyzed. Combining with the tectonic explanation of spatial and temporal continuity of the abnormal phenomena, the analyzed results indicate that the infrared radiation anomalies detected by the AATSR BT data with nadir view appear and enhance gradually along with the development and occurring of the earthquake, especially along the Ganzi-Yushu fault, Nu River fault and Jiali-Chayu fault; more infrared anomalies along the earthquake fault zone （Lancangjiang fault and Ning Karma Monastery-Deqin fault） are detected using the proposed synthesis analysis method, which can also characterize the activity of seismic faults more precisely.

Prospected epigenetic moderators from natural sources and drug of class NSAIDS as effective treatment options to Prostate cancer

Prostate cancer (PC) is one of the most common and leading cancer amongst the males all around the world. Depending upon it long latency and cost involved in its management and treatment, there is extensive need for more personalized and economical therapeutic approach for its effective therapy. The current review here discusses agents from natural dietary sources and drug class Non-Steroidal Antinflammatory (NSAIDS) that bears chemopreventive potential to regulate PC progression & tumour development and therefore could be devised into effective future treatment strategy against PC along with its metastatic castration-resistant form. Based on the literature search the therapeutic scope of selected agents are delineated, sighting their previous activity and prospects as epigenetic moderators in specific to particular PC causing biomarkers like over expression of AKR1C3, lost intracellular glutathione/glutathione-s-tranferases(GSH/GST) expression, DNA hypermethylation, aberrant cell proliferation and other related factors that are thought to potentiate and aggravate the onset of PC like smoking and use of other narcotics products.

Effect of Severe Temperatures and Restraint on Instability and Buckling of Elliptical Steel Columns

This paper presents the findings of an experimental research to investigate the performance of axially restrained elliptical hollow (EHS) steel columns subjected to severe hydrocarbon fire. The test programme involved 12 steel columns presenting 2 oval sections 200?×?100?×?8?mm and 300?×?150?×?8?mm and yielding 2 slenderness?λ?= 51 and 33. The 1800?mm columns were tested under loading ratios ranging between 0.2 and 0.6 of the ultimate strength determined using EC3 and under axial restraint degree ranging from 0 to 0.16.? The obtained results of axial displacements, lateral displacements, measured restraint forces, and high temperatures are presented in the paper. It was found that introducing restraint to the columns with elliptical section produces high restraint forces which reduce the time to lose lateral stability. This is more evident in cases of lower load ratios than the higher load ratios. The numerical study presented in this paper involved building a finite element model to simulate the columns behaviour in fire. The model was validated using the test results obtained from unrestrained and restrained columns fire tests. The model demonstrated good agreement in the prediction of failure times and failure mechanisms of local and overall buckling. The FEM model was then used to conduct a parametric analysis involving factors of slenderness, restraint and loading. The conclusions drawn for this research are presented at the end of the paper.

A Comparison of the Clinical and Molecular Diagnosis of Herpes Simplex Keratitis

Purpose: To compare the clinical and molecular diagnoses of Herpes Simplex Keratitis (HSK). Materials and Methods: Conjunctival swabs (after fluorescein and anaesthetic wash out) and detailed questionnaire data were obtained from 146 participants. Corneal rims and conjunctival epithelial cells were infected with Herpes Simplex Virus (HSV) type 1 or HSV2 and supernatant collected. HSV1;HSV2;Varicella Zoster Virus (VZV) and Adenovirus (ADV) DNA was assessed using two real time Polymerase Chain Reaction (PCR) methods. Results: Of the 146 participants recruited, 54 were clinically diagnosed with typical epithelial lesions and 38 with atypical epithelial lesions, 17 with old inactive HSK and 37 healthy volunteers. HSV1 DNA was detected in 28 (30%) of the 92 participants with clinically suspect HSK. Patients who presented with typical epithelial lesions had a higher positive rate (46%) than those who presented with atypical type lesions (8%), when using primers against the Glycoprotein (Gp) G region of the virus. When the same samples were retested with primers against the GpB region, the positive rate for the typical and atypical cases increased to 52% and 11% respectively. Antiviral use at the time of sampling reduced the rate of PCR positivity by 20% (p < 0.05). ADV DNA was detected in 6% of the typical cases and 8% of the atypical cases. All control participants with no history of HSK were negative for HSV1 DNA. Sample quantity was confirmed by testing for housekeeping control genes, beta-actin and beta-2 macroglobulin. PCR results from in vitro control investigations of HSV1 and 2 infected corneal rims and conjunctival epithelial cells were 100% positive for infected and 100% negative for uninfected samples when assessed using both PCR methods. Conclusions: Clinical diagnosis of typical HSK is not always confirmed by PCR. Concomitant use of an antiviral reduces levels of PCR positivity. Given this and the findings that other ocular surface pathogens may mimic HSK pathology, and that choice of gene amplification region can also affect accurate detection of HSV1 by PCR, we propose the use of a multiplex assay. This would perform PCR using primers spanning a number of different regions within one gene and would also target a number of different viral genes to ensure potentially different HSV1 viral strains or other viruses do not affect the test and lead to disagreements between the clinical and molecular diagnosis of HSK. From these findings, this paper proposes a clinical supportive algorithmic guide to manage such disagreements.

临床致病性不动杆菌的分子生物学鉴定

目的对临床致病性不动杆菌进行种属鉴定,并比较3种方法(44℃生长试验、特异性引物PCR扩增和16SrRNA测序)对鲍曼不动杆菌鉴定的特异性、准确性及应用价值。方法收集临床致病不动杆菌56株,首先接种在胰蛋白胨大豆肉汤中44℃进行培养,观察是否可以生长;其次,提取56株不动杆菌基因组DNA,用两组不同的特异性引物进行PCR扩增鉴定;最后,用通用引物对56株不动杆菌的16SrRNA进行测序鉴定。结果 56株不动杆菌中有17株可在44℃生长。经特异性引物PCR扩增鉴定,发现8株鲍曼不动杆菌和3株13TU型不动杆菌均可在44℃中较早较快生长。金标准16SrRNA测序确定56株不动杆菌中含有9个种,其中鲍曼不动杆菌和13TU型不动杆菌的鉴定结果与特异性引物PCR扩增法相同。结论应用分子生物学方法鉴定鲍曼不动杆菌具有准确、高效且可重复性高的优点,尤其是特异性PCR扩增法,可作为较难诊断的鲍曼不动杆菌的首选鉴定方法。

基于BONeS设计系统的多媒体互联网通讯仿真

ＢＯＮｅＳ是美国 Ｃａｄｅｎｃｅ公司 Ａｌｔａ Ｇｒｏｕｐ开发出的一套用于网络通讯仿真和计算机结构分析的系统设计自动化工具．介绍利用该工具进行多媒体互联网通讯仿真设计，并根据ＴＣＰ／ＩＰ的确认重发和滑动窗口流量控制机制，分析ＴＣＰ／ＩＰ协议的不同重发延迟和窗口设置方案对多媒通讯ＱｏＳ的影响．

时间序列数据分析与预处理

时间序列分析中常常遇到的一个问题是如何有效地过滤噪音和约简数据 .本文通过修改传统的离散的傅立叶变换来过滤噪音和进行数据的约简 ,并尽可能保留原始时间序列的全局变化趋势 .为检验该方法的有效性 ,本文同时提出一个新颖的数据分类算法MCC ,并用该算法对股票回报率的变化进行预测 ,实验结果显示 ,用MCC算法在预处理后的数据上进行预测 ,其预测的命中率达到 6 3.6 8% ,而在原始数据上进行预测 ,其预测的命中率只有 4 8.98% .显然 ,通过对原始数据进行噪音过滤有效地改善了预测的精度 .另外 ,数据的约简也提高了预测算法的效率 .

语音压缩技术及其应用的进展

文中介绍了语音压缩技术的基本原理和算法,并着重分析了当前流行的几种语音压缩算法的优缺点,同时介绍了相应的一些语音压缩产品,最后对这门技术发展前景作了展望。