We have created sample presentations for a variety of market sectors, including education, healthcare, restaurants, estate agents, retail, hotels, training centers and theme park attractions.

Software versions include Standalone, Standard, Corporate and Media Wall, and the industry niche UK estate agents. There are common features for each of the editions, which can be viewed online.

We have updated our Repeat Signage brochure which features some of our customers images of how they are benefiting from digital signage presentations.

Repeat Software are delighted to welcome Optima Digital Inc., as a reseller partner in the Philippines. Optima Digital has more than 60 PLDT stores in the Philippines using Repeat Signage Media Wall software.

Since its launch in 2009, Repeat Signage digital signage software is now in daily use in 31 countries across a wide variety of applications and vertical markets. A big thank you to all our customers and reseller partners.

Repeat Software, a UK software developers has awarded distribution to QBS Distribution ("QBSD"), a European software distributor based in Wembley, London.

Sligo's busy Quayside Shopping Centre promotes its shops and events on four display screens throughout the centre, keeping shoppers updated with dynamic content.

Daily Express Chief Sports Writer Neil Squires urges the EFL and its clubs to protect their long-term future once the coronavirus crisis ends.

Hear about travel to Flanders in Belgium from the Amateur Traveler. I recently traveled to 5 cities in Belgium: Antwerp, Ghent, Ieper, Bruges and Brussels. Each of these historic cities is wonderfully picturesque, even on a grey November day. 

Hear about travel to the Russian Far East as the Amateur Traveler talks to freelance travel journalist Robert Reid about his numerous journeys to this remote part of Russia.

Hear about travel to Jordan as the Amateur Traveler himself, Chris Christensen, relates stories about his visit to the country. 

The Amateur Traveler talks to David Grenewetzki about his first trip to India. His itinerary covered Mombai, Bangalore, Rajasthan, Delhi and then ended at the Indian wedding of friends. They started in Mumbai where they saw sites like the arch of India and Elephanta Caves. Near Bangalore they made a side trip to see the Jain pilgrimage site of Shravanabelagola and the palace of Tipu Sultan at Mysore. In Udaipu they splurged and stayed in both the City Palace and the Lake Palace Hotels.

Hear about Cruising Southeastern Alaska on Un-Cruise Adventures as the Amateur Traveler goes on a cruise where dressing for dinner and bingo are replaced with kayaking and bushwhacking.

Hear about travel to Mumbai India as the Amateur Traveler talks to Stephanie Hays of RealityToursAndTravel.com about travel to this crowded, noisy, vibrant city. With the background sounds of the horns of auto rickshaws we find out why a girl from Chattanooga, Tennessee ended up in India's largest city.

This episode of the Amateur Traveler talks about the recent Amateur Traveler trip to Cambodia. 7 of the 9 people who joined me on this trip also join me for the podcast to share the highlights, surprises and challenges of the trip.

Hear about travel to Scotland as the Amateur Traveler talks to Sarah from www.thegirlwiththemaptattoo.com about travel to this beautiful and historic country.

Hear about travel to Istanbul, Turkey as the Amateur Traveler talks to Christopher Mitchell from travelingmitch.com about the city where he lived for 3 years.

Hear about travel to the Yukon Territory in Canada as the Amateur Traveler talks to Stephen Reynolds from Tourism Yukon about a recent trip that I did to his home.

Hear about travel to Lombok in Indonesia as the Amateur Traveler talks to Jason Andrew Jenkins from AnEpicEducation.com about his family's recent 5 week trip to this island paradise.

Introduction: The aim of this study was to analyze patterns of persistent versus recurrent or new PET lesions in a selected patient cohort with PSA persistence following salvage lymph node dissection (SLND) and pre/post procedure prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET). Material and Methods: 16 patients were included in this multicenter study. Inclusion criteria were: a) PSMA-PET performed for biochemical recurrence before SLND (pre-SLND PET) and b) repeat PSMA-PET performed for persistently elevated PSA level (≥0.1 ng/mL) ≥6 weeks after SLND (post-SLND PET). Image analysis was performed by three independent nuclear medicine physicians applying the molecular imaging TNM system PROMISE. Lesions were confirmed by histopathology, presence on correlative CT/MRI/bone scan or PSA response after focal therapy. Results: post-SLND PET identified PCa-lesions in 88% (14/16) of patients with PSA persistence after SLND. Median PSA was 1.2 ng/mL (IQR, 0.6-2.8 ng/mL). Disease was confined to the pelvis in 56% of patients (9/16) and most of these men had common iliac (6/16, 38%) and internal iliac lymph node metastases (6/16, 38%). Extrapelvic disease was detected in 31% of patients (5/16). In pre- and post-SLND PET comparison, 10/16 had at least one lesion already detected at baseline (63% PET persistence); 4/16 had new lesions only (25% PET recurrence); 2 had no disease on post-SLND PET. All validated regions (11 regions in 9 patients) were true positive. 9/14 (64%) patients underwent repeat local therapies after SLND (7/14 radiotherapy, 2/14 surgery). Conclusion: SLND of pelvic nodal metastases was often not complete according to PSMA-PET. About two thirds of patients had PET positive nodal disease after SLND already seen on pre-SLND PSMA-PET. Notably, about one quarter of patients had new lesions, not detected by pre-surgical PSMA-PET.

Quantitative evaluation of radiolabeled Prostate-Specific Membrane Antigen (PSMA) PET scans may be used to monitor treatment response in patients with prostate cancer (PCa). To interpret longitudinal differences in PSMA uptake, the intrinsic variability of tracer uptake in PCa lesions needs to be defined. The aim of this study was to investigate the repeatability of quantitative ¹⁸F-DCFPyL (a second generation ¹⁸F-PSMA-ligand) PET/CT measurements in patients with PCa. Methods: Twelve patients with metastatic PCa were prospectively included, of which 2 were excluded from final analyses. Patients received two whole-body ¹⁸F-DCFPyL PET/CT scans (median dose 317 MBq; uptake time 120 min), within median 4 days (range 1-11 days). After semi-automatic (isocontour-based) tumor delineation, the following lesion-based metrics were derived: Tumor-to-Blood ratio (TBRmean, TBRpeak, and TBRmax), Standardized Uptake Value (SUVmean, SUVpeak, SUV_max, normalized to bodyweight), tumor volume, and total lesion tracer uptake (TLU). Additionally, patient-based Total Tumor Volume (sum of PSMA-positive tumor volumes; TTV) and Total Tumor Burden (sum of all lesion TLUs; TTB) were derived. Repeatability was analyzed using repeatability coefficients (RC) and intra-class correlations (ICC). Additionally, the effect of point spread function (PSF) image reconstruction on the repeatability of uptake metrics was evaluated. Results: In total, 36 ¹⁸F-DCFPyL PET positive lesions were analyzed (up to 5 lesions per patient). RCs of TBRmean, TBRpeak, and TBRmax were 31.8%, 31.7%, and 37.3%, respectively. For SUVmean, SUVpeak, SUV_max the RCs were 24.4%, 25.3% and 31.0%, respectively. All ICC were ≥0.97. Tumor volume delineations were well repeatable, with RC 28.1% for individual lesion volumes and RC 17.0% for TTV. TTB had a RC of 23.2% and 33.4%, when based on SUVmean and TBRmean, respectively. Small lesions (<4.2mL) had worse repeatability for volume measurements. The repeatability of SUVpeak, TLU, and all patient-level metrics were not affected by PSF-reconstruction. Conclusion: ¹⁸F-DCFPyL uptake measurements are well repeatable and can be used for clinical validation in future treatment response assessment studies. Patient-based TTV may be preferred for multicenter studies since its repeatability was both high and robust to different image reconstructions.

OBJECTIVE

Type 2 diabetes develops for many years before diagnosis. We aimed to reveal early metabolic features characterizing liability to adult disease by examining genetic liability to adult type 2 diabetes in relation to metabolomic traits across early life.

Statistical regularities in natural sounds facilitate the perceptual segregation of auditory sources, or streams. Repetition is one cue that drives stream segregation in humans, but the neural basis of this perceptual phenomenon remains unknown. We demonstrated a similar perceptual ability in animals by training ferrets of both sexes to detect a stream of repeating noise samples (foreground) embedded in a stream of random samples (background). During passive listening, we recorded neural activity in primary auditory cortex (A1) and secondary auditory cortex (posterior ectosylvian gyrus, PEG). We used two context-dependent encoding models to test for evidence of streaming of the repeating stimulus. The first was based on average evoked activity per noise sample and the second on the spectro-temporal receptive field. Both approaches tested whether differences in neural responses to repeating versus random stimuli were better modeled by scaling the response to both streams equally (global gain) or by separately scaling the response to the foreground versus background stream (stream-specific gain). Consistent with previous observations of adaptation, we found an overall reduction in global gain when the stimulus began to repeat. However, when we measured stream-specific changes in gain, responses to the foreground were enhanced relative to the background. This enhancement was stronger in PEG than A1. In A1, enhancement was strongest in units with low sparseness (i.e., broad sensory tuning) and with tuning selective for the repeated sample. Enhancement of responses to the foreground relative to the background provides evidence for stream segregation that emerges in A1 and is refined in PEG.

SIGNIFICANCE STATEMENT To interact with the world successfully, the brain must parse behaviorally important information from a complex sensory environment. Complex mixtures of sounds often arrive at the ears simultaneously or in close succession, yet they are effortlessly segregated into distinct perceptual sources. This process breaks down in hearing-impaired individuals and speech recognition devices. By identifying the underlying neural mechanisms that facilitate perceptual segregation, we can develop strategies for ameliorating hearing loss and improving speech recognition technology in the presence of background noise. Here, we present evidence to support a hierarchical process, present in primary auditory cortex and refined in secondary auditory cortex, in which sound repetition facilitates segregation.

A Brown Bear takes a quick dip while hunting for salmon at Anan Creek Bear Observatory in SE Alaska.

Preterm infants are exposed to inadequately managed painful procedures during their NICU stay, which can lead to altered pain responses. Nonpharmacologic approaches are established for the treatment of single painful procedures, but evidence for their effectiveness across time is lacking.

Oral sucrose with or without the added technique of facilitated tucking has a pain-relieving effect even in extremely premature infants undergoing repeated pain exposures; facilitated tucking alone seems to be less effective for repeated pain exposures over time. (Read the full article)

Atherosclerotic cardiovascular diseases have roots in childhood. Modification of dietary fat intake influences serum lipid and lipoprotein concentrations. Reduction of saturated fat intake is recommended to promote cardiovascular health.

Dietary counseling had a beneficial effect on saturated fat intake from ages 7 months to 19 years. The counseling reduced serum low-density lipoprotein cholesterol concentrations in both genders. It also decreased computationally estimated concentrations of intermediate-density lipoprotein cholesterol, very low-density lipoprotein–triglycerides and apolipoprotein B in boys. (Read the full article)

Administration of repeat doses of antenatal glucocorticoids to women at risk for preterm birth after an initial course reduces neonatal morbidity, without affecting rates of neurologic disability in early childhood. However, data on long-term effects on cardiometabolic health are limited.

Exposure to repeat doses of antenatal betamethasone did not increase cardiovascular risk factors at early school age. Clinicians wishing to use repeat antenatal glucocorticoids can be reassured that the risk of future cardiometabolic disease from this therapy is low. (Read the full article)

Technology like DNA testing and facial recognition has helped me piece together a family history torn apart by war. But honoring Holocaust Remembrance Day is about more than remembering the past.

Murder, vehicular assault, and drug convictions mean prison for other defendants A 64-year-old Felton man was sentenced to more than 30 years in prison for raping a child repeatedly over the course of many years starting in the late 1990s. Deputy Attorney General Kathleen Dickerson secured the sentence for Monte Brown, who in April, pleaded […]

Tesla Inc Chief Executive Elon Musk said in a podcast interview released on Thursday that the company's planned Roadster sports car would take a backseat to the development of other vehicle models.

For the Federal Reserve, 2019 has started out looking a lot like 2016: The last time uncertainty over global growth roiled financial markets for months on end.

Decades after Bhopal, lack of law enforcement and political will plagues Indian industry

The gas leak at a chemical factory in Visakhapatnam will immediately remind many in India and beyond of the 1984 Bhopal disaster, widely considered the world’s worst industrial disaster.

So far, the scale of the tragedies are very different. Eleven people are confirmed to have died in Visakhapatnam – but with hundreds hospitalised and thousands affected, there are fears the toll will rise. In Bhopal, 4,000 people died within days of the toxic gas leak from a pesticide plant in the central Indian city, and thousands more in the following years.

A tsunami kept pinging back and forth for three days after being triggered by the 8 September 2017 Mexico earthquake, posing even more risk to human life

ABSTRACT

The posttranslational Ca²⁺-dependent "clip-and-link" activity of large repeat-in-toxin (RTX) proteins starts by Ca²⁺-dependent structural rearrangement of a highly conserved self-processing module (SPM). Subsequently, an internal aspartate-proline (Asp-Pro) peptide bond at the N-terminal end of SPM breaks, and the liberated C-terminal aspartyl residue can react with a free -amino group of an adjacent lysine residue to form a new isopeptide bond. Here, we report a solution structure of the calcium-loaded SPM (Ca-SPM) derived from the FrpC protein of Neisseria meningitidis. The Ca-SPM structure defines a unique protein architecture and provides structural insight into the autocatalytic cleavage of the Asp-Pro peptide bond through a "twisted-amide" activation. Furthermore, in-frame deletion of the SPM domain from the ApxIVA protein of Actinobacillus pleuropneumoniae attenuated the virulence of this porcine pathogen in a pig respiratory challenge model. We hypothesize that the Ca²⁺-dependent clip-and-link activity represents an unconventional strategy for Gram-negative pathogens to adhere to the host target cell surface.

IMPORTANCE The Ca²⁺-dependent clip-and-link activity of large repeat-in-toxin (RTX) proteins is an exceptional posttranslational process in which an internal domain called a self-processing module (SPM) mediates Ca²⁺-dependent processing of a highly specific aspartate-proline (Asp-Pro) peptide bond and covalent linkage of the released aspartyl to an adjacent lysine residue through an isopeptide bond. Here, we report the solution structures of the Ca²⁺-loaded SPM (Ca-SPM) defining the mechanism of the autocatalytic cleavage of the Asp414-Pro415 peptide bond of the Neisseria meningitidis FrpC exoprotein. Moreover, deletion of the SPM domain in the ApxIVA protein, the FrpC homolog of Actinobacillus pleuropneumoniae, resulted in attenuation of virulence of the bacterium in a pig infection model, indicating that the Ca²⁺-dependent clip-and-link activity plays a role in the virulence of Gram-negative pathogens.

ABSTRACT

Legionella pneumophila governs its interactions with host cells by secreting >300 different "effector" proteins. Some of these effectors contain eukaryotic domains such as the RCC1 (regulator of chromosome condensation 1) repeats promoting the activation of the small GTPase Ran. In this report, we reveal a conserved pattern of L. pneumophila RCC1 repeat genes, which are distributed in two main clusters of strains. Accordingly, strain Philadelphia-1 contains two RCC1 genes implicated in bacterial virulence, legG1 (Legionella eukaryotic gene 1), and ppgA, while strain Paris contains only one, pieG. The RCC1 repeat effectors localize to different cellular compartments and bind distinct components of the Ran GTPase cycle, including Ran modulators and the small GTPase itself, and yet they all promote the activation of Ran. The pieG gene spans the corresponding open reading frames of legG1 and a separate adjacent upstream gene, lpg1975. legG1 and lpg1975 are fused upon addition of a single nucleotide to encode a protein that adopts the binding specificity of PieG. Thus, a point mutation in pieG splits the gene, altering the effector target. These results indicate that divergent evolution of RCC1 repeat effectors defines the Ran GTPase cycle targets and that modulation of different components of the cycle might fine-tune Ran activation during Legionella infection.

IMPORTANCE Legionella pneumophila is a ubiquitous environmental bacterium which, upon inhalation, causes a life-threatening pneumonia termed Legionnaires’ disease. The opportunistic pathogen grows in amoebae and macrophages by employing a "type IV" secretion system, which secretes more than 300 different "effector" proteins into the host cell, where they subvert pivotal processes. The function of many of these effector proteins is unknown, and their evolution has not been studied. L. pneumophila RCC1 repeat effectors target the small GTPase Ran, a molecular switch implicated in different cellular processes such as nucleocytoplasmic transport and microtubule cytoskeleton dynamics. We provide evidence that one or more RCC1 repeat genes are distributed in two main clusters of L. pneumophila strains and have divergently evolved to target different components of the Ran GTPase activation cycle at different subcellular sites. Thus, L. pneumophila employs a sophisticated strategy to subvert host cell Ran GTPase during infection.

ABSTRACT

Reversible repression of HIV-1 5' long terminal repeat (5'-LTR)-mediated transcription represents the main mechanism for HIV-1 to maintain latency. Identification of host factors that modulate LTR activity and viral latency may help develop new antiretroviral therapies. The heterogeneous nuclear ribonucleoproteins (hnRNPs) are known to regulate gene expression and possess multiple physiological functions. hnRNP family members have recently been identified as the sensors for viral nucleic acids to induce antiviral responses, highlighting the crucial roles of hnRNPs in regulating viral infection. A member of the hnRNP family, X-linked RNA-binding motif protein (RBMX), has been identified in this study as a novel HIV-1 restriction factor that modulates HIV-1 5'-LTR-driven transcription of viral genome in CD4⁺ T cells. Mechanistically, RBMX binds to HIV-1 proviral DNA at the LTR downstream region and maintains the repressive trimethylation of histone H3 lysine 9 (H3K9me3), leading to a blockage of the recruitment of the positive transcription factor phosphorylated RNA polymerase II (RNA pol II) and consequential impediment of transcription elongation. This RBMX-mediated modulation of HIV-1 transcription maintains viral latency by inhibiting viral reactivation from an integrated proviral DNA. Our findings provide a new understanding of how host factors modulate HIV-1 infection and latency and suggest a potential new target for the development of HIV-1 therapies.

IMPORTANCE HIV-1 latency featuring silence of transcription from HIV-1 proviral DNA represents a major obstacle for HIV-1 eradication. Reversible repression of HIV-1 5'-LTR-mediated transcription represents the main mechanism for HIV-1 to maintain latency. The 5'-LTR-driven HIV gene transcription can be modulated by multiple host factors and mechanisms. The hnRNPs are known to regulate gene expression. A member of the hnRNP family, RBMX, has been identified in this study as a novel HIV-1 restriction factor that modulates HIV-1 5'-LTR-driven transcription of viral genome in CD4⁺ T cells and maintains viral latency. These findings provide a new understanding of how host factors modulate HIV-1 infection and latency and suggest a potential new target for the development of HIV-1 therapies.

Although substantial progress has been made in depicting the molecular pathogenesis of human immunodeficiency virus type 1 (HIV-1) infection, the comprehensive mechanism of HIV-1 latency and the most promising therapeutic strategies to effectively reactivate the HIV-1 latent reservoir to achieve a functional cure for AIDS remain to be systematically illuminated. Here, we demonstrated that piwi (P element-induced Wimpy)-like RNA-mediated gene silencing 4 (PIWIL4) played an important role in suppressing HIV-1 transcription and contributed to the latency state in HIV-1-infected cells through its recruitment of various suppressive factors, including heterochromatin protein 1α/β/, SETDB1, and HDAC4. The knockdown of PIWIL4 enhanced HIV-1 transcription and reversed HIV-1 latency in both HIV-1 latently infected Jurkat T cells and primary CD4⁺ T lymphocytes and resting CD4⁺ T lymphocytes from HIV-1-infected individuals on suppressive combined antiretroviral therapy (cART). Furthermore, in the absence of PIWIL4, HIV-1 latently infected Jurkat T cells were more sensitive to reactivation with vorinostat (suberoylanilide hydroxamic acid, or SAHA), JQ1, or prostratin. These findings indicated that PIWIL4 promotes HIV-1 latency by imposing repressive marks at the HIV-1 5' long terminal repeat. Thus, the manipulation of PIWIL4 could be a novel strategy for developing promising latency-reversing agents (LRAs).

IMPORTANCE HIV-1 latency is systematically modulated by host factors and viral proteins. During this process, the suppression of HIV-1 transcription plays an essential role in promoting HIV-1 latency. In this study, we found that PIWIL4 repressed HIV-1 promoter activity and maintained HIV-1 latency. In particular, we report that PIWIL4 can regulate gene expression through its association with the suppressive activity of HDAC4. Therefore, we have identified a new function for PIWIL4: it is not only a suppressor of endogenous retrotransposons but also plays an important role in inhibiting transcription and leading to latent infection of HIV-1, a well-known exogenous retrovirus. Our results also indicate a novel therapeutic target to reactivate the HIV-1 latent reservoir.

Some black holes are way bigger than we can explain, and they may have come from supermassive stars that formed by devouring the other stars around them

If Peter Turchin is right, we face the end of a 300-year cycle, as did previous far-flung empires. 

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U.S. District Judge Gray H. Miller sentenced Robert Luis Loya to three years in prison and five years of supervised release for violating the civil rights and the sexual abuse of females in his custody.

Paul Edward Pavulak, 66, of New Castle, Del., was convicted today by a federal jury in Wilmington of child exploitation offenses.

Four corporations involved in owning and operating a fleet of vessels regularly visiting New Orleans were today sentenced to pay a $1 million penalty and banned from doing business in the United States for the next five years by Judge Carl J. Barbier.

Paul Edward Pavulak, 67, of New Castle, Del., was sentenced by U.S. District Judge Sue L. Robinson in Wilmington, Del.

Michael Carlow, a resident of Pittsburgh, Pa., was sentenced today to serve 35 months in prison for corruptly endeavoring to obstruct the Internal Revenue Service (IRS), the Justice Department and IRS announced.

A former Lorain County, Ohio, corrections officer was sentenced today to serve 18 months in prison followed by two years of supervised release after previously pleading guilty to one count of deprivation of rights under color of law.

Genomewide association studies identified four genes that could serve as diagnostic markers and/or therapeutic targets for EoE.

James Allison is not convinced Ferrari will be able to repeat its performance in Malaysia at the Chinese Grand Prix in two weeks