Novel paradigm for immunotherapy of breast cancer by engaging prophylactic immunity against hepatitis B

Background Immunotherapy of patients suffering from the human epidermal growth factor receptor 2 overexpressing (HER-2+) breast cancers with the anti-HER-2 antibodies results in increase of the patients’ overall survival. However, no prophylactic vaccine is available against HER-2+ breast cancers. Although, prophylactic vaccine for human hepatitis B virus (HBV) is very effective. Specific aim The specific aim of this work was to design, synthesize, and test bio-molecules which would engage prophylactic immunity against hepatitis B virus towards killing breast cancers cells. Methods and Results By biomolecular engineering, we have created a novel family of biomolecules: antibody (anti-HER-2) × vaccine (HBsAg) engineered constructs (AVEC: anti-HER-2 × HBsAg). These biomolecules were utilized for redirecting, accelerating, and amplifying of the vaccination-induced, prophylactic immunity originally targeted against HBV as therapeutic immunity, newly targeted against HER-2+ breast cancers. Treatment of the HER-2+ breast cancer cells with AVEC: anti-HER-2 × HBsAg in blood of the patients, vaccinated with HBsAg, rapidly increased efficacy of killing of HER-2+ breast cancer cells over that attained with the naked anti-HER-2 antibodies. Conclusion Novel antibody-vaccine engineered constructs (AVEC) facilitate redirecting, accelerating, and amplifying of prophylactic, HBV vaccination-induced immunity as immunotherapy (RAAVIIT) of HER-2+ breast cancer. We currently streamline this novel therapeutic paradigm into clinical trials of breast and other cancers

Bovine Leukemia Virus Infection in Dairy Cattle: Effect on Serological Response to Immunization against J5 Escherichia coli Bacterin

Thirteen bovine leukemia virus- (BLV-) negative and 22 BLV-positive Holstein cows were immunized with J5 Escherichia coli bacterin at dry off, three weeks before calving, during the second week after calving, and three weeks after the third immunization. Serum was collected before the initial immunization, immediately before the third and fourth immunizations, and 21 days after the fourth immunization. Anti-J5 E. coli IgM, IgG1, and IgG2 titers were determined by ELISA. Anti-J5 E. coli IgM titers did not differ significantly (P = .98) between groups. Increases in anti-J5 E. coli IgG1 titers were higher in the BLV-negative cows (P = .057). Geometric mean anti-J5 E. coli IgG2 titers increased fourfold in the BLV-negative cows, which was significantly higher (P = .007) than the twofold increase in the BLV-positive cows. Cattle infected with BLV may have impaired serologic responses following immunization with J5 bacterin, and response may differ according to antibody isotype

Stand up Paddle Surfing-An Aerobic Workout and Balance Training

AbstractOriginating from an ancient Hawaiian tradition Stand Up Paddle Surfing (SUP) is a growing pastime and sports activity in which a person stands upright on a surfboard and propels it using a single paddle. During paddling the board constantly is in an unstable condition forcing paddlers to focus on keeping balance and simultaneously propelling the board by paddling. Therefore it is expected that SUP can be a high impact aerobic workout and balance training. A total of 68 subjects performed on-water and SUP ergometer trials, during ergometer trials heart rate (HR) was permanently measured and balance was assessed before and after all trials (ergometer and on-water) using a single leg hop test on a Win Pod electronic baropedometric platform. Results of the balance tests - though for a relatively small number of participants - showed that after ergometer trials a significant improvement in stability occurred whereas it was only significant for the right foot's anteroposterior movement after on-water trials. The result of the exercise-test illustrated that the HR of beginners stays in the aerobic zone which makes SUP suitable for endurance training

The Comedy of Errors

This earliest of Shakespeare’s comedies is set in the ancient Greek town of Ephesus, where two sets of brothers had been separated in infancy during a tragic shipwreck long ago. Antipholus of Syracuse and his servant Dromio arrive in town, not knowing that it is the home of Antipholus of Ephesus and his servant, Dromio. Ephesian law forbids anyone from Syracuse to come into the town, and if caught doing so, will be put to death unless able to pay an enormous ransom. Egeon, father of the Antipholus twins, convinces the ruler of Ephesus to give him one day to find his long lost son. He is granted the time, and comic misadventures unfold as themes of mistaken identity, romantic disasters, false accusations and confusion take place. The befuddlement of the characters is even more fun for the audience to watch since we can tell the twins apart, but the characters cannot!https://digitalcommons.cedarville.edu/theatre_productions/1044/thumbnail.jp

The Beams Are Creaking

The inspiring, powerful, true story of Dietrich Bonhoeffer, the German theologian who defied the Nazis and ultimately led an assassination attempt against Hitler. Part political thriller, part love story, and leavened with moments of humor, it is filled with a compassion that reaffirms one’s faith in man.https://digitalcommons.cedarville.edu/theatre_productions/1052/thumbnail.jp

Ancient DNA reveals the timing and persistence of organellar genetic bottlenecks over 3,000 years of sunflower domestication and improvement

Here, we report a comprehensive paleogenomic study of archaeological and ethnographic sunflower remains that provides significant new insights into the process of domestication of this important crop. DNA from both ancient and historic contexts yielded high proportions of endogenous DNA, and although archaeological DNA was found to be highly degraded, it still provided sufficient coverage to analyze genetic changes over time. Shotgun sequencing data from specimens from the Eden's Bluff archaeological site in Arkansas yielded organellar DNA sequence from specimens up to 3,100 years old. Their sequences match those of modern cultivated sunflowers and are consistent with an early domestication bottleneck in this species. Our findings also suggest that recent breeding of sunflowers has led to a loss of genetic diversity that was present only a century ago in Native American landraces. These breeding episodes also left a profound signature on the mitochondrial and plastid haplotypes in cultivars, as two types were intentionally introduced from other Helianthus species for crop improvement. These findings gained from ancient and historic sunflower specimens underscore how future in-depth gene-based analyses can advance our understanding of the pace and targets of selection during the domestication of sunflower and other crop species

Riparian zones increase regional species richness by harboring different, not more, species

Riparian zones are habitats of critical conservation concern worldwide, as they are known to filter agricultural contaminants, buffer landscapes against erosion, and provide habitat for high numbers of species. Here we test the generality of the notion that riparian habitats harbor more species than adjacent upland habitats. Using previously published data collected from seven continents and including taxa ranging from Antarctic soil invertebrates to tropical rain forest lianas and primates, we show that riparian habitats do not harbor higher numbers of species, but rather support significantly different species pools altogether. In this way, riparian habitats increase regional (γ-) richness across the globe by >50%, on average. Thus conservation planners can easily increase the number of species protected in a regional portfolio by simply including a river within terrestrial biodiversity reserves. Our analysis also suggests numerous possible improvements for future studies of species richness gradients across riparian and upland habitats. First, <15% of the studies in our analysis included estimates of more than one taxonomic group of interest. Second, within a given taxonomic group, studies employed variable methodologies and sampling areas in pursuit of richness and turnover estimates. Future analyses of species richness patterns in watersheds should aim to include a more comprehensive suite of taxonomic groups and should measure richness at multiple spatial scales

Small non-coding RNA profiling in plasma extracellular vesicles of bladder cancer patients by next-generation sequencing: Expression levels of miR-126-3p and piR-5936 increase with higher histologic grades

Bladder cancer (BC) is the tenth most frequent cancer worldwide. Due to the need for recurrent cystoscopies and the lack of non-invasive biomarkers, BC is associated with a high management burden. In this respect, small non-coding RNAs (sncRNAs) have been investigated in urine as possible biomarkers for BC, but in plasma their potential has not yet been defined. The expression levels of sncRNAs contained in plasma extracellular vesicles (EVs) from 47 men with BC and 46 healthy controls were assessed by next-generation sequencing. The sncRNA profiles were compared with urinary profiles from the same subjects. miR-4508 resulted downregulated in plasma EVs of muscle-invasive BC patients, compared to controls (adj-p = 0.04). In World Health Organization (WHO) grade 3 (G3) BC, miR-126-3p was upregulated both in plasma EVs and urine, when compared to controls (for both, adj-p &lt; 0.05). Interestingly, two sncRNAs were associated with the risk class: miR-4508 with a downward trend going from controls to high risk BC, and piR-hsa-5936 with an upward trend (adj-p = 0.04 and adj-p = 0.05, respectively). Additionally, BC cases with low expression of miR-185-5p and miR-106a-5p or high expression of miR-10b-5p showed shorter survival (adj-p = 0.0013, adj-p = 0.039 and adj-p = 0.047, respectively). SncRNAs from plasma EVs could be diagnostic biomarkers for BC, especially in advanced grade

Removing systematics from the CoRoT light curves: I. Magnitude-Dependent Zero Point

This paper presents an analysis that searched for systematic effects within the CoRoT exoplanet field light curves. The analysis identified a systematic effect that modified the zero point of most CoRoT exposures as a function of stellar magnitude. We could find this effect only after preparing a set of learning light curves that were relatively free of stellar and instrumental noise. Correcting for this effect, rejecting outliers that appear in almost every exposure, and applying SysRem, reduced the stellar RMS by about 20 %, without attenuating transit signals.Comment: Accepted for publication in Astronomy and Astrophysic

Supporting Practices to Adopt Registry-Based Care (SPARC): protocol for a randomized controlled trial

Background: Diabetes is predicted to increase in incidence by 42% from 1995 to 2025. Although most adults with diabetes seek care from primary care practices, adherence to treatment guidelines in these settings is not optimal. Many practices lack the infrastructure to monitor patient adherence to recommended treatment and are slow to implement changes critical for effective management of patients with chronic conditions. Supporting Practices to Adopt Registry-Based Care (SPARC) will evaluate effectiveness and sustainability of a low-cost intervention designed to support work process change in primary care practices and enhance focus on population-based care through implementation of a diabetes registry. Methods: SPARC is a two-armed randomized controlled trial (RCT) of 30 primary care practices in the Virginia Ambulatory Care Outcomes Research Network (ACORN). Participating practices (including control groups) will be introduced to population health concepts and tools for work process redesign and registry adoption at a meeting of practice-level implementation champions. Practices randomized to the intervention will be assigned study peer mentors, receive a list of specific milestones, and have access to a physician informaticist. Peer mentors are clinicians who successfully implemented registries in their practices and will help champions in the intervention practices throughout the implementation process. During the first year, peer mentors will contact intervention practices monthly and visit them quarterly. Control group practices will not receive support or guidance for registry implementation. We will use a mixed-methods explanatory sequential design to guide collection of medical record, participant observation, and semistructured interview data in control and intervention practices at baseline, 12 months, and 24 months. We will use grounded theory and a template-guided approach using the Consolidated Framework for Implementation Research to analyze qualitative data on contextual factors related to registry adoption. We will assess intervention effectiveness by comparing changes in patient-level hemoglobin A1c scores from baseline to year 1 between intervention and control practices. Discussion: Findings will enhance our understanding of how to leverage existing practice resources to improve diabetes care in primary care practices by implementing and using a registry. SPARC has the potential to validate the effectiveness of low-cost implementation strategies that target practice change in primary care