Synthesis and antitumor activity of bithienyl-pyrimidine derivatives with electrostatic binding side chains.

A series of bithienyl-pyrimidines having cationic side chain have been developed as antitumor agents. This work illustrates the overwhelming importance of the bithienyl unit for efficient DNA binding. The X-ray structure of 4-(2',2"-thien-5-yl)2-chloropyrimidine was obtained for postulating the conformation of the bithienyl-pyrimidine moiety.     

Orally bioavailable nonpeptide vitronectin receptor antagonists containing 2-aminopyridine arginine mimetics.

A peptide RGD analog containing a novel 2-aminopyridine arginine mimetic was discovered to have good affinity and selectivity for the vitronectin receptor. Incorporation of the 2-aminopyridine arginine mimetic into the 3-oxo-1,4-benzodiazepine-2-acetic acid integrin antagonist series led to novel and potent nonpeptide vitronectin receptor antagonists with promising levels of oral bioavailability.     

Thrombin inhibitors based on a propargylglycine template

A series of novel arylsulfonylpropargylglycinamide derivatives was investigated as thrombin inhibitors in which the SAR was focused on substituents at the acetylenic terminus. Several compounds in this series were identified as potent thrombin inhibitors (Ki up to 5 nM) that are highly selective over trypsin and other serine proteases as well.     

Deoxynivalenol impair skin barrier function through the down regulation of filaggrin and claudin 1/8 in HaCaT keratinocyte

Deoxynivalenol (DON), a typical mycotoxin, is a substance that is biosynthesized mainly by the Fusarium species. It is usually found in wheat and other grains grown in the field. When it enters the human body, it causes severe diarrhea, abdominal pain, vomiting, and even death. In addition, DON is known to induce inflammation of the small and large intestine, and is also associated with the occurrence of cancer. However, until recently, the effects of DON on the human skin were unknown. To investigate how DON affects HaCaT, human immortalized keratinocytes, we used CCK-8 assay and a quantitative real-time RT-PCR method to detect changes in the expression of tight junctions and skin cell regulatory proteins. The CCK-8 assay was performed to determine the growth inhibitory concentration of keratinocytes by DON. DON affected the cell survival rate from 1 μM in a concentration dependent manner, with the minimum set as 1 μM and the maximum as 4 μM for all experiments. DON inhibited the mRNA expression of filaggrin by up to 71% and SERPINA1 up to 75%. The expression of AQP3 was reduced by up to 93% compared to the untreated control group. This may cause problems in the pH control function of the skin and weaken the function of moisturizing. In addition, in the presence of DON, the gene expression of claudin 1 and claudin 8, which are important proteins in the regulation of intercellular skin barrier, decreased by up to 47 and 80%, respectively. Snail/ Slug, suppressors of the claudin gene expression, each increased up to 625 and 974%, respectively. Also, the MMP9 gene increased by up to 515% in a concentrationdependent manner, perhaps causing a weakness of the barrier function of the skin. These results suggest that DON may causing the development of atopic skin by impairing the skin barrier and pH control of skin, as well as intestinal inflammation diseases. Therefore, particular attention should be paid to DON contamination during the development of cosmetic ingredients using grains.     

Multiple male morphs in the leaf‐footed bug Mictis longicornis (Hemiptera: Coreidae)

Species within the coreid clade (Hemiptera: Coreidae) can often be observed competing in intrasexual competitions over access to mates and territories. Coreids that partake in these competitions typically possess sexually dimorphic hind legs that are used to strike and squeeze their rivals. In addition to their weaponized legs, some coreid species also possess sexually dimorphic abdominal tubercles, which are assumed to be sexually selected weapons. Still, much remains unknown about the morphology of these structures. Here, using the species Mictis longicornis Westwood, we investigate the frequency distribution and static allometry of abdominal thickness, a measure that includes tubercle length. Furthermore, we also investigate the morphological relationship between abdominal tubercles and weaponized hind legs. We find that male abdominal thickness is best explained by a bimodal distribution, thereby describing the first observed male polymorphism in the coreid clade; a phenomenon typically associated with alternative reproductive tactics. Additionally, we find that major males are characterized primarily by having large weaponized legs and abdominal tubercles, which further suggests that abdominal tubercles are used in male–male competition.     

Making a case for the on-demand multiple distributed message queue system in a Hadoop cluster

In this paper, we present a framework that can provide users with a simple, convenient and powerful way to deploy multiple message queue system on demand in a Hadoop cluster. Specifically, we are leveraging the Apache Kafka which is one of the state of art distributed message queue systems that can achieve high throughput, low latency, and good load balancing. Our framework provides automation of setting up and starting Kafka brokers on the fly and users can leverage the framework to quickly adopt Kafka without spending much efforts on installation and configuration challenges. In addition, the framework supports users to run their Kafka-based applications without detailed knowledge about the Hadoop YARN APIs and underlying mechanisms. We present a use case of the framework to evaluate Kafka’s performance with various test cases and working scenarios. The experimental results allow Kafka’s potential users to perceive the influences of different settings on the queuing performance.     

Protein signaling networks from single cell fluctuations and information theory profiling

Protein signaling networks among cells play critical roles in a host of pathophysiological processes, from inflammation to tumorigenesis. We report on an approach that integrates microfluidic cell handling, in situ protein secretion profiling, and information theory to determine an extracellular protein-signaling network and the role of perturbations. We assayed 12 proteins secreted from human macrophages that were subjected to lipopolysaccharide challenge, which emulates the macrophage-based innate immune responses against Gram-negative bacteria. We characterize the fluctuations in protein secretion of single cells, and of small cell colonies (n = 2, 3,···), as a function of colony size. Measuring the fluctuations permits a validation of the conditions required for the application of a quantitative version of the Le Chatelier's principle, as derived using information theory. This principle provides a quantitative prediction of the role of perturbations and allows a characterization of a protein-protein interaction network.     

Summer distribution of <Emphasis Type="Italic">Noctiluca scintillans</Emphasis> and mesozooplankton in the Western and Southern East China Sea prior to the Three Gorges Dam operation

Differential tolerance of congeners with an overlapping ecological niche, to the anthropogenic activities leads to a faunal shift at spatiotemporal scales, which in turn provides an insight to the subtle changes happening in the abiotic environment. Aiming to asses the effects of influent and effluent waters of two Nuclear Power Plants (NPP-I and NPP-II), of northern Taiwan this study monitored the biography and population trajectories of two congeners of calanoid copepod, Temora discaudata and Temora turbinata from September, 1998 to April, 2009, comprising 44 sampling cruises in the southern East China Sea. The two Temora species occurred in >90% of the samples, showing differential trends of occurrence and abundance. The density of T. turbinata was higher than T. discaudata. The absolute and relative abundance of both of the Temora spp. increased significantly from inlet and outlet stations to seaward stations 500–1000 m away from land, beyond which there was a decline in density. The effects of month, season, year on abundance and occurrence of either Temora species were highly significant. The maximum and minimum abundance of T. discaudata was recorded in Aug, 1999 and March, 2000, respectively, where as those of T. turbinata was recorded in May, 2000 and March, 2000. The density, and occurrence frequency of either species showed a positive correlation with seawater temperature, but neither species showed a significant correlation with salinity. The areas around inlet and outlet stations record lower copepod density than unaffected stations. Our results point to a faunal shift within the congeners in coastal waters in the vicinity of both the NPPs. These results will be useful in assessing the ecological impact of discharge from NPPs, and in understanding the long-term population dynamics of Temora spp. which are believed to be invasive and cosmopolitan.     

Directional effect on post-stroke motor overflow characteristics

Motor overflow (MO) is an involuntary muscle activation associated with strenuous contralateral movement and may become manifested after stroke. The study was undertaken to investigate physiological correlation underlying atypical directional effect of joint movement on post-stroke MO in the affected upper limb. Thirty patients with unilateral post-stroke hemiparesis and fifteen age-matched healthy controls participated in this study. According to motor function assessed with the Fugl-Meyer arm scale, the patients were categorized into two groups of equal number with better (CVA_G; n = 15) or poorer motor functions (CVA_P; n = 15). Surface electromyography (EMG) was used to record irradiated muscle activation from eight muscles of the affected upper limb when the subjects performed maximal isometric contractions in different directions with the unaffected shoulder, elbow and wrist joints. The results showed that only MO amplitude of the CVA_G and the control groups was more sensitive to variations in direction of joint movement in the unaffected arm than the CVA_P group. The CVA_G group exhibited larger amplitudes of MO than the control analog, whereas this tendency was reversed for the CVA_P group. In terms of EMG polar plots, spatial representations of post-stroke MO were insensitive to direction of contralateral movement. The spatial representations of the CVA_G and CVA_P groups were predominated by potent flexion-abduction synergy, contrary to the typical extension adduction synergy seen in the control analog. In conclusion, post-stroke MO amplitude was subject to contralateral movement direction for healthy controls and stroke patients with better motor recovery. However, alterations in MO spatial pattern due to directional effect were not strictly related to the degree of motor deficits of the stroke victims.