Nucleoporin98-96 Function Is Required for Transit Amplification Divisions in the Germ Line of Drosophila melanogaster

Production of specialized cells from precursors depends on a tightly regulated sequence of proliferation and differentiation steps. In the gonad of Drosophila melanogaster, the daughters of germ line stem cells (GSC) go through precisely four rounds of transit amplification divisions to produce clusters of 16 interconnected germ line cells before entering a stereotypic differentiation cascade. Here we show that animals harbouring a transposon insertion in the center of the complex nucleoporin98-96 (nup98-96) locus had severe defects in the early steps of this developmental program, ultimately leading to germ cell loss and sterility. A phenotypic analysis indicated that flies carrying the transposon insertion, designated nup98-962288, had dramatically reduced numbers of germ line cells. In contrast to controls, mutant testes contained many solitary germ line cells that had committed to differentiation as well as abnormally small clusters of two, four or eight differentiating germ line cells. This indicates that mutant GSCs rather differentiated than self-renewed, and that these GSCs and their daughters initiated the differentiation cascade after zero, or less than four rounds of amplification divisions. This phenotype remained unaffected by hyper-activation of signalling pathways that normally result in excessive proliferation of GSCs and their daughters. Expression of wildtype nup98-96 specifically in the germ line cells of mutant animals fully restored development of the GSC lineage, demonstrating that the effect of the mutation is cell-autonomous. Nucleoporins are the structural components of the nucleopore and have also been implicated in transcriptional regulation of specific target genes. The nuclear envelopes of germ cells and general nucleocytoplasmic transport in nup98-96 mutant animals appeared normal, leading us to propose that Drosophila nup98-96 mediates the transport or transcription of targets required for the developmental timing between amplification and differentiation

Fracture fixation in the operative management of hip fractures (FAITH): an international, multicentre, randomised controlled trial

© 2017 Elsevier Ltd Background Reoperation rates are high after surgery for hip fractures. We investigated the effect of a sliding hip screw versus cancellous screws on the risk of reoperation and other key outcomes. Methods For this international, multicentre, allocation concealed randomised controlled trial, we enrolled patients aged 50 years or older with a low-energy hip fracture requiring fracture fixation from 81 clinical centres in eight countries. Patients were assigned by minimisation with a centralised computer system to receive a single large-diameter screw with a side-plate (sliding hip screw) or the present standard of care, multiple small-diameter cancellous screws. Surgeons and patients were not blinded but the data analyst, while doing the analyses, remained blinded to treatment groups. The primary outcome was hip reoperation within 24 months after initial surgery to promote fracture healing, relieve pain, treat infection, or improve function. Analyses followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT00761813. Findings Between March 3, 2008, and March 31, 2014, we randomly assigned 1108 patients to receive a sliding hip screw (n=557) or cancellous screws (n=551). Reoperations within 24 months did not differ by type of surgical fixation in those included in the primary analysis: 107 (20%) of 542 patients in the sliding hip screw group versus 117 (22%) of 537 patients in the cancellous screws group (hazard ratio [HR] 0·83, 95% CI 0·63–1·09; p=0·18). Avascular necrosis was more common in the sliding hip screw group than in the cancellous screws group (50 patients [9%] vs 28 patients [5%]; HR 1·91, 1·06–3·44; p=0·0319). However, no significant difference was found between the number of medically related adverse events between groups (p=0·82; appendix); these events included pulmonary embolism (two patients [\u3c1%] vs four [1%] patients; p=0·41) and sepsis (seven [1%] vs six [1%]; p=0·79). Interpretation In terms of reoperation rates the sliding hip screw shows no advantage, but some groups of patients (smokers and those with displaced or base of neck fractures) might do better with a sliding hip screw than with cancellous screws. Funding National Institutes of Health, Canadian Institutes of Health Research, Stichting NutsOhra, Netherlands Organisation for Health Research and Development, Physicians\u27 Services Incorporated

eCNN: A Block-Based and Highly-Parallel CNN Accelerator for Edge Inference

Convolutional neural networks (CNNs) have recently demonstrated superior quality for computational imaging applications. Therefore, they have great potential to revolutionize the image pipelines on cameras and displays. However, it is difficult for conventional CNN accelerators to support ultra-high-resolution videos at the edge due to their considerable DRAM bandwidth and power consumption. Therefore, finding a further memory- and computation-efficient microarchitecture is crucial to speed up this coming revolution. In this paper, we approach this goal by considering the inference flow, network model, instruction set, and processor design jointly to optimize hardware performance and image quality. We apply a block-based inference flow which can eliminate all the DRAM bandwidth for feature maps and accordingly propose a hardware-oriented network model, ERNet, to optimize image quality based on hardware constraints. Then we devise a coarse-grained instruction set architecture, FBISA, to support power-hungry convolution by massive parallelism. Finally,we implement an embedded processor---eCNN---which accommodates to ERNet and FBISA with a flexible processing architecture. Layout results show that it can support high-quality ERNets for super-resolution and denoising at up to 4K Ultra-HD 30 fps while using only DDR-400 and consuming 6.94W on average. By comparison, the state-of-the-art Diffy uses dual-channel DDR3-2133 and consumes 54.3W to support lower-quality VDSR at Full HD 30 fps. Lastly, we will also present application examples of high-performance style transfer and object recognition to demonstrate the flexibility of eCNN.Comment: 14 pages; appearing in IEEE/ACM International Symposium on Microarchitecture (MICRO), 201

The CCCTC-Binding Factor (CTCF) of Drosophila Contributes to the Regulation of the Ribosomal DNA and Nucleolar Stability

In the repeat array of ribosomal DNA (rDNA), only about half of the genes are actively transcribed while the others are silenced. In arthropods, transposable elements interrupt a subset of genes, often inactivating transcription of those genes. Little is known about the establishment or separation of juxtaposed active and inactive chromatin domains, or preferential inactivation of transposable element interrupted genes, despite identity in promoter sequences. CTCF is a sequence-specific DNA binding protein which is thought to act as a transcriptional repressor, block enhancer-promoter communication, and delimit juxtaposed domains of active and inactive chromatin; one or more of these activities might contribute to the regulation of this repeated gene cluster. In support of this hypothesis, we show that the Drosophila nucleolus contains CTCF, which is bound to transposable element sequences within the rDNA. Reduction in CTCF gene activity results in nucleolar fragmentation and reduced rDNA silencing, as does disruption of poly-ADP-ribosylation thought to be necessary for CTCF nucleolar localization. Our data establish a role for CTCF as a component necessary for proper control of transposable element-laden rDNA transcription and nucleolar stability

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Band Edge Energies and Excitonic Transition Probabilities of Colloidal CsPbX₃ (X = Cl, Br, I) Perovskite Nanocrystals

Colloidal CsPbX₃ (X = Cl, Br, and I) nanocrystals have recently emerged as preferred materials for light-emitting diodes, along with opportunities for photovoltaic applications. Such applications rely on the nature of valence and conduction band edges and optical transitions across these edges. Here we elucidate how halide compositions control both of these correlated parameters of CsPbX₃ nanocrystals. Cyclic voltammetry shows that the valence band maximum (VBM) shifts significantly to higher energies by 0.80 eV, from X = Cl to Br to I, whereas the shift in the conduction band minimum (CBM) is small (0.19 eV) but systematic. Halides contribute more to the VBM, but their contribution to the CBM is also not negligible. Excitonic transition probabilities for both absorption and emission of visible light decrease probably because of the increasing dielectric constant from X = Cl to Br to I. These band edge properties will help design suitable interfaces in both devices and heterostructured nanocrystals

Defect-Mediated Electron–Hole Separation in Colloidal Ag₂S–AgInS₂ Hetero Dimer Nanocrystals Tailoring Luminescence and Solar Cell Properties

Nanoscale heterojunctions with type-II band alignment can efficiently separate a photogenerated electron–hole pair, and therefore find applications in solar cells and photocatalysis. Here, we prepare a nanojunction in the form of Ag₂S–AgInS₂ hetero dimer nanocrystal that does not contain toxic Cd and Pb. A combination of photophysics, cyclic voltammetry, and quantum dot-sensitized solar cell properties shows that the junction/interface has a type-I band alignment, but still electron–hole separation takes place with efficacy across the interface because of defect states. The electron gets localized in a defect state within the AgInS₂ part, and the hole resides in the Ag₂S part of the hetero dimer nanocrystal. This type-II-like defect-mediated electron–hole separation, irrespective of the nature interfacial band alignment, is an interesting phenomenon, and can be utilized to tune optoelectronic properties of heterostructured nanocrystals. For example, very long (13 μS) photoluminescence lifetime has been observed for Ag₂S–AgInS₂ hetero dimer nanocrystals because of this defect-mediated spatial separation of electron and hole wave functions, which in turn improve the solar cell efficiency by more than 3 times as compared to that of AgInS₂ nanocrystals