This paper proposes Attribute Attention Network (AANet), a new architecture that integrates person attributes and attribute attention maps into a classification framework to solve the person re-identification (re-ID) problem. Many person re-ID models typically employ semantic cues such as body parts or human pose to improve the re-ID performance. Attribute information, however, is often not utilized. The proposed AANet leverages on a baseline model that uses body parts and integrates the key attribute information in an unified learning framework. The AANet consists of a global person ID task, a part detection task and a crucial attribute detection task. By estimating the class responses of individual attributes and combining them to form the attribute attention map (AAM), a very strong discriminatory representation is constructed. The proposed AANet outperforms the best state-of-the-art method [22] using ResNet-50 by 3.36% in mAP and 3.12% in Rank-1 accuracy on DukeMTMC-reID dataset. On Market1501 dataset, AANet achieves 92.38% mAP and 95.10% Rank-1 accuracy with re-ranking, outperforming [13], another state of the art method using ResNet-152, by 1.42% in mAP and 0.47% in Rank-1 accuracy. In addition, AANet can perform person attribute prediction (e.g., gender, hair length, clothing length etc.), and localize the attributes in the query image.
Calcineurin is a Ca2؉ -and calmodulin-dependent protein phosphatase that plays a key role in animal and yeast physiology. In the yeast Saccharomyces cerevisiae, calcineurin is required for survival during several environmental stresses, including high concentrations of Na ؉ , Li ؉ , and Mn 2؉ ions and alkaline pH. One role of calcineurin under these conditions is to activate gene expression through its regulation of the Crz1p transcription factor. We have identified Hph1p as a novel substrate of calcineurin. HPH1 (YOR324C) and its homolog HPH2 (YAL028W) encode tail-anchored integral membrane proteins that interact with each other in the yeast two-hybrid assay and colocalize to the endoplasmic reticulum. Hph1p and Hph2p serve redundant roles in promoting growth under conditions of high salinity, alkaline pH, and cell wall stress. Calcineurin modifies the distribution of Hph1p within the endoplasmic reticulum and is required for full Hph1p activity in vivo. Furthermore, calcineurin directly dephosphorylates Hph1p and interacts with it through a sequence motif in Hph1p, PVIAVN. This motif is related to calcineurin docking sites in other substrates, such as NFAT and Crz1p, and is required for regulation of Hph1p by calcineurin. In contrast, Hph2p neither interacts with nor is dephosphorylated by calcineurin. Ca 2؉ -induced Crz1p-mediated transcription is unaffected in hph1⌬ hph2⌬ mutants, and genetic analyses indicate that HPH1/HPH2 and CRZ1 act in distinct pathways downstream of calcineurin. Thus, Hph1p and Hph2p are components of a novel Ca 2؉ -and calcineurin-regulated response required to promote growth under conditions of high Na ؉ , alkaline pH, and cell wall stress.
The current standard of care for acute myeloid leukemia (AML) is largely ineffective with very high relapse rates and low survival rates, mostly due to the inability to eliminate a rare population of leukemic stem cells (LSCs) that initiate tumor growth and are resistant to standard chemotherapy. RNA-sequencing analysis on isolated LSCs confirmed C-type lectin domain family 12 member A (CLL1, also known as CLEC12A) to be highly expressed on LSCs but not on normal hematopoietic stem cells (HSCs) or other healthy organ tissues. Expression of CLL1 was consistent across different types of AML. We developed CLT030 (CLL1-ADC), an antibody-drug conjugate (ADC) based on a humanized anti-CLL1 antibody with 2 engineered cysteine residues linked covalently via a cleavable linker to a highly potent DNA-binding payload, thus resulting in a site-specific and homogenous ADC product. The ADC is designed to be stable in the bloodstream and to release its DNA-binding payload only after the ADC binds to CLL1-expressing tumor cells, is internalized, and the linker is cleaved in the lysosomal compartment. CLL1-ADC inhibits in vitro LSC colony formation and demonstrates robust in vivo efficacy in AML cell tumor models and tumor growth inhibition in the AML patient-derived xenograft model. CLL1-ADC demonstrated a reduced effect on differentiation of healthy normal human CD34 cells to various lineages as observed in an in vitro colony formation assay and in an in vivo xenotransplantation model as compared with CD33-ADC. These results demonstrate that CLL1-ADC could be an effective ADC therapeutic for the treatment of AML.
Nucleic acid detection is of paramount importance in monitoring of microbial pathogens in food safety and infectious disease diagnostic applications. To address these challenges, a rapid, cost-effective label-free technique for nucleic acid detection with minimal instrumentations is highly desired. Here, we present paper microchip to detect and quantify nucleic acid using colorimetric sensing modality. The extracted DNA from food samples of meat as well as microbial pathogens was amplified utilizing loop-mediated isothermal amplification (LAMP). LAMP amplicon was then detected and quantified on a paper microchip fabricated in a cellulose paper and a small wax chamber utilizing crystal violet dye. The affinity of crystal violet dye toward dsDNA and positive signal were identified by changing the color from colorless to purple. Using this method, detection of Sus scrofa (porcine) and Bacillus subtilis (bacteria) DNA was possible at concentrations as low as 1 pg/μL (3.43 × 10 copies/μL) and 10 pg/μL (2.2 × 10 copies/μL), respectively. This strategy can be adapted for detection of other DNA samples, with potential for development of a new breed of simple and inexpensive paper microchip at the point-of-need.
Current analyses of protein sequence/structure relationships have focused on expected similarity relationships for structurally similar proteins. To survey and explore the basis of these relationships, we present a general sequence/structure map that covers all combinations of similarity/dissimilarity relationships and provide novel energetic analyses of these relationships. To aid our analysis, we divide protein relationships into four categories: expected/unexpected similarity (S and S(?)) and expected/unexpected dissimilarity (D and D(?)) relationships. In the expected similarity region S, we show that trends in the sequence/structure relation can be derived based on the requirement of protein stability and the energetics of sequence and structural changes. Specifically, we derive a formula relating sequence and structural deviations to a parameter characterizing protein stiffness; the formula fits the data reasonably well. We suggest that the absence of data in region S(?) (high structural but low sequence similarity) is due to unfavorable energetics. In contrast to region S, region D(?) (high sequence but low structural similarity) is well-represented by proteins that can accommodate large structural changes. Our analyses indicate that there are several categories of similarity relationships and that protein energetics provide a basis for understanding these relationships.
BackgroundThe use of radiolabeled choline as a positron emission tomography (PET) agent for imaging primary tumors in the prostate has been evaluated extensively over the past two decades. There are, however, conflicting reports of its sensitivity and the relationship between choline PET imaging and disease staging is not fully understood. Moreover, relatively few studies have investigated the correlation between tracer uptake and histological tumor grade. This work quantified 18F-fluorocholine in tumor and healthy prostate tissue using pharmacokinetic modeling and stratified uptake parameters by histology grade. Additionally, the effect of scan time on the estimation of the kinetic exchange rate constants was evaluated, and the tracer influx parameters from full compartmental analysis were compared to uptake values quantified by Patlak and standardized uptake value (SUV) analyses. 18F-fluorocholine was administered as a 222 MBq bolus injection to ten patients with biopsy-confirmed prostate tumors, and dynamic PET data were acquired for 60 min. Image-derived arterial input functions were scaled by discrete blood samples, and a 2-tissue, 4-parameter model accounting for blood volume (2T4k+Vb) was used to perform fully quantitative compartmental modeling on tumor, healthy prostate, and muscle tissue. Subsequently, all patients underwent radical prostatectomy, and histological analyses were performed on the prostate specimens; kinetic parameters for tumors were stratified by Gleason score. Correlations were investigated between compartmental K 1 and K i parameters and SUV and Patlak slope; the effect of scan time on parameter bias was also evaluated.ResultsCholine activity curves in seven tumors, eight healthy prostate regions, and nine muscle regions were analyzed. Net tracer influx was generally higher in tumor relative to healthy prostate, with the values in the highest grade tumors markedly higher than those in lower grade tumors. Influx terms from Patlak and full compartmental modeling showed good correlation within individual tissue groups. Kinetic parameters calculated from the entire 60-min scan data were accurately reproduced from the first 30 min of acquired data (R 2 ≈ 0.9).ConclusionsStrong correlations were observed between K i and Patlak slope in tumor tissue, and K 1 and SUV were also correlated but to a lesser degree. Reliable estimates of all kinetic parameters can be achieved from the first 30 min of dynamic 18F-choline data. Although SUV, K 1, K i, and Patlak slope were found to be poor differentiators of low-grade tumor compared to healthy prostate tissue, they are strong indicators of aggressive disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-017-0269-0) contains supplementary material, which is available to authorized users.
End 2019, the zoonotic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), named COVID-19 for coronavirus disease 2019, is the third adaptation of a contagious virus following the severe acute respiratory syndrome coronavirus in 2002, SARS-CoV, and the Middle East respiratory syndrome virus in 2012, MERS-CoV. COVID-19 is highly infectious and virulent compared to previous outbreaks. We review sources, contagious routes, preventive measures, pandemic, outbreak, epidemiology of SARS-CoV, MERS-CoV and SARS-CoV-2 from 2002 to 2020 using a Medline search. We discuss the chronology of the three coronaviruses, the vulnerability of healthcare workers, coronaviruses on surface and in wastewater, diagnostics and cures, and measures to prevent spreading.
Recent developments of point-of-care (POC) diagnostic devices available for detecting pathogens to monitor infectious diseases that have made a massive impact in modern health care systems.
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