Graph inductive biases in transformers without message passing

Transformers for graph data are increasingly widely studied and successful in numerous learning tasks. Graph inductive biases are crucial for Graph Transformers, and previous works incorporate them using message-passing modules and/or positional encodings. However, Graph Transformers that use message-passing inherit known issues of message-passing, and differ significantly from Transformers used in other domains, thus making transfer of research advances more difficult. On the other hand, Graph Transformers without message-passing often perform poorly on smaller datasets, where inductive biases are more important. To bridge this gap, we propose the Graph Inductive bias Transformer (GRIT) — a new Graph Transformer that incorporates graph inductive biases without using message passing. GRIT is based on several architectural changes that are each theoretically and empirically justified, including: learned relative positional encodings initialized with random walk probabilities, a flexible attention mechanism that updates node and node-pair representations, and injection of degree information in each layer. We prove that GRIT is expressive — it can express shortest path distances and various graph propagation matrices. GRIT achieves state-of-the-art empirical performance across a variety of graph datasets, thus showing the power that Graph Transformers without message-passing can deliver

Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial

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Impetigo herpetiformis during the puerperium triggered by secondary hypoparathyroidism: a case report

A 38-year-old multiparous woman with post thyroidectomy hypoparathyroidism developed pruritic erythematous patches with multiple pustules on its margins on her thighs and groin accompanied by fever few days after delivery by caesarean section. Impetigo herpetiformis was diagnosed based on the typical clinicopathological findings. The patient was treated with intravenous fluids, calcium, Calcitrol and corticosteroids. The correction of hypocalcaemia was accompanied with rapid improvement of her skin disease and general condition. Our case is the fourth case of impetigo herpetiformis initially presented during puerperium and the first case of puerperal impetigo herpetiformis that is precipitated by secondary hypoparathyroidism. The awareness of the possible occurrence of impetigo herpetiformis during the puerperium allows early diagnosis, treatment and prevention of maternal complications

Site-specific incorporation of phosphotyrosine using an expanded genetic code.

Access to phosphoproteins with stoichiometric and site-specific phosphorylation status is key to understanding the role of protein phosphorylation. Here we report an efficient method to generate pure, active phosphotyrosine-containing proteins by genetically encoding a stable phosphotyrosine analog that is convertible to native phosphotyrosine. We demonstrate its general compatibility with proteins of various sizes, phosphotyrosine sites and functions, and reveal a possible role of tyrosine phosphorylation in negative regulation of ubiquitination

Controlled Orientation of Active Sites in a Nanostructured Multienzyme Complex

Multistep cascade reactions in nature maximize reaction efficiency by co-assembling related enzymes. Such organization facilitates the processing of intermediates by downstream enzymes. Previously, the studies on multienzyme nanocomplexes assembled on DNA scaffolds demonstrated that closer interenzyme distance enhances the overall reaction efficiency. However, it remains unknown how the active site orientation controlled at nanoscale can have an effect on multienzyme reaction. Here, we show that controlled alignment of active sites promotes the multienzyme reaction efficiency. By genetic incorporation of a non-natural amino acid and two compatible bioorthogonal chemistries, we conjugated mannitol dehydrogenase to formate dehydrogenase with the defined active site arrangement with the residue-level accuracy. The study revealed that the multienzyme complex with the active sites directed towards each other exhibits four-fold higher relative efficiency enhancement in the cascade reaction and produces 60% more D-mannitol than the other complex with active sites directed away from each other.ope

High-throughput, quantitative analyses of genetic interactions in E. coli.

Large-scale genetic interaction studies provide the basis for defining gene function and pathway architecture. Recent advances in the ability to generate double mutants en masse in Saccharomyces cerevisiae have dramatically accelerated the acquisition of genetic interaction information and the biological inferences that follow. Here we describe a method based on F factor-driven conjugation, which allows for high-throughput generation of double mutants in Escherichia coli. This method, termed genetic interaction analysis technology for E. coli (GIANT-coli), permits us to systematically generate and array double-mutant cells on solid media in high-density arrays. We show that colony size provides a robust and quantitative output of cellular fitness and that GIANT-coli can recapitulate known synthetic interactions and identify previously unidentified negative (synthetic sickness or lethality) and positive (suppressive or epistatic) relationships. Finally, we describe a complementary strategy for genome-wide suppressor-mutant identification. Together, these methods permit rapid, large-scale genetic interaction studies in E. coli

An efficient Foxtail mosaic virus vector system with reduced environmental risk

<p>Abstract</p> <p>Background</p> <p>Plant viral vectors offer high-yield expression of pharmaceutical and commercially important proteins with a minimum of cost and preparation time. The use of <it>Agrobacterium tumefaciens </it>has been introduced to deliver the viral vector as a transgene to each plant cell via a simple, nonsterile infiltration technique called "agroinoculation". With agroinoculation, a full length, systemically moving virus is no longer necessary for excellent protein yield, since the viral transgene is transcribed and replicates in every infiltrated cell. Viral genes may therefore be deleted to decrease the potential for accidental spread and persistence of the viral vector in the environment.</p> <p>Results</p> <p>In this study, both the coat protein (CP) and triple gene block (TGB) genetic segments were eliminated from <it>Foxtail mosaic virus </it>to create the "FECT" vector series, comprising a deletion of 29% of the genome. This viral vector is highly crippled and expresses little or no marker gene within the inoculated leaf. However, when co-agroinoculated with a silencing suppressor (p19 or HcPro), FECT expressed GFP at 40% total soluble protein in the tobacco host, <it>Nicotiana benthamiana</it>. The modified FoMV vector retained the full-length replicase ORF, the TGB1 subgenomic RNA leader sequence and either 0, 22 or 40 bases of TGB1 ORF (in vectors FECT0, FECT22 and FECT40, respectively). As well as <it>N. benthamiana</it>, infection of legumes was demonstrated. Despite many attempts, expression of GFP via syringe agroinoculation of various grass species was very low, reflecting the low <it>Agrobacterium</it>-mediated transformation rate of monocots.</p> <p>Conclusions</p> <p>The FECT/40 vector expresses foreign genes at a very high level, and yet has a greatly reduced biohazard potential. It can form no virions and can effectively replicate only in a plant with suppressed silencing.</p

Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes

Serum 25-hydroxyvitamin D and postmenopausal breast cancer survival: a prospective patient cohort study

Introduction: Vitamin D has been postulated to be involved in cancer prognosis. Thus far, only two studies reported on its association with recurrence and survival after breast cancer diagnosis yielding inconsistent results. Therefore, the aim of our study was to assess the effect of post-diagnostic serum 25-hydroxyvitamin D [25(OH)D] concentrations on overall survival and distant disease-free survival. Methods: We conducted a prospective cohort study in Germany including 1,295 incident postmenopausal breast cancer patients aged 50-74 years. Patients were diagnosed between 2002 and 2005 and median follow-up was 5.8 years. Cox proportional hazards models were stratified by age at diagnosis and season of blood collection and adjusted for other prognostic factors. Fractional polynomials were used to assess the true dose-response relation for 25(OH)D. Results: Lower concentrations of 25(OH)D were linearly associated with higher risk of death (hazard ratio (HR) = 1.08 per 10 nmol/L decrement; 95% confidence interval (CI), 1.00 to 1.17) and significantly higher risk of distant recurrence (HR = 1.14 per 10 nmol/L decrement; 95%CI, 1.05 to 1.24). Compared with the highest tertile (≥ 55 nmol/L), patients within the lowest tertile (< 35 nmol/L) of 25(OH)D had a HR for overall survival of 1.55 (95%CI, 1.00 to 2.39) and a HR for distant disease-free survival of 2.09 (95%CI, 1.29 to 3.41). In addition, the association with overall survival was found to be statistically significant only for 25(OH)D levels of blood samples collected before start of chemotherapy but not for those of samples taken after start of chemotherapy (P for interaction = 0.06). Conclusions: In conclusion, lower serum 25(OH)D concentrations may be associated with poorer overall survival and distant disease-free survival in postmenopausal breast cancer patients