Association of Vitamin D3 Level with Breast Cancer Risk and Prognosis in African-American and Hispanic Women.

Background: This study investigated the association of vitamin D3 levels with breast cancer risk and progression in African-Americans and Hispanics. Methods: A total of 237 African-American (Cases = 119, Control = 118) and 423 Hispanic women (Cases = 124, Control = 299) were recruited in the study. Blood samples were collected at the time of breast cancer screening and prior to cancer treatment for 4 weeks on average for the cases. The serum 25-hydroxyvitamin D (25(OH)D3) was measured at a Quest-Diagnostics facility. Results: The results showed that 69.2% of African-Americans and 37.8% of Hispanics had 25(OH)D3 levels below 20 ng/mL. The 25(OH)D3 level below 20 ng/mL was significantly associated with breast cancer in both African-Americans (OR = 2.5, 95% CI = 1.3-4.8) and Hispanics (OR = 1.9, 95% CI = 1.1-3.0). However, the predicted probabilities of breast cancer in African-Americans were significantly higher than in Hispanics (p < 0.001). The 25(OH)D3 below 20 ng/mL was significantly associated with triple negative breast cancer (TNBC) in African-Americans (OR = 5.4, p = 0.02, 95% CI = 1.4-15), but not in Hispanics in our cohort of participants. Levels of 25(OH)D3 below 26 ng/mL predicts a decrease in disease-free survival, but it was not an independent predictor. Conclusions: Our data shows an association between 25(OH)D3 levels and the risk of breast cancer. Further studies on the relationship between 25(OH)D3 level and breast cancer risk are warranted

Impact of High-Intensity Ultrasound on Strength of Surgical Mesh when Treating Biofilm Infections

The use of cavitation-based ultrasound histotripsy to treat infections on surgical mesh has shown great potential. However, any impact of the therapy on the mesh must be assessed before the therapy can be applied in the clinic. The goal of this study was to determine if the cavitation-based therapy would reduce the strength of the mesh thus compromising the functionality of the mesh. First, S. aureus biofilms were grown on surgical mesh samples and exposed to high-intensity ultrasound pulses. For each exposure, the effectiveness of the therapy was confirmed by counting the number of colony forming units (CFUs) on the mesh. Most of the exposed meshes had no CFUs with an average reduction of 5.4-log10 relative to the sham exposures. To quantify the impact of the exposure on mesh strength, the force required to tear the mesh and the maximum mesh expansion before damage were quantified for control, sham, and exposed mesh samples. There was no statistical difference between the exposed and sham/control mesh samples in terms of ultimate tensile strength and corresponding mesh expansion. The only statistical difference was with respect to mesh orientation relative to the applied load. The tensile strength increased by 1.36 N while the expansion was reduced by 1.33 mm between the different mesh orientations

Future perspectives on sustainable tribology

AbstractThis paper highlights the future perspectives of sustainable tribology by examining the economic, environmental and social impact of three tribological case studies. One case study examines the sustainability and durability of micro-CHP systems looking the tribological phenomena generated within a scroll expander system. The scroll is the main part of a specific micro-CHP system and experiences wear and cavitation damage. The tribological optimization of the scroll expander improves the sustainability of the micro-CHP unit while it has a serious economic and environmental impact to the consumers and to the society in general. Another case study is focused on friction and wear performance of lifeboat launch slipways. The causes of high friction and wear during the RNLI's lifeboat launches along an inclined slipway are investigated with a view to reducing the environmental impact due to slipway panel wear and lubricant release into the marine environment. The project encompasses the sustainable design of slipway panels using design modifications based on tribological investigations to double their lifespan, while environmental and economic impact was significantly reduced by the use of biodegradable greases and water as lubricants. The final case study involves an investigation of recycled plastic materials to replace polyurethane used on skateboard wheels, scooters and similar applications. Polyurethane (PU) is difficult to recycle. With the dwindling resources and environmental problems facing the world today, recycling for both waste reduction and resource preservation has become an increasingly important aspect of sustainability. The tribological results showed that recycled polycarbonate plastic can effectively act as a substitute to polyurethane wheels. Moreover, sustainability considerations showing the environmental benefits of the use of recycled plastics over PU include reducing the CO2 footprint by 50% and the energy consumed by 60%, among other benefits. These case studies emphasise the importance of sustainable tribology in our epoch showing that increased sustainability performance can be achieved through tribology to a significant extent in many cases, providing stability to our world and more viable long term growth to our societies

Dust properties along anomalous extinction sightlines. II. Studying extinction curves with dust models

The large majority of extinction sight lines in our Galaxy obey a simple relation depending on one parameter, the total-to-selective extinction coefficient, Rv. Different values of Rv are able to match the whole extinction curve through different environments so characterizing normal extinction curves. In this paper more than sixty curves with large ultraviolet deviations from their best-fit one parameter curve are analyzed. These curves are fitted with dust models to shed light into the properties of the grains, the processes affecting them, and their relations with the environmental characteristics. The extinction curve models are reckoned by following recent prescriptions on grain size distributions able to describe one parameter curves for Rv values from 3.1 to 5.5. Such models, here extended down to Rv=2.0, allow us to compare the resulting properties of our deviating curves with the same as normal curves in a self-consistent framework, and thus to recover the relative trends overcoming the modeling uncertainties. Such curves represent the larger and homogeneous sample of anomalous curves studied so far with dust models. Results show that the ultraviolet deviations are driven by a larger amount of small grains than predicted for lines of sight where extinction depends on one parameter only. Moreover, the dust-to-gas ratios of anomalous curves are lower than the same values for no deviating lines of sight. Shocks and grain-grain collisions should both destroy dust grains, so reducing the amount of the dust trapped into the grains, and modify the size distribution of the dust, so increasing the small-to-large grain size ratio. Therefore, the extinction properties derived should arise along sight lines where shocks and high velocity flows perturb the physical state of the interstellar medium living their signature on the dust properties. (Abridged version)Comment: 31 pages,12 figures; accepted for publication in A&

ASSET: Auto-Segmentation of the Seventeen SEgments for ventricular Tachycardia ablation in radiation therapy

There has been a recent effort to treat high-risk ventricular tachycardia (VT) patients through radio-ablation. However, manual segmentation of the VT target is complex and time-consuming. This work introduces ASSET, or Auto-segmentation of the Seventeen SEgments for Tachycardia ablation, to aid in radiation therapy (RT) planning. ASSET was retrospectively applied to CTs for 26 thoracic RT patients (13 undergoing VT ablation). The physician-defined parasternal long-axis of the left ventricle (LV) and the axes generated from principal component analysis (PCA) were compared using mean distance to agreement (MDA) and angle of separation. The manually selected right ventricle insertion point and LVs were used to apply the ASSET model to automatically generate the 17 segments of the LV myocardium (LVM). Physician-defined parasternal long-axis differed from PCA by 1.2 ± 0.3 mm MDA and 6.9 ± 0.7 degrees. Segments differed by 0.69 ± 0.29 mm MDA and 0.89 ± 0.03 Dice similarity coefficient. Running ASSET takes \u3c5 min where manual segmentation took \u3e2 h/patient. Agreement between ASSET and expert contours was comparable to inter-observer variability. Qualitative scoring conducted by three experts revealed automatically generated segmentations were clinically useable as-is. ASSET offers efficient and reliable automatic segmentations for the 17 segments of the LVM for target generation in RT planning

Monitoring activity-dependent bulk endocytosis with the genetically-encoded reporter VAMP4-pHluorin

AbstractBackgroundActivity-dependent bulk endocytosis (ADBE) is the dominant mode of synaptic vesicle (SV) endocytosis during intense neuronal activity, implicating it as a major contributor to presynaptic plasticity under these stimulation conditions. However methods to monitor this endocytosis mode have been limited to either morphological or optical observation of the uptake of large fluid phase markers.New methodWe present here a method to monitor ADBE using the genetically-encoded reporter VAMP4-pHluorin in primary neuronal cultures.ResultsIndividual nerve terminals expressing VAMP4-pHluorin display either an increase or decrease in fluorescence after stimulation terminates. The decrease in fluorescence reflects the slow acidification of large bulk endosomes to which VAMP4-pHluorin is selectively recruited. Use of VAMP4-pHluorin during sequential high frequency stimuli revealed that all nerve terminals perform ADBE, but not all do so in response to a single stimulus. VAMP4-pHluorin also displays a rapid activity-dependent decrease in fluorescence during high frequency stimulation, a response which is particularly prominent when expressed in hippocampal neurons. The molecular mechanism responsible for this decrease is still unclear, but is not due to loss of VAMP4-pHluorin from the nerve terminal.Comparison with existing methodsThis method allows the selective reporting of ADBE for the first time, when compared to previous approaches using markers of fluid phase uptake.ConclusionsThe development of VAMP4-pHluorin as a selective genetically-encoded reporter of ADBE increases the palette of approaches used to monitor this endocytosis mode both in vitro and in vivo

Characterization of designed, synthetically accessible bryostatin analog HIV latency reversing agents.

HIV latency in resting CD4+ T cell represents a key barrier preventing cure of the infection with antiretroviral drugs alone. Latency reversing agents (LRAs) can activate HIV expression in latently infected cells, potentially leading to their elimination through virus-mediated cytopathic effects, host immune responses, and/or therapeutic strategies targeting cells actively expressing virus. We have recently described several structurally simplified analogs of the PKC modulator LRA bryostatin (termed bryologs) designed to improve synthetic accessibility, tolerability in vivo, and efficacy in inducing HIV latency reversal. Here we report the comparative performance of lead bryologs, including their effects in reducing cell surface expression of HIV entry receptors, inducing proinflammatory cytokines, inhibiting short-term HIV replication, and synergizing with histone deacetylase inhibitors to reverse HIV latency. These data provide unique insights into structure-function relationships between A- and B-ring bryolog modifications and activities in primary cells, and suggest that bryologs represent promising leads for preclinical advancement

Evolution and biogeography of the endemic Roucela complex (Campanulaceae: Campanula) in the Eastern Mediterranean

At the intersection of geological activity, climatic fluctuations, and human pressure, the Mediterranean Basin – a hotspot of biodiversity – provides an ideal setting for studying endemism, evolution, and biogeography. Here, we focus on the Roucela complex (Campanula subgenus Roucela), a group of 13 bellflower species found primarily in the eastern Mediterranean Basin. Plastid and low-copy nuclear markers were employed to reconstruct evolutionary relationships and estimate divergence times within the Roucela complex using both concatenation and species tree analyses. Niche modeling, ancestral range estimation, and diversification analyses were conducted to provide further insights into patterns of endemism and diversification through time. Diversification of the Roucela clade appears to have been primarily the result of vicariance driven by the breakup of an ancient landmass. We found geologic events such as the formation of the mid-Aegean trench and the Messinian Salinity Crisis to be historically important in the evolutionary history of this group. Contrary to numerous past studies, the onset of the Mediterranean climate has not promoted diversification in the Roucela complex and, in fact, may be negatively affecting these species. This study highlights the diversity and complexity of historical processes driving plant evolution in the Mediterranean Basin

Scan Parameter Optimization for Histotripsy Treatment of S. Aureus Biofilms on Surgical Mesh

There is a critical need to develop new noninvasive therapies to treat bacteria biofilms. Previous studies have demonstrated the effectiveness of cavitation-based ultrasound histotripsy to destroy these biofilms. In this study, the dependence of biofilm destruction on multiple scan parameters was assessed by conducting exposures at different scan speeds (0.3-1.4 beam widths/sec), step sizes (0.25-0.5 beam widths), and number of passes of the focus across the mesh (2-6). For each of the exposure conditions, the number of colony forming units (CFUs) remaining on the mesh was quantified. A regression analysis was then conducted revealing that scan speed was the most critical parameter for biofilm destruction. Reducing the number of passes and the scan speed should allow for more efficient biofilm destruction in the future reducing the treatment time

Analysis of biophysical and functional consequences of Tropomyosin - fluorescent protein fusions.

The dynamic nature of actin polymers is modulated to facilitate a diverse range of cellular processes. These dynamic properties are modulated by different isoforms of Tropomyosin, which are recruited to distinct subpopulations of actin polymers to differentially modulate their functional properties. This makes them an attractive target for labelling discrete actin populations. We have assessed the effect of different fluorescent labelling strategies for this protein. Although tropomyosin fluorescent fusions decorate actin in vivo, they are either non-functional or perturb regulation of actin nucleation and cell cycle timings. Thus conclusions and physiological relevance should be carefully evaluated when using tropomyosin fusions