The complement system in age-related macular degeneration

Age-related macular degeneration (AMD) is a chronic and progressive degenerative disease of the retina, which culminates in blindness and affects mainly the elderly population. AMD pathogenesis and pathophysiology are incredibly complex due to the structural and cellular complexity of the retina, and the variety of risk factors and molecular mechanisms that contribute to disease onset and progression. AMD is driven by a combination of genetic predisposition, natural ageing changes and lifestyle factors, such as smoking or nutritional intake. The mechanism by which these risk factors interact and converge towards AMD are not fully understood and therefore drug discovery is challenging, where no therapeutic attempt has been fully effective thus far. Genetic and molecular studies have identified the complement system as an important player in AMD. Indeed, many of the genetic risk variants cluster in genes of the alternative pathway of the complement system and complement activation products are elevated in AMD patients. Nevertheless, attempts in treating AMD via complement regulators have not yet been successful, suggesting a level of complexity that could not be predicted only from a genetic point of view. In this review, we will explore the role of complement system in AMD development and in the main molecular and cellular features of AMD, including complement activation itself, inflammation, ECM stability, energy metabolism and oxidative stress.

     

The futility of decision making research

We have each spent more than 50 years doing research that has had little impact. Even more lamentable is that our field, judgment and decision making (JDM), has on the whole had little impact during that span. We attribute that failure to the use of methodologies that emphasize testing models rather than looking for differences in behavior. The “cognitive revolution” led the field astray, toward the goal of studying model fit rather than comparing observable results. With modeling as the goal, experimentation was stultified. Simple tasks became dominant. Although a poor metaphor for real decision making, the gambling paradigm has lasted forever because the inputs to the decision are known to the researcher and thus easily modeled.     

The TET enzymes

During the past decade, we have learnt that the most common DNA modification, 5-methylcytosine (5mC), playing crucial roles in development and disease, is not stable but can be actively reversed to its unmodified form via enzymatic catalysis involving the TET enzymes. These ground-breaking discoveries have been achieved thanks to technological advances in the detection of the oxidized forms of 5mC and to the boldness of individual scientists. The TET enzymes require molecular oxygen for their catalysis, making them important targets for hypoxia research. They also require special cofactors which enable additional levels of regulation. Moreover, mutations and other genetic alterations in TETs are found, especially in myeloid malignances. This review focuses on the kinetic and inhibitory properties of the TET enzymes and the role of TETs in cellular differentiation and transformation and in cancer.     

Current knowledge on exosome biogenesis and release

Exosomes are nanosized membrane vesicles released by fusion of an organelle of the endocytic pathway, the multivesicular body, with the plasma membrane. This process was discovered more than 30 years ago, and during these years, exosomes have gone from being considered as cellular waste disposal to mediate a novel mechanism of cell-to-cell communication. The exponential interest in exosomes experienced during recent years is due to their important roles in health and disease and to their potential clinical application in therapy and diagnosis. However, important aspects of the biology of exosomes remain unknown. To explore the use of exosomes in the clinic, it is essential that the basic molecular mechanisms behind the transport and function of these vesicles are better understood. We have here summarized what is presently known about how exosomes are formed and released by cells. Moreover, other cellular processes related to exosome biogenesis and release, such as autophagy and lysosomal exocytosis are presented. Finally, methodological aspects related to exosome release studies are discussed.     

Study on the Centralization Strategy of the Blood Allocation Among Different Departments within a Hospital

By far, the researches on how to distribute blood products among different departments in hospital have not been further studied, though the problem of blood shortage and wastage that caused by improper blood allocation is severe, which may endanger patient’s lives and impose considerable costs on hospitals. In order to solve this problem, this paper mainly studies on how to distribute the blood items among different departments within a hospital and investigates the allocation approach with the novel management method by centralizing the inventory of several different departments. By integrating the blood inventory requirements of some departments, the hospital could reduce the rate of blood shortage and wastage effectively, release the pressure of the occupancy of resources and reduce the bullwhip effect of blood products. This paper illustrates the centralization principle in hospital and formulates the mixed integer programming model to work out the optimal allocation network scheme and the optimal inventory setting for every department. And the results of the numerical example demonstrate that this centralization method could considerably reduce blood shortage and wastage in hospital by about 72% and 90% respectively. Furthermore, it could decrease the total cost by about 108,540 RMB a month on blood supply chain management in the hospital and improve the effect of some certain surgeries by transfusing the fresh blood to patients.     

Fuzzy Views on Black-Litterman Portfolio Selection Model

In this paper, views of investor are described in fuzzy sets, and two fuzzy Black-Litterman models are constructed with fuzzy views and fuzzy random views respectively. In the models, expected returns and uncertainty matrix of views are redefined and the views are formulated by fuzzy approaches suitably. Then the models are tested with data from Chinese financial markets. Empirical results show that the fuzzy random views model performs the best, and both the fuzzy models are better than the traditional ones, demonstrating that the fuzzy approaches can contain more information in the views and measure the uncertainty more correctly.     

Effects of Strain Rate,Temperature and Grain Size on the Mechanical Properties and Microstructure Evolutions of Polycrystalline Nickel Nanowires: A Molecular Dynamics Simulation

Through molecular dynamics(MD)simulation,the dependencies of temperature,grain size and strain rate on the mechanical properties were studied.The simulation results demonstrated that the strain rate from 0.05 to 2 ns~(–1 )affected the Young’s modulus of nickel nanowires slightly,whereas the yield stress increased.The Young’s modulus decreased approximately linearly;however,the yield stress firstly increased and subsequently dropped as the temperature increased.The Young’s modulus and yield stress increased as the mean grain size increased from 2.66 to6.72 nm.Moreover,certain efforts have been made in the microstructure evolution with mechanical properties association under uniaxial tension.Certain phenomena such as the formation of twin structures,which were found in nanowires with larger grain size at higher strain rate and lower temperature,as well as the movement of grain boundaries and dislocation,were detected and discussed in detail.The results demonstrated that the plastic deformation was mainly accommodated by the motion of grain boundaries for smaller grain size.However,for larger grain size,the formations of stacking faults and twins were the main mechanisms of plastic deformation in the polycrystalline nickel nanowire.     

Control of excessive neural circuit excitability and prevention of epileptic seizures by endocannabinoid signaling

Progress in research on endocannabinoid signaling has greatly advanced our understanding of how it controls neural circuit excitability in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses seizures by inhibiting glutamate release. In contrast, endocannabinoid signaling promotes seizures by inhibiting GABA release at inhibitory synapses. The physiological distribution of endocannabinoid signaling molecules becomes disrupted with the development of epileptic focus in patients with mesial temporal lobe epilepsy and in animal models of experimentally induced epilepsy. Augmentation of endocannabinoid signaling can promote the development of epileptic focus at initial stages. However, at later stages, increased endocannabinoid signaling delays it and suppresses spontaneous seizures. Thus, the regulation of endocannabinoid signaling at specific synapses that cause hyperexcitability during particular stages of disease development may be effective for treating epilepsy and epileptogenesis.