Fetal Testosterone and Early Autism Spectrum Disorder Related Neurodevelopmental Outcomes

Aims: Despite widely acknowledged sex bias in Autism Spectrum Disorders (ASD), the underlying mechanisms are largely unknown. The goal of this dissertation was to examine whether differences in prenatal testosterone levels are a possible mechanism underlying the observed ASD sex difference. This was accomplished through three specific aims. First, meconium was examined as a novel prenatal androgen matrix to compare androgen levels across alternate matrices obtained at the delivery time point. Second, the association between cord blood testosterone and ASD-related 12 month phenotype was estimated in a high ASD risk cohort of multiplex families. Last, we investigated the relationship between widely used antimicrobials product use with potential androgenic activity and early autistic phenotypes. Methods: Studies were based in the Early Autism Risk Longitudinal Investigation (EARLI) cohort, an enriched risk cohort following pregnant mothers who previously had a child with ASD diagnosis. Prenatal information on potential exposures, confounders, effect modifiers and two relevant biologic samples, cord blood and meconium, and early ASD-related behavioral phenotypes in the children born into the cohort were available for analysis. Results: Testosterone (T) sex difference was observed in both cord blood and meconium and there was weak correlation between cord blood and meconium androgens. Umbilical cord blood T had a weak positive association with ASD related phenotype at 12 months. We found that the association of prenatal testosterone and early ASD-related phenotype varied by the sex of older child with ASD (proband). 12 month autistic traits were unrelated to either prenatal or postpartum use of products that contain TCS or TCC. Conclusion: Meconium and cord blood were both good media to measure prenatal androgen levels may be capturing different prenatal exposure windows. The association of prenatal testosterone early ASD-related phenotype was substantially different by proband sex indicating that androgen mediated mechanisms might be more important in families with female ASD in the pedigree. We found no evidence of an association between exposure to TCS/TCC and early ASD-related phenotype.Ph.D., Epidemiology -- Drexel University, 201

Exploiting temporal information for 3D pose estimation

In this work, we address the problem of 3D human pose estimation from a sequence of 2D human poses. Although the recent success of deep networks has led many state-of-the-art methods for 3D pose estimation to train deep networks end-to-end to predict from images directly, the top-performing approaches have shown the effectiveness of dividing the task of 3D pose estimation into two steps: using a state-of-the-art 2D pose estimator to estimate the 2D pose from images and then mapping them into 3D space. They also showed that a low-dimensional representation like 2D locations of a set of joints can be discriminative enough to estimate 3D pose with high accuracy. However, estimation of 3D pose for individual frames leads to temporally incoherent estimates due to independent error in each frame causing jitter. Therefore, in this work we utilize the temporal information across a sequence of 2D joint locations to estimate a sequence of 3D poses. We designed a sequence-to-sequence network composed of layer-normalized LSTM units with shortcut connections connecting the input to the output on the decoder side and imposed temporal smoothness constraint during training. We found that the knowledge of temporal consistency improves the best reported result on Human3.6M dataset by approximately $12.2\%$ and helps our network to recover temporally consistent 3D poses over a sequence of images even when the 2D pose detector fails

Simple scheme for expanding a polarization-entangled W state by adding one photon

We propose a simple scheme for expanding a polarization-entangled W state. By mixing a single photon and one of the photons in an n-photon W state at a polarization-dependent beam splitter (PDBS), we can obtain an (n+1)-photon W state after post-selection. Our scheme also opens the door for generating n-photon W states using single photons and linear optics.Comment: 3 pages, 2 figure

A novel insight of sentinel lymph node concept based on 1-3 positive nodes in patients with pT1-2 gastric cancer

<p>Abstract</p> <p>Background</p> <p>Sentinel node (SN) biopsy has been practiced in gastric cancer in recent years, and many studies focused on the distribution of solitary lymph node metastasis (SLM) to assess the pattern of SN. In fact, there is usually more than one SN existing in gastric cancer. The distribution of SNs needs to be further re-evaluated.</p> <p>Methods</p> <p>A total of 289 patients in pT1-2 stage with 1-3 positive nodes confined to same compartment were included in this study with informed consents. The primary lesion was solitary (≤ 5.0 cm in diameter) and D2 or D3 lymph node dissection had been performed. The location of metastatic lymph nodes was analyzed retrospectively.</p> <p>Results</p> <p>Most positive nodes occurred in N1 compartment, with frequency of 79.6% to 85.7% based on site of tumor. In the lower third of stomach, no. 6 was the most common metastatic site and no. 3 was the second; the order was reversed for SLM. With increasing depth of tumor invasion, a progressively augmented nodal involvement was shown. Nearly a half appeared transverse metastasis when the tumor located at the lesser or greater curvature. Among skip metastasis, no. 7, 8a, 9 and 11p were the most common metastatic sites and the prognosis was as similar as that of patients with N1 involved only.</p> <p>Conclusions</p> <p>The 1-3 positive nodes in the same compartment should be possible SNs, and most of which are restricted in N1 in pT1-2 gastric cancer. Transversal and 2 stations lymph node metastasis are common.</p

Spatial light modulation at the nanosecond scale with an atomically thin reflector

Techniques to mold the flow of light on subwavelength scales enable fundamentally new optical systems and device applications. The realization of programmable, active optical systems with fast, tunable components is among the outstanding challenges in the field. Here, we experimentally demonstrate a few-pixel beam steering device based on electrostatic gate control of excitons in an atomically thin semiconductor with strong light-matter interactions. By combining the high reflectivity of a MoSe$_2$ monolayer with a graphene split-gate geometry, we shape the wavefront phase profile to achieve continuously tunable beam deflection with a range of 10{\deg}, two-dimensional beam steering, and switching times down to 1.6 nanoseconds. Our approach opens the door for a new class of atomically thin optical systems, such as rapidly switchable beam arrays and quantum metasurfaces operating at their fundamental thickness limit

Sensitivity to tumor development by TALEN-mediated Trp53 mutant genes in the susceptible FVB/N mice and the resistance C57BL/6 mice

Abstract Background This study was undertaken to compare the sensitivities of mice strains during tumor induction by transcription activator-like effector nucleases (TALEN)-mediated Trp53 mutant gene. Alterations of their tumorigenic phenotypes including survival rate, tumor formation and tumor spectrum, were assessed in FVB/N-Trp53em2Hwl/Korl and C57BL/6-Trp53em1Hwl/Korl knockout (KO) mice over 16weeks. Results Most of the physiological phenotypes factors were observed to be higher in FVB/N-Trp53em2Hwl/Korl KO mice than C57BL/6-Trp53em1Hwl/Korl KO mice, although there were significant differences in the body weight, immune organ weight, number of red blood cells, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count (PLT), total bilirubin (Bil-T) and glucose (Glu) levels in the KO mice relative to the wild type (WT) mice. Furthermore, numerous solid tumors were also observed in various regions of the surface skin of FVB/N-Trp53em2Hwl/Korl KO mice, but were not detected in C57BL/6-Trp53em1Hwl/Korl KO mice. The most frequently observed tumor in both the Trp53 KO mice was malignant lymphoma, while soft tissue teratomas and hemangiosarcomas were only detected in the FVB/N-Trp53em2Hwl/Korl KO mice. Conclusions Our results indicate that the spectrum and incidence of tumors induced by the TALEN-mediated Trp53 mutant gene is greater in FVB/N-Trp53em2Hwl/Korl KO mice than C57BL/6-Trp53em1Hwl/Korl KO mice over 16weeks

Therapeutic potential of CKD-506, a novel selective histone deacetylase 6 inhibitor, in a murine model of rheumatoid arthritis

Abstract Objectives Histone deacetylase (HDAC) 6 promotes inflammation. We investigated the anti-arthritic effects of CKD-506, a novel HDAC6 inhibitor, in vitro and in a murine model of arthritis as a novel treatment option for rheumatoid arthritis (RA). Methods HDAC6 was overexpressed in mouse peritoneal macrophages and RAW 264.7 cells, and the effects of a HDAC6 inhibitor CKD-506 on cytokine production and activity of NF-κB and AP-1 signaling were examined. Peripheral blood mononuclear cells (PBMCs) from RA patients and fibroblast-like synoviocytes (FLS) were activated in the presence of CKD-506. Next, regulatory T cells (Tregs) were induced from RA patients and co-cultured with healthy effector T cells (Teffs) and cell proliferation was analyzed by flow cytometry. Finally, the effects of the inhibitor on the severity of arthritis were assessed in a murine model of adjuvant-induced arthritis (AIA). Results Overexpression of HDAC6 induced macrophages to produce TNF-α and IL-6. The inhibitory effect of CKD-506 was mediated via blockade of NF-κB and AP-1 activation. HDAC6 inhibition reduced TNF-α and IL-6 production by activated RA PBMCs. CKD-506 inhibited production of MMP-1, MMP-3, IL-6, and IL-8 by activated FLS. In addition, CKD-506 inhibited proliferation of Teffs directly and indirectly by improving iTreg function. In AIA rats, oral CKD-506 improved clinical arthritis in a dose-dependent manner. A combination of sub-therapeutic CKD-506 and methotrexate exerted a synergistic effect. Conclusion The novel HDAC6 inhibitor CKD-506 suppresses inflammatoryresponses by monocytes/macrophages, improves Treg function, and ameliorates arthritis severity in a murine model of RA. Thus, CKD-506 might be a novel and effective treatment option for RA

Evaluation of top-down mass spectral identification with homologous protein sequences

BACKGROUND: Top-down mass spectrometry has unique advantages in identifying proteoforms with multiple post-translational modifications and/or unknown alterations. Most software tools in this area search top-down mass spectra against a protein sequence database for proteoform identification. When the species studied in a mass spectrometry experiment lacks its proteome sequence database, a homologous protein sequence database can be used for proteoform identification. The accuracy of homologous protein sequences affects the sensitivity of proteoform identification and the accuracy of mass shift localization. RESULTS: We tested TopPIC, a commonly used software tool for top-down mass spectral identification, on a top-down mass spectrometry data set of Escherichia coli K12 MG1655, and evaluated its performance using an Escherichia coli K12 MG1655 proteome database and a homologous protein database. The number of identified spectra with the homologous database was about half of that with the Escherichia coli K12 MG1655 database. We also tested TopPIC on a top-down mass spectrometry data set of human MCF-7 cells and obtained similar results. CONCLUSIONS: Experimental results demonstrated that TopPIC is capable of identifying many proteoform spectrum matches and localizing unknown alterations using homologous protein sequences containing no more than 2 mutations