Bubble nucleation and jetting inside a millimetric droplet

In this work, we present experiments and simulations on the nucleation and successive dynamics of laser-induced bubbles inside liquid droplets in free-fall motion, i.e. a case where the bubbles are subjected to the influence of a free boundary in all directions. The droplets of a millimetric size are released from a height of around 20\,cm and acquire a velocity of around 2\,m/s at the moment the bubble is nucleated. Within this droplet, we have investigated the nucleation of secondary bubbles induced by the rarefaction wave that is produced when the shock wave emitted by the laser-induced plasma reflects at the drop surface. Interestingly, three-dimensional clusters of cavitation bubbles are observed. Their shape is compared with the negative pressure distribution computed with a CFD model and allows us to estimate a cavitation threshold value. High-speed recordings of the drop/bubble dynamics are complemented by the velocity and pressure fields simulated for the same initial conditions. The effect of the proximity of a curved free surface on the jetting dynamics of the bubbles was qualitatively assessed by classifying the cavitation events using a non-dimensional stand-off parameter which depends on the drop size, the bubble maximum radius and the relative position of the bubble inside the drop. Here, we found that the curvature of the free surface does not play a determinant role on the jet dynamics, being the distance to the surface the dominant parameter. The oscillation of the laser-induced bubbles promote the onset of Rayleigh-Taylor and Rayleigh-Plateau instabilities, observed on the drop's surface. The specific mechanisms leading to the destabilisation of the droplet surface were identified through a careful inspection of the high speed images

Decreased cortical thickness mediates the relationship between premature birth and cognitive performance in adulthood

Cortical thickness (CTh) reflects cortical properties such as dendritic complexity and synaptic density, which are not only vulnerable to developmental disturbances caused by premature birth but also highly relevant for cognitive performance. We tested the hypotheses whether CTh in young adults is altered after premature birth and whether these aberrations are relevant for general cognitive abilities. We investigated CTh based on brain structural magnetic resonance imaging and surface‐based morphometry in a large and prospectively collected cohort of 101 very premature‐born adults (<32 weeks of gestation and/or birth weight [BW] below 1,500 g) and 111 full‐term controls at 26 years of age. Cognitive performance was assessed by full‐scale intelligence quotient (IQ) using the Wechsler Adult Intelligence Scale. CTh was reduced in frontal, parietal, and temporal associative cortices predominantly in the left hemisphere in premature‐born adults compared to controls. We found a significant positive association of CTh with both gestational age and BW, particularly in the left hemisphere, and a significant negative association between CTh and intensity of neonatal treatment within limited regions bilaterally. Full‐scale IQ and CTh in the left hemisphere were positively correlated. Furthermore, CTh in the left hemisphere acted as a mediator on the association between premature birth and full‐scale IQ. Results provide evidence that premature born adults have widespread reduced CTh that is relevant for their general cognitive performance. Data suggest lasting reductions in cortical microstructure subserving CTh after premature birth

Beyond solid-state lighting: Miniaturization, hybrid integration, and applications og GaN nano- and micro-LEDs

Gallium Nitride (GaN) light-emitting-diode (LED) technology has been the revolution in modern lighting. In the last decade, a huge global market of efficient, long-lasting and ubiquitous white light sources has developed around the inception of the Nobel-price-winning blue GaN LEDs. Today GaN optoelectronics is developing beyond lighting, leading to new and innovative devices, e.g. for micro-displays, being the core technology for future augmented reality and visualization, as well as point light sources for optical excitation in communications, imaging, and sensing. This explosion of applications is driven by two main directions: the ability to produce very small GaN LEDs (microLEDs and nanoLEDs) with high efficiency and across large areas, in combination with the possibility to merge optoelectronic-grade GaN microLEDs with silicon microelectronics in a fully hybrid approach. GaN LED technology today is even spreading into the realm of display technology, which has been occupied by organic LED (OLED) and liquid crystal display (LCD) for decades. In this review, the technological transition towards GaN micro- and nanodevices beyond lighting is discussed including an up-to-date overview on the state of the art

Nuclear receptor coregulator SNP discovery and impact on breast cancer risk

<p>Abstract</p> <p>Background</p> <p>Coregulator proteins are "master regulators", directing transcriptional and posttranscriptional regulation of many target genes, and are critical in many normal physiological processes, but also in hormone driven diseases, such as breast cancer. Little is known on how genetic changes in these genes impact disease development and progression. Thus, we set out to identify novel single nucleotide polymorphisms (SNPs) within SRC-1 (NCoA1), SRC-3 (NCoA3, AIB1), NCoR (NCoR1), and SMRT (NCoR2), and test the most promising SNPs for associations with breast cancer risk.</p> <p>Methods</p> <p>The identification of novel SNPs was accomplished by sequencing the coding regions of these genes in 96 apparently normal individuals (48 Caucasian Americans, 48 African Americans). To assess their association with breast cancer risk, five SNPs were genotyped in 1218 familial BRCA1/2-mutation negative breast cancer cases and 1509 controls (rs1804645, rs6094752, rs2230782, rs2076546, rs2229840).</p> <p>Results</p> <p>Through our resequencing effort, we identified 74 novel SNPs (30 in NCoR, 32 in SMRT, 10 in SRC-3, and 2 in SRC-1). Of these, 8 were found with minor allele frequency (MAF) >5% illustrating the large amount of genetic diversity yet to be discovered. The previously shown protective effect of rs2230782 in SRC-3 was strengthened (OR = 0.45 [0.21-0.98], p = 0.04). No significant associations were found with the other SNPs genotyped.</p> <p>Conclusions</p> <p>This data illustrates the importance of coregulators, especially SRC-3, in breast cancer development and suggests that more focused studies, including functional analyses, should be conducted.</p

Parametric Investigations of the Induced Shear Stress by a Laser-Generated Bubble

The present paper focuses on the simulation of the growth and collapse of a bubble in the vicinity of a wall. Both liquid and gas phases are assumed compressible, and their interaction is handled with the volume-of-fluid method. The main interest is to quantify the influence of the induced shear stress and pressure pulse in the vicinity of the wall for a variety of bubble sizes and bubble–wall distances. The results are validated against prior experimental results, such as the measurements of the bubble size, induced pressure field, and shear stress on the wall. The simulation predictions indicate that the wall in the vicinity of the bubble is subjected both to high shear stresses and large pressure pulses because of the growth and collapse of the bubble. In fact, pressure levels of 100 bar or more and shear stresses up to 25 kPa have been found at localized spots on the wall surface, at the region around the bubble. Moreover, the simulations are capable of providing additional insight to the experimental investigation, as the inherent limitations of the latter are avoided. The present work may be considered as a preliminary investigation in optimizing bubble energy and wall generation distance for ultrasound cleaning applications

Identification of a DMBT1 polymorphism associated with increased breast cancer risk and decreased promoter activity

According to present estimations, the unfavorable combination of alleles with low penetrance but high prevalence in the population might account for the major part of hereditary breast cancer risk. Deleted in Malignant Brain Tumors 1 (DMBT1) has been proposed as a tumor suppressor for breast cancer and other cancer types. Genomewide mapping in mice further identified Dmbt1 as a potential modulator of breast cancer risk. Here, we report the association of two frequent and linked single-nucleotide polymorphisms (SNPs) with increased breast cancer risk in women above the age of 60 years: DMBT1 c.-93C>T, rs2981745, located in the DMBT1 promoter; and DMBT1 c.124A>C, p.Thr42Pro, rs11523871(odds ratio [OR]=1.66, 95% confidence interval [CI]=1.21-2.29, P=0.0017; and OR=1.66; 95% CI=1.21-2.28, P=0.0016, respectively), based on 1,195 BRCA1/2 mutation-negative German breast cancer families and 1,466 unrelated German controls. Promoter studies in breast cancer cells demonstrate that the risk-increasing DMBT1 -93T allele displays significantly decreased promoter activity compared to the DMBT1 -93C allele, resulting in a loss of promoter activity. The data suggest that DMBT1 polymorphisms in the 5'-region are associated with increased breast cancer risk. In accordance with previous results, these data link decreased DMBT1 levels to breast cancer risk

Prevalence of pathogenic BRCA1/2 germline mutations among 802 women with unilateral triple-negative breast cancer without family cancer history

Background: There is no international consensus up to which age women with a diagnosis of triple-negative breast cancer (TNBC) and no family history of breast or ovarian cancer should be offered genetic testing for germline BRCA1 and BRCA2 (gBRCA) mutations. Here, we explored the association of age at TNBC diagnosis with the prevalence of pathogenic gBRCA mutations in this patient group. Methods: The study comprised 802 women (median age 40 years, range 19–76) with oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2 negative breast cancers, who had no relatives with breast or ovarian cancer. All women were tested for pathogenic gBRCA mutations. Logistic regression analysis was used to explore the association between age at TNBC diagnosis and the presence of a pathogenic gBRCA mutation. Results: A total of 127 women with TNBC (15.8%) were gBRCA mutation carriers (BRCA1: n = 118, 14.7%; BRCA2: n = 9, 1.1%). The mutation prevalence was 32.9% in the age group 20–29 years compared to 6.9% in the age group 60–69 years. Logistic regression analysis revealed a significant increase of mutation frequency with decreasing age at diagnosis (odds ratio 1.87 per 10 year decrease, 95%CI 1.50–2.32, p &lt; 0.001). gBRCA mutation risk was predicted to be &gt; 10% for women diagnosed below approximately 50 years. Conclusions: Based on the general understanding that a heterozygous mutation probability of 10% or greater justifies gBRCA mutation screening, women with TNBC diagnosed before the age of 50 years and no familial history of breast and ovarian cancer should be tested for gBRCA mutations. In Germany, this would concern approximately 880 women with newly diagnosed TNBC per year, of whom approximately 150 are expected to be identified as carriers of a pathogenic gBRCA mutation

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations