Portable universal tensile testing machine for studying mechanical properties of superelastic biomaterials

A portable universal tensile testing machine for single and cyclic loading of superelastic biomaterials is presented. It’s an alternative to large-sized stationary universal testing machines. The machine is designed to obtain uniaxial cyclic tension stress-strain curves of materials with a low elastic modulus, including biological tissues. Its portability allows using it in various conditions: classrooms, production laboratories, and in the field. An interface has been developed to connect it to a computer. Computer output of experimental data allows recording and displaying load-displacement curves, setting the number of cycles, limits, and rate of cyclic deformation. Several examples of testing various biomaterials are presented. The functional advantage of the device is the wide tensile testing speed range of 0.01-10 mm/s and cyclic loading, which allow capturing viscoelastic and superelastic behavior of biomaterials.

Real and predicted lung function after anatomical lung resections (review of literature)

The function of the respiratory parenchyma remaining after lung resection is one of the determining factors of the immediate result of the operation and the postoperative quality of life. A number of studies have been conducted to objectify the preoperative prognosis of the functional safety limit of thoracic interventions using a variety of methods and formulas. Unfortunately, until now, there is no convincing data on the correctness of at least one of the proposed methods for predicting respiratory function. The process of rehabilitation of postoperative ventilation function in the lungs is affected not only by the volume of parenchymal resection, but also by the area of resection, the method and trauma of access, the severity of emphysema, intraoperative trauma of mediastinal structures, postoperative progression of pulmonary fibrosis, etc., and video assisted surgery and segmental resections do not provide an obvious functional advantage in the long term after operations. During the first year after anatomical resection of the lung, functional indicators usually improve. Reasons (or reason) of such improvements are not always clear and may be associated with compensatory growth of the pulmonary parenchyma in a number of patients.

Highly-potent, synthetic APOBEC3s restrict HIV-1 through deamination-independent mechanisms

The APOBEC3 (A3) genes encode cytidine deaminase proteins with potent antiviral and anti-retroelement activity. This locus is characterized by duplication, recombination, and deletion events that gave rise to the seven A3s found in primates. These include three single deaminase domain A3s (A3A, A3C, and A3H) and four double deaminase domain A3s (A3B, A3D, A3F, and A3G). The most potent of the A3 proteins against HIV-1 is A3G. However, it is not clear if double deaminase domain A3s have a generalized functional advantage to restrict HIV-1. In order to test whether superior restriction factors could be created by genetically linking single A3 domains into synthetic double domains, we linked A3C and A3H single domains in novel combinations. We found that A3C/A3H double domains acquired enhanced antiviral activity that is at least as potent, if not better than, A3G. Although these synthetic double domain A3s package into budding virions more efficiently than their respective single domains, this does not fully explain their gain of antiviral potency. The antiviral activity is conferred both by cytidine-deaminase dependent and independent mechanisms, with the latter correlating to an increase in RNA binding affinity. T cell lines expressing this A3C-A3H super restriction factor are able to control replicating HIV-1ΔVif infection to similar levels as A3G. Together, these data show that novel combinations of A3 domains are capable of gaining potent antiviral activity to levels similar to the most potent genome-encoded A3s, via a primarily non-catalytic mechanism.

Recent achievements in CAR-T cell immunotherapy for glioblastoma treatment

Glioblastoma remains the most common and aggressive primary brain tumor today. Because of the neuroanatomical location of glioblastoma, conventional chemotherapy and radiation therapy have limited efficacy in patients with these tumors. Over the past decade, antitumor immunotherapy has become widespread among modern therapeutic approaches. The importance of immunotherapeutic methods lies in their ability to increase the effectiveness of cancer treatment and prevent relapses by enhancing the systemic and local immune response against tumor cells.One of the most promising directions in modern immunotherapy is CAR-T therapy, or adoptive cell therapy using genetically modified T-lymphocytes. The functional advantage of CAR-T therapy is its ability to genetically modify lymphocytes, leading to their activation in vitro.This review examines the key principles of CAR-T therapy and analyzes the published results of clinical trials for the treatment of glioblastoma using several modifications of CAR-T cells.

Evaluating machine learning methodologies for identification of cancer driver genes

Cancer is driven by distinctive sorts of changes and basic variations in genes. Recognizing cancer driver genes is basic for accurate oncological analysis. Numerous methodologies to distinguish and identify drivers presently exist, but efficient tools to combine and optimize them on huge datasets are few. Most strategies for prioritizing transformations depend basically on frequency-based criteria. Strategies are required to dependably prioritize organically dynamic driver changes over inert passengers in high-throughput sequencing cancer information sets. This study proposes a model namely PCDG-Pred which works as a utility capable of distinguishing cancer driver and passenger attributes of genes based on sequencing data. Keeping in view the significance of the cancer driver genes an efficient method is proposed to identify the cancer driver genes. Further, various validation techniques are applied at different levels to establish the effectiveness of the model and to obtain metrics like accuracy, Mathew’s correlation coefficient, sensitivity, and specificity. The results of the study strongly indicate that the proposed strategy provides a fundamental functional advantage over other existing strategies for cancer driver genes identification. Subsequently, careful experiments exhibit that the accuracy metrics obtained for self-consistency, independent set, and cross-validation tests are 91.08%., 87.26%, and 92.48% respectively.

Cross-reactive TCR with alloreactivity for immunodominant HIV-1 epitope Gag TL9 with enhanced control of viral infection

Although both HLA B*81:01 and HLA B*42:01 are members of the B7 supertype and can present many of the same HIV-1 epitopes, the identification of a dual-reactive T cell phenotype was unexpected, since structural data suggested that TL9 peptide binds to each allele in a distinct conformation. How the dual-reactive TCR recognizes these radically distinct p-MHC surfaces is revealed by our structural study, that the introduction of TCR T18A induces a molecular switch of the TL9 peptide in B4201 to approach its conformation in B8101. Most importantly, unique docking of CDR3β towards MHC but not peptide ligand strengthens the peptide tolerance of T18A, extends the ability of TCR to adapt mutations. Moreover, the high affinity of dual active TCR for WT and escape mutant TL9 highlights the functional advantage of the alloreactive phenotype.

Diffusive search and trajectories on tubular networks: a propagator approach

Several organelles in eukaryotic cells, including mitochondria and the endoplasmic reticulum, form interconnected tubule networks extending throughout the cell. These tubular networks host many biochemical pathways that rely on proteins diffusively searching through the network to encounter binding partners or localized target regions. Predicting the behavior of such pathways requires a quantitative understanding of how confinement to a reticulated structure modulates reaction kinetics. In this work, we develop both exact analytical methods to compute mean first passage times and efficient kinetic Monte Carlo algorithms to simulate trajectories of particles diffusing in a tubular network. Our approach leverages exact propagator functions for the distribution of transition times between network nodes and allows large simulation time steps determined by the network structure. The methodology is applied to both synthetic planar networks and organelle network structures, demonstrating key general features such as the heterogeneity of search times in different network regions and the functional advantage of broadly distributing target sites throughout the network. The proposed algorithms pave the way for future exploration of the interrelationship between tubular network structure and biomolecular reaction kinetics. Graphic Abstract

The function of consciousness is to generate experience

Why would we do anything at all if the doing was not doing something to us? In other words: What is consciousness good for? Here, reversing classical views, according to many of which subjective experience is a mere epiphenomenon that affords no functional advantage, we propose that the core function of consciousness is precisely to enable subject-level experience. “What it feels like” is endowed with intrinsic value, and it is precisely the value agents associate with their experiences that explains why we do certain things and avoid others. Thus, we argue that it is only in virtue of the fact that conscious agents experience things and care about those experiences that they are motivated to act in certain ways and that they prefer some states of affairs vs. others. In this sense, conscious experience functions as a mental currency of sorts, which not only endows mental states with intrinsic value, but also makes it possible for conscious agents to compare vastly different experiences in a common subject-centered space — a feature that readily explains the fact that consciousness is unified. If, as we argue, the function of consciousness is to endow agents with subjective experience, then the hard problem of consciousness seems to dissolve.

How Associative Thinking Influences Scene Perception

Perception of our external environment is not isolated from the influence of our internal thoughts. Here, we investigate the nature of their interaction. We argue that a common associative mechanism underlies both the perception of scenes and our internal thoughts, and in three experiments hypothesize that there is a functional advantage to an associative thought pattern in the perception of scenes. Experiments 1 and 2 showed that associative thinking indeed facilitates scene perception, an effect that evolved over the course of the experiments. Experiment 3 showed that associative thinking hinders the perception of individual, isolated objects, in which associative information is minimized, but that object perception is facilitated when associative thinking is reduced. This double dissociation reveals that a match between the orientation of internal and external processing is key for perception, suggesting that an associative mind is more receptive of externally perceived associative information.

Highly-potent, synthetic APOBEC3s restrict HIV-1 through deamination-independent mechanisms

The A POBEC3 ( A3 ) genes encode cytidine deaminase proteins with potent antiviral and anti-retroelement activity. This locus is characterized by duplication, recombination, and deletion events that gave rise to the seven A3 s found in primates. These include three single deaminase domain A3s ( A3A , A3C , and A3H ) and four double deaminase domain A3s ( A3B , A3D , A3F , and A3G ). The most potent of the A3 proteins against HIV-1 is A3G. However, it is not clear if double deaminase domain A3s have a generalized functional advantage to restrict HIV-1. In order to test whether superior restriction factors could be created by genetically linking single A3 domains into synthetic double domains, we combined A3C and A3H single domains in novel combinations. We found that A3C/A3H double domains acquired enhanced antiviral activity that is at least as potent, if not better than, A3G. These synthetic double domain A3s have more efficiency of packaging into budding virions than their respective single domains, but this does not fully explain their gain of antiviral potency. The antiviral activity is conferred both by cytidine-deaminase dependent and independent mechanisms, with the latter correlating to an increase in RNA binding affinity. T cell lines expressing this A3C-A3H super restriction factor are able to control replicating HIV-1DVif infection to similar levels as A3G. Together, these data show that novel combinations of A3 domains are capable of gaining potent antiviral activity to levels similar to the most potent genome-encoded A3s, via a primarily non-catalytic mechanism.