The hydrated and highly charged extracellular matrix (ECM) plays a vital role in many biological processes. Therefore, mimicking this environment is of great interest in material science as well as biomedical research. In this thesis, an ECM mimetic is presented based on hyaluronic acid also called hyaluronan (HA) as one of the ECM's abundant negatively charged components. Due to HA's unique properties, this anionic biopolymer was chosen as biological "module" to design biocompatible charge defined hydrogels in a synthetic biology approach. By varying the degree of chemical modification on the carboxyl groups of the glucuronic acid moiety of HA in addition to differently charged but structurally similar heteroaromatic crosslinkers, the charge density of the hydrogels presented in this thesis can be adjusted. Using thiolation as chemical modification together with two armed crosslinkers carrying unsaturated end groups, the thiol-Michael addition click reaction can be employed for byproduct free crosslinking of HA chains. The composition of the presented hydrogels remains constant and hydrogels with the same degree of thiolation and differently charged heteroaromatic crosslinker cores even result in the same covalent connectivity of the network. I could show that size defined HA with an average molecular weight of 74 kDa is suitable for homogeneous and reproducible hydrogel formation at degrees of thiolation from 18% to 36%. Additionally, the presented hydrogels show a high stability over time, with constant mechanical stiffness over the course of at least four weeks.
Using a set of hydrogels synthesized from 74 kDa HA with three different degrees of
thiolation in the range of 18% to 33% and one neutral and one structurally similar,
positively charged crosslinker, physico-chemical properties were monitored. Two general
trends could be observed for mechanical stiffness in the form of Young's moduli
ranging from 0.44 kPa to 6.31 kPa, swelling ratios and mesh sizes between 53.54nm
to 183.76nm. (1) With increasing degree of thiolation, mechanical stiffness increases
whereas swelling ratios and respective mesh sizes decrease. (2) At each individual degree
of thiolation, hydrogels with the charged crosslinker show twice as high Young's
moduli and roughly halved swelling ratios and mesh sizes, compared to the same hydrogels
with uncharged crosslinkers. Furthermore, swelling ratios of the presented
polyelectrolyte hydrogels are highly influenced by the ionic strength of the swelling
solution but independent of the solution's pH at physiological salt concentration.
Biological properties, as for example enzymatic degradability, show the trends described
for physico-chemical characterization. (1) Half-lives of hydrogels in hyaluronidase
and hyaluronate lyase solutions are increasing with increasing degree of thiolation
from 2.5 h to 11.7 h in hyaluronidase with the uncharged crosslinker and (2) for each
individual degree of thiolation, half-lives for hydrogels with the charged crosslinkers are always larger than for respective hydrogels with the uncharged crosslinker. Furthermore,
cell adhesion of fibroblasts, lymph endothelial cells and breast cancer cells is
(1) increasing with increasing degree of thiolation. (2) It could also be observed, that
cells adhere better on hydrogels with charged crosslinkers, compared to hydrogels with
the same degree of thiolation with uncharged crosslinkers.
For all of these trends in physico-chemical as well as biological properties, two influencing
factors could clearly be determined in this thesis. Firstly, correlation of all
presented properties with the negative network charge of each individual hydrogel could
be observed: With decreasing negative network charge, hydrogels are becoming stiffer,
show lower swelling capacity and smaller mesh sizes, degradation by hyaluronan degrading
enzymes becomes slower, and more cells are able to adhere to their surface.
Secondly, the aromatic core of the crosslinker seems to be another important factor
for material properties. The naturally occurring pyridinium causes considerably stiffer
hydrogels with smaller mesh sizes and lower swelling ratios compared to a structurally
similar triazolium based crosslinker.
To conclude, a charge defined hydrogel system could be presented, mimicking the
hydrated ECM niche, in a minimal model adjusted for studying non-integrin mediated
cell attachment. From results obtained by characterizing the material properties, I
suggest a strong influence of secondary interactions on physico-chemical and biological
properties of the ECM. Both electrostatic interactions, resulting from negative
network charge of the hydrogels, as well as aromatic core interactions due to different
heteroaromats used in crosslinker design are critically influencing hydrogel properties in
a specific way. With the establishment of this defined system further studies on charge
dependent ECM characteristics as well as application in three dimensional (3D) tissue
engineering, drug delivery or regenerative medicine are possible, given the opportunity
to specifically tune material properties by changing the secondary interactions within
the network.


This is about women, poverty and vulnerability of HIV/AIDS in Moree and Asebu in the Abura-Asebu-Kwamankese District in the Central Region of Ghana. The main objective of the study is to find out whether poverty actually makes women vulnerable to HIV/AIDS in the two communities, thus Moree and Asebu. The study employed the use of Actor Oriented theories such as agency, action, power and structures in structuration theory. It also makes use of risk theories, feminist geographies and the concepts of space, place and time.Multiple methods within the qualitative approach were used, in the data collection. These included administration of a semi structured interview guide, which covered a purposive sample of 30 respondents of which 80 percent were female and 20 percent males who were ordinary local people in Moree and Asebu. 27 in-depth interviews using unstructured interview guide were conducted among key informants. Focus group discussion and observations were also conducted. The primary data was complemented with secondary data from the Ghana HIV Sentinel Surveillance Surveys, the Ghana Poverty Reduction Strategy, yearly report on HIV cases in the Abura-Asebu- Kwamankese District and the district profile of Abura-Asebu-Kwamankese District.The study further reveals that the triggering effect of poverty to HIV infection is something that cannot be done away with. Women were seen to be worst affected with poverty. These poor conditions have led to these females adapting to various coping strategies with life, which make them vulnerable to HIV/infection. This is because women are more at risk and are likely to adopt risky sexual behaviours that could put them in high-risk position for infection. The study reveals that the masculinity of the society has made females dependent on males and this constrains them from entering into any economic venture and negotiating for protective sex. It was realised also that the causes of female poverty and the coping strategies that were likely to be adopted by the people within the fishing community is slightly different from females in the farming community. Majority of the findings were analysed qualitatively, however, I quantified only a few. Based on the findings, conclusions and recommendations were drawn.


Background: Staphylococci are major cause of nosocomial blood stream infections.This local surveillance study was carry out to monitor frequency of occurrence of Staphylococcus aureus and coagulase-negative staphylococci (CoNS) in blood stream infections and the incidence of methicillin-resistant (MET-R) strains. Materials and methods: During the period January – December 2006, 9840 blood specimens were analyzed and microrganisms from positive samples were collected. Bacterial identifications were performed according to the standard methods (Murray, 2003).We evaluated, in particular, the antibiotic-resistance phenotype of staphylococci employing disk diffusion test as suggested by the CLSI (2006). The following antimicrobial agents were tested: oxacillin, penicillin, amoxiciclin-clavulanate, cefalotin, cefamandole, imipenem, teicoplanin, linezolid, ciprofloxacin, erythromycin, clindamicin, rifampicin, trimethoprim-sulfamethoxazole, gentamicin, doxiciclin, fosfomycin. Results: The microrganisms isolated were 551: 370 Gram-positives (67%), 131 Gram-negatives (24%), 11 anaerobes (2%) and 39 mycetes (7%). In particular, 121 S. epidermidis, 75 S. aureus, 42 S. haemolyticus and other 39 CoNS were analyzed: methicillin-resistance occurred in more than 80% of S.aureus strains collected from Intensive Care Units (ICU) and in about 50 % of those isolated from other divisions. In CoNS the incidence of MET-R ranged from 30 to 80 %, the higher values were registered among S. epidermidis and S. haemolyticus. MET-R strains were characterized by high resistance rates even to ciprofloxacin (from 47 to 100%), erythromycin (from 70 to 100%), and in same cases to gentamicin (from 23 to 86%) also. Conclusions: Staphylococci are the prevalent cause of blood stream infections.The distinctive feature of MET-R strains is their resistance not only to all b-lactam antibiotics, but also to a wide range of other antimicrobial agents. However, the glycopeptide teicoplanin remains 100% effective against MET-R S.aureus and S. epidermidis strains.


Small cell cancers are aggressive tumors with unfavorable prognosis. Small cell bladder carcinomas are a particularly troublesome and poorly differentiated tumor where little is known and in which few targeted therapeutic options exist for molecularly defined patients. We therefore sought to characterize both common and actionable aberrant pathways in small cell bladder tumors to serve as a guide for therapeutic development. Utilizing a combination of deep targeted capture and whole-genome sequencing approaches, we characterized the mutational and DNA copy number alteration spectrum of twenty patients with small-cell bladder cancer including multi-region profiling of a subset of cases with mixed small cell and urothelial histologies. Integrating molecular, clinical, and pathway data along with comparative genomic analyses of 371 urothelial bladder and small cell lung cancers, we identified histology- and lineage-specific lesions and significant differences in the prevalence of specific pathway aberrations. Whole-genome sequencing revealed structurally complex tumors and, in some cases, somatic hypermutation, including one sample harboring more than 150,000 clonal mutations. Aberrations in G1/S cell cycle progression appear to be pathognomonic in small cell tumors. Furthermore, additional lesions affecting both pro/anti apoptotic as well as metabolic pathways occurred in patterns that are distinct from other small-cell and bladder cancers. In total, 85% of small cell bladder cancer samples contain at least one potentially clinically actionable lesion. These results indicate that integrative genomic analyses of small-cell bladder cancer facilitates therapeutic development and pathway targeting in a complex mutational landscape. Citation Format: Matthew T. Chang, Saurabh Asthana, Gopakumar Iyer, Neil Desai, Hikmat Al-Ahmadie, Jocelyn Chapman, Bernard H. Bochner, Jonathan E. Rosenberg, Dean F. Bajorin, David B. Solit, Barry S. Taylor. The landscape of actionable genomic lesions in small cell bladder cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-316. doi:10.1158/1538-7445.AM2014-LB-316


We improved the procedure for lipophilic-oxygen radical absorbance capacity (L-ORAC) measurement for better repeatability and intermediate precision. A sealing film was placed on the assay plate, and glass vials and microdispensers equipped with glass capillaries were used. The antioxidant capacities of food extracts can be evaluated by this method with nearly the same precision as antioxidant solutions.


A MapReduce job consists of two phases that are processed in a map queue and a redeuce queue, respectively. The map queue is characterized by the processor sharing discpline, and the reduce queue by a multi-server station. A reduce task is composed of two sequential steps: the copy/shuffle step and the reduce function step. A synchronization barrier between the map and reduce phases complicates the process: the copy/shuffle step can overlap with the map phase, but its finish point and the start of the reduce function step have to be strictly after the completion of the map phase of the same job. This dependency can result in an interesting criticality phenomenon for the job delay distribution in MapReduce scheduling. We refine the logarithmic asymptotics that has been established for heavy-tailed MapReduce jobs by studying the exact asymptotics. The analysis reveals that the MapReduce framework combines the features of both processor sharing and first in first out disciplines.


Objectives
The gut microbiota produces numerous metabolites from dietary nutrients that can circulate systemically and influence the host physiology. Bacterial enzymes convert dietary L-tryptophan (Trp) to indole, from which several metabolites can be formed by mammalian and bacterial enzymes. The bacterial metabolite indole propionic acid (IPA) is anti-inflammatory, neuroprotective and has been linked to a lower risk of type 2 diabetes. Little is known about which bacteria are responsible for IPA formation. Pomegranates (Pom) are excellent sources of ellagitannins (ET) and ellagic acid (EA) with prebiotic function. Therefore, it was our hypothesis that long-term Pom consumption will change bacterial Trp metabolite formation.

Methods
We performed a 12-month, randomized, double-blind, placebo-controlled trial of pomegranate juice in middle-aged and older, healthy adults. Nineteen subjects (ages 50-60) were randomized to consume 8 oz of pomegranate juice (the Wonderful Company, LLC) (N = 11) or placebo drink (N = 8) every day. The placebo drink contained high fructose corn syrup, Pom essence and flavor and FD&C Red#40, Blue#1. Stool samples were collected at baseline and after 1 year of Pom J consumption. Bacterial composition was determined using 16S rRNA microbiome sequencing. Plasma IPA concentrations were determined by HPLC. Correlation between fecal bacterial content and plasma IPA was evaluated in all samples using Spearman's analysis.

Results
The IPA was significantly reduced in the placebo group (P = 0.017), while there was no change in the Pom J group (P = 0.458). The change in plasma IPA during one year of Pom J compared to placebo drink consumption was significantly different (P = 0.028). At 12 months, plasma IPA concentration was significantly positively correlated with the relative proportion of Roseburia (0.57), Lachnospira (0.53) in the phylum Firmicutes; Sutterella (0.63) in the phylum Proteobacterium and Collinsella (0.46) in the phylum Actinobacteria. A significant negative correlation was observed with the relative proportion of Campylobacteraceae (-0.46).

Conclusions
Formation of IPA associated with a microbial profile supported by Pom J consumption might contribute to the cardiovascular health benefits of Pom.

Funding Sources
Supported by Center for Human Nutrition, UCLA.


The Cretaceous Dakota Sandstone in Cimarron County comprised three sandstone units and intervening mudrocks; it overlies the Kiowa Shale Member of the Purgatoire Formation. Deposits include shoreface, beach (foreshore) and dune, estuarine and tidal channel, marine marginal bay and swamp/marsh in a generally progradational sequences associated with marine regression in the Western Interior. The shoreface sand, characterized by ripple lamination, bioturbation and the trace fossils Teichichnus and Thalassinoides, is fine-grained, 5-10 m (15-30 ft) thick and grades into the underlying Kiowa Shale. Beach and associated dune deposits are 2-5 m (6-16 ft) thick, medium to fine-grained, medium to thick-bedded, tabular-planar cross-bedded, and lenticular; cross-bed paleocurrent headings are northeasterly and northwesterly. Estuarine channel deposits are 3-5 m (10 to 16 ft) thick, trough to tabular-planar cross-bedded, and medium to coarse-grained with local conglomerate overlying the scoured base which commonly cuts into the Kiowa Shale or overlying shoreface sandstone; rip-up clasts and wood pieces are common but trace fossils are rare; southeasterly and southwesterly paleocurrents predominate. Tidal channel deposits are thinner (up to 2 m of 6 ft) and finer grained (medium to fine-grained) that the estuarine channel deposits; they occur within fine-grained sandstone and mudrock sequences, are trough cross-bedded, and commonlymore » contain trace fossils (e.g., Skolithos) and wood fragments. Marine marginal (tidal flat or bay.) deposits comprise fine-grained sandstone, siltstone and interbedded shale, that are 1-3m (3-10 ft) thick with abundant burrows, small ripple marks, and parallel lamination. These grade into the fine to very fine-grained sandstones, siltstones, shales, and coals of the swamp/marsh deposits that are 1-5m (3-16 ft) thick and contain ripple marks, burrows, other trace fossils, and parallel lamination.« less


Background Chronic care management (CCM) and community health worker (CHW) interventions hold promise for managing complex chronic conditions such as diabetes and related comorbidities. This qualitative study examines facilitators and barriers to the implementation of an expanded CCM intervention that explicitly incorporated program staff, clinic staff, CHWs, and partnerships with community-based organizations to enhance diabetes management among Mexican-origin adults. Method Grounded theory was used to analyze interviews conducted in 2018 with 24 members of the CCM team, including program staff, clinic staff, and community-based program partner staff. Results Three themes emerged that characterize perceived facilitators and barriers to CCM implementation, based on analysis of interviews: (1) understanding roles and responsibilities across organizations, (2) building relationships across organizations, and (3) coordinating delivery of the model among different organizations. First, structured meetings and colocated workspaces enhanced understanding of CCM roles for each team member and across organizations. Barriers to understanding CCM roles were more common during the early stages of CCM implementation and amongst staff who did not participate in regular meetings. Second, regular meetings facilitated development of relationships across organizations to enhance implementation of the CCM model. In contrast, limited relationship building among some CCM team members served as a barrier to implementation. Third, CHWs and case review meetings fostered communication and coordination across the CCM model. Conclusions Results suggest the importance of understanding roles and building relationships among multidisciplinary teams to ensure effective communication and coordination of care.


The International Institute for Sustainable Development (IISD) contributes to sustainable development by advancing policy recommendations on international trade and investment, economic policy, climate change and energy, and management of natural and social capital, as well as the enabling role of communication technologies in these areas. We report on international negotiations and disseminate knowledge gained through collaborative projects, resulting in more rigorous research, capacity building in developing countries, better networks spanning the North and the South, and better global connections among researchers, practitioners, citizens and policy-makers.IISD's vision is better living for all—sustainably; its mission is to champion innovation, enabling societies to live sustainably. IISD is registered as a charitable organization in Canada and has 501(c)(3) status in the United States. IISD receives core operating support from the Government of Canada, provided through the International Development Research Centre (IDRC), from the Danish Ministry of Foreign Affairs and from the Province of Manitoba. The Institute receives project funding from numerous governments inside and outside Canada, United Nations agencies, foundations and the private sector.Head Office161 Portage Avenue East, 6th Floor, Winnipeg, Manitoba, Canada R3B 0Y4 Tel: +1 (204) 958-7700 | Fax: +1 (204) 958-7710 | Website: www.iisd.orgClimate Resilience and Food Security A framework for planning and monitoring June 2013This document is an output from a project funded by the U.K. Department for International Development (DFID) for the benefit of developing countries. However, the views expressed and information contained in it are not necessarily those of or endorsed by DFID, which can accept no responsibility for such views or information or for any reliance placed on them. Acknowledgements: The research team acknowledges the helpful comments and support of its Advisory Committee, in particular Natasha Grist (ODI), Peter Bieler (SDC), Dr Fikret Berkes (Univ of Manitoba), Julie Lennox (UN ECLAC), and Mirza Castro (FAO Honduras).


This study aims to analyze the process of innovation in the poultry production chain of a cooperative of western Santa Catarina, Brazil. The object of study was an agribusiness that coordinates the development of the main activities. This is a case study with a qualitative approach. Interviews were conducted with six managers of the agro-industry, ranging from the production of dies to the distribution of the finished products, through incubation activities, production of feed and poultry, as well as slaughter and processing. We verified that the object of this study mainly develops incremental innovations that are largely based on suppliers of both inputs as machinery and equipment, in regard to process innovations. In the case of product innovations, there is the use of internal sources of knowledge, especially by the sectors of R&D and product and process engineering, considering rare the cooperation or partnerships with external agents, such as research centers, universities and competitors.


The paper's focus is on the module division dynamically in the virtual assembly sequencing process for the product family, which will affect the module variant quality seriously. Most research merely divides the module on their functions, without paying the attention on which the module division is beneficial for the latter assembly process. Considered assembly relationships as a key constraint, a new variant module division measure based on Extension Logic is presented. Since the tolerances existing everywhere in the assembly process, the connection analysis is employed to build a constraint function on the tolerance. Physical constraints contain mating and combination constraints. After the dynamical position for different parts, the mating constraint is defined as the movement opposition between two mechanical elements including face alignment mating, shaft and hole mating or face against mating. Then the extension radiation model could be generated. According the average value of the relationship function to realize the module division, the product structure is divided into several sub-assemblies. As the main problem in virtual assembly is process collisions, a modified integer coded Particle Swarm Optimization Algorithm is used. Here every part is mapped to corresponding particle. The result is performed in the virtual environment of software DELMIA. At last the extension cluster method in this paper is compared with the direct dynamic cluster method. A case study is performed on virtual assembly of high power Light Emitting Diodes automatic sorting machine manufactured by a factory.Copyright © 2008 by ASME


Ernest Hemingway and John Steinbeck were among the few early 20th century American writers to incorporate the Spanish language into their work, making vanguard experiments in bilingual fiction. More often than not, this was to show their affinity for the working-class Spanish or Mexican people they were depicting. In this living within, between, and sometimes outside of two cultures, Hemingway and Steinbeck are not unlike early Chicano writers, with whom they share, in a limited way, a kind of bilingualism. Their way with language has special appeal to a new generation of bilingual American readers that lives on the border between the United States and Mexico and speaks that mix-and-match argot called everything from Spanglish to Tex/Mex to calo.


The variation of O/N2 (reference to N2 column density 1017 cm−2) and nitric oxide radiative emission flux exiting the thermosphere have been studied over the Northern Hemisphere during the superstorm event of 7–12 November 2004. The data have been obtained from Global Ultraviolet Imager (GUVI) and Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) on board the National Aeronautics and Space Administration (NASA)'s Thermosphere, Ionosphere, Mesosphere Energetics and Dynamics (TIMED) satellite. The NO radiative flux is observed to show an anti‐correlation with O/N2 on a global scale. Both NO radiative flux and O/N2 ratio show equatorward motion with maximum penetration in western longitude sectors. A local variation of O, O2, and N2 densities have been calculated using NRLMSISE‐00 model over a midlatitude location (55°N,180°E). On a local scale, model calculated O/O2 and O/N2 ratios are found to follow the observations made by GUVI. The collisional excitation of NO with atomic oxygen is the most dominant process for the total cooling rate. The SABER‐retrieved NO cooling rate (CR) at a local site suggests an enhancement during the storm period with the peak emission rate closely correlated to the progression of the storm. The peak emission altitude of NO CR moves upward during the main phase of the storm. The NO abundance has been calculated by using cooling rate and Nitric Oxide Empirical Model (NOEM) model. Both these suggest a vary large (3–15 times) increase in NO density during the storm, which is required to account the changes in NO radiative flux. A similar kind of enhancement in NO abundance is also noticed in Student Nitric Oxide Explorer observations during intense geomagnetic storms.


The gut microbiota plays a role in nonalcoholic fatty liver disease (NAFLD), but data about gut dysbiosis in Asians with NAFLD remains scarce. We analyzed the differences in fecal microbiota between adults with and without NAFLD. This cross-sectional study examined adults with histology-proven NAFLD (25 nonalcoholic fatty liver (NAFL) patients, 25 nonalcoholic steatohepatitis (NASH) patients, and 25 living liver donors (healthy controls)). The taxonomic composition of the gut microbiota was determined by 16S ribosomal RNA gene sequencing of stool samples. The NAFL and NASH groups showed lower total bacterial diversity and richness than the controls. NAFLD patients had higher levels of the phylum Bacteroidetes and lower levels of Firmicutes than controls. The genus Ruminococcaceae UCG-010, family Ruminococcaceae, order Clostridiales, and class Clostridia were less abundant in patients with NAFL or NASH than healthy individuals. The lipopolysaccharide biosynthesis pathway was differentially enriched in the NASH group. This study examined the largest number of Asian patients with biopsy-proven NAFL and NASH in terms of dysbiosis of the gut microbiota in NAFLD patients. NAFLD patients had higher levels of Bacteroidetes and lower levels of Firmicutes. These results are different from research from western countries and could provide different targets for therapies by region.


We studied the distributio of the Chapman's blue (Polyommatus thersites) in central Slovenia and its habitat choice was carried out in order to define conservation measures that will enable the long term survivour of this species in central Slovenia, but also wider in similar areas in Europe.
We found that the population of the Chapman's blue is stable in the surveyed area at gravels of the Sava River. From 17. 5. to 8. 6.2017, we conducted 17 fieldwork days in the survey area. During this time, we marked 152 specimens, of which 75 were males and 77 were females, with MRR method. The daily sizes of the population, estimated with the Jolly Seber method, ranged between 80 to 190 specimens. The numbers are unusual for this species as they normally occur in low densities in central Slovenia.
At the survey area were several separate habitats of The larval host plant sainfoin (Onobrychis spp.) was present in separate patches in the surveyed area and migrations among them was common. During the migrations, the specimens flew over the meadow areas and the dirt tracks. Chapman's blue was most often caught within host plant patches (77%), but several specimens were caught also outside them. The homerange of specimens caught more than once included larger part of the area included in the study.
According to our estimation, the habitat of the Chapman's Blue at the survey area is in relatively good condition, although illegal waste dumps and overgrowing with invasive plant species are present. It is important that the measures for improving the larval habitat are continued, as for example, with removal of invasive plant species. Also monitoring of the abundance of this endangered species with transect counts is still required. It is important to raise public awareness regarding the significant role of butterflies in the environment. Contribution to this could be done with the introduction of the nature tourism in the area of Sava gravels. Carefully planned activities related to butterflies could be an advantage both for the conservation of the endangered species and for the local community and its touristic offer.


Agents are computational systems interacting with dynamic, and non-entirely predictable environments. They decide for themselves, on the basis of their individual beliefs, goals, etc., how to respond to the environment. An agent is usually motivated to achieve a feasible objective by means of the collaboration of other agents. For example, lifting a heavy table may be impossible without help. However, it can be done by simply asking others for help. The process of gaining collaboration can take many forms. However, some tasks need more detailed communication to generate an explicit mutually acceptable agreement through negotiation. This paper presents a new method to solve the inverse kinematic problem of a redundant robot using the agents paradigm. This method guarantees rapid convergence of the robot to desired position, with substantially good accuracy. The originality of the proposed approach is its ability to overcome some of the standard problems such as the computation of the inverse or pseudoinverse Jacobian matrix, problem of singularity, redundancy, and considerably increased computational complexity, etc.


Purpose of reviewAllergen-specific immunotherapy is the only specific, dose-dependent and time-dependent and disease-modifying strategy for the treatment of allergy associated with clinical improvement and biological tolerance which may persist years after discontinuation. Recent findingsSuccessful immunotherapy in respiratory allergy is associated with the immunodeviation of Th2 response to a more protective allergen-specific Th1 cells and with the induction of interleukin-10 (IL-10)/transforming growth factor (TGF)-&bgr;-producing T regulatory cells in blood and inflamed airways. Subcutaneous treatment and sublingual treatments induce similar alterations which are dose-dependent and time-dependent. SummaryThis study provides an update on the immunological T-cell responses during subcutanous immunotherapy and sublingual immunotherapy, giving a unifying view of the redirecting mechanisms and regulating mechanisms elicited by these treatments.


Matcha is a powdered green tea obtained from the Camellia sinensis L. plant intended for both "hot" and "cold" consumption. It is a rich source of bioactive ingredients, thanks to which it has strong antioxidant properties. In this research, an organoleptic evaluation was carried out, and the physical characteristics (i.e., instrumental color measurement (L*a*b*), water activity, water solubility index (WSI), water holding capacity (WHC) of 10 powdered Matcha green teas, and in the 2.5% Matcha water solutions, pH, °Brix and osmolality were tested. Also, the content of phenolic ingredients, i.e., selected phenolic acids, flavonoids and total polyphenols, was assessed. The content of chlorophyll, vitamin C and antioxidant potential were also examined. Matcha M-4 was used to design two functional model beverages, in the form of ready-to-use powdered drinks, consisting of Matcha green tea, protein preparations, inulin, maltodextrin and sugar. The obtained powdered drink, when dissolved in the preferred liquid (water, milk, juice), is regenerative, high-protein and rich in bioactive ingredients from the Matcha drink, with prebiotic properties derived from the added inulin. The beverage is also characterized by low osmolality. It can be recommended as a regenerating beverage for a wide group of consumers, athletes and people with deficiencies, among others protein, and elderly people, as well as in the prevention and supportive treatment of bone and joint tissue diseases.


Owner‐managers of small businesses invariably cite word of mouth recommendations as the principal way in which they attract new customers. Marketing theory is under‐developed in this field with little empirical evidence about the recommending behaviour of small business customers and referral groups. The case study of an independent health club reported here illustrates how these processes can be researched and the results used to influence word of mouth recommendations. The owner‐manager of the club carried out some basic research on his customer base in order to identify the types of members who were most active in recommending the club, and the stimuli that led to recommendations being made. A key finding was that newer members were more likely to recommend than those who had been members for some time, contradicting the implications of relationship marketing theories that long standing customers generate most recommendations. Membership more than doubled following a number of activities designed to increase recommending behaviour. The most important stimuli to recommendations were believed to be involvement with the club, incentives and experiential factors. The case study indicates that word of mouth strategies benefit from research to find out which customers are recommending the business, what they are recommending about the business and what prompts them to do so.


Ten Aureobasidium isolates were collected from bathroom surfaces in Thailand. They were identified as Aureobasidium pullulans. Cell extracts from all isolates were tested for antifungal activities against four selected Aspergillus species using a paper disc diffusion and conidial germination inhibition assay. BM1, KT1, HKW1 and HKW2 extracts inhibited Aspergillus terreus, whereas KT1 and BM1 extracts also inhibited Aspergillus fumigatus. BM1 extract alone inhibited Aspergillus flavus. From TLC analysis, an antifungal compound with an identical Rf to that of aureobasidin A was found in all extracts. Antifungal tests of TLC-separated compounds supported the paper disc diffusion and conidial germination inhibition assays.


Author(s): Lehmann, Lynn Wayne | Advisor(s): Carey, Michael F | Abstract: Eukaryotic transcription requires the concerted action of numerous proteins including activators, co-activators, the general transcription factors (GTFs), RNA polymerase II (RNA Pol II), chromatin remodelers and modifiers, and chromatin- binding effector proteins. Although many of the components of the preinitiation complex (PIC) have been described, a comprehensive understanding of all preinitiation components and what affects chromatin modifications have on PIC formation remains vague. This doctoral thesis investigates the composition and function of eukaryotic PICs in HeLa and mouse embryonic stem cells. Using Multi Dimensional Protein Identification Technology (MuDPIT), others in the lab showed that most transcription components necessary for initiation were present in in vitro formed PICs in both cell types. Additionally, numerous chromatin remodeling proteins, elongation factors, and chromatin modifying enzymes were also identified proteomically. Intriguingly, two major co-activator complexes SAGA and Mediator, ranked among the highest activator-inducible proteins as detected by MuDPIT analysis. I generated HeLa nuclear extracts immuno-depleted of Mediator and SAGA and performed mechanism-based immobilized template experiments on chromatin to show both complexes interact with GAL4-VP16 directly, and do not compete for promoter access. I also used the immobilized template to show that Mediator, but not SAGA, serves as the main scaffold to recruit the PIC machinery. Genome-wide, enrichment patterns of Mediator, RNA Pol II, TATA-binding protein, and mRNA levels strongly correlate suggesting a prominent role for Mediator in PIC assembly. Lastly, I used in vitro transcription assays to show that SAGA is required for activated transcription on chromatin. Overall, these data support a working model where Mediator serves as the main co-activator complex, contributing to PIC formation, stability, and function, while SAGA acts after PIC formation, conferring activity to PICs on chromatin.Although the role of histone tail modifications and subsequent effector binding proteins is an area of considerable study, the role that histone modifications play in PIC formation and activity is poorly understood. This thesis examines the role of the Chromodomain Helicase DNA-binding protein 1 (CHD1), known to bind histone H3 trimethylated at Lysine 4, in PIC assembly and function. I purified murine CHD1 to near homogeneity using a baculovirus-based insect cell system, and prepared the samples used for identification of CHD1-interacting proteins by MuDPIT of associated proteins from HeLa nuclear extracts. My collaborator on this project, Justin Lin, used purified CHD1 to show that the protein stimulates transcription on chromatin and further activates transcription on H3K4me3 chromatin. Further, mechanistic experiments performed by others in the lab revealed that CHD1 recruitment to immobilized templates is dependent on Mediator and enhanced by H3K4me3. Our in vitro and in vivo experiments suggested that Mediator and CHD1 interact to enhance transcription. The summation of these data support a model where Mediator acts to support both PIC assembly and the binding of CHD1 to PICs, with H3K4me3 providing a second interaction platform responsible for the recruitment of CHD1 to active genes. In an opposing role, chromatin modifications also play a role in establishing and maintaining a silent transcriptional state. In the final chapter of this thesis, I investigate the affects of Polycomb Repressive Complex 1 (PRC1) on PIC formation and activity. I purified PRC1 and investigated the role of the complex in PIC assembly and function on H3K27me3 templates. I show that PRC1 can both block and dissociate the majority of PIC components including Mediator, SAGA, elongation factors and the general transcription factors to silence transcription. Notably, the ability of GAL4-VP16 and TATA-binding protein (TBP) to bind promoters was retained in the presence of PRC1. I again used immobilized template experiments with purified Mediator, TFIID, and PRC1 to show that PRC1 specifically blocks Mediator but not TFIID. Utilizing previously reported genome-wide binding in mouse embryonic stem cells, we showed that Ring1b and TBP displayed enriched binding profiles at developmental genes, and this enrichment significantly correlated with reduced expression as compared to genes enriched for Mediator, TBP, and Ring1b. In summary, the results of this study highlight a possible role for TFIID and PRC1 in co-regulating the expression of developmental genes.


Background: Preclinical evidence shows that short-term fasting protects normal cells, while cancer cells are sensitized to chemotherapy. Furthermore, a specifically designed very low calorie, low amino acid substitution diet ("Fasting Mimicking Diet", FMD) has similar effects on chemotherapy as short-term fasting. This trial evaluates the impact of FMD on tolerance to and efficacy of neoadjuvant chemotherapy in women with HER2-negative early breast cancer. Trial design: DIRECT is a Dutch, randomized, open-label multicenter phase II/III trial. Women receiving neoadjuvant TAC courses (docetaxel/adriamycin/cyclophosphamide; day 1, q 3 weeks with G-CSF support at day 2) will be randomized with or without FMD for 3 days prior to and the day of chemotherapy and 3 days prior to surgery. Eligibility criteria: Eligible women are WHO 0-2, age ≥18 years, HER2-negative, stage II or III breast cancer and adequate bone marrow, liver and renal function, BMI > 19kg/m2 and absence of diabetes mellitus. Study endpoints: The primary endpoints are grade III/IV toxicity (phase II) and the pathologic complete response rate (pCR) (phase III). Secondary endpoints are grade I/II toxicity, metabolic and inflammatory response to chemotherapy, DNA damage, apoptosis, immunology and nutrient sensing pathways in the tumor, biomarkers as single nucleotide polymorphisms, Ki67 and tumor stroma/ratio, patient9s quality of life and (disease free) survival. Optional side studies include chemotherapy-induced DNA damage and nutrient sensing pathways in leukocytes and proteomics. Statistical Methods: Using a 5% significance level based on the two-sided Fisher9s exact test with a power of 80%, 128 patients (64/arm) will be enrolled to show a 50% decrease of grade III/IV adverse events in the experimental arm (phase II) and 250 patients (125/arm) are needed to show an improvement of the pCR rate from 18% to 36% (phase III). Target accrual: Recruitment will start in September 2013. The expected end of accrual of 250 patients from multiple centers in the Netherlands will be the last quarter of 2015. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT3-1-03.


Novel computational methods for understanding relationships between ligands and all possible biological targets have emerged in recent years. Proteins are connected to each other based on the similarity of their ligands or based on the similarity of their binding sites. The assumption is that compounds sharing chemical similarity should share targets and that targets with a similar binding site should also share ligands. A large number of computational techniques have been developed to assess ligand and binding site similarity, which can be used to make quantitative predictions of the most probable biological target of a given compound. This review covers the recent advances in new computational methods for relating biological targets based on the similarity of their binding sites. Binding site comparisons are used for the prediction of their most likely ligands, their possible cross reactivity and selectivity. These comparisons can also be used to infer the function of novel uncharacterized proteins.


Researches about tsunamis showed that a huge mass of water movement caused not only life and property losses on coastal areas, but also caused severe damages on ocean ecosystem due to huge mass of sand movements and tsunami backwash flow. In this study, it is aimed to understand the horizontal changes in suspended sediment concentration in water, originated from the tsunami run up and backwash flow with an experimental setup. This study has showed that the tsunami induced sediment transport has two layer sediment clouds as it is observed and the empirical equations have verified this fact


Purpose Speech-language pathologists (SLPs) work with a variety of populations at risk for poor autobiographical and episodic memory. The purpose of this tutorial is to describe autobiographical memory and how it is affected in children with autism spectrum disorder, attention-deficit/hyperactivity disorder, hearing loss, and childhood trauma, as well as provide clinicians with practical strategies for supporting autobiographical memory in each of these clinical populations. Method This tutorial reviews the literature on (a) autobiographical and episodic memory in typical development; (b) its relation to theory of mind, personal narrative skills, and executive functions; (c) elaborative reminiscing in typical development; (d) how autobiographical memory is impaired in children with autism spectrum disorder, attention-deficit/hyperactivity disorder, hearing loss, and childhood trauma; and (e) strategies for supporting autobiographical memory in each clinical population. Conclusions When adequately prepared, SLPs are uniquely situated to address autobiographical and episodic memory in their work with children, families, and related professionals. This is a long-overdue focus of such great clinical import that justifies its inclusion in the traditional training and preparation of SLPs. Adapting elaborative reminiscing strategies for use with various clinical populations is promising for facilitating healthy EM development and related cognitive functions.


Background: 1.3% of people in Iran are positive for anti-HBc antibody.The objective of this study is to determine the rate of seroconversion in those with persistent isolated anti-HBc after vaccination. Materials and Methods: In a quasi-experimental study, 94 persons with isolated anti-HBc antibody who were referred to Tehran Blood Transfusion Organization between 2002 and 2004 were selected through a convenient sampling. They were given recombinant hepatitis B vaccine on 0, 1 and 6 months. Immunization was defined by anti-HBs antibody titer |≥|10 mIU/mL, 1-2 months after administration of the last dose. Results: Response to HB vaccination consisted of 28%, 62% and 76% after each injection, respectively. The total response rate was 80% (n=75). Nineteen (20%) persons were negative for anti-HBs even after three doses of HB vaccination. Factors associated with decreased response to vaccination were positive anti-HBe (OR=6.4, P=0.008), history of bloodletting (OR=3.1, P=0.039) and prior history of being HBsAg positive (OR=5.6, P=0.002). Conclusion: Although there were some differences between the response rates after each vaccine injections observed in our study and similar ones, the total response was nearly the same.


This paper addresses the problem of design rule correct routing, i.e. the avoidance of illegal wiring patterns during routing. These illegal wiring patterns are due to the set of design rules accompanying each specific technology. To avoid software tuning for different technologies, the routing space is modelled as a grid graph, and all design rules are described in terms of the grid graph, including rules that describe illegal wiring patterns. The problem of finding valid, (i.e. containing no illegal wiring patterns) minimum cost connections is shown to be NP-complete, even for single nets. Although this restriction occurs in most technologies, literature does not mention any routing algorithm capable of handling these situations correctly. Two heuristics are presented to solve the routing problem, both ensuring all paths found to be valid.<<ETX>>


Machine learning was employed on the experimental crystal structures of the Cambridge Structural Database (CSD) to derive an intermolecular force field for all available types of atoms (general force field). The obtained pairwise interatomic potentials of the general force field allow for the fast and accurate calculation of intermolecular Gibbs energy. The approach is based on three postulates regarding Gibbs energy: the lattice energy must be below zero, the crystal structure must be a local minimum, and, if available, the experimental and the calculated lattice energy must coincide. The parametrized general force field was then validated regarding these three conditions. First, the experimental lattice energy was compared with the calculated energies. The observed errors were found to be in the order of experimental errors. Second, Gibbs lattice energy was calculated for all structures available in the CSD. Their energy values were found to be below zero in 99.86% of the cases. Finally, 500 random structures were minimized, and the change in density and energy was examined. The mean error in the case of density was below 4.06%, and for energy it was below 5.7%. The obtained general force field calculated Gibbs lattice energies of 259 041 known crystal structures within a few hours. Since Gibbs energy defines the reaction energy, the calculated energy can be used to predict chemical-physical properties of crystals, for instance, the formation of co-crystals, polymorph stability and solubility.


The object of the study is the process of determining the quality of the life of the population. The subject of the study is methodological approaches, methods for determining the quality of life that affect the quality of working life and indicate the usefulness of investing in improving the overall level of staff development. The goal of the paper is to provide the theoretical justification of factors that affect the quality of life of the population of regions grounding on the assessment of indicators to study the usefulness of investing to support and develop this phenomenon. The objectives of the article are to analyze the factors that affect the quality of life, to select and substantiate the components of the quality of life assessment of the population of regions, to draft proposals on the composition of the system of indicators for assessing the quality of life. The following methods are used in the study – the systematic one, logical and historical approaches, analysis and synthesis, induction and deduction, monographic analysis. Results. The quality of life is considered as a complex concept that characterizes the degree of satisfaction with the conditions of a person being; the quality of working life including labour, the physical and social environment at an enterprise, the system of management, the relationship between the labour and non-labour sphere constitute a very significant part of the mentioned phenomenon. The components and factors that affect the quality of the life of population are grouped as those that directly affect the quality (the quality of working life, living conditions, environment, satisfaction with life), and those that indirectly affect the quality of life (the demographic situation, financial security, legal support, health protection, education, social environment). Factors and the system of indicators for assessing the quality of the life of the population in regions are specified on the basis of the components that have been proved and suggested additionally – ecological condition and the quality of the working life of workers of the enterprises located in regions. Conclusions. The analysis enabled revealing a number of factors that affect the quality of the life of the population of Ukraine, determining the most common of them and the features of their impact and taking into account new trends in the society, economy and politics to classify these factors depending on their impact on the object of the research that is on an individual as those that directly affect the quality the life of the population, and those indirectly affect the quality of life of the population. The monographic analysis enabled identifying and justifying the system of indicators of the quality of the life of the population in the regions of Ukraine.


The existence and stability of defect superlattice solitons in parity—time (PT) symmetric superlattice and simple-lattice complex potentials are reported. Compared with defect simple-lattice solitons in similar potentials, the defect soliton in superlattice has a wider stable range than that in simple-lattice. The solitons' power increases with increasing propagation constant. For the positive defect, the solitons are stable in the whole region where solitons exist in the semi-infinite gap. For the zero defect, the solitons are unstable at the edge of the band. For the negative defect, the solitons propagate with the shape of Y at low propagation constant and propagate stably at the large one.


Macroeconomic and financial time series are often tested for the presence of non-linearity effects. Sometimes, small patches of extremal observations may wrongly influence non-linearity tests. In this paper, a robust analysis of the Lagrange multiplier (LM) test for GARCH components is suggested. With Monte-Carlo simulation we show that extreme observations might cause over-estimation of the number of GARCH components, with the main contribution consisting by introducing the forward search method into the GARCH model family. Using robust estimators of regression coefficients and graphical displays of results, the effect of influential observations on estimates can be efficiently monitored. Analysing macroeconomic and financial time series we show that identifying the order of a GARCH model can be unduly influenced by a few isolated large values, and extremal observations affect p-values and t-statistics in an unexpected manner. Copyright © 2004 John Wiley & Sons, Ltd.


Fixed drug eruption (FDE) is a well-defined hyperpigmented patch that recurs in a fixed location each time a particular drug is taken. Common causative agents of FDE are non-steroidal anti-inflammatory drugs, non-narcotic analgesics, sedatives, anticonvulsants, sulfonamides, and tetracycline. We report a 33-year-old male who presented with a recurrent, localized, brownish-to-erythematous macule and papules on the peri-philtrum area two hours after taking valacyclovir. Three episodes of valacyclovir ingestion for treatment of Herpes simplex virus infection provoked a similar skin rash at the same site. Histopathology results showed vacuolar degeneration in the basal layer of the epidermis, pigmentary incontinence, and perivascular inflammatory cell infiltration in the papillary dermis. Although patch test and skin prick test showed negative responses to acyclovir and valacyclovir, an intradermal test showed a positive reaction only to valacyclovir. The oral provocation test to acyclovir and valacyclovir showed a positive reaction only to valacyclovir. Through drug history, histopathological examination, patch test, intradermal test, and oral provocation test, we established a final diagnosis of FDE due to valacyclovir without cross-reactivity to acyclovir. To find alternative therapeutic drugs, we suggest diagnostic tests with not only the suspected drugs, but also other drugs in the same class.


After traumatic brain injury (TBI), patients usually live with significant disability and socioeconomic burdens. Acute exposure to alcohol is considered a major risk factor for TBI. Numerous studies have examined whether alcohol exposure is related to the risk of mortality in patients with TBI, yet the results remain inconsistent. We performed a meta-analysis to assess whether acute alcohol exposure affects the mortality rate of TBI patients. We searched PubMed, EMBASE, and the Cochrane Library up to November 2015 for relevant studies. We screened studies based on their inclusion criteria and selected the studies that reported mortality rate, which included 18 observational studies. We used R to analyze the included data. An initial result showed that the presence of a positive blood alcohol concentration (BAC) had no significant relation with mortality rate (OR = 0.92, 95% CI = 0.83 to 1.01), but there was notable heterogeneity along with variable results according to sensitivity analysis. For the BAC-positive population, low BAC (1 to 100 mg/dl) carried a higher risk of mortality than moderate BAC (100 to 230 mg/dl) (OR = 1.40, 95% CI = 1.09 to 1.81), moderate and high BAC as a single category (>100 mg/dl) (OR = 1.57, 95% CI = 1.28 to 1.94), or high BAC (>230 mg/dl) (OR = 1.76, 95% CI = 1.34 to 2.30). However, moderate BAC did not increase the mortality risk when compared with high BAC (OR = 1.20, 95% CI = 0.89 to 1.63). Whether positive BAC at the time of admission after TBI reduces mortality rate compared with the rate under negative BAC remains unknown. In addition, low BAC (1 to 100 mg/dl) poses a risk of mortality compared with higher BAC. Further studies assessing the effect of alcohol between the BAC-positive group and the BAC-negative group are still needed.


This article investigates the seed exomorphic characteristics of 14 taxa of Lepidium L. in Brassicaceae by light microscope and scanning electron microscope (SEM). The exomorphic characteristics of the seed are size, seed shape, seed colour, seed wings, and seed surface pattern. All characteristics of the seeds are described, illustrated, and compared in this article. The results of SEM at higher magnification showed 6 types of seed surface patterns: tuberculate, reticulate, ruminate, reticulate-tuberculate, reticulate-areolate, and reticulate-fovate. In these seed surface patterns, there were diagnostic characteristics and differences at the specific level for Lepidium.


Metabolic syndrome is highly prevalent in vascular patients and has a significant impact on the outcomes of vascular interventions. It comprises of a set of metabolically driven risk factors, including truncal obesity, dyslipidemia, elevated blood pressure and elevated fasting blood glucose. Increased insulin resistance within the context of obesity and hypertension contributes to atherogenic dyslipidemia, hyperglycemia, and prothrombotic and proinflammatory states which lead to the adverse impact of metabolic syndrome on the response to injury and on atherosclerotic disease progression. This review focuses on the complex biology of metabolic syndrome and its relevance to management of vascular patients, including outcomes and implications for the coronary, cerebrovascular and lower-extremity vascular beds.


In the fully customized service mode and highly customized service mode, the process of services is a project from the essence. Project-Oriented Company is a new organizational structure adapts to the development requirements of service. This paper analyzes the features of project-oriented service company and points out the key factor to establish a project-oriented service company is knowledge management. In order to have a better knowledge management, the paper makes a cause analysis of the knowledge loss in project-oriented service company, and based on this explores two knowledge management models.


There is growing concern about the level of antimicrobial use and antimicrobial resistance in food producing animals. An area of opportunity to reduce antimicrobial use could be in the treatment of young calves during the first week following arrival at calf rearing facilities. Group metaphylaxis is common due to the unknown age and history of calves that undergo several stressful events prior to arrival, such as transportation, co-mingling and variable periods of fasting. It may be possible to reduce antimicrobial use at this stage in the production cycle without sacrificing animal health and welfare if the calves at highest risk of morbidity and mortality could be identified and treated in a highly selective manner. Recent studies have identified indicators of future risk for morbidity and mortality that can be measured at arrival such as biomarkers and physical exam factors. Bovine haematology, when used in conjunction with clinical examination findings, could be used to improve disease diagnosis. The objective of this study was to assess the utility of leukocyte differential cell counts taken at the time of arrival at a calf rearing facility and 72 hours post arrival for determining mortality risk during the production cycle.


The Medical Council of India (MCI) must be commended for its efforts to introduce definitive criteria for appointments and promotions for teachers in medical institutions. On June 8, 2017, the MCI issued a circular[1] to amend the Minimum Qualifications for Teachers in Medical Institutions Regulations, 1998 (henceforth Regulations, 1998).[2] The amendment clarifies the minimum qualifications required for various postgraduate teaching positions in medical colleges. It indicates MCI's sustained engagement with qualifications of teachers in medical colleges, with the aim of enhancing the quality of teaching and thereby the quality of medical professionals passing out. However, we believe that these efforts continue to be inadequate in addressing the varied issues that face medical education and the educators in India.


[1] We use teleseismic P and S delay times and shear wave splitting measurements to constrain isotropic and anisotropic heterogeneity in the mantle beneath the southern East Pacific Rise (SEPR). The data comprise 462 P and S delay times and 18 shear wave splitting observations recorded during the Mantle Electromagnetic and Tomography (MELT) Experiment. We estimate the mantle melt content (F) and temperature (T) variation from the isotropic velocity variation. Our results indicate that the maximum variation in F beneath our array is between zero and ∼1.2%, and maximum variation in T is between zero and ∼100 K. We favor an explanation having partial contributions from both T and F. We approximate the seismic anisotropy of the upper mantle with hexagonal symmetry, consistent with the assumption of two dimensionality of mantle flow. Our new tomographic technique uses a nonlinear inversion of P and slow S polarization delay times to simultaneously solve for coupled VP and VS heterogeneity throughout the model and for the magnitude of anisotropy within discrete domains. The domain dimensions and the dip of the anisotropy are fixed for each inversion but are varied in a grid search, obtaining the misfit of the models to the body wave delay data and to split times of vertically propagating S waves. The data misfit and the isotropic heterogeneity are sensitive to domain dimensions and dip of anisotropy. In a region centered beneath the SEPR the best average dip of the hexagonal symmetry axis is horizontal or dipping shallowly (<30°) west. Given the resolution of our data, a subaxial region characterized by vertically aligned symmetry axes may exist but is limited to be <80 km deep. We infer that the mantle flow beneath the SEPR is consistent with shallow asthenospheric return flow from the direction of the South Pacific superswell.


Background: Hypertension is the most important risk factor for cardiovascular morbidity and mortality. Blood pressure control rates are as low as 17% to 31% in patients diagnosed with hypertension in high-income countries; control rates are likely poorer in low- to middle- and low-income countries. Blood pressure control rates are as low as 17% to 31% in patients diagnosed with hypertension in high-income countries; control rates are likely poorer in low- to middle- and low- income countries. Overall, 43% to 66% of patients fail to adhere to their prescribed antihypertensive medications, and after 1 year, ≈40% of patients with hypertension may stop their initial drug treatment. Objective: The aim of the study was to evaluate the effects of single pill combination antihypertensive drugs on the adherence to treatment, blood pressure control and cardiovascular events vs. free-combination therapy. Methods: We enrolled 192 adult hypertensive patients not older than 79 years, with untreated or uncontrolled hypertension despite previously receiving free combination antihypertensive therapy, between November 2020 and March 2022. Patients treated with single pill combination (SPC) were compared with an arm of the same size (n = 96) and matched by age and gender who received a standard free combination (FC) antihypertensive therapy. Results: There were significant reductions from baseline to month 6 of follow-up in office SBP in the SPC group vs. reduction in FC group (21.9 vs. 13.1 mmHg; p < 0.0001). There were significant reductions from baseline to month 6 of follow-up in office DBP in the SPC group vs. group with free-combination therapy (13.7 vs. 8.0 mmHg; p < 0.0001). At 6 months, 94 participants (98%) were still prescribed the SPC therapy. At the final 6-month study visit, 84.2% of patients in the SPC therapy group were adherent to the prescribed antihypertensive therapy vs. 52% of patients in the FC group. Target BP values (mean 24h ambulatory systolic/diastolic BP < 130/80 mmHg) were reached by more recipients of SPC than free-combination therapy (78.2% vs. 46.3%, p < 0.05) at month 6 of follow-up. Conclusion: Treatment with single pill combinations (SPC), is the emerging best practice for safe, effective, rapid, and convenient hypertension control. It improves the affordability, adherence and control of arterial hypertension.


BACKGROUND
Nasolabial fold (NLF) is an important anatomic sign of facial aging. However, the dynamic biomechanical relationships between the facial mimetic muscles (FMMs) and the NLF remain unclear.

OBJECTIVE
This study aimed to investigate the dynamic biomechanical relationships between the FMM and various NLF by finite-element analysis (FEA).

METHODS
The 3-dimentional computer-aided design (3D CAD) model of the skin-muscle-maxillofacial bone in the NLF was established by using the engineering design module of the Computer-Aided 3-dimensional Interactive Application (CATIA) software. This CAD model was then imported into the Hypermesh software to set element type, mesh, and material properties. Finally, the 3D FEA model of the skin-muscle-maxillofacial bone in the NLF was generated, and then exported and uploaded into the Abaqus software with HM format for mechanical force loading and biomechanical analysis.

RESULTS
A 3D FEA model of the skin-muscle-maxillofacial bone in the NLF was successfully established by using the Mimics, Geomagic Studio, CATIA, Hypermesh, and Abaqus softwares. This FEA model had a good geometrical resemblance and good biomechanical properties. This provided an ideal biomechanical model for the study of deformation and the biomechanics of soft tissues, such as the NLF. The FEA was applied to the biomechanical simulation of the NLF. We established five effective FEA models to study the dynamic biomechanical relationships between the NLF and the FMM. The dynamic biomechanical relationships between the NLF and the FMM were preliminarily determined by computer simulating different types of mechanical force loadings.

CONCLUSION
The FEA is an effective method to simulate the dynamic biomechanical relationships between the NLF and the FMM. Through the FEA simulation described in this study, we could preliminarily conclude that the formation of different types of NLF is mainly due to the coordinated contraction of various FMM. Moreover, not all FMM are involved in all types of NLF. According to the results of the FEA simulations in this study, it is worthwhile considering investigating the role of botulinum toxin in improving the morphology of the NLF in the near future.


In this work we present a detailed investigation of the dielectric properties of the oxyborate Fe2OBO3 . This compound exhibits a high dielectric constant at room temperature (epsivr' > 103) for frequencies up to 104 Hz. An impedance spectroscopy analysis of the data reveals an important extrinsic contribution to these high epsivr' values. In order to eliminate the extrinsic contribution, we have sandwiched the sample in-between two mica layers, obtaining relatively high values of epsivr' at room temperature for this kind of oxides (epsivr' ~ 45). The temperature dependence of the remaining intrinsic contribution shows a jump, that at high frequencies occurs at the temperature at which a rearrangement of the charge-order pattern takes place and at low frequencies occurs at temperatures close to the onset of the antiferromagnetic long-range order. This suggests a certain coupling between the electronic, magnetic and dielectric properties in this compound.


OBJECTIVE
Given that most effective alcohol harm-reduction laws specify the blood alcohol concentration (BAC) that constitutes illegal behavior (e.g., the .08% breath alcohol concentration legal limit), interventions that allow drinkers to accurately estimate their BACs, and thus better assess their risk, have potential importance to long-term driving-under-the-influence prevention efforts. This study describes a field experiment designed to test the impact on drinking of providing "Know Your Limit" (KYL) BAC estimation cards to individuals in a natural drinking environment.

METHOD
We randomly sampled 1,215 U.S. residents as they entered Mexico for a night of drinking, interviewed them, and randomly assigned them to one of six experimental conditions. Participants were reinterviewed and breath-tested when they returned to the United States. The experimental conditions included providing generic warnings about drinking and driving, giving out gender-specific BAC calculator cards (KYL cards), and providing incentives to moderate their drinking.

RESULTS
Cueing participants about the risks of drunk driving resulted in significantly lower BACs (relative to control) for participants who indicated that they would drive home. Providing KYL matrixes did not reduce BACs, and, in fact, some evidence suggests that KYL cards undermined the effect of the warning.

CONCLUSIONS
KYL information does not appear to be an effective tool for reducing drinking and driving. Implications for prevention and future research are discussed.


We formulate the problem of surface deformations as the integration in the least square sense of a discrete vector-valued 1-forms obtained as the result of applying smooth stretching and rotation fields to the discrete differential of the 0-form defined by the vertex coordinates of a polygon mesh graph. Simple algorithms result from this formulation, which reduces to the solution of sparse linear systems. The method handles large angle rotations in one step and is invariant to rotations, translations, and scaling. We also introduce the integration of 1-forms along spanning trees as a heuristic to speed up the convergence of iterative solvers.


We describe the fabrication of elliptical Au nanodisk arrays as a localized surface plasmon resonance (LSPR) sensing substrate for clinical immunoassay via thermal nanoimprint lithography (NIL) and enhancement in the sensitivity of the detection of the prostate-specific antigen (PSA) using the precipitation of 5-bromo-4-chloro-3-indolyl phosphate p-toluidine/nitro blue tetrazolium (BCIP/NBT), catalyzed by alkaline phosphatase. Au nanodisks were fabricated on glass through an unconventional tilted evaporation, which could preserve the thickness of imprinted resists and create an undercut beneficial to the subsequent lift-off process without any damage to pattern dimension and the glass while removing the residual polymers. To investigate the optically anisotropic property of the LSPR sensors, a probe light with linear polarization parallel to and perpendicular to the long axis of the elliptical nanodisk array was utilized, and their sensitivity to the bulk refractive index (RI) was measured as 327 and 167 nm/RIU, respectively. To our knowledge, this is the first application of enzyme-substrate reaction to sandwich immunoassay-based LSPR biosensors that previously suffered from a low sensitivity due to the short penetration depth of the plasmon field, especially when large-sized antibodies were used as bioreceptors. As a result, a large change in local refractive index because of the precipitation on the Au nanodisks amplified the wavelength shift of the LSPR peak in the vis-NIR spectrum, resulting in femtomolar detection limits, which was ∼10(5)-fold lower than the label-free detection without the enzyme precipitation. This method can be extended easily to the other clinical diagnostics with a high sensitivity.


The aim of this study was to calculate microdosimetric distributions for low energy electrons simulated using the Monte Carlo track structure code Geant4-DNA. Tracks for monoenergetic electrons with kinetic energies ranging from 100 eV to 1 MeV were simulated in an infinite spherical water phantom using the Geant4-DNA extension included in Geant4 toolkit version 10.2 (patch 02). The microdosimetric distributions were obtained through random sampling of transfer points and overlaying scoring volumes within the associated volume of the tracks. Relative frequency distributions of energy deposition f(>E)/f(>0) and dose mean lineal energy (y¯D) values were calculated in nanometer-sized spherical and cylindrical targets. The effects of scoring volume and scoring techniques were examined. The results were compared with published data generated using MOCA8B and KURBUC. Geant4-DNA produces a lower frequency of higher energy deposits than MOCA8B. The y¯D values calculated with Geant4-DNA are smaller than those calculated using MOCA8B and KURBUC. The differences are mainly due to the lower ionization and excitation cross sections of Geant4-DNA for low energy electrons. To a lesser extent, discrepancies can also be attributed to the implementation in this study of a new and fast scoring technique that differs from that used in previous studies. For the same mean chord length (l¯), the y¯D calculated in cylindrical volumes are larger than those calculated in spherical volumes. The discrepancies due to cross sections and scoring geometries increase with decreasing scoring site dimensions. A new set of y¯D values has been presented for monoenergetic electrons using a fast track sampling algorithm and the most recent physics models implemented in Geant4-DNA. This dataset can be combined with primary electron spectra to predict the radiation quality of photon and electron beams.


Although Quebec has gone through a period of strong economic growth, it is now struggling with a new labour shortage caused by the shrinking labor pool. Ironically, many foreign-educated immigrants face difficulties associated with entering the labour market and integrating into the workforce. Specifically, recent immigrants from African, Asian, and Latin American countries, who are considered part of visible minority groups, have faced barriers to entry. This paper focuses on the Latin American economic immigrant group and argues that the gap on human and social capital of minority group immigrants and majority group Quebecers cannot be explained simply by analyzing racially motivated actions. Rather, Quebec as a White colonial settler society plays a much more important role in making it very difficult for skilled immigrants to get equal levels of income. By analyzing postcolonial concepts, this document underlines how language politics, notions of citizenship and global neoliberal capitalism have shaped a harsh labour market that contributes to structural causes for inequality among skilled Latin American immigrants in Quebec.


We synthesized a quasi-two-dimensional distorted triangular lattice antiferromagnet Ca3CoNb2O9, in which the effective spin of Co2+ is 1/2 at low temperatures, whose magnetic properties were studied by dc susceptibility and magnetization techniques. The x-ray diffraction confirms the quality of our powder samples. The large Weiss constant θCW∼ −55 K and the low Neel temperature TN∼ 1.45 K give a frustration factor f = | θCW/TN | ≈ 38, suggesting that Ca3CoNb2O9 resides in strong frustration regime. Slightly below TN, deviation between the susceptibility data under zero-field cooling (ZFC) and field cooling (FC) is observed. A new magnetic state with 1/3 of the saturate magnetization Ms is suggested in the magnetization curve at 0.46 K. Our study indicates that Ca3CoNb2O9 is an interesting material to investigate magnetism in triangular lattice antiferromagnets with weak anisotropy.


The Statutes of the ad hoc Tribunals grant prosecutorial staff functional immunity, which aims to protect them against undue interference by states. Defence counsel, however, is not mentioned. As a result, it is unclear if counsel enjoy any such protection, and if so, what shape or form this may take. While the ad hoc Tribunals' Statutes are silent on this matter, the arrests of defence counsel in Croatia and Rwanda have forced the ICTY and ICTR to address this omission, which has generated a body of case law that will provide the starting point for this article. Th e different decisions can be classified into three distinct approaches, which will accordingly be scrutinized. This article will advocate a principled approach to defence counsel immunity, consisting of functional and personal immunity, as well as a principled approach to the waiver thereof. This will both ensure the necessary protection of an effective defence, while preventing these immunity arrangements to result in impunity.


This study addresses a new digital calibration filter design for cascaded ΣΔ modulators with finite amplifier gain. A recent approach based on the H-infinity loop shaping method to this problem has the merit of obviating the use of an estimation or adaptive digital correction scheme, which thus reduces the complexity of circuit implementation. For the approach to be successful, it is critical to find an appropriate weighting function so as to make the gain responses of the uncertain noise transfer function (NTF) in a proper shape for improving signal-to-noise ratio (SNR). However, the search of such a weighting function is difficult in general. Moreover, the introduced weighting function increases filter order and hence circuit complexity. To circumvent this difficulty and the inherited drawbacks, this study presents a new noise shaping method for the problem. Considering that it is hard to decide the optimal shape of the uncertain NTF a priori, the authors propose a dual-band design to achieve the shape adjustment task. In particular, the range of lower frequency band is determined by SNR performance evaluation rather than being arbitrarily given a priori. This step is crucial and increases the chance of finding a better filter.


A case of a 33 year old man with type I of pseudohypoparathyroidism associated with hypercalcitoninaemia and deficiency of prolactin and growth hormone is reported. The diagnosis of pseudohypoparathyroidism was made by recognition of the classic skeletal signs of Albright's osteodystrophy and confirmed by an infusion test with parathyroid hormone, which revealed a lack of both a cyclic AMP and phospaturic response. By investigation of the endocrine status the function of the pituitary/thyroid and pituitary/testis axes as well as the adrenal cortex was observed to be normal. The basal prolactin concentration was however, lower than normal and a lack of response in the growth hormone level in two glucagon tests was observed. Furthermore the basal calcitonin level was higher than normal and by provacation with pentagastrine the calcitonin secretion was very high despite an only slightly decreased serum calcium level. By operation the thyroid gland was normal and by light microscopy of a biopsy no signs of medullary carcinoma was observed. No good explanation for the high calcitonin basal level and secretion was found.


Palinpinon geothermal field (Negros Island, Philippines) is a high temperature, liquid dominated geothermal system in an active volcanic island arc setting. Previous workers have made parallels between the geological setting, mineral deposition and hydrothermal alteration styles recognised at Palinpinon with those that characterise several types of magmatic hydrothermal ore deposits (e.g., porphyry, skarn, and high and low sulphidation epithermal systems).
Igneous rock formations on southern Negros Island have medium K, calc-alkaline, basaltic to dacitic compositions. The Middle Miocene Lower Puhagan Volcanic Formation is part of a volcanic sequence that is traceable throughout the Visayas region. It formed during southeasterly-directed subduction of the Sulu Sea oceanic basin beneath the Sulu arc. Late Miocene to Early Pliocene times marked a period of regional subsidence and marine sedimentation during which a thick sequence ( < 1500 m) of calcareous sediments was deposited (Okoy Formation). Locally in the southern Negros region, magmatism during Early Pliocene to Recent times produced a thick (< 2600 m) sequence of volcanic and volcaniclastic rocks (Southern Negros and Cuemos Volcanic Formations). During this time, diorites to quartz diorites of the Puhagan dikes (\(^{40}Ar/^{39} Ar= 4.2-4.1 Ma\)) and the Nasuji Pluton (\(^{40}Ar/^{39} Ar= 0.7-0.3 Ma\)) intruded the Middle Miocene, Late Miocene and Early-Late Phocene rock units.
The igneous rocks at Palinpinon have adakitic geochemical signatures and are associated with Nb-enriched basalts. This is interpreted to indicate that magmatism in this region has been influenced by the melting of subducted oceanic basalt. Considering the regional tectonic history, the most likely scenarios for the generation of slab melts are considered to be: (1) melting of relatively young (< 20 Ma) oceanic crust during the Middle Miocene; (2) initiation of east-directed subduction along the Negros-Sulu Trench during Early Pliocene times; and (3) melting of young (< 10-20 Ma) oceanic crust during Late Pliocene times.
Hydrothermal alteration at Palinpinon is spatially associated with the Puhagan dikes and the Nasuji Pluton. Only incipient calc-silicate alteration is spatially associated with the Puhagan dikes. In the Nasuji-Sogongon region, the hydrothermal alteration assemblages spatially associated with the Nasuji Pluton are K-silicate (biotite), calc-silicate, hypogene advanced argillic, propylitic and distal ilhte assemblages. Fluid inclusion evidence indicates that magmatic-hydrothermal fluids associated with the final stages of magma crystallisation and the formation of a biotite alteration assemblage and associated veins had homogenisation temperatures of 267° to> 600°C and salinities of 26 to 56 eq.wt.% NaCl. PIXE analyses show that these fluids were endowed with base metals (e.g., up to 0.2 wt.% Cu). Age determinations on hydrothermal biotite (\(^{40}Ar/^{39}Ar= 0.7-0.6 Ma\)), alunite (K/Ar = 0.9-0.8 Ma) and illite (K/Ar = 0.7 Ma) demonstrate that these assemblages all formed contemporaneously with the Nasuji Pluton, implying a genetic link between intrusion emplacement and the formation of porphyry, high sulphidation epithermal and low sulphidation epithermal alteration assemblages.
The Early Pliocene age of the Puhagan dikes establishes they are not the heat source to the current geothermal system, which must be a much younger 'blind' intrusion situated beyond depths drilled in the Puhagan area. The emplacement of this intrusion, at depths greater than 2.5 km, occurred within the last 0.8 Ma and provides the heat source for present-day geothermal activity. Distinctive high temperature hypogene hydrothermal alteration types have developed at depths greater than 2 km and include calc-silicate and biotite alteration zones. Parts of the biotite alteration zone are in thermal equilibrium with the present-day geothermal system. The lack of a hypogene advanced argillic alteration zone in the Puhagan region is interpreted to indicate that the intrusion has been emplaced at depths great enough for lithostatic confining pressures to hinder or prevent magma degassing.
With ongoing hydrothermal convection, areas of propylitic alteration have developed as halos surrounding the Puhagan magmatic-hydrothermal alteration zones. At shallow crustal levels (< 2 km), low sulphidation (illite) alteration assemblages overprint the biotite and hypo gene advanced argillic alteration types associated with the Nasuji Pluton and are in thermal equilibrium with the present-day geothermal system. Therefore, it is possible that biotite and illite alteration assemblages in the Puhagan region either have a protracted history of formation, or else have formed during two discrete time periods in the past 0.8 Ma. Lastly, perched aquifers of steam-heated acid sulphate water have altered regions above the water table to an advanced argillic (steam-heated) alteration assemblage. The percolation of these waters down near-vertical permeable structures (i.e., faults and joints), results in steeply dipping zones of steam-heated advanced argillic alteration.
The current geothermal hydrology at Palinpinon is grossly influenced by permeable zones related to faults and lithological boundaries. The upflow zone is situated at a fault intersection (Ticala and Lagunao Faults) and the main northeasterly outflow zone is parallel to NE-striking faults (Ticala and Puhagan Faults). The neutral chloride reservoir water chemistry is affected by boiling, mixing and conductive cooling. Boiling occurs close to the region of upflow and is mainly restricted to narrow zones of permeability. Mixing occurs peripherally to the upflow zone. The proposed end-member mixing solutions are steam-heated sulphate and meteoric waters. Steam-heated sulphate waters are sourced from perched aquifers in the vadose zone beneath areas of high elevation. Hybrid neutral chloride - sulphate waters have chemistries influenced by host rock dissolution and have not attained chemical equilibrium. In contrast, hybrid neutral chloride - meteoric waters have chemistries that are closer to chemical equilibrium with the host rock. Conductive cooling occurs in the northeasterly outflow zone and water chemistries influenced by this process are also close to chemical equilibrium with the host rock.
The occurrence of base and precious metal scale deposits in several geothermal wells demonstrates that the present-day deep reservoir fluid is capable of transporting and depositing base and precious metals. However, trace metal analysis of the deep reservoir fluids shows they are undersaturated with respect to gold (1-4 μg/kg). Chemical modelling of Palinpinon geothermal water predicts that boiling should be the most effective mechanism for base and precious metal deposition. Boiling of the neutral chloride water is predicted to produce sulphide assemblages similar to those seen in well scale deposits. Mixing with acid bearing sulphate waters can also produce these sulphide assemblages, but does so less efficiently, and the deposition of gold and silver is predicted to occur only at much lower temperatures (i.e., < 110°C). In terms of the mineralogy and the sequence of mineral deposition, mixing with meteoric water is predicted to produce the same results as conductive cooling of the neutral chloride water. Based on fluid modelling results, neither can be considered effective deposition mechanisms for base and precious metal mineralisation.
Despite indications that both the early magmatic-hydrothermal fluids and the modern hydrothermal fluids were, and are, capable of metal transportation, base and precious metal deposition is not strongly developed at Palinpinon. Geochemical assays of drillcore and drillcuttings show base and precious metal concentrations to be one to two orders of magnitude below ore grade ( 0.6 kb) during emplacement of the intrusions may account for this apparent lack of permeability in the magmatic-hydrothermal domain. These elevated pressures would also hinder any metal-bearing magmatic brines from ascending to form ore at shallower levels. Therefore, for base and/or precious metal ore deposition to occur at Palinpinon, a resurgence of magmatism may be required, with an influx of metal-bearing brines and gases, and significant fault dilation and/or phreatic/phrcatomagmatic breccia formation to provide favourable permeability for these fluids to escape and form mineralised ore horizons at shallow crustal levels.


The concentrations of toluene and dichloromethane in the vicinity of factories that emitted a large amount of toluene or dichloromethane into the atmosphere were determined for the comparison of observed and estimated concentrations using a Gaussian dispersion model (METI-LIS model). Greater concentrations of toluene and dichloromethane than the guideline value described in the Air Quality Guidelines for Europe, second edition, were measured in the vicinity of factories (270 and 470 μ g/m3 for toluene and 510 and 660 μ g/m3 for dichloromethane). Toluene and dichloromethane may have some adverse health effects on the local population in the vicinity of the emission source. Although the estimated concentrations in the vicinity of the emission source by the METI-LIS model involved a large margin of error, the proposed correction approach with only one weekly measurement reduced the estimation error of annual average concentrations. The proposed method could be useful for the management of ambient environment of emission source, due to no difficulty in modifying the input parameters of METI-LIS that required highly specialized knowledge.


We consider the reliable robust tracking controller design problem against actuator faults and control surface damages for a LTI system with input disturbance. First, models of actuator faults and control surface damages are presented. Then a reliable tracking controller design method is developed, which guarantees the closed-loop system stability, optimizes the tracking performance of the system in normal operations, and maintains an acceptable low-level tracking performance of the system in the event of actuator faults and/of control surface damages. This method is based on LQ/H/sub /spl infin// tracking performance indices and multi-objective optimization in terms of linear matrix inequalities. A numerical example of an F-16 aircraft model and its simulation results are given.


Fuel cell stack performance strongly depends on the uniformity of the flow distribution over the fuel cells. Typically, numerical flow simulations are used to design the small flow geometries of a stack but experimental validation of the simulated flow is mostly lacking. To measure the flow distribution within these small geometries a specific Laser Doppler Velocimeter has been developed that uses light with low spatial coherence (multimode light) and fluorescent tracer particles. A spatial resolution of less than 100 µm even close to the wall is achieved. Comparing the measurement results of this MM-LDVsensor with other experimental and numerical data revealed a very good agreement for a model configuration. Therefore, this tested and validated sensor was applied to the flow within the real geometry of a fuel cell stack manifold to gain a deeper knowledge of the flow configuration and to generate a benchmark for CFD-based fuel cell design.


In clinical transfusion and transplantation medicine, AB0 is the most important blood group system. A and B antigens are synthesized by glycosyltransferases A and B encoded by co-dominantly inherited A and B genes. The 0 phenotype derives from a single nucleotide deletion; the resulting stop codon in the exon 7 of glycosyltransferase A leads to a lack of glycosylation activity to A and/or B. The DNA structure of the three major alleles of the human blood group AB0 system was first described in 1990. Besides the 4 major AB0 blood groups (A, B, AB, 0), weak expression variants commonly occur. Beside introns and exons, two regions were found to be critical for transcriptional activity of AB0 genes: a promotor sequence upstream of the translation start site and a CBF/NF-Y-binding enhancer element. However, the molecular basis for the weak expression levels of AB0 blood group receptors is not fully understood. Here we asked whether microRNA´s may play a role in the regulation of blood group A and B antigens. MiRNA9s are small, non-protein encoding RNA sequences that bind to the 39 untranslated region (UTR) of target mRNAs resulting in translation repression or mRNA degradation. By distinct complementary approaches, including gene array analysis and overexpression of glycosyltransferase specific micro-RNAs (miRNAs) in primary hematopoietic stem cells, we identify here that miR-331-3p and miR-1908-5p directly target glycosyltransferase A and B. Consistently, overexpression of miR-331-3p and -1908-5p in hematopoietic stem cells (HSCs) leads to a 30-50% reduction of blood group A antigens per cell in differentiated RBCs. Downregulation of endogenous miR-1908-5p but not miR-331-3p leads to increased amount of blood group A antigen per red blood cell compared to control cells. This discrepancy between the effects of downregulation of miR-1908-5p and of miR-331-3p is likely explained by the constitutive expression levels of both miRNAs during erythropoiesis. In particular, miR-1908-5p is expressed throughout erythroid differentiation, while miR-331 displays low expression, thus, further downregulation of miR-331-3p could not further affect blood group A antigen levels. Furthermore miR-331-3p and -1908-5p were enhanced in red blood cells of A weak variants. Sequencing of the 39UTR of 6 A weak variants revealed the presence of more miRNA binding sites for miR-1908-5p compared to normal controls. These data identify microRNAs as regulators of blood group glycosyltransferase expression, thereby extending our understanding of blood group regulation in carriers of weak blood group variants. Regulating blood groups by microRNAs could pave the way for the development of universal blood. Disclosures No relevant conflicts of interest to declare.


Background: With the aging of the population and the use of video terminals, the incidence of Conjunctivochalasis is getting higher, and related research is increasing. So our research aimed to use visualization software to display the research trends of Conjunctivochalasis. Methods: Retrieved the document (from 1986 to 2017) of conjunctivochalasis in the web of science core collection, analyzed by Citespace V. Results: The main language is English. Article is the key type of document. The average annual number of publications in the time period from 2008 to 2017 was 11.6, which was significantly higher than the period from 1994 to 2007, indicating that the total number of publications has been continuously developed. The law of frequency quoted showed an upward trend yearly. Furthermore, we can find out that Japan, USA, and People's Republic of China were the most productive countries, Kyoto Prefectural University of Medicine was the most prolific institution, Shanghai Jiaotong University is a key institution. The average IF of journals was 3.0508. Cornea and Canadian Journal of Ophthalmology are core journals. Tseng SCG is the most active scholar. All cited author contributed to 5 classifications. Di PMA paper is a classic literature. Huang YK paper can be regarded as the frontier document. All cited-reference dedicated to 7 categories. Conjunctivochalasis is the hot topic, related to observe indicators, risk factors, treatment, graded diagnosis of conjunctivochalasis, etc. In addition, fibroblast was research hotspot. At length, the cluster map of keyword was divided into 7 categories. Conclusion: This research will help relevant clinicians and researchers to accurately and quickly grasp the research trends in the field, and continue to conduct new research on the basis.


Employing correlation consistent basis sets of quadruple-zeta quality and applying both multireference configuration interaction and single-reference coupled cluster methodologies, we studied the electronic and geometrical structure of the [V,O,H](0,+) species. The electronic structure of HVO(0,+) is explained by considering a hydrogen atom approaching VO(0,+), while VOH(0,+) molecules are viewed in terms of the interaction of V(+,2+) with OH(-). The potential energy curves for H-VO(0,+) and V(0,+)-OH have been constructed as functions of the distance between the interacting subunits, and the potential energy curves have also been determined as functions of the H-V-O angle. For the stationary points that we have located, we report energies, geometries, harmonic frequencies, and dipole moments. We find that the most stable bent HVO(0,+) structure is lower in energy than any of the linear HVO(0,+) structures. Similarly, the most stable state of bent VOH is lower in energy than the linear structures, but linear VOH(+) is lower in energy than bent VOH(+). The global minimum on the potential energy surface for the neutral species is the X(3)A" state of bent HVO, although the X(5)A" state of bent VOH is less than 5 kcal/mol higher in energy. The global minimum on the potential surface for the cation is the X(4)Σ(-) state of linear VOH(+), with bent VOH(+) and bent HVO(+) both more than 10 kcal/mol higher in energy. For the neutral species, the bent geometries exhibit significantly higher dipole moments than the linear structures.


Hyperkalemia is common in patients with ESRD, undergoing hemodialysis (HD), and is associated with an increase in hospitalization and mortality. Residual kidney function in long-term dialysis patients is associated with lower morbidity and mortality in HD patients. Although the 2015 National Kidney Foundation-Kidney Disease Outcomes Quality Initiate (NKD-KDOQI) guidelines allow the reduction in the weekly HD dose for patients with a residual kidney urea clearance (Kur) >3 mL/min/1.73 m2, very few centers adjust the dialysis dose based on these criteria. In our center, the pattern of incremental hemodialysis (iHD) with once-a-week schedule (1 HD/W) has been an option for a group of patients showing very good results. This pattern is maintained as long as residual diuresis is >1,000 mL/24 h, Kur is >4 mL/min, and there is no presence of edema or volume overload, as well as no analytical parameters persistently outside the advisable range (serum phosphorus >6 mg/dL or potassium [K+] >6.5 mmol/L). Management of hyperkalemia in HD patients includes reduction of dietary intake, dosing of medications that contribute to hyperkalemia, and use of cation-exchange resins such as calcium or sodium polystyrene sulfonate. Two newer potassium binders, patiromer sorbitex calcium and sodium zirconium cyclosilicate, have been safely used for potassium imbalance treatment in patients with ESRD in HD with a conventional regimen of thrice weekly, but has not yet been studied in 1 HD/W schedules. We present the case of a 76-year-old woman in iHD (1 HD/W) treated with patiromer for severe HK and describe her clinical characteristics and outcomes. In addition, we review the corresponding literature. Based on these data, it can be anticipated that the use of patiromer may overcome the risk of hyperkalemia in patients with incident ESRD treated with less-frequent HD regimens.