This Looks Like Those: Illuminating Prototypical Concepts Using Multiple Visualizations

We present ProtoConcepts, a method for interpretable image classification combining deep learning and case-based reasoning using prototypical parts. Existing work in prototype-based image classification uses a ``this looks like that'' reasoning process, which dissects a test image by finding prototypical parts and combining evidence from these prototypes to make a final classification. However, all of the existing prototypical part-based image classifiers provide only one-to-one comparisons, where a single training image patch serves as a prototype to compare with a part of our test image. With these single-image comparisons, it can often be difficult to identify the underlying concept being compared (e.g., ``is it comparing the color or the shape?''). Our proposed method modifies the architecture of prototype-based networks to instead learn prototypical concepts which are visualized using multiple image patches. Having multiple visualizations of the same prototype allows us to more easily identify the concept captured by that prototype (e.g., ``the test image and the related training patches are all the same shade of blue''), and allows our model to create richer, more interpretable visual explanations. Our experiments show that our ``this looks like those'' reasoning process can be applied as a modification to a wide range of existing prototypical image classification networks while achieving comparable accuracy on benchmark datasets

Cicatricial Alopecia

Cicatricial alopecia represents a group of disorders sharing a final pathway of destruction followed by replacement with fibrous tissue of the hair follicle unit. Cicatricial alopecia is classified into two categories, namely primary cicatricial alopecia, in which the hair follicle is the sole target of a progressive inflammatory process in a group of diverse skin or systemic diseases, and secondary cicatricial alopecia, referring to the hair follicle destruction as a result of a nonspecific disruption of the dermis. Permanent hair loss may also occur in the late phases of some nonscarring alopecias that are called “biphasic alopecias.” Based on the pathological characteristics, the lesions of primary cicatricial alopecia are divided into lymphocyte-predominant subgroup, neutrophil-predominant subgroup, or mixed subgroup. In principle, the primary goal of the treatment aims to attenuate the progression of the inflammatory and the scarring processes at the earliest phase of the disease. In clinical practice, the lymphocyte-predominant lesions are treated with immunosuppressive agents, whereas the neutrophil-predominant lesions are treated with antimicrobials or dapsone. As the efficacy of medication treatment against the cicatricial alopecia varies significantly, autologous hair transplantation is recommended to patients who have a relatively stable primary or a secondary cicatricial alopecia

Increased HIV Incidence in Men Who Have Sex with Men Despite High Levels of ART-Induced Viral Suppression: Analysis of an Extensively Documented Epidemic

Background: There is interest in expanding ART to prevent HIV transmission, but in the group with the highest levels of ART use, men-who-have-sex-with-men (MSM), numbers of new infections diagnosed each year have not decreased as ART coverage has increased for reasons which remain unclear. Methods: We analysed data on the HIV-epidemic in MSM in the UK from a range of sources using an individual-based simulation model. Model runs using parameter sets found to result in good model fit were used to infer changes in HIV-incidence and risk behaviour. Results: HIV-incidence has increased (estimated mean incidence 0.30/100 person-years 1990–1997, 0.45/100 py 1998–2010), associated with a modest (26%) rise in condomless sex. We also explored counter-factual scenarios: had ART not been introduced, but the rise in condomless sex had still occurred, then incidence 2006–2010 was 68% higher; a policy of ART initiation in all diagnosed with HIV from 2001 resulted in 32% lower incidence; had levels of HIV testing been higher (68% tested/year instead of 25%) incidence was 25% lower; a combination of higher testing and ART at diagnosis resulted in 62% lower incidence; cessation of all condom use in 2000 resulted in a 424% increase in incidence. In 2010, we estimate that undiagnosed men, the majority in primary infection, accounted for 82% of new infections. Conclusion: A rise in HIV-incidence has occurred in MSM in the UK despite an only modest increase in levels of condomless sex and high coverage of ART. ART has almost certainly exerted a limiting effect on incidence. Much higher rates of HIV testing combined with initiation of ART at diagnosis would be likely to lead to substantial reductions in HIV incidence. Increased condom use should be promoted to avoid the erosion of the benefits of ART and to prevent other serious sexually transmitted infections

Evolutionary History of the Vertebrate Mitogen Activated Protein Kinases Family

Background: The mitogen activated protein kinases (MAPK) family pathway is implicated in diverse cellular processes and pathways essential to most organisms. Its evolution is conserved throughout the eukaryotic kingdoms. However, the detailed evolutionary history of the vertebrate MAPK family is largely unclear. Methodology/Principal Findings: The MAPK family members were collected from literatures or by searching the genomes of several vertebrates and invertebrates with the known MAPK sequences as queries. We found that vertebrates had significantly more MAPK family members than invertebrates, and the vertebrate MAPK family originated from 3 progenitors, suggesting that a burst of gene duplication events had occurred after the divergence of vertebrates from invertebrates. Conservation of evolutionary synteny was observed in the vertebrate MAPK subfamilies 4, 6, 7, and 11 to 14. Based on synteny and phylogenetic relationships, MAPK12 appeared to have arisen from a tandem duplication of MAPK11 and the MAPK13-MAPK14 gene unit was from a segmental duplication of the MAPK11-MAPK12 gene unit. Adaptive evolution analyses reveal that purifying selection drove the evolution of MAPK family, implying strong functional constraints of MAPK genes. Intriguingly, however, intron losses were specifically observed in the MAPK4 and MAPK7 genes, but not in their flanking genes, during the evolution from teleosts to amphibians and mammals. The specific occurrence of intron losses in the MAPK4 and MAPK7 subfamilies might be associated with adaptive evolution of the vertebrates by enhancing the gen

Molecular Characterization of HIV-1 CRF01_AE in Mekong Delta, Vietnam, and Impact of T-Cell Epitope Mutations on HLA Recognition (ANRS 12159)

To date, 11 HIV-1 subtypes and 48 circulating recombinant forms have been described worldwide. The underlying reason why their distribution is so heterogeneous is not clear. Host genetic factors could partly explain this distribution. The aim of this study was to describe HIV-1 strains circulating in an unexplored area of Mekong Delta, Vietnam, and to assess the impact of optimal epitope mutations on HLA binding.We recruited 125 chronically antiretroviral-naive HIV-1-infected subjects from five cities in the Mekong Delta. We performed high-resolution DNA typing of HLA class I alleles, sequencing of Gag and RT-Prot genes and phylogenetic analysis of the strains. Epitope mutations were analyzed in patients bearing the HLA allele restricting the studied epitope. Optimal wild-type epitopes from the Los Alamos database were used as reference. T-cell epitope recognition was predicted using the immune epitope database tool according to three different scores involved in antigen processing (TAP and proteasome scores) and HLA binding (MHC score). with a Vietnamese specificity held by two different haplotypes. The percentage of homology between Mekong and B consensus HIV-1 sequences was above 85%. Divergent epitopes had TAP and proteasome scores comparable with wild-type epitopes. MHC scores were significantly lower in divergent epitopes with a mean of 2.4 (±0.9) versus 2 (±0.7) in non-divergent ones (p<0.0001).Our study confirms the wide predominance of CRF01_AE in the Mekong Delta where patients harbor a specific HLA pattern. Moreover, it demonstrates the lower MHC binding affinity among divergent epitopes. This weak immune pressure combined with a narrow genetic diversity favors immune escape and could explain why CRF01_AE is still predominant in Vietnam, particularly in the Mekong area

A Review on the Extraction, Bioactivity, and Application of Tea Polysaccharides

Tea is a non-alcoholic drink containing various active ingredients, including tea polysaccharides (TPSs). TPSs have various biological activities, such as antioxidant, anti-tumor, hypoglycemic, and anti-cancer activities. However, TPSs have a complex composition, which significantly limits the extraction and isolation methods, thus limiting their application. This paper provides insight into the composition, methodological techniques for isolation and extraction of the components, biological activities, and functions of TPSs, as well as their application prospects

Geraniol: A Potential Defense-Related Volatile in “Baiye No. 1” Induced by <i>Colletotrichum camelliae</i>

Plants produce and emit a large variety of volatiles that have multiple defense-related functions in response to abiotic or biotic stresses. In comparison with studies on plant volatile–herbivore interactions, little research has been carried out on plant volatile–microbe interactions. In the present paper, tea volatile–Colletotrichum camelliae interactions were studied. The results of emitted volatiles following infection with C. camelliae in “Baiye No. 1” showed that healthy tea plants contained 68 kinds of volatiles, while infected tea plants contained 76 kinds of volatiles. Five volatiles, namely, geraniol, linalool, methyl salicylate, (E)-3-hexen-1-ol, and α-farnesene, were found to have a relatively large content variation in infected tea plants, with increments of 7.903%, −2.247%, 2.770%, −6.728%, and 3.848%, respectively. The fungicidal activity results of the five volatiles against C. camelliae showed that geraniol had the best activity, with MIC and MBC values of 0.5 and 1 mg·mL−1, respectively. Thus, geraniol was selected for subsequent studies. The effects of geraniol on the mycelia and cell structures of C. camelliae were investigated by scanning electron microscopy (SEM) and transmission electron microscope (TEM). The results showed that the mycelia were significantly disrupted, and the cell structures were damaged. The effects of geraniol on the related enzymes of C. camelliae were assessed. The results showed that cellulase activity increased, malondialdehyde content increased, and the activity of defense enzymes was inhibited, thereby inhibiting the growth of pathogens. This study provides the first evidence that geraniol is a defense-related function volatile of “Baiye No. 1” in response to C. camelliae stress. It also provides valuable information and enriches the chemical ecology of tea plant diseases for the research field on defensive substances of microbe-induced plant volatiles

Mechanically strong and multifunctional nano-nickel aerogels based epoxy composites for ultra-high electromagnetic interference shielding and thermal management

With the development of highly integrated electronic equipment, electromagnetic pollution and heat congregation have become serious problems. Electromagnetic interference (EMI) shielding materials with high thermal conductivity and mechanical properties are highly desirable. Herein, the reduced graphene oxide/Ni nanowire aerogels (GNiA) were firstly prepared via hydrothermal reducing process and freeze-drying. Subsequently, using epoxy (EP) as a polymer matrix, the GNiA/EP composites with high compression strength of 147 MPa were fabricated by vacuum filtration and curing. The GNiA endows the composites with great electromagnetic wave loss, as well as improved phonon propagation efficiency, resulting in the super high EMI SE. With the GNiA content of 12.14 wt%, the EMI SE and thermal conductivity of GNiA/EP composites can reach as high as 85 dB and 1.69 W/(m·K) respectively. The obtained GNiA/EP composites provide a strategy to meet the demand for electronic equipment for new-generation EMI shielding materials

X-Linked RNA-Binding Motif Protein Modulates HIV-1 Infection of CD4+ T Cells by Maintaining the Trimethylation of Histone H3 Lysine 9 at the Downstream Region of the 5′ Long Terminal Repeat of HIV Proviral DNA

HIV-1 latency featuring silence of transcription from HIV-1 proviral DNA represents a major obstacle for HIV-1 eradication. Reversible repression of HIV-1 5′-LTR-mediated transcription represents the main mechanism for HIV-1 to maintain latency. The 5′-LTR-driven HIV gene transcription can be modulated by multiple host factors and mechanisms. The hnRNPs are known to regulate gene expression. A member of the hnRNP family, RBMX, has been identified in this study as a novel HIV-1 restriction factor that modulates HIV-1 5′-LTR-driven transcription of viral genome in CD4+ T cells and maintains viral latency. These findings provide a new understanding of how host factors modulate HIV-1 infection and latency and suggest a potential new target for the development of HIV-1 therapies.Reversible repression of HIV-1 5′ long terminal repeat (5′-LTR)-mediated transcription represents the main mechanism for HIV-1 to maintain latency. Identification of host factors that modulate LTR activity and viral latency may help develop new antiretroviral therapies. The heterogeneous nuclear ribonucleoproteins (hnRNPs) are known to regulate gene expression and possess multiple physiological functions. hnRNP family members have recently been identified as the sensors for viral nucleic acids to induce antiviral responses, highlighting the crucial roles of hnRNPs in regulating viral infection. A member of the hnRNP family, X-linked RNA-binding motif protein (RBMX), has been identified in this study as a novel HIV-1 restriction factor that modulates HIV-1 5′-LTR-driven transcription of viral genome in CD4+ T cells. Mechanistically, RBMX binds to HIV-1 proviral DNA at the LTR downstream region and maintains the repressive trimethylation of histone H3 lysine 9 (H3K9me3), leading to a blockage of the recruitment of the positive transcription factor phosphorylated RNA polymerase II (RNA pol II) and consequential impediment of transcription elongation. This RBMX-mediated modulation of HIV-1 transcription maintains viral latency by inhibiting viral reactivation from an integrated proviral DNA. Our findings provide a new understanding of how host factors modulate HIV-1 infection and latency and suggest a potential new target for the development of HIV-1 therapies