BreCaHAD: A dataset for breast cancer histopathological annotation and diagnosis

Objectives: Histopathological tissue analysis by a pathologist determines the diagnosis and prognosis of most tumors, such as breast cancer. To estimate the aggressiveness of cancer, a pathologist evaluates the microscopic appearance of a biopsied tissue sample based on morphological features which have been correlated with patient outcome. Data description: This paper introduces a dataset of 162 breast cancer histopathology images, namely the breast cancer histopathological annotation and diagnosis dataset (BreCaHAD) which allows researchers to optimize and evaluate the usefulness of their proposed methods. The dataset includes various malignant cases. The task associated with this dataset is to automatically classify histological structures in these hematoxylin and eosin (H&E) stained images into six classes, namely mitosis, apoptosis, tumor nuclei, non-tumor nuclei, tubule, and non-tubule. By providing this dataset to the biomedical imaging community, we hope to encourage researchers in computer vision, machine learning and medical fields to contribute and develop methods/tools for automatic detection and diagnosis of cancerous regions in breast cancer histology images. © 2019 The Author(s)

Ionic high-pressure form of elemental boron

Boron is an element of fascinating chemical complexity. Controversies have shrouded this element since its discovery was announced in 1808: the new 'element' turned out to be a compound containing less than 60-70 percent of boron, and it was not until 1909 that 99-percent pure boron was obtained. And although we now know of at least 16 polymorphs, the stable phase of boron is not yet experimentally established even at ambient conditions. Boron's complexities arise from frustration: situated between metals and insulators in the periodic table, boron has only three valence electrons, which would favour metallicity, but they are sufficiently localized that insulating states emerge. However, this subtle balance between metallic and insulating states is easily shifted by pressure, temperature and impurities. Here we report the results of high-pressure experiments and ab initio evolutionary crystal structure predictions that explore the structural stability of boron under pressure and, strikingly, reveal a partially ionic high-pressure boron phase. This new phase is stable between 19 and 89 GPa, can be quenched to ambient conditions, and has a hitherto unknown structure (space group Pnnm, 28 atoms in the unit cell) consisting of icosahedral B12 clusters and B2 pairs in a NaCl-type arrangement. We find that the ionicity of the phase affects its electronic bandgap, infrared adsorption and dielectric constants, and that it arises from the different electronic properties of the B2 pairs and B12 clusters and the resultant charge transfer between them.Comment: Published in Nature 453, 863-867 (2009

Fluxes and Warping for Gauge Couplings in F-theory

We compute flux-dependent corrections in the four-dimensional F-theory effective action using the M-theory dual description. In M-theory the 7-brane fluxes are encoded by four-form flux and modify the background geometry and Kaluza-Klein reduction ansatz. In particular, the flux sources a warp factor which also depends on the torus directions of the compactification fourfold. This dependence is crucial in the derivation of the four-dimensional action, although the torus fiber is auxiliary in F-theory. In M-theory the 7-branes are described by an infinite array of Taub-NUT spaces. We use the explicit metric on this geometry to derive the locally corrected warp factor and M-theory three-from as closed expressions. We focus on contributions to the 7-brane gauge coupling function from this M-theory back-reaction and show that terms quadratic in the internal seven-brane flux are induced. The real part of the gauge coupling function is modified by the M-theory warp factor while the imaginary part is corrected due to a modified M-theory three-form potential. The obtained contributions match the known weak string coupling result, but also yield additional terms suppressed at weak coupling. This shows that the completion of the M-theory reduction opens the way to compute various corrections in a genuine F-theory setting away from the weak string coupling limit.Comment: 46 page

Escherichia coli can survive stress by noisy growth modulation.

Gene expression can be noisy, as can the growth of single cells. Such cell-to-cell variation has been implicated in survival strategies for bacterial populations. However, it remains unclear how single cells couple gene expression with growth to implement these strategies. Here, we show how noisy expression of a key stress-response regulator, RpoS, allows E. coli to modulate its growth dynamics to survive future adverse environments. We reveal a dynamic positive feedback loop between RpoS and growth rate that produces multi-generation RpoS pulses. We do so experimentally using single-cell, time-lapse microscopy and microfluidics and theoretically with a stochastic model. Next, we demonstrate that E. coli prepares for sudden stress by entering prolonged periods of slow growth mediated by RpoS. This dynamic phenotype is captured by the RpoS-growth feedback model. Our synthesis of noisy gene expression, growth, and survival paves the way for further exploration of functional phenotypic variability

Serine/threonine protein phosphatase 6 modulates the radiation sensitivity of glioblastoma

Increasing the sensitivity of glioblastoma cells to radiation is a promising approach to improve survival in patients with glioblastoma multiforme (GBM). This study aims to determine if serine/threonine phosphatase (protein phosphatase 6 (PP6)) is a molecular target for GBM radiosensitization treatment. The GBM orthotopic xenograft mice model was used in this study. Our data demonstrated that the protein level of PP6 catalytic subunit (PP6c) was upregulated in the GBM tissue from about 50% patients compared with the surrounding tissue or control tissue. Both the in vitro survival fraction of GBM cells and the patient survival time were highly correlated or inversely correlated with PP6c expression (R2=0.755 and −0.707, respectively). We also found that siRNA knockdown of PP6c reduced DNA-dependent protein kinase (DNA-PK) activity in three different GBM cell lines, increasing their sensitivity to radiation. In the orthotopic mice model, the overexpression of PP6c in GBM U87 cells attenuated the effect of radiation treatment, and reduced the survival time of mice compared with the control mice, while the PP6c knocking-down improved the effect of radiation treatment, and increased the survival time of mice. These findings demonstrate that PP6 regulates the sensitivity of GBM cells to radiation, and suggest small molecules disrupting or inhibiting PP6 association with DNA-PK is a potential radiosensitizer for GBM

Activation of DNA-PK by Ionizing Radiation Is Mediated by Protein Phosphatase 6

DNA-dependent protein kinase (DNA-PK) plays a critical role in DNA damage repair, especially in non-homologous end-joining repair of double-strand breaks such as those formed by ionizing radiation (IR) in the course of radiation therapy. Regulation of DNA-PK involves multisite phosphorylation but this is incompletely understood and little is known about protein phosphatases relative to DNA-PK. Mass spectrometry analysis revealed that DNA-PK interacts with the protein phosphatase-6 (PP6) SAPS subunit PP6R1. PP6 is a heterotrimeric enzyme that consists of a catalytic subunit, plus one of three PP6 SAPS regulatory subunits and one of three ankyrin repeat subunits. Endogenous PP6R1 co-immunoprecipitated DNA-PK, and IR enhanced the amount of complex and promoted its import into the nucleus. In addition, siRNA knockdown of either PP6R1 or PP6 significantly decreased IR activation of DNA-PK, suggesting that PP6 activates DNA-PK by association and dephosphorylation. Knockdown of other phosphatases PP5 or PP1γ1 and subunits PP6R3 or ARS-A did not reduce IR activation of DNA-PK, demonstrating specificity for PP6R1. Finally, siRNA knockdown of PP6R1 or PP6 but not other phosphatases increased the sensitivity of glioblastoma cells to radiation-induced cell death to a level similar to DNA-PK deficient cells. Our data demonstrate that PP6 associates with and activates DNA-PK in response to ionizing radiation. Therefore, the PP6/PP6R1 phosphatase is a potential molecular target for radiation sensitization by chemical inhibition

Genome wide association mapping of grain arsenic, copper, molybdenum and zinc in rice (Oryza sativa L.) grown at four international field sites

Peer reviewedPublisher PD

Tooth Brushing, Flossing, and Preventive Dental Visits by Detroit-area Residents in Relation to Demographic and Socioeconomic Factors

A survey was conducted to identify (a) factors that influence preventive dental behaviors and (b) target groups for interventions. Data were collected in face-to-face interviews with a probability sample of 662 dentate adults living in the Detroit tricounty area. The interviews included questions about demographic and socioeconomic variables and about three preventive behaviors: brushing, flossing, and preventive dental visits. All behaviors were positively associated with socioeconomic status. Females were more likely than males to perform each of the behaviors at the recommended frequency. The behaviors were only weakly associated with age. Whites were more likely than nonwhites to make regular dental visits, but frequency of brushing and flossing did not vary substantially across racial groups. The impact of race on frequency of dental visits was reduced when socioeconomic status was statistically controlled. Findings suggest that socioeconomic status, race, and sex remain important considerations when planning dental health education or other interventions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65274/1/j.1752-7325.1993.tb02692.x.pd

Single-tooth replacement: factors affecting different prosthetic treatment modalities

<p>Abstract</p> <p>Background</p> <p>The choice between several treatment options for replacing a single missing tooth is influenced by clinical, dentist- and patient-immanent factors. This study aimed to determine the patient factors that would affect the treatment decision to replace a single missing tooth and to assess the satisfaction with several options.</p> <p>Method</p> <p>200 volunteers involved (121 females and 79 males) divided into four groups, Group A: consisted of patients with conventional fixed partial dentures or patients with resin bonded fixed partial dentures. Group B: consisted of patients who received removable partial dentures while Group C: consisted of patients who received a single implant supported crown, and a control group D: consisted of patients who received no treatment. Data were collected using a questionnaire.</p> <p>Results</p> <p>The highest percentage of males within groups (58%) was within the removable prostheses category. The majority of the subjects in the study reported that the main reason for replacing a missing tooth was for esthetic and function. Most important factor affecting the choice between treatment modalities was damaging the neighboring teeth. Pain, post operative sensitivity and dental phobia were important factors in choosing the prosthesis type and affected the control group patients not to have any treatment. The highest satisfaction percentage among groups studied was recorded for dental implants then FPD groups, while the least percentage were in both the control and RPD groups, for all aspects of function, esthetic and speech efficiency.</p> <p>Conclusions</p> <p>The final choice between FPD, RPD and implant depended on several factors which affected the decision making; among these is cost and patients' awareness of the different treatment options.</p

Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms

Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10-36), SULT2A1 (rs2637125; p = 2.61×10-19), ARPC1A (rs740160; p = 1.56×10-16), TRIM4 (rs17277546; p = 4.50×10-11), BMF (rs7181230; p = 5.44×10-11), HHEX (rs2497306; p = 4.64×10-9), BCL2L11 (rs6738028; p = 1.72×10-8), and CYP2C9 (rs2185570; p = 2.29×10-8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS