How does patent litigation influence dynamic risk for market competitors?

Many recent studies have discussed the appropriateness of various patent measurement indicators, as well as the differences in the positioning of patented technologies, while there is little discussion on the risk transmission of enterprises when faced with infringement litigation. This study used the bivariate EGARCH (Exponential Generalized Autoregressive Conditional Heteroskedasticity) model with DCC (Dynamic Conditional Correlations) to investigate the dynamic risk transmission of patent litigation between market competitors in the smartphone industry. Empirical results revealed that when facing lawsuits from market challengers, the market leader faces fewer risks when handling patent infringement litigations. In addition, the risk reactions of competitors during patent wars may widely differ. Investors should consider the patent infringement litigations when measuring the dynamic risks of share prices, and determining the optimal configuration of asset portfolios in response. First published online: 03 Nov 201

Identification of New Genetic Risk Variants for Type 2 Diabetes

Although more than 20 genetic susceptibility loci have been reported for type 2 diabetes (T2D), most reported variants have small to moderate effects and account for only a small proportion of the heritability of T2D, suggesting that the majority of inter-person genetic variation in this disease remains to be determined. We conducted a multistage, genome-wide association study (GWAS) within the Asian Consortium of Diabetes to search for T2D susceptibility markers. From 590,887 SNPs genotyped in 1,019 T2D cases and 1,710 controls selected from Chinese women in Shanghai, we selected the top 2,100 SNPs that were not in linkage disequilibrium (r2<0.2) with known T2D loci for in silico replication in three T2D GWAS conducted among European Americans, Koreans, and Singapore Chinese. The 5 most promising SNPs were genotyped in an independent set of 1,645 cases and 1,649 controls from Shanghai, and 4 of them were further genotyped in 1,487 cases and 3,316 controls from 2 additional Chinese studies. Consistent associations across all studies were found for rs1359790 (13q31.1), rs10906115 (10p13), and rs1436955 (15q22.2) with P-values (per allele OR, 95%CI) of 6.49×10−9 (1.15, 1.10–1.20), 1.45×10−8 (1.13, 1.08–1.18), and 7.14×10−7 (1.13, 1.08–1.19), respectively, in combined analyses of 9,794 cases and 14,615 controls. Our study provides strong evidence for a novel T2D susceptibility locus at 13q31.1 and the presence of new independent risk variants near regions (10p13 and 15q22.2) reported by previous GWAS

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

Identification of Functionally Important Residues in the Protease Domain of Factor Ix That Are Critical for Binding Factor Xia, Tfpi, and Antibodies

This work describes the consequences of alanine scanning mutagenesis on 19 positions (within residues 185-301) of the catalytic domain of factor IX (FIX). R248 and K293 are critical for the secretion of FIX. Mutations at K265 and at E277 yielded novel FIX with 2-3 times better clotting activities compared to that of wild type. Both factor XIa ( FXIa) and the factor VIIa-tissue factor (TF) complex effectively catalyzed the activation of all the tested mutants except for three. Mutations at residues E235, E242, and E245 impaired factor IX's activation by FXIa but not by VIIa-TF, suggesting the mechanisms for cleavage of FIX by the two enzyme systems are different based on this and our previous finding (Chang YJ et al., 2002, J. Biol. Chem, p. 25393-9). All of the 19 mutations had little effect on the binding of FIX to factor VIIIa and antithrombin III ( ATIII). However, FIX with Ala at K265 exhibited 10-fold increase in binding TFPI, which suggests that this residue may render function of the 99-loop involved in the substrate specificity in the serine protease family. Besides being an important part of the substrate and inhibitor binding, this region (residues 185-301) is also an epitope for monoclonal antibody A-5. We found that an electrostatic surface composed of discontinuous amino acids of K201, D203, K228, R 252, and D276 is the epitope for A-5 (Smith KJ., and Ono K., 1984, Thrombosis Res. p. 211-4, and Hamaguchi et al., 1994, Blood, p. 1837-42). These residues constitute a highly charged surface opposite to the factor VIIIa binding surface . Since their Ala-mutant counterparts were either almost as active as, or slightly less active than wild-type FIX in clotting function, this side of FIX, although may not be very important for FIX in binding factor VIIIa, is a strong antigenic determinant. Taken together, we conclude that the surface-exposed residues within positions 185-301 of FIX are highly charged and antigenic. A-5 might exert its inhibitory effect by affecting the global conformation of this region. Moreover, this region although may not be important for the interaction of FIX with factor VIIIa, VIIa -TF and ATIII, is critical for interacting with FXIa and TFPI

Identification of a New Ca Dinucleotide Repeat in the Human Factor Viii Gene

We describe the identification of a new CA dinucleotide repeat marker for the diagnosis of haemophilia A carriers. The marker (CA-6) is present in intron 6 as a single copy 5 kb upstream of exon 7. Of 195 and 118 X chromosomes from normal individuals and haemophilia A patients, respectively, we observed three alleles of CA-6 with 12-14 repetitions [( CA)(12-14)]. The frequencies were 0.5% and 0% for (CA)(12), 99% and 95.8% for (CA)(13), and 0.5% and 4.2% for (CA)(14) in normals and patients respectively. We conclude that the low polymorphism of the CA-6 marker renders it less useful for the diagnosis of Chinese haemophilia A carriers

[[alternative]]The Volunteer Management--A Case Study Of Kaohsiung Museum Of Fine Arts

[[abstract]]　　本研究係採用深度訪談、資料分析、問卷調查等方式，來分析高雄市立美術館的志工管理模式，主要的研究發現如下：　　一、高美館志工之基本特質參與高美館之志工的主要基本特徵為：女性占大多數、年齡以51-60歲為主、家庭狀況以人數為4人的家庭為最普遍、且家中有小孩的家庭，其小孩的年齡也普遍居15歲以上、有工作者占大多數、而職業方面則以公教單位為主、教育程度則集中於專科及大學、志工資歷方面則以1-3年為最多。　 　　在參與動機方面，主要以擴大生活圈以及服務社會最主，而參與的管道，以透過館內成員介紹為最高，其次為透過媒體宣導，而在參與志工之後，個人覺得最大的收獲，以擴展人生經驗為最屬，而且幾乎所有志工在未來一年均傾向繼續參與高美館志工，且大多數志工最近一年有捐款行為，且最常捐款對象為社會服務及慈善團體。　 二、高美館志工管理(一)志工需求評估：有賴於志工小組長與服務員小組長之間協調志工人力的配置與調度，以避免人力閒置。　　(二)工作設計：工作設計則包含志工簽到時間、工作調配、請假事宜、用餐規定、值勤時注意事項、以及值勤例行性工作等。　　(三)志工招募：館方的志工招募方式主要分為兩個部份，一為透過朋友告之，二為透過媒體發佈招募消息。　　(四)面試與協調：館方透過面試來了解進入館內擔任志工者，其對志願服務的看法、對館方的認知情況，以及了解此人的觀念與意願。面試的執行是由推廣組會同義工小組中的培訓組來協調，以便選出合適的志工作為面試官。　　(五)引導與訓練：館方採取全體館員一齊加入管理工作，以便使得許多管理問題得以有效解決，另一方面也能塑造一良好的志工組織氣氛；在訓練方面，則包含職前訓練以及在職訓練，而此兩項業務則歸屬於推廣組承辦，職前訓練方面，因為導覽志工是屬較專業的部份，因此要在服務前給予在職訓練，而在職訓練內容則是針對相關展品給予安排培訓課程。　　(六)激勵與福利：高美館給予志工最好的激勵方式就是讓志工增長知識，給予志工學習的空間，讓志工自覺能把活動辦的很好。福利方面，館方則提供服裝、保險、誤餐便當、硬體設備、以及自強旅遊等規劃。　　(七)績效評估：館方大多以服務時數來作為績效的評估標準，評估後，對於志工的留任與離任方面，高美館的流動率並不高，而對於不適任的志工，館方予以不續聘處理，並以三個月的試用期淘汰不適任者。　　(八)專業人員的參與：專業人員意指館方的服務員，當志工遇及問題時，志工小組長擔任督導兼受理處理問題，面對急迫性之問題，則由服務員配合著志工業務的推展執行。　　三、高美館志工的優勢與困境根據訪談內容，高美館的志工管理有著三項優勢，包括：提供身心障礙者參與志工的機會、每年固定舉辦志工大會、並且讓志工能到別的館所作交流。志工管理的困境上，則以經費來源與預算逐年縮減，為最大的志工管理難題。志工本身在執勤上的困境，則包括部份參觀民眾或極少數志工違反館方展品安全規定之行為的發生，或而不聽勸說的情形。　[[abstract]]　　In this research, we want to explore the situation of volunteer management of Kaohsiung Museum of Fine Aarts by using the methods of questionnaire , literature and interview. The total valid questionnaires received are 269. The most important findings about volunteer management are as follows:　　1. The evaluation of volunteers demand rely on volunteer leaders and steward leaders for coordinating the volunteer deploy.2. The designation of volunteers includes : the time to sign in , the deploy of job , asking to leave , routine procedure.3. The recruitment of volunteers include two chief ways : friends and mass media .4. Interview : Interview is helpful for museum to realize people’s attitude and desire of voluntary service , and the recognition of museum.5. Train : The train includes orientation and on-the-job training .6. Encouragement : The best encouragement way that museum provides is let the volunteers to learn and let volunteers feel that they can do the things right.7. Performance of Evaluation : The museum use hours of service as the standard of evaluation.

Lack of Thromboxane Synthase Prevents Hypertension and Fetal Growth Restriction after High Salt Treatment during Pregnancy.

Preeclampsia (PE) is a potentially fatal pregnancy-related hypertensive disorder characterized by poor placenta development that can cause fetal growth restriction. PE-associated pathologies, including thrombosis, hypertension, and impaired placental development, may result from imbalances between thromboxane A2 (TXA2) and prostacyclin. Low-dose aspirin, which selectively inhibits TXA2 production, is used to prevent high-risk PE. However, the role of TXA2 in aspirin-mediated protective effects in women with PE is not understood fully. In this study, we examined the role of prostanoids in PE using human samples and an induced PE mouse model. We demonstrated that the administration of salted drinking water (2.7% NaCl) to wild-type mice resulted in elevated placental TXA2 synthase (TXAS) and plasma TXA2, but not prostacyclin, levels, which was also found in our clinical PE placenta samples. The high salt-treated wild-type pregnant mice had shown unchanged maternal body weight, hypertension (MAP increase 15 mmHg), and decreased pup weight (~50%) and size (~24%), but these adverse effects were ameliorated in TXAS knockout (KO) mice. Moreover, increased expression of interleukin-1β and downstream phosphorylated-p38-mitogen-activated protein kinase were concordant with apoptosis induction in the placentas of salt water-treated wild-type mice. These alterations were not observed in TXAS KO mice. Together, our data suggest that TXA2 depletion has anti-PE effects due to the prevention of hypertension and placental damage through downregulation of the interleukin-1β pathway

Embryonic Cul4b is important for epiblast growth and location of primitive streak layer cells.

Cul4b-null (Cul4bΔ/Y) mice undergo growth arrest and degeneration during the early embryonic stages and die at E9.5. The pathogenic causes of this lethality remain incompletely characterized. However, it has been hypothesized that the loss of Cul4b function in extraembryonic tissues plays a key role. In this study, we investigated possible causes of death for Cul4b-null embryos, particularly in regard to the role of embryonic Cul4b. First, we show that the loss of embryonic Cul4b affects the growth of the inner cell mass in vitro and delays epiblast development during the gastrulation period at E6.5~E7.5 in vivo, as highlighted by the absence of the epiblastic transcription factor Brachyury from E6.5~E7.5. Additionally, at E7.5, strong and laterally expanded expression of Eomes and Fgf8 signaling was detected. Sectioning of these embryos showed disorganized primitive streak layer cells. Second, we observed that Mash2-expressing cells were present in the extraembryonic tissues of Cul4b-deficient embryos at E6.5 but were absent at E7.5. In addition, the loss of Cul4b resulted in decreased expression of cyclin proteins, which are required for the cell cycle transition from G1 to S. Taken together, these observations suggest that the embryonic expression of Cul4b is important for epiblast growth during E6.5~E7.5, and the loss of Cul4b results in either delayed growth of the epiblast or defective localization of primitive streak layer cells. As a result, the signaling activity mediated by the epiblast for subsequent ectoplacental cone development is affected, with the potential to induce growth retardation and lethality in Cul4bΔ/Y embryos

Hybrid EDM and Grinding Hard Materials Using A Metal Matrix Composite Electrode

ABSTRACT Electrical discharge machining (EDM) has been shown to be a versatile method for machining difficult-to-work materials including heated-treated steels, tungsten carbides and various conductive ceramics. However, low machining efficiency is one of the main EDM disadvantages. The topic of how to reduce machining time and maintains reasonable accuracy has always been of research interest. The main object of the present work was to develop an electrical discharge machining and grinding (EDMG) methodology to remove the re-solidified layer through the grinding induced by a metal matrix composite electrode prior to the re-solidified layer solidification. A metal matrix composite (Cu/SiC p ) electrode, with an electroless pretreatment of Cu coating on SiC p to enhance bonding status between Cu and SiC p , with a rotating device was made and employed to study the EDMG technology. Machinabilities of mold material, HPM50 mold steel and P20 WC/Co, were investigated by the combined technologies of EDMG. The machined surfaces of these materials were examined by scanning electron microscopy （SEM）and their surface roughness measured by a profile meter. From the experimental results, it was found that higher material removal rate and lower surface roughness can be achieved when suitable electrode rotating speed, SiC p size and working current are chosen. In addition, the surface roughness of both materials could be improved as compared with that following the EDM process