gebhart/patrepeval huggingface dataset:
A new immunohistochemistry prognostic score (IPS) for recurrence and survival in resected pancreatic neuroendocrine tumors (PanNET) (2016)

Pancreatic neuroendocrine tumor (PanNET) is a neoplastic entity in which few prognostic factors are well-known. Here, we aimed to evaluate the prognostic significance of N-myc downstream-regulated gen-1 (NDRG-1), O6-methylguanine DNA methyltransferase (MGMT) and Pleckstrin homology-like domain family A member 3 (PHLDA-3) by immunohistochemistry (IHC) and methylation analysis in 92 patients with resected PanNET and follow-up longer than 24 months. In multivariate analyses, ki-67 and our immunohistochemistry prognostic score (IPS-based on MGMT, NDRG-1 and PHLDA-3 IHC expression) were independent prognostic factors for disease-free-survival (DFS), while age and IPS were independent prognostic factors for overall survival (OS). Our IPS could be a useful prognostic biomarker for recurrence and survival in patients following resection for PanNET.
Understanding selenium and glutathione as antiviral factors in COVID-19: Does the viral Mpro protease target host selenoproteins and glutathione synthesis? (2020)

Glutathione peroxidases (GPX), a family of antioxidant selenoenzymes, functionally link selenium and glutathione, which both show correlations with clinical outcomes in COVID-19. Thus, it is highly significant that cytosolic GPX1 has been shown to interact with an inactive C145A mutant of Mpro, the main cysteine protease of SARS-CoV-2, but not with catalytically active wild-type Mpro. This seemingly anomalous result is what might be expected if GPX1 is a substrate for the active protease, leading to its fragmentation. We show that the GPX1 active site sequence is substantially similar to a known Mpro cleavage site, and is identified as a potential cysteine protease site by the Procleave algorithm. Proteolytic knockdown of GPX1 is highly consistent with previously documented effects of recombinant SARS-CoV Mpro in transfected cells, including increased reactive oxygen species and NF-kappaB activation. Because NF-kappaB in turn activates many pro-inflammatory cytokines, this mechanism could contribute to increased inflammation and cytokine storms observed in COVID-19. Using web-based protease cleavage site prediction tools, we show that Mpro may be targeting not only GPX1, but several other selenoproteins including SELENOF and thioredoxin reductase 1, as well as glutamate-cysteine ligase, the rate-limiting enzyme for glutathione synthesis. This hypothesized proteolytic knockdown of components of both the thioredoxin and glutaredoxin systems is consistent with a viral strategy to inhibit DNA synthesis, to increase the pool of ribonucleotides for RNA synthesis, thereby enhancing virion production. The resulting “collateral damage” of increased oxidative stress and inflammation would be exacerbated by dietary deficiencies of selenium, glutathione and glutathione precursors.
Antileukemia Effects of Notch-Mediated Inhibition of Oncogenic PLK1 in B-Cell Acute Lymphoblastic Leukemia (2019)

In B-cell acute lymphoblastic leukemia (B-ALL), activation of Notch signaling leads to cell-cycle arrest and apoptosis. We aimed to harness knowledge acquired by understanding a mechanism of Notch-induced cell death to elucidate a therapeutically viable target in B-ALL. To this end, we identified that Notch activation suppresses Polo-like kinase 1 (PLK1) in a B-ALL-specific manner. We identified that PLK1 is expressed in all subsets of B-ALL and is highest in Philadelphia-like (Ph-like) ALL, a high-risk subtype of disease. We biochemically delineated a mechanism of Notch-induced PLK1 downregulation that elucidated stark regulation of p53 in this setting. Our findings identified a novel posttranslational cascade initiated by Notch in which CHFR was activated via PARP1-mediated PARylation, resulting in ubiquitination and degradation of PLK1. This led to hypophosphorylation of MDM2<sup>Ser260</sup>, culminating in p53 stabilization and upregulation of BAX. shRNA knockdown or pharmacologic inhibition of PLK1 using BI2536 or BI6727 (volasertib) in B-ALL cell lines and patient samples led to p53 stabilization and cell death. These effects were seen in primary human B-ALL samples <i>in vitro</i> and in patient-derived xenograft models <i>in vivo</i> These results highlight PLK1 as a viable therapeutic target in B-ALL. Efficacy of clinically relevant PLK1 inhibitors in B-ALL patient-derived xenograft mouse models suggests that use of these agents may be tailored as an additional therapeutic strategy in future clinical studies.
Increased production of interleukin-6 by T lymphocytes from patients with multiple myeloma. (1996)

Alterations in T lymphocyte functions may affect other cellular components of the immune system. Several lymphokines produced by T cells are involved in the proliferation and differentiation of human B lymphocytes. Alterations in the secretion of these molecules may be implicated in the development of B cell lymphoproliferative diseases. We have investigated the production of interleukin-2 (IL-2) and interleukin-6 (IL-6) by T lymphocytes from 14 patients with multiple myeloma (MM) and 16 healthy controls. The phenotypical and functional characteristics of these T lymphocytes were also studied. The proliferative response to vegetal lectin phytohemagglutinin (PHA) stimulation was decreased in T lymphocytes from MM patients (p < 0.01). This defective proliferative response cannot be ascribed to either defective IL-2 production or diminished receptor expression, since neither of these parameters showed a significant difference between MM patients and healthy controls (p < 0.05). However, the defective proliferative response of T lymphocytes from MM patients was reverted by the addition of saturating amounts of exogenous IL-2 (p > 0.05) but not by exogenous IL-6 (p < 0.05). The IL-6 production by PHA-stimulated T lymphocytes from the MM patients was significantly higher than in healthy controls (p < 0.01). We conclude that T lymphocytes from MM patients show a functional alteration with a defective proliferative response to PHA that is reverted by exogenous addition of IL-2. After lectin stimulation, the production of IL-2 by T lymphocytes from those patients was normal, while IL-6 secretion was increased.
Selective Hydrogenation for Fine Chemical Synthesis (2014)

Hydrogenation is an important and widely applied reaction in chemical industry. Supported ionic liquid (IL) type catalysts have shown good performance in various hydrogenation reactions. This chapter introduces a few case studies where supported IL catalysis has been applied in hydrogenation reactions. The case studies highlight the novelty of supported IL catalyst (SILCA) catalysts. Selective hydrogenation of α,ß-unsaturated aldehydes, ketones, and esters, in general, is a versatile pathway to obtain many interesting products that can be used in perfumes, hardening of fats, preparation of pharmaceuticals, and synthesis of organic intermediates. SILCAs have been successfully demonstrated to act as catalysts in chemoselective hydrogenations, and thus an analogous concept has been applied for the synthesis of chiral metal complexes in ILs supported on heterogeneous catalysts.
Towards Dependability in Everyday Software Using Software Telemetry (2006)

Application-level software dependability is difficult to ensure. Thus it's typically used only in custom systems and is achieved using one-of-a-kind, handcrafted solutions. We are interested in understanding whether and how these techniques can be applied to more common, lower-end systems. To this end, we have adapted a condition-based maintenance (CBM) approach called the multivariate state estimation technique (MSET). This approach automatically creates sophisticated statistical models that predict system failure well before failures occur, leading to simpler and more successful recoveries. We have packaged this approach in the Software Dependability Framework (SDF). The SDF consists of instrumentation and data management libraries, a CBM module, performance visualization tools, and a software architecture that supports system designers. Finally, we evaluated our framework on a simple video game application. Our results suggest that we can cheaply and reliably predict impending runtime failures and respond to them in time to improve the system's dependability
EPEN-27. Epigenetic dissection of spinal ependymomas (SP-EPN) separates tumors with and withoutNF2 mutation (2022)

Abstract Ependymomas encompass multiple, clinically relevant tumor types based on localization, genetic alterations, and epigenetic and transcriptomic profiles. Tumors belonging to the methylation class of spinal ependymoma (SP-EPN) represent the most common intramedullary neoplasms in children and adults. However, molecular data of SP-EPN are scarce, and clear treatment recommendations are lacking. The only known recurrent genetic events in SP-EPN are loss of chromosome 22q and NF2 mutations. Yet, it remains unclear whether SP-EPN with germline or sporadic NF2 mutations or with NF2 wild type status differ clinically or molecularly. To provide a comprehensive molecular profile of SP-EPN, we integrated epigenetic, genomic, transcriptomic, and histological analyses of up to 237 cases. Clustering of methylation data revealed two distinct molecular SP-EPN subtypes. The distribution of NF2 mutated cases differed significantly across these subtypes (p &amp;lt;0.0001): The vast majority of tumors harboring either a previously known NF2 germline mutation or a sporadic mutation were assigned to subtypes A, whereas subtype B tumors mainly contained NF2 wild type sequences. In addition, subtype A tumors showed a lower frequency of MGMT promoter methylation (p= 0.018) and contained almost all pediatric patients of the cohort. Whole-exome sequencing (30 cases) identified numerous mutations in NF2 wild type and mutated tumors. Mutated genes in NF2 wild type tumors were enriched for genes associated with cell cycle and cytoskeleton. RNA sequencing revealed two distinct transcriptional groups with upregulation of proliferative genes in one group and upregulation of cilial genes in the other group. The molecular subtypes displayed subtle, but significant differences in the appearance of histopathological characteristics, such as surfaces, inflammation, and hyalinized vessels. Investigation of clinical parameters is ongoing and will complete the picture of SP-EPN heterogeneity as an important basis for future clinical decision-making.
A Decrease in GTP Content is Associated with Aerial Mycelium Formation in Streptomyces MA406-A-1 (1986)

Aerial mycelium formation by Streptomyces sp. MA406-A-1, a formycin-producing strain, was suppressed by the presence of excess nutrient. In such suppressed cultures, decoyinine, which specifically inhibits GMP synthetase, initiated the formation of aerial mycelium at concentrations which only partially inhibited growth. The intracellular GTP pool of organisms growing in liquid culture markedly decreased on the addition of decoyinine. Decoyinine was also effective in initiating aerial mycelium formation of three other Streptomyces spp. examined. Regardless of the successful initiation of aerial mycelium formation, the ability of the cells to produce antibiotics (formycin or actinomycin D) did not increase, but decreased, on the addition of decoyinine. It is concluded that aerial mycelium formation by Streptomyces results from a decrease in the pool of GTP (or GDP), whereas antibiotic synthesis results from a different signal(s).
Eddy Current Method for Low Temperature Resistivity Measurements (1967)

A modified mutual inductance bridge incorporating a commercial phase-lock amplifier has been used to measure low temperature bulk resistivities in the range from 1 to 10 000 nΩ cm. No electrical contact is required with the spherical metal samples, so that possible heat leakage along electrical leads is eliminated, and measurements can be made below 40 mdeg Kelvin using a dilution refrigerator. The bridge circuit, capable of determining resistivity changes with a precision of better than 0.3%, is described.
Microbiology of the Atmosphere-Rock Interface: How Biological Interactions and Physical Stresses Modulate a Sophisticated Microbial Ecosystem (2009)

Life at the atmosphere-lithosphere boundary is an ancient terrestrial niche that is sparsely covered by thin subaerial biofilms. The microbial inhabitants of these biofilms (a) have adapted to all types of terrestrial/subaerial stresses (e.g., desiccation, extreme temperatures, low nutrient availability, intense solar radiation), (b) interact with minerals that serve as both a dwelling and a source of mineral nutrients, and (c) provoke weathering of rocks and soil formation. Subaerial communities comprise heterotrophic and phototrophic microorganisms that support each other's lifestyle. Major lineages of eubacteria associated with the early colonization of land (e.g., Actinobacteria, Cyanobacteria) are present in these habitats along with eukaryotes such as microscopic green algae and ascomycetous fungi. The subaerial biofilm inhabitants have adapted to desiccation, solar radiation, and other environmental challenges by developing protective, melanized cell walls, assuming microcolonial architectures and symbiotic lifestyles. How these changes occurred, their significance in soil formation, and their potential as markers of climate change are discussed below.
Linking Capacity Development to GOOS Monitoring Networks to Achieve Sustained Ocean Observation (2018)

Developing enduring capacity to monitor ocean life requires investing in people and their institutions to build infrastructure, ownership, and long-term support networks. International initiatives can enhance access to scientific data, tools and methodologies, and develop local expertise to use them, but without ongoing engagement may fail to have lasting benefit. Linking capacity development and technology transfer to sustained ocean monitoring is a win-win proposition. Trained local experts will benefit from joining global communities of experts who are building the comprehensive Global Ocean Observing System (GOOS). This two-way exchange will benefit scientists and policy makers in developing and developed countries. The first step toward the GOOS is complete: identification of an initial set of biological Essential Ocean Variables (EOVs) that incorporate the GEO Essential Biological Variables (EBVs), and link to the physical and biogeochemical EOVs. EOVs provide a globally consistent approach to monitoring where the costs of monitoring oceans can be shared and where capacity and expertise can be transferred globally. Integrating monitoring with existing international reporting and policy development connects ocean observations with agreements underlying many countries’ commitments and obligations, including under SDG 14, thus catalysing progress towards sustained use of the ocean. Combining scientific expertise with international capacity development initiatives can help meet the need of developing countries to engage in the agreed UN initiatives including new negotiations for management of Biodiversity Beyond National Jurisdiction, and the needs of the global community to understand how the ocean is changing.
Phosphoprotein phosphatase 1 (PP1) is a component of the isolated sea urchin mitotic apparatus (1994)

A protein component of isolated mitotic apparatus having a relative molecular mass of 62,000 (p62) is a substrate of a calcium/calmodulin dependent protein kinase, and the phosphorylation of p62 in vitro correlates directly with microtubule disassembly. In vivo experiments have determined the phosphorylation of p62 increases after fertilization; maximum incorporation of phosphate occurs during late metaphase/early anaphase and decreases thereafter. Because the level of p62 is constant throughout the cell cycle [Johnston and Sloboda, 1992: J. Cell Biol. 119:843-54] the decrease in phosphorylation of p62 observed after anaphase onset is most likely due to the action of a phosphatase. By examination of the relative amount of phosphorylated p62 which remained radiolabeled as a function of time using a standard in vitro phosphorylation assay, the activity of a phosphoprotein phosphatase capable of dephosphorylating p62 in the isolated mitotic apparatus was observed. To characterize the p62 phosphatase, okadaic acid and calyculin A were used to inhibit the dephosphorylation of p62 in vitro. It was found that specific concentrations of okadaic acid (50-500 nM) and of calyculin A (10-100 nM) were effective at inhibiting the dephosphorylation of p62 in vitro. Lower concentrations of either inhibitor had a negligible effect on dephosphorylation of p62. These data indicate the presence of phosphoprotein phosphatase type 1 activity associated with mitotic apparatus isolated from sea urchin embryos using the procedures described here. The implications of these findings relative to our understanding of the regulation of mitosis and cytokinesis are discussed.
Circulating Epithelial Cells in Intraductal Papillary Mucinous Neoplasms and Cystic Pancreatic Lesions (2017)

Circulating epithelial cells staining with potential pancreas-specific markers have been found in patients with IPMNs, even without malignancy. Circulating epithelial cells may help to differentiate patients with high-grade IPMN from lower grades of dysplasia and other pancreatic cysts.
The genome sequence of Samia ricini, a new model species of lepidopteran insect (2020)

Samia ricini, a gigantic saturniid moth, has the potential to be a novel lepidopteran model species. Since S. ricini is much more tough and resistant to diseases than the current model species Bombyx mori, the former can be easily reared compared to the latter. In addition, genetic resources available for S. ricini rival or even exceed those for B. mori: at least 26 eco-races of S. ricini are reported and S. ricini can hybridise with wild Samia species, which are distributed throughout Asian countries, and produce fertile progenies. Physiological traits such as food preference, integument colour, larval spot pattern, etc. are different between S. ricini and wild Samia species so that those traits can be the target for forward genetic analysis. In order to facilitate genetic research in S. ricini, we determined the whole genome sequence of S. ricini. The assembled genome of S. ricini was 458 Mb with 155 scaffolds, and the N50 length of the assembly was approximately 21 Mb. 16,702 protein coding genes were predicted in the assembly. Although the gene repertoire of S. ricini was not so different from that of B. mori, some genes, such as chorion genes and fibroin genes, seemed to have specifically evolved in S. ricini.
Caloric Restriction and Experimental Tumorigenesis (1993)

Although dietary guidance directed to the reduction of cancer risk emphasizes reduction in fat intake, this article documents evidence from animal studies that caloric balance either through reduced intake or increased expenditure of energy without a reduction in fat is even more effective in controlling tumor growth.
The Fourier transform of linearly varying functions with polygonal support (1991)

New formulas for the two-dimensional Fourier transform of functions with polygonal support and linear amplitude variation are derived from the corresponding formula for a constant function. These expressions, valid for all nonzero values of the transform variable k, are superior to those previously reported, which fail when k is perpendicular or parallel to any edge of the polygon. These transforms have applications in diffraction theory and computational electromagnetics.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Robust Discriminative Response Map Fitting with Constrained Local Models (2013)

We present a novel discriminative regression based approach for the Constrained Local Models (CLMs) framework, referred to as the Discriminative Response Map Fitting (DRMF) method, which shows impressive performance in the generic face fitting scenario. The motivation behind this approach is that, unlike the holistic texture based features used in the discriminative AAM approaches, the response map can be represented by a small set of parameters and these parameters can be very efficiently used for reconstructing unseen response maps. Furthermore, we show that by adopting very simple off-the-shelf regression techniques, it is possible to learn robust functions from response maps to the shape parameters updates. The experiments, conducted on Multi-PIE, XM2VTS and LFPW database, show that the proposed DRMF method outperforms state-of-the-art algorithms for the task of generic face fitting. Moreover, the DRMF method is computationally very efficient and is real-time capable. The current MATLAB implementation takes 1 second per image. To facilitate future comparisons, we release the MATLAB code and the pre-trained models for research purposes.
208. Neural Stem Cell Mediated Oncolytic Virotherapy for Ovarian Cancer (2016)

Intro. Oncolytic virotherapy is a promising novel cancer treatment that uses replication-competent viruses to induce cancer cell death. While clinical trials are underway for a variety of solid tumors; success has been hampered by rapid immune-mediated clearance/neutralization of the viral vectors, and poor viral distribution to tumor satellites dispersed throughout normal tissue. Neural stem cells (NSCs) are ideal cell carriers that could overcome viral delivery hurdles due to their intrinsic tumor-tropism and penetration capabilities. Our lab has established a well-characterized, non-immunogenic human NSC line that can selectively distribute to many different solid tumors. Most recently, we observed impressive selectivity and penetration of peritoneal ovarian cancer metastases after intraperitoneal NSC administration. We have engineered our NSCs to produce a conditionally replication-competent adenovirus, CRad-Survivin-pk7 (NSC.CRad-S-pk7). This virus has two notable genetic modifications: (1) a polylysine fiber addition that enables high affinity binding to cell-surface proteoglycans, thus promoting viral entry into the target cell; and (2) a E1A transcriptional modification which prevents viral replication in the the absence of the surviving promoter, a gene over-expressed in many cancers. Clinical grade equivalent research banks of the NSC. CRad-S-pk7 cells have demonstrated safety and efficacy in orthotopic glioma models, but have not yet been tested in a metastatic ovarian cancer model. We hypothesize that NSCs are able to selectively distribute this virus to ovarian metastases, and provide protection from immune-mediated clearance and neutralization. Our long-term goal is to demonstrate efficacy and safety of NSC. CRad-S-pk7 for targeted selective tumor killing in patients suffering from stage III ovarian cancer. Methods. Two million NSC and NSC. CRad-S-pk7 cells were injected IP into nude mice containing established human peritoneal ovarian (OVCAR8 and SKOV3) metastases. After 7 days, tissue was assessed for viral distribution and activity using standard immunological and tumor-lysate viral titration assays, respectively. Results. The results suggest that the viral payload does not interfere with the NSC tumor-tropism or penetration (Fig 1). NSC-mediated viral distribution was confirmed via immunohistochemistry, and the presence of active virus within lysed peritoneal tumors was assessed. Significant tumor killing was observed in both OVCAR8 and SKOV3 ovarian cancer cells after 5 days of culture with diluted tumor lysates (1:10 and 1:100) derived from mice that received NSC. CRad-S-pk7 injections (Fig 2). No killing was observed when cancer cells were cultured with tumor lysates derived from mice that received parental NSCs. These results demonstrate that NSC. CRad-S-pk7 can selectively penetrate peritoneal ovarian metastases and produce CRad-S-pk7 adenovirus following IP administration. Studies underway include free virus distribution and pharmacokinetic comparisons.