Superhydrophobic Anticorrosive Phosphonate–Siloxane Films Formed on Zinc with Different Surface Morphology

The composition, structure, and protective and hydrophobic properties of nanoscale films formed layer-by-layer in solutions of sodium dodecylphosphonate (SDDP) and vinyltrimethoxysilane or n-octyltriethoxysilane (OTES) on the zinc surface with different morphologies were studied by SEM, XPS, water contact angle measurements, and electrochemical and corrosion tests. The protective, hydrophobic properties of phosphonate–siloxane films on zinc and their stability in a corrosive media are determined both by the initial surface morphology and composition of the surface oxide layer, and by the nature of inhibitors. It was shown that preliminary laser texturing of the zinc surface is preferable than chemical etching to enhance the anticorrosive properties of the resulting thin films. The most stable films with excellent superhydrophobic and protective properties in atmospheres of high humidity and salt spray are formed on the zinc surface with fractal morphology during layer-by-layer passivation with SDDP and OTES.     

SOLEIL: single-objective lens inclined light sheet localization microscopy

High-NA light sheet illumination can improve the resolution of single-molecule localization microscopy (SMLM) by reducing the background fluorescence. These approaches currently require custom-made sample holders or additional specialized objectives, which makes the sample mounting or the optical system complex and therefore reduces the usability of these approaches. Here, we developed a single-objective lens-inclined light sheet microscope (SOLEIL) that is capable of 2D and 3D SMLM in thick samples. SOLEIL combines oblique illumination with point spread function PSF engineering to enable dSTORM imaging in a wide variety of samples. SOLEIL is compatible with standard sample holders and off-the-shelve optics and standard high NA objectives. To accomplish optimal optical sectioning we show that there is an ideal oblique angle and sheet thickness. Furthermore, to show what optical sectioning delivers for SMLM we benchmark SOLEIL against widefield and HILO microscopy with several biological samples. SOLEIL delivers in 15 μm thick Caco2-BBE cells a 374% higher intensity to background ratio and a 54% improvement in the estimated CRLB compared to widefield illumination, and a 184% higher intensity to background ratio and a 20% improvement in the estimated CRLB compared to HILO illumination.     

The impact of anthracyclines in intermediate and high-risk HER2-negative early breast cancer—a pooled analysis of the randomised clinical trials PlanB and SUCCESS C

Background Anthracycline/cyclophosphamide-taxane-containing chemotherapy (AC-T) is the standard of care in the adjuvant treatment of HER2-negative early breast cancer (EBC), but recent studies suggest omission of anthracyclines for reduced toxicity without compromising efficacy.Methods Based on individual patient data (n = 5924) pooled from the randomised Phase III trials PlanB and SUCCESS C, we compared disease-free survival (DFS) and overall survival (OS) between intermediate to high-risk HER2-negative EBC-patients treated with either six cycles of docetaxel/cyclophosphamide (TC6) or an AC-T regime using univariable and adjusted multivariable Cox regression models.Results AC-T conferred no significant DFS or OS advantage in univariable (DFS: hazard ratio (HR) for TC vs. AT 1.05, 95% confidence interval (CI): 0.89–1.24, P = 0.57; OS: HR 1.00, 95% CI: 0.80–1.26, P = 1.00) and adjusted multivariable analysis (DFS: HR 1.01, 95% CI: 0.86–1.19, P = 0.91; OS: HR 0.97, 95% CI: 0.77–1.22, P = 0.79). Patients receiving TC6 had significantly fewer grade 3–4 adverse events. Exploratory subgroup analysis showed that AC-T was associated with significantly better DFS and OS in pN2/3 patients, specifically in those with lobular histology.Conclusion For most patients with HER2-negative EBC, AC-T is not associated with a survival benefit compared to TC6. However, patients with lobular pN2/pN3 tumours seem to benefit from anthracycline-containing chemotherapy.Subject terms: Randomized controlled trials, Breast cancer     

The New Associationism: A Neural Explanation for the Predictive Powers of Cerebral Cortex

The ability to predict is the most importantability of the brain. Somehow, the cortex isable to extract regularities from theenvironment and use those regularities as abasis for prediction. This is a most remarkableskill, considering that behaviourallysignificant environmental regularities are noteasy to discern: they operate not only betweenpairs of simple environmental conditions, astraditional associationism has assumed, butamong complex functions of conditions that areorders of complexity removed from raw sensoryinputs. We propose that the brain's basicmechanism for discovering such complexregularities is implemented in the dendritictrees of individual pyramidal cells in thecerebral cortex. Pyramidal cells have 5–8principal dendrites, each of which is capableof learning nonlinear input-to-outputtransfer functions. We propose that eachdendrite is trained, in learning its transferfunction, by all the other principal dendritesof the same cell. These dendrites teach eachother to respond to their separate inputs withmatching outputs. Exposed to differentbut related information about the sensoryenvironment, principal dendrites of the samecell tune to functions over environmentalconditions that, while different, arecorrelated. As a result, the cell as awhole tunes to the source of the regularitiesdiscovered by the cooperating dendrites,creating a new representation. When organizedinto feed-forward/feedback layers, pyramidalcells can build their discoveries on thediscoveries of other cells, graduallyuncovering nature's hidden order. Theresulting associative network is powerfulenough to meet a troubling traditionalobjection to associationism: that it is toosimple an architecture to implement rationalprocesses.     

Primary Multidrug-Resistant Mycobacterium tuberculosis in 2 Regions,Eastern Siberia,Russian Federation

Of 235 Mycobacterium tuberculosis isolates from patients who had not received tuberculosis treatment in the Irkutsk oblast and the Sakha Republic (Yakutia), eastern Siberia, 61 (26%) were multidrug resistant. A novel strain, S 256, clustered among these isolates and carried eis-related kanamycin resistance, indicating a need for locally informed diagnosis and treatment strategies.     

Migration,health, and socioenvironmental safety net among children of Dhaka,Bangladesh

This study quantifies the diarrhea burden among migrant children under age 5 (who have migrated due to environmental degradation) in Dhaka. We used a multifactor socioepidemiological as well as environmental approach with pretested questionnaires and observations. It was found that 52% of the children were affected by diarrhea. Disability-adjusted life years (DALYs) lost was reduced manifold with the increase of mothers' behavioral determinants. Health losses were 1,718 fold with significant coefficient (β) in the migrant group. DALYs lost were significantly associated with socioenvironmental factors such as mother's illiteracy (β = .18; p < .001), no hand wash before eating (β = .08; p = .004), and no hand wash after defecation (β = .10; p < .001). This puts emphasis clearly on the awareness at household level, especially of mothers and children under age 5 in Dhaka, Bangladesh, in formulating migration-related policies.     

Comprehensive genomic profiling of metastatic collecting duct carcinoma,renal medullary carcinoma,and clear cell renal cell carcinoma

Introduction and ObjectiveUnlike clear cell renal cell carcinoma (CCRCC), collecting duct carcinoma (CDC) and renal medullary carcinoma (RMC) are rare tumors that progress rapidly and appear resistant to current systemic therapies. We queried comprehensive genomic profiling to uncover opportunities for targeted therapy and immunotherapy.Material and MethodsDNA was extracted from 40 microns of formalin-fixed, paraffin-embedded specimen from relapsed, mCDC (n = 46), mRMC (n = 24), and refractory and metastatic (m) mCCRCC (n = 626). Comprehensive genomic profiling was performed, and Tumor mutational burden (TMB) and microsatellite instability (MSI) were calculated. We analyzed all classes of genomic alterations.ResultsmCDC had 1.7 versus 2.7 genomic alterations/tumor in mCCRCC ( = 0.04). Mutations in VHL (P < 0.0001) and TSC1 (P = 0.04) were more frequent in mCCRCC. SMARCB1 (P < 0.0001), NF2 (P = 0.0007), RB1 (P = 0.02) and RET (P = 0.0003) alterations were more frequent in mCDC versus mCCRCC. No VHL alterations in mRMC and mCDC were identified. SMARCB1 genomic alterations were significantly more frequent in mRMC than mCDC (P = 0.0002), but were the most common alterations in both subtypes. Mutations to EGFR, RET, NF2, and TSC2 were more frequently identified in mCDC versus mRMC. The median TMB and MSI-High status was low with <1% of mCCRC, mCDC, and mRMC having ≥ 20 mut/Mb.ConclusionGenomic alteration patterns in mCDC and mRMC differ significantly from mCCRCC. Targeted therapies for mCDC and mRMC appear limited with rare opportunities to target alterations in receptor tyrosine kinase and MTOR pathways. Similarly, TMB and absence of MSI-High status in mCDC and mRMC suggest resistance to immunotherapies.