Two-time winners Germany will take on Iceland, the Czech Republic, Slovenia and the Faroe Islands in Group 5 following the qualifying group stage draw in Nyon.

Gamla Ullevi, Gothenburg will stage the 2021 UEFA Women's Champions League final

16 May 2013The Regulatory Reform (Scotland) Bill was introduced in the Scottish Parliament on 27 March 2013. This briefing provides background information on existing regulatory regimes, and the introduction of the Bill.

13 January 2013This briefing provides a summary of the parliamentary scrutiny of the Regulatory Reform (Scotland) Bill prior to Stage 3 proceedings which are scheduled to take place on 16 January 2014.

8 May 2014This briefing summarises Stage 1 and Stage 2 consideration of the Procurement (Reform) (Scotland) Bill, introduced in the Parliament on 3rd October 2013.

Earlier genetic and inhibitor studies have shown that epigenetic regulation of gene expression is critical for malaria parasite survival in multiple life stages and a promising target for new anti-malarials. We therefore evaluated the activity of 350 diverse epigenetic inhibitors against multiple stages of Plasmodium falciparum. We observed ≥90% inhibition at 10 μM for 28% of compounds against asexual blood stages and early gametocytes, of which a third retained ≥90% inhibition at 1 μM.

The 10,700-capacity Pabellón Príncipe Felipe in Zaragoza will host the UEFA Futsal Cup finals in April involving Spain's Inter FS and Barcelona plus Portugal's Sporting CP and Győr of Hungary.

Romania and Slovakia will stage the U19 EURO final tournaments in 2021 and 2022 respectively.

Choral students at Penn State Behrend typically end the semester with a concert. This year, because of COVID-19, they tried something different: a virtual cabaret.

The 2018 UEFA Super Cup will be played on 15 August of next year at Tallinn's Lilleküla Stadium, the first senior UEFA final in Estonia in the centenary of that republic's creation.

The 2019 UEFA Super Cup will be played at Beşiktaş Park in Istanbul on Wednesday 14 August of that year, the third major UEFA final to be played in the Turkish city.

The UEFA Youth League's relevance is emphasised by the list of talented young players who have graduated from the junior competition to star at the very top of the game.

Europe's representatives Portugal, Russia, Italy, Ukraine, Kazakhstan, Azerbaijan and Spain all secured top-two finishes in the group stage to reach the last 16.

Governor Jack Markell today joined Delaware State Housing Authority Director Anas Ben Addi and other federal, state, and local officials to celebrate Delaware Homeownership Month and to announce the extension of a program that allows first-time homebuyers to claim a credit on their federal income taxes.

OMNIvision works behind the scenes at TeenStreet, OM’s international youth congress, providing top quality video for thousands of teens.

Almaty Arena will stage April's finals involving hosts Kairat, Barça, holders Inter FS and Sporting CP.

A controlled burn on a 43-acre former farm field along U.S. Route 301 will provide fertile ground for "Delaware's first pollinator mitigation site" - where state officials hope native wildflowers will flourish to restore lost habitat for pollinators such as bees and birds. The Delaware Forest Service  conducted the successful firing operation on March 20 in cooperation DelDOT and DNREC's Division of Fish and Wildlife, which supplied valuable personnel, logistical support, and equipment. Thanks to favorable weather conditions and DelDOT lane adjustments on U.S. 301 North, the four-hour burn caused minimal disruptions to traffic and virtually no smoke effects on the adjacent Spring Mill housing development.

With this exercise, the state’s new council of ministers — 33 cabinet and 10 state — has hit the maximum limit, capped at 15 per cent of the Vidhan Sabha strength of 288.

Besides the Integrated L-40 stages, HAL is also manufacturing the riveted structures, propellant tanks, feed lines of PSLV, GSLV MKII and GSLV MKIII launch vehicles and structures of various satellites for the space agency.

At least two candidates have already entered the clinical evaluation stage, according to the World Health Organization (WHO).

New York needs Broadway to be alive and well, so that tourism, hotels and restaurants do well, observed the spokesperson of a Broadway performers' association, citing a study showing that Broadway contributes nearly $15 billion to the local economy

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In a region of the world where coal is still king, there is room for renewables. This was a takeaway from the Ministerial Address and Joint Opening Keynote at POWERGEN Asia and Asian Utility Week. The two annual events kicked off Tuesday, Sept. 3, in Kuala Lumpur, Malaysia.

In a region of the world where coal is still king, there is room for renewables. This was a takeaway from the Ministerial Address and Joint Opening Keynote at POWERGEN Asia and Asian Utility Week. The two annual events kicked off Tuesday, Sept. 3, in Kuala Lumpur, Malaysia.

In a region of the world where coal is still king, there is room for renewables. This was a takeaway from the Ministerial Address and Joint Opening Keynote at POWERGEN Asia and Asian Utility Week. The two annual events kicked off Tuesday, Sept. 3, in Kuala Lumpur, Malaysia.

This rule establishes criteria that hospitals and physicians must meet to qualify as "meaningful users" of electronic health records and receive further financial incentives in Stage 2 of the HITECH Act Electronic Health Record Incentive Program. The program, part of the economic stimulus package, is providing billions of dollars in Medicare and Medicaid incentives to spur widespread adoption of EHRs.

This rule establishes criteria for electronic health records software that qualifies for Stage 2 of the HITECH Act Electronic Health Record Incentive Program. The program, part of the economic stimulus package, is providing billions of dollars in Medicare and Medicaid incentives to hospitals and physicians to spur widespread adoption of EHRs.

The commissioner for the digital portfolio, Margrethe Vestager, warned that "without the technology, it will be very difficult to open [society] to the degree that we all want" - since new outbreaks might surge back until there is a vaccine.

Lukashenko, who has ruled Belarus since 1994, has called fears over the coronavirus a "psychosis" and variously suggested drinking vodka, visiting saunas or playing ice hockey to beat the disease.

Madrid and Barcelona will not progress to the next phase of Spain's exit from one of Europe’s strictest lockdowns that will allow bars, restaurants and places of worship to reopen in some areas from Monday, the government announced.

NEW YORK INTERNATIONAL AUTO SHOW – HARMAN, the premium global audio and infotainment group (NYSE:HAR), is making a strong showing at this year’s New York International Auto Show, with a range of leading automakers featuring HARMAN branded audio systems in vehicles debuting at the show. In addition to the new vehicles– which run the gamut from modern sedans to sports cars, minivans and crossover SUVs – HARMAN technology and solutions can be found in automaker booths throughout the show, a reflection of HARMAN’s longstanding auto partnerships and unmatched industry achievements.

It’s the most wonderful time of year again. That’s right, CES 2016 is upon us! This year in Las Vegas, you will experience firsthand a great suite of premium innovations from HARMAN - the premier connected technologies company for automotive, consumer and enterprise markets - featuring HARMAN’s unique approach to design and engineering. Can’t wait until January to see what’s new? Here’s a sneak peak of what to expect for CES and the year ahead. HARMAN will demonstrate the latest innovations and technologies in lifestyle audio and connected car to illustrate the future of connected lifestyle experiences.

LOS ANGELES, CA – HARMAN International Industries, Inc. (NYSE:HAR), the premium audio and infotainment group, will have a major presence at the 137th Audio Engineering Society Convention as it returns to the Los Angeles Convention Center Thursday, October 9 through Sunday, October 12 for the first time in twelve years. HARMAN, the premiere sponsor of both the annual AES President’s Reception and the AES Student Zone, will present several research papers, highlight new Professional audio equipment, and demonstrate the company’s latest innovative music restoration technology, Clari-Fi, throughout the week.

Thousands of cyclists took over streets in the center of the Slovenian capital Ljubljana on Friday evening to protest against the government of Prime Minister Janez Jansa and the restrictions it has imposed to fight the coronavirus.

Thousands of cyclists took over streets in the center of the Slovenian capital Ljubljana on Friday evening to protest against the government of Prime Minister Janez Jansa and the restrictions it has imposed to fight the coronavirus.

At this year’s North American International Auto Show (NAIAS) in Detroit, HARMAN and its automotive partners brought the latest evolution of premium in-car experiences that reflect and seamlessly connect with your lifestyle. Ensuring users are...

Opera singer Victoria Robertson is accustomed to performing on stages much bigger than the five-foot wide front porch of her San Diego home. But with concert venues closed and work at a standstill due to the coronavirus pandemic, she decided to make the most of it.

A Backstage Pass with Christopher Dragon: Creating that HARMAN Experience at the World's Largest Technology Show Around the world, many companies are preparing to close out the year, but for HARMAN, it’s time to head to Las Vegas once again for the...

This year's Tour of Spain will not go through Portugal as planned because of the COVID-19 crisis, organisers said on Saturday.

Title: LeAnn Rimes Brings Battle With Psoriasis to Center Stage
Category: Health News
Created: 4/23/2010 10:10:00 AM
Last Editorial Review: 4/26/2010 12:00:00 AM

ABSTRACT

Cryptosporidium parvum and Cryptosporidium hominis have emerged as major enteric pathogens of infants in the developing world, in addition to their known importance in immunocompromised adults. Although there has been recent progress in identifying new small molecules that inhibit Cryptosporidium sp. growth in vitro or in animal models, we lack information about their mechanism of action, potency across the life cycle, and cidal versus static activities. Here, we explored four potent classes of compounds that include inhibitors that likely target phosphatidylinositol 4 kinase (PI4K), phenylalanine-tRNA synthetase (PheRS), and several potent inhibitors with unknown mechanisms of action. We utilized monoclonal antibodies and gene expression probes for staging life cycle development to define the timing of when inhibitors were active during the life cycle of Cryptosporidium parvum grown in vitro. These different classes of inhibitors targeted different stages of the life cycle, including compounds that blocked replication (PheRS inhibitors), prevented the segmentation of daughter cells and thus blocked egress (PI4K inhibitors), or affected sexual-stage development (a piperazine compound of unknown mechanism). Long-term cultivation of C. parvum in epithelial cell monolayers derived from intestinal stem cells was used to distinguish between cidal and static activities based on the ability of parasites to recover from treatment. Collectively, these approaches should aid in identifying mechanisms of action and for designing in vivo efficacy studies based on time-dependent concentrations needed to achieve cidal activity.

IMPORTANCE Currently, nitazoxanide is the only FDA-approved treatment for cryptosporidiosis; unfortunately, it is ineffective in immunocompromised patients, has varied efficacy in immunocompetent individuals, and is not approved in infants under 1 year of age. Identifying new inhibitors for the treatment of cryptosporidiosis requires standardized and quantifiable in vitro assays for assessing potency, selectivity, timing of activity, and reversibility. Here, we provide new protocols for defining which stages of the life cycle are susceptible to four highly active compound classes that likely inhibit different targets in the parasite. We also utilize a newly developed long-term culture system to define assays for monitoring reversibility as a means of defining cidal activity as a function of concentration and time of treatment. These assays should provide valuable in vitro parameters to establish conditions for efficacious in vivo treatment.

ABSTRACT

The ubiquitous parasite Toxoplasma gondii exhibits an impressive ability to maintain chronic infection of its host for prolonged periods. Despite this, little is known regarding whether and how T. gondii bradyzoites, a quasi-dormant life stage residing within intracellular cysts, manipulate the host cell to maintain persistent infection. A previous proteomic study of the cyst wall, an amorphous layer of proteins that forms underneath the cyst membrane, identified MYR1 as a putative cyst wall protein in vitro. Because MYR1 is known to be involved in the translocation of parasite-derived effector proteins into the host cell, we sought to determine whether parasites transitioning toward the bradyzoite life stage retain the capacity to translocate proteins via this pathway. By epitope tagging the endogenous loci of four known effectors that translocate from the parasitophorous vacuole into the host cell nucleus, we show, by immunofluorescence assays, that most effectors accumulate in the host nucleus at early but not late time points after infection, during the tachyzoite-to-bradyzoite transition and when parasites further along the bradyzoite differentiation continuum invade a new host cell. We demonstrate that the suppression of interferon gamma signaling, which was previously shown to be mediated by the effector TgIST, also occurs in the context of prolonged infection with bradyzoites and that TgIST export is a process that occurs beyond the early stages of host cell infection. These findings have important implications regarding how this highly successful parasite maintains persistent infection of its host.

IMPORTANCE Toxoplasma bradyzoites persist within tissue cysts and are refractory to current treatments, serving as a reservoir for acute complications in settings of compromised immunity. Much remains to be understood regarding how this life stage successfully establishes and maintains persistent infection. In this study, we investigated whether the export of parasite effector proteins into the host cell occurs during the development of in vitro tissue cysts. We quantified the presence of four previously described effectors in host cell nuclei at different time points after bradyzoite differentiation and found that they accumulated largely during the early stages of infection. Despite a decline in nuclear accumulation, we found that one of these effectors still mediated its function after prolonged infection with bradyzoites, and we provide evidence that this effector is exported beyond early infection stages. These findings suggest that effector export from within developing tissue cysts provides one potential mechanism by which this parasite achieves chronic infection.

Background

COPD patients account for a large proportion of lung transplants; lung transplantation survival benefit for COPD patients is not well established.

The bioprocessing industry uses recombinant mammalian cell lines to generate therapeutic biologic drugs. To ensure consistent product quality of the therapeutic proteins, it is imperative to have a controlled production process. Regulatory agencies and the biotechnology industry consider cell line "clonal origin" an important aspect of maintaining process control. Demonstration of clonal origin of the cell substrate, or production cell line, has received considerable attention in the past few years, and the industry has improved methods and devised standards to increase the probability and/or assurance of clonal derivation. However, older production cell lines developed before the implementation of these methods, herein referred to as "legacy cell lines," may not meet current regulatory expectations for demonstration of clonal derivation. In this article, the members of the IQ Consortium Working Group on Clonality present our position that the demonstration of process consistency and product comparability of critical quality attributes throughout the development life cycle should be sufficient to approve a license application without additional genetic analysis to support clonal origin, even for legacy cell lines that may not meet current day clonal derivation standards. With this commentary, we discuss advantages and limitations of genetic testing methods to support clonal derivation of legacy cell lines and wish to promote a mutual understanding with the regulatory authorities regarding their optional use during early drug development, subsequent to Investigational New Drug (IND) application and before demonstration of product and process consistency at Biologics License Applications (BLA) submission.

OBJECTIVE

To investigate factors related to glycemic management among members of a professional cycling team with type 1 diabetes over a 7-day Union Cycliste Internationale World Tour stage race.

OBJECTIVE

There is a controversy over the association between obesity and end-stage renal disease (ESRD) in people with or without type 2 diabetes; therefore, we examined the effect of BMI on the risk of ESRD according to glycemic status in the Korean population.

Dietary protein residue can result in microbial generation of various toxic metabolites in the gut, such as ammonia. A prebiotic is "a substrate that is selectively utilised by host microorganisms conferring a health benefit" (G. R. Gibson, R. Hutkins, M. E. Sanders, S. L. Prescott, et al., Nat Rev Gastroenterol Hepatol 14:491–502, 2017, https://doi.org/10.1038/nrgastro.2017.75). Prebiotics are carbohydrates that may have the potential to reverse the harmful effects of gut bacterial protein fermentation. Three-stage continuous colonic model systems were inoculated with fecal samples from omnivore and vegetarian volunteers. Casein (equivalent to 105 g protein consumption per day) was used within the systems as a protein source. Two different doses of inulin-type fructans (Synergy1) were later added (equivalent to 10 g per day in vivo and 15 g per day) to assess whether this influenced protein fermentation. Bacteria were enumerated by fluorescence in situ hybridization with flow cytometry. Metabolites from bacterial fermentation (short-chain fatty acid [SCFA], ammonia, phenol, indole, and p-cresol) were monitored to further analyze proteolysis and the prebiotic effect. A significantly higher number of bifidobacteria was observed with the addition of inulin together with reduction of Desulfovibrio spp. Furthermore, metabolites from protein fermentation, such as branched-chain fatty acids (BCFA) and ammonia, were significantly lowered with Synergy1. Production of p-cresol varied among donors, as we recognized four high producing models and two low producing models. Prebiotic addition reduced its production only in vegetarian high p-cresol producers.

IMPORTANCE Dietary protein levels are generally higher in Western populations than in the world average. We challenged three-stage continuous colonic model systems containing high protein levels and confirmed the production of potentially harmful metabolites from proteolysis, especially replicates of the transverse and distal colon. Fermentations of proteins with a prebiotic supplementation resulted in a change in the human gut microbiota and inhibited the production of some proteolytic metabolites. Moreover, we observed both bacterial and metabolic differences between fecal bacteria from omnivore donors and vegetarian donors. Proteins with prebiotic supplementation showed higher Bacteroides spp. and inhibited Clostridium cluster IX in omnivore models, while in vegetarian modes, Clostridium cluster IX was higher and Bacteroides spp. lower with high protein plus prebiotic supplementation. Synergy1 addition inhibited p-cresol production in vegetarian high p-cresol-producing models while the inhibitory effect was not seen in omnivore models.

Scabies is a frequent cutaneous infection caused by the mite Sarcoptes scabiei in a large number of mammals, including humans. As the resistance of S. scabiei against several chemical acaricides has been previously documented, the establishment of alternative and effective control molecules is required. In this study, the potential acaricidal activity of beauvericin was assessed against different life stages of S. scabiei var. suis and in comparison with dimpylate and ivermectin, two commercially available molecules used for the treatment of S. scabiei infection in animals and/or humans. The toxicity of beauvericin against cultured human fibroblast skin cells was evaluated using an MTT proliferation assay. In our in vitro model, developmental stages of S. scabiei were placed in petri dishes filled with Columbia agar supplemented with pig serum and different concentrations of the drugs. Cell sensitivity assays demonstrated low toxicity of beauvericin against primary human fibroblast skin cells. At 0.5 and 5 mM, beauvericin showed higher activity against adults and eggs of S. scabiei compared to dimpylate and ivermectin. These results revealed that the use of beauvericin is promising and might be considered for the treatment of S. scabiei infection.