Deep learning for reconstructing protein structures from cryo-EM density maps: recent advances and future directions

Cryo-Electron Microscopy (cryo-EM) has emerged as a key technology to determine the structure of proteins, particularly large protein complexes and assemblies in recent years. A key challenge in cryo-EM data analysis is to automatically reconstruct accurate protein structures from cryo-EM density maps. In this review, we briefly overview various deep learning methods for building protein structures from cryo-EM density maps, analyze their impact, and discuss the challenges of preparing high-quality data sets for training deep learning models. Looking into the future, more advanced deep learning models of effectively integrating cryo-EM data with other sources of complementary data such as protein sequences and AlphaFold-predicted structures need to be developed to further advance the field

Free-flap reconstitutions of head and neck defects after oncologic ablation

Background: Head and neck cancers are the sixth most common cancers worldwide. The primary treatment modality for most head and neck cancers is surgery with reconstruction of resultant defects. Reconstruction of these defects is a unique challenge as it has to not only restore integrity but also function and often cosmesis. The objective of this study was to assess the utility of free flaps in the reconstruction of these defects, done in a tertiary care centre in a three-tier city in India. Methodology: We analyzed the computerized medical records of the last 3 years in this retrospective study carried out in the department of head and neck oncology at the cancer centre. The study included cases that had undergone surgery for head and neck cancer and underwent free flap reconstruction. Results: Out of the 1061 cases requiring reconstruction after an oncologic ablation, 201 cases underwent free flap reconstruction. For defects requiring Facio cutaneous reconstruction, the radial forearm was the preferred donor free flap site, while the fibula was the preferred donor site for mandibular reconstructions survival rate was 94.5%, with factors like age and comorbidities like diabetes and hypertension or habits like cigarette smoking or tobacco chewing not affecting survival rates. Twenty cases of minor flap complications were observed. Conclusions: Free flap reconstructions for head and neck defects after oncologic ablation have been a boon with good survival rates and immense flexibility of use, giving good cosmetic and functional outcomes. Our study shows that a significant number of free flap reconstructions can be done in a tertiary care centre in a three-tier city in India with an internationally comparable survival rate

Free-flap reconstitutions of head and neck defects after oncologic ablation

Background: Head and neck cancers are the sixth most common cancers worldwide. The primary treatment modality for most head and neck cancers is surgery with reconstruction of resultant defects. Reconstruction of these defects is a unique challenge as it has to not only restore integrity but also function and often cosmesis. The objective of this study was to assess the utility of free flaps in the reconstruction of these defects, done in a tertiary care centre in a three-tier city in India. Methodology: We analyzed the computerized medical records of the last 3 years in this retrospective study carried out in the department of head and neck oncology at the cancer centre. The study included cases that had undergone surgery for head and neck cancer and underwent free flap reconstruction. Results: Out of the 1061 cases requiring reconstruction after an oncologic ablation, 201 cases underwent free flap reconstruction. For defects requiring Facio cutaneous reconstruction, the radial forearm was the preferred donor free flap site, while the fibula was the preferred donor site for mandibular reconstructions survival rate was 94.5%, with factors like age and comorbidities like diabetes and hypertension or habits like cigarette smoking or tobacco chewing not affecting survival rates. Twenty cases of minor flap complications were observed. Conclusions: Free flap reconstructions for head and neck defects after oncologic ablation have been a boon with good survival rates and immense flexibility of use, giving good cosmetic and functional outcomes. Our study shows that a significant number of free flap reconstructions can be done in a tertiary care centre in a three-tier city in India with an internationally comparable survival rate

Bianchi Type I Massive String Magnetized Barotropic Perfect Fluid Cosmological Model in General Relativity

Bianchi type I massive string cosmological model with magnetic field of barotropic perfect fluid distribution through the techniques used by Latelier and Stachel, is investigated. To get the deterministic model of the universe, it is assumed that the universe is filled with barotropic perfect fluid distribution. The magnetic field is due to electric current produced along x-axis with infinite electrical conductivity. The behaviour of the model in presence and absence of magnetic field together with other physical aspects is further discussed.Comment: 10 pages, no figure. Chin. Phys. Lett., Vol. 24, No. 8 (2007), to appea

Testing the solar LMA region with KamLAND data

We investigate the potential of 3 kiloTon-years(kTy) of KamLAND data to further constrain the $\Delta m^2$ and $\tan^2\theta$ values compared to those presently allowed by existing KamLAND and global solar data. We study the extent, dependence and characteristics of this sensitivity in and around the two parts of the LMA region that are currently allowed. Our analysis with 3 kTy simulated spectra shows that KamLAND spectrum data by itself can constrain $\Delta m^2$ with high precision. Combining the spectrum with global solar data further tightens the constraints on allowed values of $\tan^2\theta$ and $\Delta m^2$. We also study the effects of future neutral current data with a total error of 7% from the Sudbury Neutrino Observatory. We find that these future measurements offer the potential of considerable precision in determining the oscillation parameters (specially the mass parameter).Comment: 16 pages, to appear in J Phys.

Bianchi Type V Viscous Fluid Cosmological Models in Presence of Decaying Vacuum Energy

Bianchi type V viscous fluid cosmological model for barotropic fluid distribution with varying cosmological term $\Lambda$ is investigated. We have examined a cosmological scenario proposing a variation law for Hubble parameter $H$ in the background of homogeneous, anisotropic Bianchi type V space-time. The model isotropizes asymptotically and the presence of shear viscosity accelerates the isotropization. The model describes a unified expansion history of the universe indicating initial decelerating expansion and late time accelerating phase. Cosmological consequences of the model are also discussed.Comment: 10 pages, 3 figure

Overview of ceramic matrix composite research at NASA Glenn Research Center

In support of NASA’s Aeronautics Research Mission, the Glenn Research Center in Cleveland, OH, has been developing and assessing the performance of high temperature SiC/SiC ceramic matrix composites (CMCs), both with and without protective coatings, for turbine engine applications. Combinations of highly creep-resistant SiC fibers, advanced 3D weaves, durable environmental barrier coatings (EBCs), and a 2700°F-capable hybrid SiC matrix have been evaluated. The effects of steam and thermal gradients on composite durability and means of monitoring and modeling damage are also being investigated. Additional studies focused on understanding the creep of SiC fibers and the behavior of SiC/SiC minicomposites that are being tested under a range of conditions are helping GRC model the thermomechanical behavior of SiC/SiC CMCs. Higher TRL (Technology Readiness Level) testing is being pursued, and SiC/SiC composites with alternate matrices providing self-healing capability are being explored. An overview of those studies will be provided. The development and validation of models for predicting the effects of the environment on the durability of CMCs and EBCs and other operating-environment challenges including the effect of CMAS (calcium magnesium aluminosilicate) degradation of EBCs will be discussed. Previous oxide/oxide composite development efforts will also be reviewed

Mitochondrial uncoupler DNP induces coexistence of dual-state hyper-energy metabolism leading to tumor growth advantage in human glioma xenografts

IntroductionCancer bioenergetics is an essential hallmark of neoplastic transformation. Warburg postulated that mitochondrial OXPHOS is impaired in cancer cells, leading to aerobic glycolysis as the primary metabolic pathway. However, mitochondrial function is altered but not entirely compromised in most malignancies, and that mitochondrial uncoupling is known to increase the carcinogenic potential and modifies treatment response by altering metabolic reprogramming. Our earlier study showed that transient DNP exposure increases glycolysis in human glioma cells (BMG-1). The current study investigated the persistent effect of DNP on the energy metabolism of BMG-1 cells and its influence on tumor progression in glioma xenografts.MethodsBMG-1 cells were treated with 2,4-dinitrophenol (DNP) in-vitro, to establish the OXPHOS-modified (OPM-BMG) cells. Further cellular metabolic characterization was carried out in both in-vitro cellular model and in-vivo tumor xenografts to dissect the role of metabolic adaptation in these cells and compared them with their parental phenotype. Results and DiscussionChronic exposure to DNP in BMG-1 cells resulted in dual-state hyper-energy metabolism with elevated glycolysis++ and OXPHOS++ compared to parental BMG-1 cells with low glycolysis+ and OXPHOS+. Tumor xenograft of OPM-BMG cells showed relatively increased tumor-forming potential and accelerated tumor growth in nude mice. Moreover, compared to BMG-1, OPM-BMG tumor-derived cells also showed enhanced migration and invasion potential. Although mitochondrial uncouplers are proposed as a valuable anti-cancer strategy; however, our findings reveal that prolonged exposure to uncouplers provides tumor growth advantage over the existing glioma phenotype that may lead to poor clinical outcomes

Building the Largest Spectroscopic Sample of Ultracompact Massive Galaxies with the Kilo Degree Survey

Ultracompact massive galaxies (ucmgs), i.e., galaxies with stellar masses M∗ > 8× 10-10 M⊙ and effective radii R e< 1.5 kpc, are very rare systems, in particular at low and intermediate redshifts. Their origin as well as their number density across cosmic time are still under scrutiny, especially because of the paucity of spectroscopically confirmed samples. We have started a systematic census of ucmg candidates within the ESO Kilo Degree Survey, together with a large spectroscopic follow-up campaign to build the largest possible sample of confirmed ucmgs. This is the third paper of the series and the second based on the spectroscopic follow-up program. Here, we present photometrical and structural parameters of 33 new candidates at redshifts 0.15≲ z≲ 0.5 and confirm 19 of them as ucmgs, based on their nominal spectroscopically inferred M and R e. This corresponds to a success rate of ∼ 58%, nicely consistent with our previous findings. The addition of these 19 newly confirmed objects allows us to fully assess the systematics on the system selection-and to finally reduce the number density uncertainties. Moreover, putting together the results from our current and past observational campaigns and some literature data, we build the largest sample of ucmgs ever collected, comprising 92 spectroscopically confirmed objects at 0.1≲ z≲ 0.5. This number raises to 116, allowing for a 3σ tolerance on the M∗ and Re thresholds for the ucmg definition. For all these galaxies, we have estimated the velocity dispersion values at the effective radii, which have been used to derive a preliminary mass-velocity dispersion correlation

KiDS ultracompact massive galaxies sp. obs.

Ultracompact massive galaxies (UCMGs), i.e., galaxies with stellar masses M*>8x1010M☉ and effective radii Re<1.5kpc, are very rare systems, in particular at low and intermediate redshifts. Their origin as well as their number density across cosmic time are still under scrutiny, especially because of the paucity of spectroscopically confirmed samples. We have started a systematic census of UCMG candidates within the ESO Kilo Degree Survey, together with a large spectroscopic follow-up campaign to build the largest possible sample of confirmed UCMGs. This is the third paper of the series and the second based on the spectroscopic follow-up program. Here, we present photometrical and structural parameters of 33 new candidates at redshifts 0.15≲z≲0.5 and confirm 19 of them as UCMGs, based on their nominal spectroscopically inferred M* and Re. This corresponds to a success rate of ∼58% , nicely consistent with our previous findings. The addition of these 19 newly confirmed objects allows us to fully assess the systematics on the system selection-and to finally reduce the number density uncertainties. Moreover, putting together the results from our current and past observational campaigns and some literature data, we build the largest sample of ucmgs ever collected, comprising 92 spectroscopically confirmed objects at 0.1≲z≲0.5. This number raises to 116, allowing for a 3σ tolerance on the M* and Re thresholds for the ucmg definition. For all these galaxies, we have estimated the velocity dispersion values at the effective radii, which have been used to derive a preliminary mass-velocity dispersion correlation