Genotypic and phenotypic analysis of familial male breast cancer shows under representation of the HER2 and basal subtypes in BRCA-associated carcinomas

BACKGROUND: Male breast cancer (MBC) is an uncommon and relatively uncharacterised disease accounting for <1% of all breast cancers. A significant proportion occurs in families with a history of breast cancer and in particular those carrying BRCA2 mutations. Here we describe clinicopathological features and genomic BRCA1 and BRCA2 mutation status in a large cohort of familial MBCs. METHODS: Cases (n=60) included 3 BRCA1 and 25 BRCA2 mutation carries, and 32 non-BRCA1/2 (BRCAX) carriers with strong family histories of breast cancer. The cohort was examined with respect to mutation status, clinicopathological parameters including TNM staging, grade, histological subtype and intrinsic phenotype. RESULTS: Compared to the general population, MBC incidence was higher in all subgroups. In contrast to female breast cancer (FBC) there was greater representation of BRCA2 tumours (41.7% vs 8.3%, p=0.0008) and underrepresentation of BRCA1 tumours (5.0% vs 14.4%, p=0.0001). There was no correlation between mutation status and age of onset, disease specific survival (DSS) or other clincopathological factors. Comparison with sporadic MBC studies showed similar clinicopathological features. Prognostic variables affecting DSS included primary tumour size (p=0.003, HR:4.26 95%CI 1.63-11.11), age (p=0.002, HR:4.09 95%CI 1.65-10.12), lymphovascular (p=0.019, HR:3.25 95%CI 1.21-8.74) and perineural invasion (p=0.027, HR:2.82 95%CI 1.13-7.06). Unlike familial FBC, the histological subtypes seen in familial MBC were more similar to those seen in sporadic MBC with 46 (76.7%) pure invasive ductal carcinoma of no special type (IDC-NST), 2 (3.3%) invasive lobular carcinomas and 4 (6.7%) invasive papillary carcinoma. A further 8 (13.3%) IDC-NST had foci of micropapillary differentiation, with a strong trend for co-occurrence in BRCA2 carriers (p=0.058). Most tumours were of the luminal phenotype (89.7%), with infrequent HER2 (8.6%) and basal (1.7%) phenotype tumours seen. CONCLUSION: MBC in BRCA1/2 carriers and BRCAX families is different to females. Unlike FBC, a clear BRCA1 phenotype is not seen but a possible BRCA2 phenotype of micropapillary histological subtype is suggested. Comparison with sporadic MBCs shows this to be a high-risk population making further recruitment and investigation of this cohort of value in further understanding these uncommon tumours

Atomic Layer Deposition to Fine-Tune the Surface Properties and Diameters of Fabricated Nanopores

Atomic layer deposition of alumina enhanced the molecule sensing characteristics of fabricated nanopores by fine-tuning their surface properties, reducing 1/f noise, neutralizing surface charge to favor capture of DNA and other negative polyelectrolytes, and controlling the diameter and aspect ratio of the pores with near single Ångstrom precision. The control over the chemical and physical nature of the pore surface provided by atomic layer deposition produced a higher yield of functional nanopore detectors.Molecular and Cellular BiologyPhysicsChemistry and Chemical BiologyEngineering and Applied Science

Variations in export production, lithogenic sediment transport and iron fertilization in the Pacific sector of the Drake Passage over the past 400 kyr

Changes in Southern Ocean export production have broad biogeochemical and climatic implications. Specifically, iron fertilization likely increased subantarctic nutrient utilization and enhanced the efficiency of the biological pump during glacials. However, past export production in the subantarctic southeastern Pacific is poorly documented, and its connection to Fe fertilization, potentially related to Patagonian Ice Sheet dynamics, is unknown. We report biological productivity changes over the past 400 kyr, based on a combination of 230Thxs-normalized and stratigraphy-based mass accumulation rates of biogenic barium, organic carbon, biogenic opal and calcium carbonate as indicators of paleo-export production in a sediment core upstream of the Drake Passage (57.5∘ S, 70.3∘ W). In addition, we use fluxes of iron and lithogenic material as proxies for terrigenous input, and thus potential micronutrient supply. Stratigraphy-based mass accumulation rates are strongly influenced by bottom-current dynamics, which result in variable sediment focussing or winnowing at our site. Carbonate is virtually absent in the core, except during peak interglacial intervals of the Holocene, and Marine Isotope Stages (MIS) 5 and 11, likely caused by transient decreases in carbonate dissolution. All other proxies suggest that export production increased during most glacial periods, coinciding with high iron fluxes. Such augmented glacial iron fluxes at the core site were most likely derived from glaciogenic input from the Patagonian Ice Sheet promoting the growth of phytoplankton. Additionally, glacial export production peaks are also consistent with northward shifts of the Subantarctic and Polar Fronts, which positioned our site south of the Subantarctic Front and closer to silicic acid-rich waters of the Polar Frontal Zone. However, glacial export production near the Drake Passage was lower than in the Atlantic and Indian sectors of the Southern Ocean, which may relate to complete consumption of silicic acid in the study area. Our results underline the importance of micro-nutrient fertilization through lateral terrigenous input from South America rather than eolian transport and exemplify the role of frontal shifts and nutrient limitation for past productivity changes in the Pacific entrance to the Drake Passage

Санитарно-эпидемиологическая экспертиза импортной пищевой продукции и продовольственного сырья как составляющая профилактического направления транспортной медицины

Санітарно епідеміологічна експертиза імпортної харчової продукції й продовольчої сировини (далі експертиза) є одним з пріоритетних напрямів діяльності транспортних підрозділів санепідслужби. Здійснюючи функцію по контролю, виявленню та попередженню впливу небезпечних факторів, пов’язаних з перевезенням вантажів, вона є однією зі складових частин профілактичного напряму транспортної медицини. Експертиза імпортованої продукції харчового призначення нерозривно пов’язана та базується на загальних принципах всієї державної політики у сфері безпеки харчової продукції та продовольчої сировини. Основою для проведення усього комплексу робіт санітарно епідеміологічного направлення є нормативна база, яка була сформована в нашій країні кілька десятиліть назад. Механізм визначення безпеки продукції та ті критерії оцінки, які були закладені в її основі, вимагають перегляду у відповідності з вимогами сьогодення та враховуючи розвиток міжнародних відносин. Зроблені деякі кроки у цьому напрямку. Наприклад, визначення експертизи у законі «Про внесення змін до закону України «Про якість та безпеку харчових продуктів та продовольчої сировини» поряд зі встановленням відповідності продукції нормативним вимогам передбачає оцінку ризику дії шкідливих факторів у процесі обігу харчових продуктів, що відповідає сучас ним вимогам до вирішення задач профілактичного напрямку, запобігання шкідливого впливу факторів, керування санітарно-епідеміологічною ситуацією взагалі та на етапі транспортування харчових грузів зокрема. Такий підхід потрібно враховувати при подальшому необхідному перегляді та формуванні нової нормативної бази.Sanіtarу epidemiological examination of imported foodstuffs and edible raw materials (then «examination») is one of the priority directions of transport sanіtarу epidemiological servise. Examination controls, discovers and prevents an influence of dangerous factors while in transportation of loads. So it’s one of the component of the transport medicine preventive activity. Examination of import foodstuffs and edible raw materials inseparably linked with and based on general principles of the food safety state policy. The foundation of the sanitary service work is the normative base, that was formed in our country about twenty years ago. It is necessary to review the mechanism of the food safety determination and its criteria in accordance with requirements of present day time and with account of the development of the international relations. One of taken steps in this direction is a characteristic of examination in law «About contributing the modification to law of the Ukraine «About quality and safety of foodstuffs and foodraw materials» where along with determination of the products correspondence to the normative requirements is provided forrisk assessment of the harmful factors in process of the turn of the food stuffs. Such approach corresponds with modern requests to decision of the prophylactic problems, prevention bad influence dangerous factors, management sanіtarу epidemiological situation in general and in step of transportation food cargo in particular. And it should be taken into account during the further necessary process of revision and forming the new normative base

Polarization Pendellösung and the Generation of Circularly Polarized X Rays with a Quarter-Wave Plate

A continuously tunable x-ray compensator that works in conjunction with synchrotron-radiation sources has been developed. The phenomena of polarization Pendellösung has been observed during its normal operation and the generation of circularly polarized x rays is verified through an observation of the magnetic Compton effect.Physic

Deglacial and Holocene sea-ice and climate dynamics in the Bransfield Strait, northern Antarctic Peninsula

The reconstruction of past sea-ice distribution in the Southern Ocean is crucial for an improved understanding of ice-ocean-Atmosphere feedbacks and the evaluation of Earth system and Antarctic ice sheet models. The Antarctic Peninsula (AP) has been experiencing a warming since the start of regular monitoring of the atmospheric temperature in the 1950s. The associated decrease in sea-ice cover contrasts the trend of growing sea-ice extent in East Antarctica. To reveal the long-Term sea-ice history at the northern Antarctic Peninsula (NAP) under changing climate conditions, we examined a marine sediment core from the eastern basin of the Bransfield Strait covering the last Deglacial and the Holocene. For sea-ice reconstructions, we focused on the specific sea-ice biomarker lipid IPSO25, a highly branched isoprenoid (HBI), and sea-ice diatoms, whereas a phytoplankton-derived HBI triene (C25:3) and warmer open-ocean diatom assemblages reflect predominantly ice-free conditions. We further reconstruct ocean temperatures using glycerol dialkyl glycerol tetraethers (GDGTs) and diatom assemblages and compare our sea-ice and temperature records with published marine sediment and ice core data. A maximum ice cover is observed during the Antarctic Cold Reversal 13ĝ€¯800-13ĝ€¯000 years before present (13.8-13ĝ€¯ka), while seasonally ice-free conditions permitting (summer) phytoplankton productivity are reconstructed for the late Deglacial and the Early Holocene from 13 to 8.3ĝ€¯ka. An overall decreasing sea-ice trend throughout the Middle Holocene coincides with summer ocean warming and increasing phytoplankton productivity. The Late Holocene is characterized by highly variable winter sea-ice concentrations and a sustained decline in the duration and/or concentration of spring sea ice. Overall diverging trends in GDGT-based TEX86L and RI-OH' subsurface ocean temperatures (SOTs) are found to be linked to opposing spring and summer insolation trends, respectively.Financial support was provided through the Helmholtz Research grant no. VH-NG-1101. Partial support from the centres IDEAL (grant no. FONDAP 15150003) and COPAS (grant nos. AFB170006 and FB210021), Chile, and the Spanish Ministry of Economy, Industry and Competitivity grant no. CTM2017-89711-C2--P, co-funded by the European Union through FEDER funds, is acknowledged. The article processing charges for this open-access publication were covered by the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI)

Patterned growth of single-walled carbon nanotube arrays from a vapor-deposited Fe catalyst

Single-walled carbon nanotubes have been grown on a variety of substrates by chemical vapor deposition using low-coverage vacuum-deposited iron as a catalyst. Ordered arrays of suspended nanotubes ranging from submicron to several micron lengths have been obtained on Si, SiO2,SiO2, Al2O3,Al2O3, and Si3N4Si3N4 substrates that were patterned on hundred nanometer length scales with a focused ion beam machine. Electric fields applied during nanotubegrowth allow the control of growth direction. Nanotube circuits have been constructed directly on contacting metal electrodes of Pt/Cr patterned with catalysts. Patterning with solid iron catalyst is compatible with modern semiconductor fabrication strategies and may contribute to the integration of nanotubes in complex device architectures.Physic

Resonant versus nonresonant nuclear excitation of 115 In by positron annihilation

We have measured the resonant cross section σn for nuclear excitation of 115In via the radiationless annihilation of a positron with a K-shell electron using a monoenergetic positron beam and a thin In target. We find an upper limit on the resonant cross section σn<4.3×10−26cm2 at a 99% confidence level, compared to the cross section σβ=1.7×10−25cm2 determined by two previous measurements of nuclear excitation of 115In using the broad spectrum of positrons from the beta decay of 64Cu. Together these results imply the existence of a hitherto unidentified nonresonant channel for nuclear excitation via energetic positrons.Physic