Large vision-language models, such as Contrastive Vision-Language Pre-training (CLIP), pre-trained on large-scale image–text datasets, have demonstrated robust zero-shot transfer capabilities across ...various downstream tasks. To further enhance the few-shot recognition performance of CLIP, Tip-Adapter augments the CLIP model with an adapter that incorporates a key-value cache model constructed from the few-shot training set. This approach enables training-free adaptation and has shown significant improvements in few-shot recognition, especially with additional fine-tuning. However, the size of the adapter increases in proportion to the number of training samples, making it difficult to deploy in practical applications. In this paper, we propose a novel CLIP adaptation method, named Proto-Adapter, which employs a single-layer adapter of constant size regardless of the amount of training data and even outperforms Tip-Adapter. Proto-Adapter constructs the adapter’s weights based on prototype representations for each class. By aggregating the features of the training samples, it successfully reduces the size of the adapter without compromising performance. Moreover, the performance of the model can be further enhanced by fine-tuning the adapter’s weights using a distance margin penalty, which imposes additional inter-class discrepancy to the output logits. We posit that this training scheme allows us to obtain a model with a discriminative decision boundary even when trained with a limited amount of data. We demonstrate the effectiveness of the proposed method through extensive experiments of few-shot classification on diverse datasets.
The response regulator RpaB plays a central role in transcriptional regulation of photosynthesis-related genes in cyanobacteria. RpaB is phosphorylated by its cognate histidine kinase Hik33 and ...functions as both an activator and repressor under low-light conditions, whereas its phosphorylation level and DNA binding activity promptly decrease upon the upshift of photon flux density, causing changes in gene expression profile. In this study, we assessed the possibility of redox regulation of DNA binding activity of RpaB in Synechocystis sp. PCC 6803 by the addition of inhibitors of photosynthetic electron transport, 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) and 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), or the reducing agent dithiothreitol (DTT) under different photon flux densities. Analysis of phosphorylation level by phos-tag SDS-PAGE revealed that reduction of QA and increase in the availability of reducing equivalents at the acceptor side of PSI can independently trigger dephosphorylation of RpaB. Nevertheless, chromatin affinity purification revealed that dephosphorylation of RpaB did not cause decrease in its DNA binding activity when the acceptor side of PSI is in oxidized state. The redox state-dependent regulation by an unidentified thiol other than Cys59 of RpaB is prerequisite for phosphorylation-dependent regulation of DNA binding activity. Environmental signals recognized by Hik33 and metabolic signals recognized as the availability of reducing equivalents must be integrated at the master regulator RpaB, attaining the flexible regulation of acclimatory responses.
Enzyme‐catalyzed 4+2 cycloaddition has been proposed to be a key transformation process in various natural product biosynthetic pathways. Recently Fsa2 was found to be involved in stereospecific ...trans‐decalin formation during the biosynthesis of equisetin, a potent HIV‐1 integrase inhibitor. To understand the mechanisms by which fsa2 determines the stereochemistry of reaction products, we sought an fsa2 homologue that is involved in trans‐decalin formation in the biosynthetic pathway of an enantiomerically opposite analogue, and we found phm7, which is involved in the biosynthesis of phomasetin. A decalin skeleton with an unnatural configuration was successfully constructed by gene replacement of phm7 with fsa2, thus demonstrating enzymatic control of all stereochemistry in the 4+2 cycloaddition. Our findings highlight enzyme‐catalyzed 4+2 cycloaddition as a stereochemically divergent step in natural product biosynthetic pathways and open new avenues for generating derivatives with different stereochemistry.
Everything's under control: Fsa2 is responsible for stereoselective decalin formation during equisetin biosynthesis. Phm7, an Fsa2 homologue, is involved in stereoselective decalin formation in the enantiomerically opposite equisetin analogue phomasetin. A decalin skeleton with an unnatural configuration was successfully constructed by gene replacement, thus demonstrating enzymatic control of all stereochemistry in the 4+2 cycloaddition.
To collect clinical information and
mutation data on patients with Blau syndrome and to evaluate their prognosis.
Fifty patients with
mutations were analysed. The activity of each
mutant was ...evaluated in HEK293 cells by reporter assay. Clinical information was collected from medical records through the attending physicians.
The study population comprised 26 males and 24 females aged 0-61 years. Thirty-two cases were sporadic, and 18 were familial from 9 unrelated families. Fifteen different mutations in
were identified, including 2 novel mutations (p.W490S and D512V); all showed spontaneous nuclear factor kappa B activation, and the most common mutation was p.R334W. Twenty-six patients had fever at relatively early timepoints in the disease course. Forty-three of 47 patients had a skin rash. The onset of disease in 9 patients was recognised after BCG vaccination. Forty-five of 49 patients had joint lesions. Thirty-eight of 50 patients had ocular symptoms, 7 of which resulted in blindness. After the diagnosis of Blau syndrome, 26 patients were treated with biologics; all were antitumour necrosis factor agents. Only 3 patients were treated with biologics alone; the others received a biologic in combination with methotrexate and/or prednisolone. None of the patients who became blind received biologic treatment.
In patients with Blau syndrome, severe joint contractures and blindness may occur if diagnosis and appropriate treatment are delayed. Early treatment with a biologic agent may improve the prognosis.
Cerebral vasculitis owing to chronic graft-versus-host disease (GVHD) is very rare. To our knowledge, only 2 cases have been reported. We describe the first case of superficial temporal artery-middle ...cerebral artery (STA-MCA) bypass for cerebral vasculitis owing to GVHD.
A 59-year-old woman presented with right upper extremity weakness and dysarthria 33 months after undergoing matching allogenic bone marrow transplantation. The patient had STA-MCA bypass for MCA occlusion and resting cerebral blood flow in the left MCA area improved.
Although the mechanism of cerebral vasculitis after chronic GVHD is not known, cerebral vasculitis that causes cerebrovascular disease long after bone marrow transplantation should be considered. In this case, an STA-MCA bypass was efficient for the repeated ischemic attacks owing to cerebral vasculitis. Moreover, it is important to select the optimal recipient vessels to area originated neurologic symptoms.
Asexual spores (conidia) are reproductive structures that play a crucial role in fungal distribution and survival. As fungal conidia are, in most cases, etiological agents of plant diseases and ...fungal lung disease, their stress resistance and interaction with their hosts have drawn increasing attention. In the present study, we investigated whether environmental temperature during conidiation affects the stress tolerance of the conidia of the human pathogenic fungus Aspergillus fumigatus. Conidia from a 25°C culture showed a lower tolerance to heat (60°C) and oxidative (H2O2) stresses and a marked resistance to ultraviolet radiation exposure, compared with those produced at 37 and 45°C. The accumulation of trehalose was lower in the conidia from the 25°C culture. Furthermore, the conidia from the 25°C culture showed darker pigmentation and increased transcripts of dihydroxynaphthalene (DHN)-melanin biosynthesis-related genes (i.e., pksP, arp1, and arp2). An RNA-sequencing analysis revealed that the transcription level of the trypacidin (tpc) gene cluster, which contains 13 genes, was sharply and coordinately activated in the conidia from the 25°C culture. Accordingly, trypacidin was abundant in the conidia from the 25°C culture, whereas there was little trypacidin in the conidia from the 37°C culture. Taken together, these data show that the environmental temperature during conidiation affects conidial properties such as stress tolerance, pigmentation, and mycotoxin accumulation. To enhance our knowledge, we further explored the temperature-dependent production of DHN-melanin and trypacidin in clinical A. fumigatus isolates. Some of the isolates showed temperature-independent production of DHN-melanin and/or trypacidin, indicating that the conidia-associated secondary metabolisms differed among the isolates.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tetramic acid containing a decalin ring such as equisetin and phomasetin is one of the characteristic scaffolds found in fungal bioactive secondary metabolites. Polyketide (PKS)-nonribosomal peptide ...synthetase (NRPS) hybrid enzyme is responsible for the synthesis of the polyketide scaffold conjugated with an amino acid. PKS-NRPS hybrid complex programs to create structural diversity in the polyketide backbone have begun to be investigated, yet mechanism of control of the stereochemistry in a decalin formation via a Diels-Alder cycloaddition remains uncertain. Here, we demonstrate that fsa2, which showed no homology to genes encoding proteins of known function, in the fsa cluster responsible for equisetin and fusarisetin A biosynthesis in Fusarium sp. FN080326, is involved in the control of stereochemistry in decalin formation via a Diels-Alder reaction in the equisetin biosynthetic pathway.
•Fusarisetin A biosynthetic gene cluster was identified in Fusarium sp. FN080326.•Equisetin is a biosynthetic intermediate of fusarisetin A.•(3S,6R)-diastereomer of equisetin was isolated from the fsa2 deletion mutant.•Fsa2 is involved in the stereoselective decalin formation of equisetin.
With the recent advances in e-commerce, it has become important to recommend not only mass-produced daily items, such as books, but also items that are not mass-produced. In this study, we present an ...algorithm for real estate recommendations. Automatic property recommendations are a highly difficult task because no identical properties exist in the world, occupied properties cannot be recommended, and users rent or buy properties only a few times in their lives. For the first step of property recommendation, we predict users' preferences for properties by combining content-based filtering and Multi-Layer Perceptron (MLP). In the MLP, we use not only attribute data of users and properties, but also deep features extracted from property floor plan images. As a result, we successfully predict users' preference with a Matthews Correlation Coefficient (MCC) of 0.166.
Decalin-containing tetramic acid is a bioactive scaffold primarily produced by filamentous fungi. The structural diversity of this group of compounds is generated by characteristic enzymes of fungal ...biosynthetic pathways, including polyketide synthase/nonribosomal peptide synthetase hybrid enzymes and decalin synthase, which are responsible for the construction of a linear polyenoyl tetramic acid structure and stereoselective decalin formation via the intramolecular Diels-Alder reaction, respectively. Compounds that differed only in the decalin configuration were collected from genetically engineered mutants derived from decalin-containing tetramic acid-producing fungi and used for a structure-activity relationship study. Our evaluation of biological activities, such as cytotoxicity against several cancer cell lines and antibacterial, antifungal, antimalarial, and mitochondrial inhibitory activities, demonstrated that the activity for each assay varies depending on the decalin configurations. In addition to these known biological activities, we revealed that the compounds showed inhibitory activity against the insect steroidogenic glutathione S-transferase Noppera-bo. Engineering the decalin configurations would be useful not only to find derivatives with better biological activities but also to discover overlooked biological activities.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this study, we investigated the effects of laboratory-scale silage preparation using a plastic bag and incubation on the early-instar larval viability and egg hatchability of fall armyworms (FAWs) ...inoculated into corn. In experiments performed to evaluate the effects on larval viability, the impacts of vacuum and anaerobic conditions were assessed as factors expected to influence larval viability after silage preparation. In the experiment that evaluated the effects on egg hatchability, the effects of enclosed fresh corn or fermented corn silage were examined. In the experiment that evaluated the effects of vacuum during silage preparation, no viable larvae were detected in anaerobic conditions, regardless of the length of incubation time (24 h or 14 days). In the experiment that confirmed the effects of carbon dioxide (CO2) gas during silage preparation, no viable larvae were noted under enclosed CO2 conditions, regardless of the incubation period (24 h or 14 days). After 3 days of silage preparation, we also found that egg hatchability was 0.05%. These results suggest that forage corn contaminated with FAW has a reduced larval viability rate and egg hatchability in the early stages of silage preparation, suggesting a low chance of FAW spreading from corn silage prepared under airtight conditions.
PDF
