In-water neutron and gamma dose determination for a new Cf-252 brachytherapy source

Recently, the Oak Ridge National Laboratory (ORNL) successfully encapsulated a new generation of medical grade Cf-252 sources having intensities and size comparable to that of the widely used high-dose-rate (HDR) Ir-192 brachytherapy sources. Advent of the new sources, therefore, marked a new era for Cf-252-based neutron brachytherapy (NBT). As part of source calibration and characterization process, a study has been conducted at Georgia Tech lately on determining the neutron and gamma dose rates in water surrounding the new Cf-252 source. A Lucite-walled water phantom was built for this study. The neutron and gamma dose rates were determined both by ion chamber measurements and by Monte Carlo code MCNP. The results show that the measured neutron absorbed dose rates were approximately 25% lower than that predicted by MCNP for all dose positions in water, suggesting that the Cf-252 content of the new source is actually 25% lower than the ORNL's estimate. The measured gamma absorbed dose rates in water, on the contrary, are higher than that predicted by MCNP. The differences between the measured and MCNP-predicted gamma doses are not uniform for all dose positions; they are most pronounced (~a factor of two) at the distance of 1 cm, and fall to approximately 30% at distances 2 cm and beyond. These results suggest that the spectrum of gamma rays emitted from the new Cf-252 source may contain significantly more low-energy gamma rays than the previously published spectrum used in MCNP.M.S.Committee Chair: Dr. C.-K. Chris Wang; Committee Member: Dr. Nolan E. Hertel; Committee Member: Dr. Sang Hyun Ch

Cardiac Tissue Engineering: Implications for Pediatric Heart Surgery

Children with severe congenital malformations, such as single-ventricle anomalies, have a daunting prognosis. Heart transplantation would be a therapeutic option but is restricted due to a lack of suitable donor organs and, even in case of successful heart transplantation, lifelong immune suppression would frequently be associated with a number of serious side effects. As an alternative to heart transplantation and classical cardiac reconstructive surgery, tissue-engineered myocardium might become available to augment hypomorphic hearts and/or provide new muscle material for complex myocardial reconstruction. These potential applications of tissue engineered myocardium will, however, impose major challenges to cardiac tissue engineers as well as heart surgeons. This review will provide an overview of available cardiac tissue-engineering technologies, discuss limitations, and speculate on a potential application of tissue-engineered heart muscle in pediatric heart surgery

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Molecular Basis for the Generation in Pigs of Influenza A Viruses with Pandemic Potential

Genetic and biologic observations suggest that pigs may serve as “mixing vessels” for the generation of human-avian influenza A virus reassortants, similar to those responsible for the 1957 and 1968 pandemics. Here we demonstrate a structural basis for this hypothesis. Cell surface receptors for both human and avian influenza viruses were identified in the pig trachea, providing a milieu conducive to viral replication and genetic reassortment. Surprisingly, with continued replication, some avian-like swine viruses acquired the ability to recognize human virus receptors, raising the possibility of their direct transmission to human populations. These findings help to explain the emergence of pandemic influenza viruses and support the need for continued surveillance of swine for viruses carrying avian virus genes

Изучение минерального состава палеозойских пород-коллекторов Калинового нефтегазоконденсатного месторождения (Томская область)

Выпускная квалификационная работа посвящена определению сложного минерального состава палеозойских отложений ХХХХХ нефтегазоконденсатного месторождения методом инфракрасной спектроскопии с преобразованием Фурье. Изучены образцы керна, отобранного из скважины Х данного месторождения. Полученные результаты сопоставлены с результатами работы отечественных и зарубежных исследователей. Внесен вклад в систематизацию знаний по интерпретации спектров инфракрасного поглощения.The graduation thesis is devoted to identification of complex mineral composition of Paleozoic sedimentary rocks in ХХХХХ oil-gas-condensate field by FTIR. The core samples from one well of this field were investigated. The obtained results are compared with the results of the work of domestic and foreign researchers. The classification of infrared spectra was supplemented

Sexual dimorphism in cancer: Insights from transcriptional signatures in kidney tissue and renal cell carcinoma

International audienceSexual dimorphism in cancer incidence and outcome is widespread. Understanding the underlying mechanisms is fundamental to improve cancer prevention and clinical management. Sex disparities are particularly striking in kidney cancer: across diverse populations, men consistently show unexplained 2-fold increased incidence and worse prognosis. We have characterized genome-wide expression and regulatory networks of 609 renal tumors and 256 non-tumor renal tissues. Normal kidney displayed sex-specific transcriptional signatures, including higher expression of X-linked tumor suppressor genes in women. Sex-dependent genotype–phenotype associations unraveled women-specific immune regulation. Sex differences were markedly expanded in tumors, with male-biased expression of key genes implicated in metabolism, non-malignant diseases with male predominance and carcinogenesis, including markers of tumor infiltrating leukocytes. Analysis of sex-dependent RCC progression and survival uncovered prognostic markers involved in immune response and oxygen homeostasis. In summary, human kidney tissues display remarkable sexual dimorphism at the molecular level. Sex-specific transcriptional signatures further shape renal cancer, with relevance for clinical management

The HDAC inhibitors trichostatin A and suberoylanilide hydroxamic acid exhibit multiple modalities of benefit for the vascular pathobiology of sickle transgenic mice

The vascular pathobiology of sickle cell anemia involves inflammation, coagulation, vascular stasis, reperfusion injury, iron-based oxidative biochemistry, deficient nitric oxide (NO) bioavailability, and red cell sickling. These disparate pathobiologies intersect and overlap, so it is probable that multimodality therapy will be necessary for this disease. We have, therefore, tested a histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), for efficacy in reducing endothelial activation. We found that pulmonary vascular endothelial VCAM-1 and tissue factor (TF) expression (both are indicators of endothelial activation) are powerfully and significantly inhibited by TSA. This is seen both with pretreatment before the inducing stress of hypoxia/reoxygenation (NY1DD sickle transgenic mouse), and upon longer-term therapy after endothelial activation has already occurred (hBERK1 sickle mouse at ambient air). In addition, TSA prevented vascular stasis in sickle mice, it exhibited activity as an iron chelator, and it induced expression of the antisickling hemoglobin, hemoglobin F. Notably, the TSA analog SAHA (suberoylanilide hydroxaminc acid) that is already approved for human clinical use exhibits the same spectrum of biologic effects as TSA. We suggest that SAHA possibly could provide true, multimodality, salubrious effects for prevention and treatment of the chronic vasculopathy of sickle cell anemia