Ultrastructure of cytoplasmic fragments in human cleavage stage embryos

Purpose: The goal of this study was to evaluate the ultrastructure of cytoplasmic fragments along with the effect of cytoplasmic fragment and perivitelline space coarse granulation removal (cosmetic microsurgery) from embryos before embryo transfer on ART outcomes. Methods: One hundred and fifty intracytoplasmic sperm injection cycles with male factor infertility were included in this prospective study. Patients were divided into three groups of case (n = 50), sham (n = 50), and control (n = 50). Embryos with 10–50 % fragmentation were included in this study. Cosmetic microsurgery and zona assisted hatching were only performed in case and sham groups respectively. Extracted fragments were evaluated ultrastructurally by transmission electron microscopy (TEM). Rates of clinical pregnancy, live birth, miscarriage, multiple pregnancies, and congenital anomaly in the three groups were also compared. Results: Micrographs from TEM showed that mitochondria were the most abundant structures found in the fragments along with mitochondria-vesicle complexes, Golgi apparatus, primary lysosomes, and vacuoles. There were no significant differences in demographic characteristics, laboratory and clinical data, or embryo morphological features between the groups. The rate of clinical pregnancy in control, sham, and case groups had no significant differences (24, 18, and 18 %, respectively). The rates of live birth, miscarriage, multiple pregnancy, and congenital anomaly were also similar between the different groups. Conclusions: Our data demonstrated that cosmetic microsurgery on preimplantation embryos had no beneficial effect on ART outcomes in unselected groups of patients. As mitochondria are the most abundant organelles found in cytoplasmic fragments, fragment removal should be performed with more caution in embryos with moderate fragmentation

Chemical Inhibition of Wild-Type p53-Induced Phosphatase 1 (WIP1/PPM1D) by GSK2830371 Potentiates the Sensitivity to MDM2 Inhibitors in a p53-Dependent Manner

Sensitivity to MDM2 inhibitors is widely different among responsive TP53 wild-type cell lines and tumors. Understanding the determinants of MDM2 inhibitor sensitivity is pertinent for their optimal clinical application. Wild-type p53-inducible phosphatase-1 (WIP1) encoded by PPM1D, is activated, gained/amplified in a range of TP53 wild-type malignancies, and is involved in p53 stress response homeostasis. We investigated cellular growth/proliferation of TP53 wild-type and matched mutant/null cell line pairs, differing in PPM1D genetic status, in response to Nutlin-3/RG7388 ± a highly selective WIP1 inhibitor, GSK2830371. We also assessed the effects of GSK2830371 on MDM2 inhibitor-induced p53Ser15 phosphorylation, p53-mediated global transcriptional activity, and apoptosis. The investigated cell line pairs were relatively insensitive to single-agent GSK2830371. However, a non–growth-inhibitory dose of GSK2830371 markedly potentiated the response to MDM2 inhibitors in TP53 wild-type cell lines, most notably in those harboring PPM1D-activating mutations or copy number gain (up to 5.8-fold decrease in GI50). Potentiation also correlated with significant increase in MDM2 inhibitor–induced cell death endpoints that were preceded by a marked increase in a WIP1 negatively regulated substrate, phosphorylated p53Ser15, known to increase p53 transcriptional activity. Microarray-based gene expression analysis showed that the combination treatment increases the subset of early RG7388-induced p53 transcriptional target genes. These findings demonstrate that potent and selective WIP1 inhibition potentiates the response to MDM2 inhibitors in TP53 wild-type cells, particularly those with PPM1D activation or gain, while highlighting the mechanistic importance of p53Ser15 and its potential use as a biomarker for response to this combination regimen. Mol Cancer Ther; 15(3); 379–91. ©2016 AACR

Chi8: a GPU program for detecting significant interacting SNPs with the Chi-square 8-df test

BACKGROUND: Determining interacting SNPs in genome-wide association studies is computationally expensive yet of considerable interest in genomics. FINDINGS: We present a program Chi8 that calculates the Chi-square 8 degree of freedom test between all pairs of SNPs in a brute force manner on a Graphics Processing Unit. We analyze each of the seven WTCCC genome-wide association studies that have about 5000 total case and controls and 400,000 SNPs in an average of 9.6 h on a single GPU. We also study the power, false positives, and area under curve of our program on simulated data and provide a comparison to the GBOOST program. Our program source code is freely available from http://www.cs.njit.edu/usman/Chi8

Feature Cross Search via Submodular Optimization

In this paper, we study feature cross search as a fundamental primitive in feature engineering. The importance of feature cross search especially for the linear model has been known for a while, with well-known textbook examples. In this problem, the goal is to select a small subset of features, combine them to form a new feature (called the crossed feature) by considering their Cartesian product, and find feature crosses to learn an \emph{accurate} model. In particular, we study the problem of maximizing a normalized Area Under the Curve (AUC) of the linear model trained on the crossed feature column. First, we show that it is not possible to provide an $n^{1/\log\log n}$-approximation algorithm for this problem unless the exponential time hypothesis fails. This result also rules out the possibility of solving this problem in polynomial time unless $\mathsf{P}=\mathsf{NP}$. On the positive side, by assuming the \naive\ assumption, we show that there exists a simple greedy $(1-1/e)$-approximation algorithm for this problem. This result is established by relating the AUC to the total variation of the commutator of two probability measures and showing that the total variation of the commutator is monotone and submodular. To show this, we relate the submodularity of this function to the positive semi-definiteness of a corresponding kernel matrix. Then, we use Bochner's theorem to prove the positive semi-definiteness by showing that its inverse Fourier transform is non-negative everywhere. Our techniques and structural results might be of independent interest.Comment: Accepted to ESA 2021. Authors are ordered alphabeticall

Synthetic data shuffling accelerates the convergence of federated learning under data heterogeneity

In federated learning, data heterogeneity is a critical challenge. A straightforward solution is to shuffle the clients' data to homogenize the distribution. However, this may violate data access rights, and how and when shuffling can accelerate the convergence of a federated optimization algorithm is not theoretically well understood. In this paper, we establish a precise and quantifiable correspondence between data heterogeneity and parameters in the convergence rate when a fraction of data is shuffled across clients. We prove that shuffling can quadratically reduce the gradient dissimilarity with respect to the shuffling percentage, accelerating convergence. Inspired by the theory, we propose a practical approach that addresses the data access rights issue by shuffling locally generated synthetic data. The experimental results show that shuffling synthetic data improves the performance of multiple existing federated learning algorithms by a large margin

Comprehensive Analysis of Coronal Mass Ejection Mass and Energy Properties Over a Full Solar Cycle

The LASCO coronagraphs, in continuous operation since 1995, have observed the evolution of the solar corona and coronal mass ejections (CMEs) over a full solar cycle with high quality images and regular cadence. This is the first time that such a dataset becomes available and constitutes a unique resource for the study of CMEs. In this paper, we present a comprehensive investigation of the solar cycle dependence on the CME mass and energy over a full solar cycle (1996-2009) including the first in-depth discussion of the mass and energy analysis methods and their associated errors. Our analysis provides several results worthy of further studies. It demonstrates the possible existence of two event classes; 'normal' CMEs reaching constant mass for $>10$ R_{\sun} and 'pseudo' CMEs which disappear in the C3 FOV. It shows that the mass and energy properties of CME reach constant levels, and therefore should be measured, only above \sim 10 R_\sun. The mass density (g/R_\sun^2) of CMEs varies relatively little ($<$ order of magnitude) suggesting that the majority of the mass originates from a small range in coronal heights. We find a sudden reduction in the CME mass in mid-2003 which may be related to a change in the electron content of the large scale corona and we uncover the presence of a six-month periodicity in the ejected mass from 2003 onwards.Comment: 42 pages, 16 figures, To appear in Astrophysical Journa

The Pathological Chabges of Male Goat Infected by Haemonclus contortus (Rudolphi, 1803)

Pathological aspects of abomasum, intestine, liver, spleen, heart , bone marrow and lymphnode caused by H. contortus were examined. Twelve bucks. six to eight month of ages were divided into 4 groups. which were infected by 0 (DO). 200 (D200). 400 (D400). and 600 (D600) h r d stage larvae of H. contortus. Larvae was administered orally 3 times a week for 8 weeks. Patological aspects including macro and microscopic findings were studied for enteritis, abomasitis, extramedullary haemopoietic centre forming, germinal centre activity of spleen and lymphnode and activity of bone marrow

Fuchs Heterochromic Iridocyclitis-Associated Glaucoma: A Retrospective Comparison of Primary Ahmed Glaucoma Valve implantation and Trabeculectomy with MMC

Purpose: To compare the safety and efficacy of a primary trabeculectomy with mitomycin C (T) and an Ahmed glaucoma valve (AGV) implantation in patients with Fuchs heterochromic iridocyclitis (FHIC) related glaucoma, a rare complication of an uncommon form of uveitis. Design: Retrospective comparative case series. Method: Twenty-six patients with uncontrolled FHIC-associated glaucoma received T (n=12) or an AGV (n=14). Primary outcome measures were the surgical success defined as IOP ≤ 21 mmHg and decreased ≥ 20% from the baseline and no secondary glaucoma surgery. Secondary outcome measures were the number of glaucoma medications, complications, best corrected visual acuity (BCVA), and intraocular pressure. Results: The follow-up (mean±SD) was 34.0±17.7 in T and 33.4±18.6 months in AGV (p = 0.837). The cumulative probability of success rate at the final follow-up at three years was 41.7% for T and 85.7% for AGV. There was no significant difference in complications between the two groups (P>0.05). The mean preoperative IOP in T was 23.4±3.3 mmHg and 21.6±5.2 mmHg at the final visit (P= 0.041). In AGV, the preoperative IOP was 24±7.8 and 17.1±2.6 mmHg at the final visit (P= 0.003), respectively. AGV had a significantly lower average IOP at the final follow-up visit compared to T (P= 0.018). The number of glaucoma medications at baseline was 3.3±0.5 in T and 3±0.6 in AGV (P= 0.233). This decreased significantly to 2.4±1.0 and 1.7±0.6 at the final follow-up (P= 0.008 and 0.002, respectively). Patients in AGV needed fewer glaucoma medications (P= 0.041). BCVA was equal in both groups and did not change (p>0.05). Conclusion: Primary AGV had a higher success rate than T in the management of FHIC-associated glaucoma. The risk of cataract formation and progression was significantly higher following T in these patients