We consider extending the modal logic KD45, commonly taken as the baseline system for belief, with propositional quantifiers that can be used to formalize natural language sentences such as ...“everything I believe is true” or “there is something that I neither believe nor disbelieve.” Our main results are axiomatizations of the logics with propositional quantifiers of natural classes of complete Boolean algebras with an operator (BAOs) validating KD45. Among them is the class of complete, atomic, and completely multiplicative BAOs validating KD45. Hence, by duality, we also cover the usual method of adding propositional quantifiers to normal modal logics by considering their classes of Kripke frames. In addition, we obtain decidability for all the concrete logics we discuss.
Classifying the sub-categories of an object from the same super-category (e.g., bird species and cars) in fine-grained visual classification (FGVC) highly relies on discriminative feature ...representation and accurate region localization. Existing approaches mainly focus on distilling information from high-level features. In this paper, by contrast, we show that by integrating low-level information (e.g., color, edge junctions, texture patterns), performance can be improved with enhanced feature representation and accurately located discriminative regions. Our solution, named Attention Pyramid Convolutional Neural Network (AP-CNN), consists of 1) a dual pathway hierarchy structure with a top-down feature pathway and a bottom-up attention pathway, hence learning both high-level semantic and low-level detailed feature representation, and 2) an ROI-guided refinement strategy with ROI-guided dropblock and ROI-guided zoom-in operation, which refines features with discriminative local regions enhanced and background noises eliminated. The proposed AP-CNN can be trained end-to-end, without the need of any additional bounding box/part annotation. Extensive experiments on three popularly tested FGVC datasets (CUB-200-2011, Stanford Cars, and FGVC-Aircraft) demonstrate that our approach achieves state-of-the-art performance. Models and code are available at https://github.com/PRIS-CV/AP-CNN_Pytorch-master.
The key to solving fine-grained image categorization is finding discriminate and local regions that correspond to subtle visual traits. Great strides have been made, with complex networks designed ...specifically to learn part-level discriminate feature representations. In this paper, we show that it is possible to cultivate subtle details without the need for overly complicated network designs or training mechanisms - a single loss is all it takes. The main trick lies with how we delve into individual feature channels early on, as opposed to the convention of starting from a consolidated feature map. The proposed loss function, termed as mutual-channel loss (MC-Loss), consists of two channel-specific components: a discriminality component and a diversity component. The discriminality component forces all feature channels belonging to the same class to be discriminative, through a novel channel-wise attention mechanism. The diversity component additionally constraints channels so that they become mutually exclusive across the spatial dimension. The end result is therefore a set of feature channels, each of which reflects different locally discriminative regions for a specific class. The MC-Loss can be trained end-to-end, without the need for any bounding-box/part annotations, and yields highly discriminative regions during inference. Experimental results show our MC-Loss when implemented on top of common base networks can achieve state-of-the-art performance on all four fine-grained categorization datasets (CUB-Birds, FGVC-Aircraft, Flowers-102, and Stanford Cars). Ablative studies further demonstrate the superiority of the MC-Loss when compared with other recently proposed general-purpose losses for visual classification, on two different base networks. Codes are available at: https://github.com/dongliangchang/Mutual-Channel-Loss.
Alcoholic liver disease claims two million lives per year. We previously reported that autophagy protected against alcohol-induced liver injury and steatosis by removing damaged mitochondria. ...However, the mechanisms for removal of these mitochondria are unknown. Parkin is an evolutionarily conserved E3 ligase that is recruited to damaged mitochondria to initiate ubiquitination of mitochondrial outer membrane proteins and subsequent mitochondrial degradation by mitophagy. In addition to its role in mitophagy, Parkin has been shown to have other roles in maintaining mitochondrial function. We investigated whether Parkin protected against alcohol-induced liver injury and steatosis using wild-type (WT) and Parkin knockout (KO) mice treated with alcohol by the acute-binge and Gao-binge (chronic plus acute-binge) models. We found that Parkin protected against liver injury in both alcohol models, likely because of Parkin's role in maintaining a population of healthy mitochondria. Alcohol caused greater mitochondrial damage and oxidative stress in Parkin KO livers compared with WT livers. After alcohol treatment, Parkin KO mice had severely swollen and damaged mitochondria that lacked cristae, which were not seen in WT mice. Furthermore, Parkin KO mice had decreased mitophagy, β-oxidation, mitochondrial respiration, and cytochrome c oxidase activity after acute alcohol treatment compared with WT mice. Interestingly, liver mitochondria seemed able to adapt to alcohol treatment, but Parkin KO mouse liver mitochondria had less capacity to adapt to Gao-binge treatment compared with WT mouse liver mitochondria. Overall, our findings indicate that Parkin is an important mediator of protection against alcohol-induced mitochondrial damage, steatosis, and liver injury.
The accumulation of reactive oxygen species (ROS) plays a pivotal role in the development of various diseases, including cancer. Elevated ROS levels cause oxidative stress, resulting in detrimental ...effects on organisms and enabling tumors to develop adaptive responses. Targeting these enhanced oxidative stress protection mechanisms could offer therapeutic benefits with high specificity, as normal cells exhibit lower dependency on these pathways. MTH1 (mutT homolog 1), a homolog of
's MutT, is crucial in this context. It sanitizes the nucleotide pool, preventing incorporation of oxidized nucleotides, thus safeguarding DNA integrity. This study explores MTH1's potential as a therapeutic target, particularly in cancer treatment, providing insights into its structure, function, and role in disease progression.
The plant hormone ethylene regulates ripening in climacteric fruits. The phytohormone abscisic acid (ABA) affects ethylene biosynthesis, but whether ethylene influences ABA biosynthesis is unknown. ...To explore this possibility, we investigated the interactions between the ABA biosynthesis genes
and the ethylene response transcription factor PpERF3 in peach fruit. The ABA content increased during fruit maturation and reached a peak at stage S4 III. The increase was greatly inhibited by the ethylene inhibitor 1-MCP, which also suppressed
expression.
shared a similar expression profile with
, encoding a rate-limiting enzyme involved in ABA biosynthesis, during fruit ripening. A yeast one-hybrid assay suggested that the nuclear-localized PpERF3 might bind to the promoters of
. PpERF3 increased the expression of
as shown by dual-luciferase reporters, promoter-GUS assays and transient expression analyses in peach fruit. Collectively, these results suggest that ethylene promotes ABA biosynthesis through PpERF3's regulation of the expression of ABA biosynthesis genes
.
Mutations in γ-aminobutyric acid (GABA) transporter 1 (GAT-1)-encoding SLC6A1 have been associated with myoclonic atonic epilepsy and other phenotypes. We determined the patho-mechanisms of the ...mutant GAT-1, in order to identify treatment targets.
We conducted whole-exome sequencing of patients with myoclonic atonic epilepsy (MAE) and characterized the seizure phenotypes and EEG patterns. We studied the protein stability and structural changes with homology modeling and machine learning tools. We characterized the function and trafficking of the mutant GAT-1 with 3H radioactive GABA uptake assay and confocal microscopy. We utilized different models including a knockin mouse and human astrocytes derived from induced pluripotent stem cells (iPSCs). We focused on astrocytes because of their direct impact of astrocytic GAT-1 in seizures.
We identified four novel SLC6A1 variants associated with MAE and 2 to 4 Hz spike-wave discharges as a common EEG feature. Machine learning tools predicted that the variant proteins are destabilized. The variant protein had reduced expression and reduced GABA uptake due to endoplasmic reticular retention. The consistent observation was made in cortical and thalamic astrocytes from variant-knockin mice and human iPSC-derived astrocytes. The Slc6a+/A288V mouse, representative of MAE, had increased 5–7 Hz spike-wave discharges and absence seizures.
SLC6A1 variants in various locations of the protein peptides can cause MAE with similar seizure phenotypes and EEG features. Reduced GABA uptake is due to decreased functional GAT-1, which, in thalamic astrocytes, could result in increased extracellular GABA accumulation and enhanced tonic inhibition, leading to seizures and abnormal EEGs.
•SLC6A1 variants associated with MAE showed heterogenous functional deficit of GAT-1.•Increased 2–4 Hz SWDs are common in patients while increased 5–7 SWDs are common in mice with SLC6A1 variants.•The variants destabilized the GAT-1 protein and reduced GABA uptake.•The variant protein caused ER retention and reduced cell surface expression.•Astrocytic deficit of GAT-1 could cause seizures in the variant knockin mice.
Salmonella Typhimurium, one of the most common Salmonella spp. serovars, is recognized as a globally important foodborne pathogen. In this study, bacteriophage LPST144 against S. Typhimurium ...(ATCC13311) was isolated from sewage and selected owing to its excellent lytic capacity. After genome sequence analysis, the endolysin from LPST144 was cloned and expressed, and its lytic activity was verified. Morphological analysis showed that bacteriophage LPST144 belongs to Podoviridae family and Caudovirales order, and could completely inhibit host bacterial growth within 7 h at multiplicity of infection of 0.01–1000. Genome analysis indicated LPST144 genome comprised a 39,050 bp DNA with 43 putative open reading frames, of which 27 were annotated to known functions. No genes associated with lysogeny, antibiotic resistance and virulence factor were found. Putative endolysin LysT144 could significant decrease OD600nm from 0.80 to 0.14 against chloroform-treated S. Typhimurium within 30 min. Endolysin LysT144 remained highly active at pH ranging from 6.0 to 12.0, temperature below 50 °C, and NaCl concentration below 300 mM. Besides, LysT144 also exhibited extensive and broad spectrum of host bacteria strains, including multiple antibiotic-resistant Salmonella. Therefore, the bacteriophage LPST144 and its endolysin could be used as potential antibacterial agents for Salmonella control in food industry.
•Bacteriophage LPST144 against S. Typhimurium was isolated and characterized.•LPST144 completely inhibited the growth of host bacteria within 7 h.•The genome of LPST144 was analyzed and identified as a new member of the T7 virus.•LysT144 presented a remarkably inhibition on its host strain and MDR bacteria.
is responsible for a wide range of infections and is a constant threat to public health, particularly in light of emerging antibiotic resistance. The use of bacteriophages and phage endolysins as ...specific antibacterial agents is a promising strategy to control this bacterial infection. Endolysins are important proteins during the process of bacteria lysis by bacteriophages. In this study, we identify a novel endolysin, named LysSE24. LysSE24 was predicted to possess
-acetylmuramidases activity, with a molecular mass of ca. 17.4 kDa and pI 9.44. His-tagged LysSE24 was heterologously expressed and purified by Ni-NTA chromatography. LysSE24 exhibited optimal bactericidal activity against
Enteritidis ATCC 13076 at a concentration of 0.1 μM.
population (measured by OD
) decreased significantly (
< 0.05) after 10 min of incubation in combination with the outer membrane permeabilizer in vitro. It also showed antibacterial activity against a panel of 23 tested multidrug-resistant
strains. Bactericidal activity of LysSE24 was evaluated in terms of pH, temperature, and ionic strength. It was very stable with different pH (4.0 to 10.0) at different temperatures (20 to 60 °C). Both K
and Na
at concentrations between 0.1 to 100 mM showed no effects on its bactericidal activity, while a high concentration of Ca
and Mg
showed efficacy. Transmission electron microscopy revealed that exposure to 0.1 μM LysSE24 for up to 5 min caused a remarkable modification of the cell shape of
Enteritidis ATCC 13076. These results indicate that recombinant LysSE24 represents a promising antimicrobial activity against
, especially several multidrug-resistant
strains. Further studies can be developed to improve its bactericidal activity without the need for pretreatment with outer membrane-destabilizing agents by synthetic biology methods.
The tuberous sclerosis-associated neuropsychiatric disorders (TAND) have not previously been studied in China. We aimed to assess the psychiatric level of individuals with TAND using the Mini ...International Neuropsychiatric Interview for Children (MINI-KID) in China.
A total of 83.16% of individuals (79/95) had at least one TAND, and 70.53% (67/95) had an intellectual disability. The MINI-KID tool diagnosed 16 neuropsychiatric diseases, the most common of which were attention-deficit/hyperactivity disorder (ADHD) (51.58%, 49/95) and social anxiety disorder (30.53%, 29/95). The number of children with psychiatric diseases in the tuberous sclerosis complex (TSC) group was significantly greater than the number in the typically developing group (P < 0.0001). Notably, 69.47% (66/95) had two or more psychiatric disorders. Pervasive developmental disorder (PDD) was often co-morbid with other psychiatric disorders.
This study used the structured and systematic MINI-KID scale to determine the diagnosis of psychiatric co-morbidities in a relatively large sample, suggesting a higher rate. By comparing the status of individuals with TSC with typically developing children, the results suggests that neuropsychiatric co-morbidities are significantly higher in individuals with TSC. Research has revealed the frequent presence of two, three or more neuropsychiatric diseases in individuals with TSC.
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