MP2-Based Composite Extrapolation Schemes Can Predict Core-Ionization Energies for First-Row Elements with Coupled-Cluster Level Accuracy.

X-ray photoelectron spectroscopy (XPS) measures core-electron binding energies (CEBEs) to reveal element-specific insights into the chemical environment and bonding. Accurate theoretical CEBE prediction aids XPS interpretation but requires proper modeling of orbital relaxation and electron correlation upon core-ionization. This work systematically investigates basis set selection for extrapolation to the complete basis set limit of CEBEs from ΔMP2 and ΔCC energies across 94 -edges in diverse organic molecules.

Protein Condensate Atlas from predictive models of heteromolecular condensate composition.

Biomolecular condensates help cells organise their content in space and time. Cells harbour a variety of condensate types with diverse composition and many are likely yet to be discovered. Here, we develop a methodology to predict the composition of biomolecular condensates.

Kernel-elastic autoencoder for molecular design.

We introduce the kernel-elastic autoencoder (KAE), a self-supervised generative model based on the transformer architecture with enhanced performance for molecular design. KAE employs two innovative loss functions: modified maximum mean discrepancy (m-MMD) and weighted reconstruction (). The m-MMD loss has significantly improved the generative performance of KAE when compared to using the traditional Kullback-Leibler loss of VAE, or standard maximum mean discrepancy.

ChemSpaceAL: An Efficient Active Learning Methodology Applied to Protein-Specific Molecular Generation.

The incredible capabilities of generative artificial intelligence models have inevitably led to their application in the domain of drug discovery. Within this domain, the vastness of chemical space motivates the development of more efficient methods for identifying regions with molecules that exhibit desired characteristics. In this work, we present a computationally efficient active learning methodology and demonstrate its applicability to targeted molecular generation.

ChemSpaceAL: An Efficient Active Learning Methodology Applied to Protein-Specific Molecular Generation.

The incredible capabilities of generative artificial intelligence models have inevitably led to their application in the domain of drug discovery. Within this domain, the vastness of chemical space motivates the development of more efficient methods for identifying regions with molecules that exhibit desired characteristics. In this work, we present a computationally efficient active learning methodology that requires evaluation of only a subset of the generated data in the constructed sample space to successfully align a generative model with respect to a specified objective.

Theoretical and Data-Driven Approaches for Biomolecular Condensates.

Biomolecular condensation processes are increasingly recognized as a fundamental mechanism that living cells use to organize biomolecules in time and space. These processes can lead to the formation of membraneless organelles that enable cells to perform distinct biochemical processes in controlled local environments, thereby supplying them with an additional degree of spatial control relative to that achieved by membrane-bound organelles. This fundamental importance of biomolecular condensation has motivated a quest to discover and understand the molecular mechanisms and determinants that drive and control this process.

Serological fingerprints link antiviral activity of therapeutic antibodies to affinity and concentration.

The effectiveness of therapeutic monoclonal antibodies (mAbs) against variants of the SARS-CoV-2 virus is highly variable. As target recognition of mAbs relies on tight binding affinity, we assessed the affinities of five therapeutic mAbs to the receptor binding domain (RBD) of wild type (A), Delta (B.1.

Both COVID-19 infection and vaccination induce high-affinity cross-clade responses to SARS-CoV-2 variants.

The B.1.1.

Microfluidic Antibody Affinity Profiling Reveals the Role of Memory Reactivation and Cross-Reactivity in the Defense Against SARS-CoV-2.

Recent efforts in understanding the course and severity of SARS-CoV-2 infections have highlighted both potentially beneficial and detrimental effects of cross-reactive antibodies derived from memory immunity. Specifically, due to a significant degree of sequence similarity between SARS-CoV-2 and other members of the coronavirus family, memory B-cells that emerged from previous infections with endemic human coronaviruses (HCoVs) could be reactivated upon encountering the newly emerged SARS-CoV-2, thus prompting the production of cross-reactive antibodies. Determining the affinity and concentration of these potentially cross-reactive antibodies to the new SARS-CoV-2 antigens is therefore particularly important when assessing both existing immunity against common HCoVs and adverse effects like antibody-dependent enhancement (ADE) in COVID-19.

New Frontiers for Machine Learning in Protein Science.

Protein function is fundamentally reliant on inter-molecular interactions that underpin the ability of proteins to form complexes driving biological processes in living cells. Increasingly, such interactions are recognised as being formed between proteins that exist on a broad spectrum of dynamic conformational states and levels of intrinsic disorder. Additionally, the sizes of the structures formed can range from simple binary complexes to large dynamic biomolecular condensates measuring 100 nm or more.

Machine learning-aided protein identification from multidimensional signatures.

The ability to determine the identity of specific proteins is a critical challenge in many areas of cellular and molecular biology, and in medical diagnostics. Here, we present a macine learning aided microfluidic protein characterisation strategy that within a few minutes generates a three-dimensional fingerprint of a protein sample indicative of its amino acid composition and size and, thereby, creates a unique signature for the protein. By acquiring such multidimensional fingerprints for a set of ten proteins and using machine learning approaches to classify the fingerprints, we demonstrate that this strategy allows proteins to be classified at a high accuracy, even though classification using a single dimension is not possible.

Antibody Affinity Governs the Inhibition of SARS-CoV-2 Spike/ACE2 Binding in Patient Serum.

The humoral immune response plays a key role in suppressing the pathogenesis of SARS-CoV-2. The molecular determinants underlying the neutralization of the virus remain, however, incompletely understood. Here, we show that the ability of antibodies to disrupt the binding of the viral spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell, the key molecular event initiating SARS-CoV-2 entry into host cells, is controlled by the affinity of these antibodies to the viral antigen.

Learning the molecular grammar of protein condensates from sequence determinants and embeddings.

Intracellular phase separation of proteins into biomolecular condensates is increasingly recognized as a process with a key role in cellular compartmentalization and regulation. Different hypotheses about the parameters that determine the tendency of proteins to form condensates have been proposed, with some of them probed experimentally through the use of constructs generated by sequence alterations. To broaden the scope of these observations, we established an in silico strategy for understanding on a global level the associations between protein sequence and phase behavior and further constructed machine-learning models for predicting protein liquid-liquid phase separation (LLPS).

Appraisal of wheat genomics for gene discovery and breeding applications: a special emphasis on advances in Asia.

We discussed the most recent efforts in wheat functional genomics to discover new genes and their deployment in breeding with special emphasis on advances in Asian countries. Wheat research community is making significant progress to bridge genotype-to-phenotype gap and then applying this knowledge in genetic improvement. The advances in genomics and phenomics have intrigued wheat researchers in Asia to make best use of this knowledge in gene and trait discovery.

Ribozyme-catalysed RNA synthesis using triplet building blocks.

RNA-catalyzed RNA replication is widely believed to have supported a primordial biology. However, RNA catalysis is dependent upon RNA folding, and this yields structures that can block replication of such RNAs. To address this apparent paradox, we have re-examined the building blocks used for RNA replication.

[Results of surgical and combined treatment for nonsmall cell lung cancer with postoperative radiation therapy in a mode of hypofranctionation. Post II. Relapse-free survival and survival without locoregional recurrence].

Conducting postoperative radiotherapy in a mode of hypofranctionation with SFD-3Gy to TFD-36-39Gy (EQD2 = 43,246,8Gy) in combined treatment of patients with non-small cell lung cancer allows significantly increasing a 5-year disease-free survival at IIB-IIIB stages of the disease (pN1-2) as well as the central cancer, squamous cell morphological type of tumor after surgery in a volume of lob-bilobectomy. The clearest effect of postoperative radiotherapy is assessed by survival without locoregional recurrence where radiation therapy in the adjuvant setting allows achieving a statistically significant increase in local control of the disease to the level of 85-95% regardless of stage of the disease, tumor size, regional lymph nodes lesion and the surgical treatment.

[MICROCLIMATE CONDITION IN SUBWAY CARS IN THE SUMMER PERIOD OF THE YEAR].

There are presented the results of the work, which aims to identify the relationship between the temperature of air in the salons of subway cars from the heat output of passengers in different people occupancy of cars during "peak hours", and to determine the efficacy offorced air handling regular ventilation or air conditioning system to remove the elevated heat load on passengers. In the work there was used the method of calculating the amount of heat output of 215 passengers (nominal fullness of the chamber) and the simulation method of heat and moisture output of the same number of passengers. The operating system of ventilation has been shown to fail to decline the average temperature of the air in the passenger compartment to the optimum values and most efficient approach for the reducing the heat load on the passengers is the use of air conditioning systems.

[Middle fraction radiotherapy for non-small cell lung cancer. Effect of increasing the total focal dose].

There were evaluated retrospectively the immediate and long-term results of radiotherapy in 259 patients with non-small cell lung cancer stages I-IV who had contraindications to surgery. Irradiation was carried out by middle fraction with single focal dose 3-4 Gr. We compared the results of treatment in two groups of patients differed in volume of total focal dose: I group (124 patients)--45 Gy, II group (125 patients)--60 Gy.

Catalysts from synthetic genetic polymers.

The emergence of catalysis in early genetic polymers such as RNA is considered a key transition in the origin of life, pre-dating the appearance of protein enzymes. DNA also demonstrates the capacity to fold into three-dimensional structures and form catalysts in vitro. However, to what degree these natural biopolymers comprise functionally privileged chemical scaffolds for folding or the evolution of catalysis is not known.

[The effect of the antioxidant ionol as a liposome component on the function of the isolated and ischemic heart].

The anti-ischemic and toxic effects of different doses of the antioxidant ionol (butyl hydroxytoluene, BHT) introduced into the Krebs-Henseleit medium composed of monolayer liposomes of egg phospholipids before or 30 minutes after total ischemia of the heart were studied on a model of perfusion of isolated Wistar rat heart by the method of Langendorff-Fallen. It has been demonstrated that ionol, after its addition to the perfusate in the preischemic period, exerts an anti-ischemic effect in concentrations of 10(-6), 3 x 10(-6) and 10(-5) M; in the postischemic period, in concentrations of 3 x 10(-6) and 10(-5); the protective effect of ionol in the postischemic period is less pronounced. In higher doses (3 x 10(-5) and 10(-4) M) ionol produces a toxic action which is more remarkable and is less reversible in respect to the ischemized than to the nonischemized heart, and is realized rather through the dysfunction of heart muscle relaxation.

[A variant of an operation of varicose veins of the esophagus and cardia in patients with portal hypertension syndrome].

On analysing universal experience, the authors suggest their variant of operation on varicose veins of the esophagus and cardia with the use of Doppler ultrasonography and intraoperative packing of the veins with a radiocontrast foamy polymer. With this method the flow of blood in the venous collaterals of the stomach and esophagus can be arrested more radically during the operation, which considerably reduces the percentage of recurrent bleeding from these veins.

[Anti-ischemic action of a 1-hydroxy-2,2,6,6-tetramethylpiperidine derivative from a series of nitroxyl bioantioxidants].

The experiments have been performed on 216 Wistar rats to examine anti-ischaemic action of the 1-hydroxy-2,2,6,6-tetramethyl-piperidine derivative (I), whose antioxidant properties were, earlier shown for model systems. Introduction of I (10(-4) M) into the perfusion medium and the subsequent storage (37 degrees C) of isolated liver was shown to decrease the accumulation of lipid peroxidation products (MDA). Compound I administrated (5 x 10(-6)-10(-5) M) in perfuse medium of isolated (Langendorff method) and ischemized (30 min, 37 degrees C) heart improves contractile function (Pmax) and decreases end-diastolic pressure at postischaemic period.

[Disorders of cardiac contractile function in ischemic shock; the protective effect of antioxidants and liposomes made from egg phospholipids].

Experiments were made on Wistar rats with 6h tourniqueting of the hind limbs to study animal survival rate, myocardial contractile function and protective action of antioxidants and egg phospholipid liposomes during ischemic shock. It has been shown that reperfusion of the limbs leads to a high animal lethality, make lower myocardial contractile function and coronary flow of the hearts isolated from rats following a 6h reperfusion of the limbs. Well-known antioxidant butylated hydroxytoluene and a new antioxidant tetramethylpiperidine derivative bring animal lethality down and improve coronary flow and contractile function of the isolated heart.

[A method of suturing of dilated cardial veins in patients with portal hypertension].

Ultrasonic fluorometry used in 22 patients with portal hypertension facilitates the detection, marking the venous trunks of the cardia with inflammatory alterations of the mucosa. Intraoperative control of surgical treatment with the help of ultrasonic fluorometry allows operations to be performed more radically and to considerably reduce the intraoperative blood loss.