58 research outputs found
Why my photos look sideways or upside down? Detecting Canonical Orientation of Images using Convolutional Neural Networks
Image orientation detection requires high-level scene understanding. Humans
use object recognition and contextual scene information to correctly orient
images. In literature, the problem of image orientation detection is mostly
confronted by using low-level vision features, while some approaches
incorporate few easily detectable semantic cues to gain minor improvements. The
vast amount of semantic content in images makes orientation detection
challenging, and therefore there is a large semantic gap between existing
methods and human behavior. Also, existing methods in literature report highly
discrepant detection rates, which is mainly due to large differences in
datasets and limited variety of test images used for evaluation. In this work,
for the first time, we leverage the power of deep learning and adapt
pre-trained convolutional neural networks using largest training dataset
to-date for the image orientation detection task. An extensive evaluation of
our model on different public datasets shows that it remarkably generalizes to
correctly orient a large set of unconstrained images; it also significantly
outperforms the state-of-the-art and achieves accuracy very close to that of
humans
The SIRT1 Deacetylase Suppresses Intestinal Tumorigenesis and Colon Cancer Growth
Numerous longevity genes have been discovered in model organisms and altering their function results in prolonged lifespan. In mammals, some have speculated that any health benefits derived from manipulating these same pathways might be offset by increased cancer risk on account of their propensity to boost cell survival. The Sir2/SIRT1 family of NAD+-dependent deacetylases is proposed to underlie the health benefits of calorie restriction (CR), a diet that broadly suppresses cancer in mammals. Here we show that CR induces a two-fold increase SIRT1 expression in the intestine of rodents and that ectopic induction of SIRT1 in a β-catenin-driven mouse model of colon cancer significantly reduces tumor formation, proliferation, and animal morbidity in the absence of CR. We show that SIRT1 deacetylates β-catenin and suppresses its ability to activate transcription and drive cell proliferation. Moreover, SIRT1 promotes cytoplasmic localization of the otherwise nuclear-localized oncogenic form of β-catenin. Consistent with this, a significant inverse correlation was found between the presence of nuclear SIRT1 and the oncogenic form of β−catenin in 81 human colon tumor specimens analyzed. Taken together, these observations show that SIRT1 suppresses intestinal tumor formation in vivo and raise the prospect that therapies targeting SIRT1 may be of clinical use in β−catenin-driven malignancies
In Vivo Fate and Activity of Second- versus Third-Generation CD19-Specific CAR-T Cells in B Cell Non-Hodgkin's Lymphomas
Second-generation (2G) chimeric antigen receptors (CARs) targeting CD19 are highly active against B cell malignancies, but it is unknown whether any of the costimulatory domains incorporated in the CAR have superior activity to others. Because CD28 and 4-1BB signaling activate different pathways, combining them in a single third-generation (3G) CAR may overcome the limitations of each individual costimulatory domain. We designed a clinical trial in which two autologous CD19-specific CAR-transduced T cell products (CD19.CARTs), 2G (with CD28 only) and 3G (CD28 and 4-1BB), were infused simultaneously in 16 patients with relapsed or refractory non-Hodgkin's lymphoma. 3G CD19.CARTs had superior expansion and longer persistence than 2G CD19.CARTs. This difference was most striking in the five patients with low disease burden and few circulating normal B cells, in whom 2G CD19.CARTs had limited expansion and persistence and correspondingly reduced area under the curve. Of the 11 patients with measurable disease, three achieved complete responses and three had partial responses. Cytokine release syndrome occurred in six patients but was mild, and no patient required anti-IL-6 therapy. Hence, 3G CD19.CARTs combining 4-1BB with CD28 produce superior CART expansion and may be of particular value when treating low disease burden in patients whose normal B cells are depleted by prior therapy. CD19.CAR-T cells are highly active against B cell malignancies, but the optimal CAR structure is controversial. Ramos et al. show that combining 4-1BB and CD28 endodomains produces superior CD19-CAR-T cell expansion and persistence compared to CD28 alone and that these cells are clinically effective and safe in aggressive lymphomas
The plant-based immunomodulator curcumin as a potential candidate for the development of an adjunctive therapy for cerebral malaria
The clinical manifestations of cerebral malaria (CM) are well correlated with underlying major pathophysiological events occurring during an acute malaria infection, the most important of which, is the adherence of parasitized erythrocytes to endothelial cells ultimately leading to sequestration and obstruction of brain capillaries. The consequent reduction in blood flow, leads to cerebral hypoxia, localized inflammation and release of neurotoxic molecules and inflammatory cytokines by the endothelium. The pharmacological regulation of these immunopathological processes by immunomodulatory molecules may potentially benefit the management of this severe complication. Adjunctive therapy of CM patients with an appropriate immunomodulatory compound possessing even moderate anti-malarial activity with the capacity to down regulate excess production of proinflammatory cytokines and expression of adhesion molecules, could potentially reverse cytoadherence, improve survival and prevent neurological sequelae. Current major drug discovery programmes are mainly focused on novel parasite targets and mechanisms of action. However, the discovery of compounds targeting the host remains a largely unexplored but attractive area of drug discovery research for the treatment of CM. This review discusses the properties of the plant immune-modifier curcumin and its potential as an adjunctive therapy for the management of this complication
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Cutaneous T-cell lymphoma-associated Leser-Trélat sign: report and world literature review
Background: The sign of Leser-Trélat is characterizedby the sudden appearance of seborrheic keratosesassociated with an underlying malignancy. Objectives:An elderly man who developed multiple new-onsetseborrheic keratoses temporally associated witha diagnosis of mycosis fungoides is described andlymphoma-associated Leser-Trélat sign is reviewed.Methods: Pubmed was used to search the followingterms: cutaneous T-cell lymphoma, Leser-Trélat,leukemia, lymphoma, mycosis fungoides, and Sézarysyndrome. Papers with these terms and referencescited within these papers were reviewed. Results:An 84-year-old man developed multiple seborrheickeratoses temporally associated with a diagnosisof mycosis fungoides is presented. He was treatedwith bexarotene and achieved clinical remission;the number of seborrheic keratoses also decreased.Lymphoma-associated Leser-Trélat sign has beenobserved not only with mycosis fungoides but alsoother lymphomas and leukemias. Conclusions: Thesign of Leser-Trélat is predominantly associated withsolid organ adenocarcinomas. Albeit less common, aneruptive onset of seborrheic keratoses can also occurin association with hematopoietic malignancies
Adult Atopic Dermatitis with Comorbid Atopic Disease is Associated with Increased Risk of Infections: A Population-Based Cross-Sectional Study
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Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene polymorphism in pulmonary tuberculosis in the Indian population
A variant of the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene is known to be associated with susceptibility to autoimmune diseases and bacterial infections as it acts as an important regulator of T-cell activation. The objective of this study was to evaluate whether PTPN22-C1858T polymorphism is associated with the resistance to pulmonary tuberculosis (PTB). Single-nucleotide polymorphism of PTPN22-C1858T (rs2476601) was genotyped in 124 patients with PTB and 130 healthy controls from India using restriction fragment length polymorphism and direct sequencing of the amplified DNA. The frequencies of genotypes CC, CT, and TT were 100%, 0%, and 0%, respectively, in PTB; and 99.2%, 0.8% and 0%, respectively, in healthy control individuals. These values did not differ significantly between the patients and controls. The mutant allele C1858T was found to be a rare allele in Indian population
Comparison of microalgae cultivation in photobioreactor, open raceway pond, and a two-stage hybrid system
In the wake of intensive fossil fuel usage and CO2 accumulation in the environment, research is targeted towards sustainable alternate bioenergy that can suffice the growing need for fuel and also that leaves a minimal carbon footprint. Oil production from microalgae can potentially be carried out more efficiently, leaving a smaller footprint and without competing for arable land or biodiverse landscapes. However, current algae cultivation systems and lipid induction processes must be significantly improved and are threatened by contamination with other algae or algal grazers. To address this issue, we have developed an efficient two-stage cultivation system using the marine microalga Tetraselmis sp. M8. This hybrid system combines exponential biomass production in positive pressure air lift-driven bioreactors with a separate synchronized high-lipid induction phase in nutrient deplete open raceway ponds. A comparison to either bioreactor or open raceway pond cultivation system suggests that this process potentially leads to significantly higher productivity of algal lipids. Nutrients are only added to the closed bioreactors while open raceway ponds have turnovers of only a few days, thus reducing the issue of microalgal grazers
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