TREX1 is expressed by microglia in normal human brain and increases in regions affected by ischemia

BACKGROUND: Mutations in the three-prime repair exonuclease 1 (TREX1) gene have been associated with neurological diseases, including Retinal Vasculopathy with Cerebral Leukoencephalopathy (RVCL). However, the endogenous expression of TREX1 in human brain has not been studied. METHODS: We produced a rabbit polyclonal antibody (pAb) to TREX1 to characterize TREX1 by Western blotting (WB) of cell lysates from normal controls and subjects carrying an RVCL frame-shift mutation. Dual staining was performed to determine cell types expressing TREX1 in human brain tissue. TREX1 distribution in human brain was further evaluated by immunohistochemical analyses of formalin-fixed, paraffin-embedded samples from normal controls and patients with RVCL and ischemic stroke. RESULTS: After validating the specificity of our anti-TREX1 rabbit pAb, WB analysis was utilized to detect the endogenous wild-type and frame-shift mutant of TREX1 in cell lysates. Dual staining in human brain tissues from patients with RVCL and normal controls localized TREX1 to a subset of microglia and macrophages. Quantification of immunohistochemical staining of the cerebral cortex revealed that TREX1 CONCLUSIONS: TREX1 is expressed by a subset of microglia in normal human brain, often in close proximity to the microvasculature, and increases in the setting of ischemic lesions. These findings suggest a role for TREX

Natural products against toxoplasma gondii and Leishmania tropica

Thesis. M.Sc. American University of Beirut. Department of Experimental Pathology, Immunology and Microbiology. Faculty of Medicine 2019. W 4 H154n 2019; Advisor: Dr. Hiba El Hajj, PhD, Associate Professor, Department of Experimental Pathology, Microbiology and Immunology ; Co-advisor: Dr. Antoine Abou Fayad, PhD, Assistant Professor, Department of Experimental Pathology, Microbiology and Immunology ; Committee members: Dr. Ghassan M. Matar, PhD, Professor and Chairperson, Department of Experimental Pathology, Microbiology and Immunology ; Nisrine Rizk, MD, Department of Internal Medicine.Includes bibliographical references (leaves 74-87)Parasitoses, including toxoplasmosis and cutaneous leishmaniasis, are infections that still pose health problems, which raise from moderate to even fatal outcomes, especially in low and middle income countries. Toxoplasmosis is caused by Toxoplasma gondii, a highly prevalent protozoan parasite, of medical, veterinary and economic impact. Following an acute infection, the disease evolves, under the tight control of the host immune system, into a persistent chronic toxoplasmosis (CT). In immunocompetent hosts, CT manifests as latent tissue cysts that impact host behavior and correlate with several neuro-pathologies and cancers. In immunocompromised patients, reactivation of CT can become life threatening. Several drugs are available to control acute toxoplasmosis (AT); however, they associate with side effects. Currently, there is no approved therapy affecting the viability and number of tissue cysts in CT, which urges the need for novel therapeutic strategies. Cutaneous leishmaniasis (CL) is a neglected tropical disease, classified by the WHO as one of the most uncontrolled spreading diseases with no recent advances in its treatment. CL was lately introduced to Lebanon, following the large-scale displacement of refugees from endemic Syria. Leishmania Tropica represents the predominant etiologic agent of CL in our region. Therapies against CL include physical and chemical methods. Among topical treatments, paromomycin and intralesional injections of pentavalent antimonials are widely used but seem to be less effective against L. tropica species. In addition, these compounds have several limitations, including the need for repetitive painful injections, high cost, poor availability, and known systemic toxicity. Therefore, it is of high interest to find novel drugs against CL. Microorganisms are well known for their ability to produce secondary metabolites. A significant number of clinically utilized medications are based on these natural products or their inspired derivatives. Actinomycetes are mainly soil d

The Conceptual Politics of Democracy Promotion: The Venezuela Case

In 1970 Giovanni Sartori articulated what he saw as the greatest challenge to political science in an increasingly globalized worldconceptual stretching. Sartori was referring to the traveling of western concepts eastward and proposed the use of a conceptual ladder to help inform the decisions political scientists make regarding the concepts they wish to travel. This paper seeks to push the boundaries of Sartori’s critique beyond academia to include policy; a subject where a dynamic and informative relationship between academia and policy should exist, but are instead faced with a one-dimensional arrangement. In that vein, this paper consists of three main parts. The first employs a brief historiography of the conceptual debate between, largely, Schumpeterian and Dahlian definitions of democracy where two main schools of thought will be sketched. The second evokes Venezuela's recent political history to illustrate how the United States Government has, at different times, employed various definitions, and standards, of democracy to describe the Venezuelan regime. The third seeks to establish how American oscillation between standards erodes the value reference point of democracy and draw out the implications of this. In particular, the third part unpacks what this erosion should mean moving forward for academics engaged in the conceptual politics of democracy. In sum, the instrumentalizing of the ambiguity of the concept—democracy—by oscillating between Schumpeterian and Dahlian standards devalues the concept. And unless the academic debate regarding democratic theory begins to account for this devaluation, democracy may well be emptied of its substance.

Utility of EUS following endoscopic polypectomy of high-risk rectosigmoid lesions

BACKGROUND: The utility of endoscopic ultrasound (EUS) compared with standard white light endoscopy (WLE) following recent polypectomy of high-risk colorectal polyps is unknown. OBJECTIVE: To assess the incremental yield of EUS after endoscopic polypectomy of a high-risk rectal lesion. DESIGN: Retrospective cohort. SETTING: Tertiary referral center. MATERIALS AND METHODS: Patients referred for EUS following attempted endoscopic resection of a high-risk rectal neoplasm, defined as a tubulovillous adenoma, tubular adenoma with high-grade dysplasia, carcinoid, carcinoma in-situ or adenocarcinoma (CA). INTERVENTIONS: Sigmoidoscopy ± mucosal biopsy and EUS ± fine-needle aspiration (FNA) to evaluate for: (1) Residual polyp/tumor in the rectal wall or (2) peritumoral adenopathy. MAIN OUTCOME: Sensitivity and specificity for detection of residual neoplasia for WLE ± biopsy (WLE/BX) and EUS ± FNA for cancer (CA group) or benign disease (non-CA group). The incremental yield of EUS defined as: (1) Residual intramural neoplasia not present on WLE ± BX and; (2) abnormal peritumoral adenopathy. RESULTS: A total of 70 patients (mean age 64 ± 11 years, 61% male) with a final diagnosis of CA (n = 38) and non-CA (n = 32) were identified. There was no difference between the sensitivity and specificity of WLE alone (65% and 84%), WLE with biopsy (71% and 95%), and EUS (59% and 84%), for the detection of residual neoplasia (P > 0.05 for all). EUS identified 3 masses missed by WLE, all in the CA group. A malignant (n = 2) or benign (n = 3) node was identified in 5 (13%) CA patients; EUS-FNA in two showed residual malignancy in one and a reactive lymph node (LN) in one. No LNs were identified in the non-CA patients. LIMITATIONS: Retrospective design, incomplete follow-up in some patients. CONCLUSION: Following endoscopic polypectomy of high-risk rectal neoplasia, the incremental yield of EUS compared with WLE/BX for evaluation of residual disease appears limited, especially in patients with benign disease

Artificial Intelligence-Based Methods for Fusion of Electronic Health Records and Imaging Data

Healthcare data are inherently multimodal, including electronic health records (EHR), medical images, and multi-omics data. Combining these multimodal data sources contributes to a better understanding of human health and provides optimal personalized healthcare. Advances in artificial intelligence (AI) technologies, particularly machine learning (ML), enable the fusion of these different data modalities to provide multimodal insights. To this end, in this scoping review, we focus on synthesizing and analyzing the literature that uses AI techniques to fuse multimodal medical data for different clinical applications. More specifically, we focus on studies that only fused EHR with medical imaging data to develop various AI methods for clinical applications. We present a comprehensive analysis of the various fusion strategies, the diseases and clinical outcomes for which multimodal fusion was used, the ML algorithms used to perform multimodal fusion for each clinical application, and the available multimodal medical datasets. We followed the PRISMA-ScR guidelines. We searched Embase, PubMed, Scopus, and Google Scholar to retrieve relevant studies. We extracted data from 34 studies that fulfilled the inclusion criteria. In our analysis, a typical workflow was observed: feeding raw data, fusing different data modalities by applying conventional machine learning (ML) or deep learning (DL) algorithms, and finally, evaluating the multimodal fusion through clinical outcome predictions. Specifically, early fusion was the most used technique in most applications for multimodal learning (22 out of 34 studies). We found that multimodality fusion models outperformed traditional single-modality models for the same task. Disease diagnosis and prediction were the most common clinical outcomes (reported in 20 and 10 studies, respectively) from a clinical outcome perspective.Comment: Accepted in Nature Scientific Reports. 20 page

Breaking Stress Criterion That Changes Everything We Know about Materials Failure

The perennial deficiencies of the failure models in the materials field have profoundly and significantly impacted all associated technical fields that depend on accurate failure predictions. The heart of this study is the presentation of a methodology that identifies a newly derived one-parameter criterion as the only general failure theory for noncompressible, homogeneous, and isotropic materials subjected to multiaxial states of stress and various boundary conditions, providing the solution to this longstanding problem. This theory is the counterpart and companion piece to the theory of elasticity and is in a formalism that is suitable for broad application. Utilizing advanced finite-element analysis, the maximum internal breaking stress corresponding to the maximum applied external force is identified as a unified and universal material failure criterion for determining the structural capacity of any system, regardless of its geometry or architecture. A comparison between the proposed criterion and methodology against design codes reveals that current provisions may underestimate the structural capacity by 2.17 times or overestimate the capacity by 2.096 times. It also shows that existing standards may underestimate the structural capacity by 1.4 times or overestimate the capacity by 2.49 times. The proposed failure criterion and methodology will pave the way for a new era in designing unconventional structural systems composed of unconventional materials. © 2023 American Society of Civil Engineers

International Liability for Damages Caused by Satellites and other Space Vehicles in light of Outer Space Treaties

The research aims to describe the provisions of international liability of the damage caused by satellites and other spacecraft as well as addressing the definition of outer space and its nature. Then, it covers the role of the United Nations (UN) in its organization through adoption of several resolutions and agreements detailing the provisions that are relevant to the registration of launched vehicles into space and the rules of liability resulting from damages that may be caused. In conclusion, the study holds that states bear an absolute liability when damages occur on the ground or while the aircraft is in the air or by applying fault-based approach in the other cases. Consequently, there are several flaws in the liability system, most notably the absence of mandatory and effective dispute settlement mechanisms and the failure to extend compensation for all affected entities

The Mechanical Modeling of Liquid Crystal Elastomers

Liquid crystal elastomers are exotic anisotropic materials endowing the energetic effects of liquid crystals to elastomeric rubber-like networks. Applications of these materials are advancing over the past 20 years, with the most recent being in soft robotics and artificial muscles. The unique properties, which make these materials particularly suitable to the aforementioned applications, is their coupled mechanical phenomena. This allows for configurable soft behavior, in addition to the thermal and light activation, thus causing large spontaneous strains in these materials. This dissertation’s aim is to investigate the root physical phenomena causing the material’s mechanical behavior in addition to accurately modeling its mechanical response. Accordingly, a review on the Neoclassical free energy model including liquid crystals, the resulting soft elasticity, and improvements in the literature is first explored. Additionally, a derivation of the Neoclassical free energy density using the tools of statistical mechanics is included. Afterwards, a framework with the ca-pability of handling the kinematic descriptors of liquid crystal elastomers is developed, with the main difference from classical mechanics being the balance of angular momentum. The Clausius-Duhem inequality is utilized to obtain two thermodynamically consistent theories. The first models a viscoelastic medium with a single viscous director which is claimed to be suitable for monodomain liquid crystal elastomers. The second possesses a pair of viscously evolving orthogonal unit vectors along with two viscous scalar variables describing a biaxial microstructure, which is claimed to be suitable for polydomain liquid crystal elastomers. The first model is then numerically implemented into a finite element solution of the governing equations for the class of problems with no director gradients. Following that, the aforementioned model’s capabilities in capturing the material’s behavior are demonstrated through three representative examples. Additionally, an important point that is shown through the examples is that a material point calculation is insufficient in modeling the behavior of liquid crystal elastomers. Solving the boundary value problem is essential for prediction of the correct behavior. Moreover, the difficulties in the implementation and finite element analysis of liquid crystal elastomers are tackled