The geographic distribution of onchocerciasis in the 20 participating countries of the African Programme for Onchocerciasis Control:(2) pre-control endemicity levels and estimated number infected

BACKGROUND: The original aim of the African Programme for Onchocerciasis Control (APOC) was to control onchocerciasis as a public health problem in 20 African countries. In order to identify all high risk areas where ivermectin treatment was needed to achieve control, APOC used Rapid Epidemiological Mapping of Onchocerciasis (REMO). REMO involved spatial sampling of villages to be surveyed, and examination of 30 to 50 adults per village for palpable onchocercal nodules. REMO has now been virtually completed and we report the results in two articles. A companion article reports the delineation of high risk areas based on expert analysis. The present article reports the results of a geostatistical analysis of the REMO data to map endemicity levels and estimate the number infected. METHODS: A model-based geostatistical analysis of the REMO data was undertaken to generate high-resolution maps of the predicted prevalence of nodules and of the probability that the true nodule prevalence exceeds the high risk threshold of 20%. The number infected was estimated by converting nodule prevalence to microfilaria prevalence, and multiplying the predicted prevalence for each location with local data on population density. The geostatistical analysis included the nodule palpation data for 14,473 surveyed villages. RESULTS: The generated map of onchocerciasis endemicity levels, as reflected in the prevalence of nodules, is a significant advance with many new endemic areas identified. The prevalence of nodules was > 20% over an area of 2.5 million km2 with an estimated population of 62 million people. The results were consistent with the delineation of high risk areas of the expert analysis except for borderline areas where the prevalence fluctuated around 20%. It is estimated that 36 million people would have been infected in the APOC countries by 2011 if there had been no ivermectin treatment. CONCLUSIONS: The map of onchocerciasis endemicity levels has proven very valuable for onchocerciasis control in the APOC countries. Following the recent shift to onchocerciasis elimination, the map continues to play an important role in planning treatment, evaluating impact and predicting treatment end dates in relation to local endemicity levels

SQCD: A Geometric Apercu

We take new algebraic and geometric perspectives on the old subject of SQCD. We count chiral gauge invariant operators using generating functions, or Hilbert series, derived from the plethystic programme and the Molien-Weyl formula. Using the character expansion technique, we also see how the global symmetries are encoded in the generating functions. Equipped with these methods and techniques of algorithmic algebraic geometry, we obtain the character expansions for theories with arbitrary numbers of colours and flavours. Moreover, computational algebraic geometry allows us to systematically study the classical vacuum moduli space of SQCD and investigate such structures as its irreducible components, degree and syzygies. We find the vacuum manifolds of SQCD to be affine Calabi-Yau cones over weighted projective varieties.Comment: 49 pages, 1 figur

The immune cell landscape in kidneys of patients with lupus nephritis.

Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies

The FUN30 Chromatin Remodeler, Fft3, Protects Centromeric and Subtelomeric Domains from Euchromatin Formation

The chromosomes of eukaryotes are organized into structurally and functionally discrete domains. This implies the presence of insulator elements that separate adjacent domains, allowing them to maintain different chromatin structures. We show that the Fun30 chromatin remodeler, Fft3, is essential for maintaining a proper chromatin structure at centromeres and subtelomeres. Fft3 is localized to insulator elements and inhibits euchromatin assembly in silent chromatin domains. In its absence, euchromatic histone modifications and histone variants invade centromeres and subtelomeres, causing a mis-regulation of gene expression and severe chromosome segregation defects. Our data strongly suggest that Fft3 controls the identity of chromatin domains by protecting these regions from euchromatin assembly

Uncertainty driven pooling network for microvessel segmentation in routine histology images

Lymphovascular invasion (LVI) and tumor angiogenesis are correlated with metastasis, cancer recurrence and poor patient survival. In most of the cases, the LVI quantification and angiogenic analysis is based on microvessel segmentation and density estimation in immunohistochemically (IHC) stained tissues. However, in routine H&E stained images, the microvessels display a high level of heterogeneity in terms of size, shape, morphology and texture which makes microvessel segmentation a non-trivial task. Manual delineation of microvessels for biomarker analysis is labor-intensive, time consuming, irreproducible and can suffer from subjectivity among pathologists. Moreover, it is often beneficial to account for the uncertainty of a prediction when making a diagnosis. To address these challenges, we proposed a framework for microvessel segmentation in H&E stained histology images. The framework extends DeepLabV3+ by using an improved dice coefficient based custom loss function and also incorporating an uncertainty prediction mechanism. The proposed method uses an aligned Xception model, followed by atrous spatial pyramid pooling for feature extraction at multiple scales. This architecture counters the challenge of segmenting blood vessels of varying morphological appearance. To incorporate uncertainty, random transformations are introduced at test time for a superior segmentation result and simultaneous uncertainty map generation, highlighting ambiguous regions. The method is evaluated using 1167 images of size 512×512 pixels, extracted from 13 WSIs of oral squamous cell carcinoma (OSCC) tissue at 20x magnification. The proposed net-work achieves state-of-the-art performance compared to current semantic segmentation deep neural networks (FCN-8, U-Net, SegNet and DeepLabV3+)

Structure-Function Analysis of Human TYW2 Enzyme Required for the Biosynthesis of a Highly Modified Wybutosine (yW) Base in Phenylalanine-tRNA

Posttranscriptional modifications are critical for structure and function of tRNAs. Wybutosine (yW) and its derivatives are hyper-modified guanosines found at the position 37 of eukaryotic and archaeal tRNAPhe. TYW2 is an enzyme that catalyzes α-amino-α-carboxypropyl transfer activity at the third step of yW biogenesis. Using complementation of a ΔTYW2 strain, we demonstrate here that human TYW2 (hTYW2) is active in yeast and can synthesize the yW of yeast tRNAPhe. Structure-guided analysis identified several conserved residues in hTYW2 that interact with S-adenosyl-methionine (AdoMet), and mutation studies revealed that K225 and E265 are critical residues for the enzymatic activity. We previously reported that the human TYW2 is overexpressed in breast cancer. However, no difference in the tRNAPhe modification status was observed in either normal mouse tissue or a mouse tumor model that overexpresses Tyw2, indicating that hTYW2 may have a role in tumorigenesis unrelated to yW biogenesis

Analysis of Locally Coupled 3D Manipulation Mappings Based on Mobile Device Motion

We examine a class of techniques for 3D object manipulation on mobile devices, in which the device's physical motion is applied to 3D objects displayed on the device itself. This "local coupling" between input and display creates specific challenges compared to manipulation techniques designed for monitor-based or immersive virtual environments. Our work focuses specifically on the mapping between device motion and object motion. We review existing manipulation techniques and introduce a formal description of the main mappings under a common notation. Based on this notation, we analyze these mappings and their properties in order to answer crucial usability questions. We first investigate how the 3D objects should move on the screen, since the screen also moves with the mobile device during manipulation. We then investigate the effects of a limited range of manipulation and present a number of solutions to overcome this constraint. This work provides a theoretical framework to better understand the properties of locally-coupled 3D manipulation mappings based on mobile device motion

HMGB2 orchestrates the chromatin landscape of senescence-associated secretory phenotype gene loci

Cellular senescence is a stable cell growth arrest that is characterized by the silencing of proliferation-promoting genes through compaction of chromosomes into senescence-associated heterochromatin foci (SAHF). Paradoxically, senescence is also accompanied by increased transcription of certain genes encoding for secreted factors such as cytokines and chemokines, known as the senescence-associated secretory phenotype (SASP). How SASP genes are excluded from SAHF-mediated global gene silencing remains unclear. In this study, we report that high mobility group box 2 (HMGB2) orchestrates the chromatin landscape of SASP gene loci. HMGB2 preferentially localizes to SASP gene loci during senescence. Loss of HMGB2 during senescence blunts SASP gene expression by allowing for spreading of repressive heterochromatin into SASP gene loci. This correlates with incorporation of SASP gene loci into SAHF. Our results establish HMGB2 as a novel master regulator that orchestrates SASP through prevention of heterochromatin spreading to allow for exclusion of SASP gene loci from a global heterochromatin environment during senescence