gebhart/patrepeval huggingface dataset:
Insights into Oncogenesis from Circadian Timing in Cancer Stem Cells (2021)

Cancer and circadian rhythms are linked in several ways, through immunomodulatory, neuroendocrine, and metabolic pathways. The circadian timing system consists of interacting circadian clocks in organs throughout the body that contain cells endowed with self-sustaining molecular circadian oscillations. Circadian rhythms are spontaneously generated by specific transcription and translation feedback cycles. Cancer cells emerging from these rhythmic tissues are subjected to daily physiological rhythms imposed by the circadian system, and some transformed cells have their own intrinsic circadian clocks. The role of these circadian clock cells in cancer prevention and oncogenesis remains to be fully explored. Nevertheless, evidence suggests that new cancers are fostered by degradation of the circadian system's rhythmic properties. In contrast, circadian clocks within cancer cells might aid in their survival if they provide benefits such as an ability to synchronize with daily nutrient availability or circadian rhythms in immune cell activity. Here, we address new evidence challenging the simplicity of carcinogenesis models that depend solely on the importance of minimized cancer risk provided by well-aligned and robust circadian clocks in the body. The biology of cancer stem cells and the benefits they may receive from their own rhythmic and non-rhythmic expressions of core circadian clock genes are examined with a focus on gliomas and liver cancer stem cells, along with possibilities for timed medical interventions.
Expression of the Neurotensin/Neuromedin N Gene in the Gut (1999)

Embryologic development of the gastrointestinal (GI) tract represents an important clinical topic, but one that has been, to date, poorly understood. The human GI tract arises during the fourth week of gestation from gut-derived endoderm contacting splanchnic mesoderm (1). Development of the mammalian intestine continues in a cranial to caudal fashion with eventual lining of the entire small bowel and colon by villi (2–5). By the end of the second trimester the human fetal colon has switched to the adult phenotype with loss of the villous architecture and repression of the small intestinal-like pattern of gene expression (6–9). Not only does the gut undergo this broad differential specialization resulting in the functionally and morphologically distinct small bowel and colon but, in addition, a complicated regional differentiation of gene expression and cell lineage patterns are established and maintained along the entire length of the duodenal-to-ileal axis (5,10–12). Furthermore, with maturation and aging, the gut continues to alter its pattern of gene expression and rate of proliferative activity and, in certain instances, can revert to a fetal phenotype or “dedifferentiated” state as noted by expression of fetal genes in ectopic locations (e.g., colon cancers) (9,13–16). Delineating the factors regulating gut differentiation are crucial to our understanding of not only normal gut development and maturation, but also aberrant gut growth. To achieve these goals, “model” intestinal genes are required to better elucidate the complex cellular mechanisms regulating the region-specific patterns of expression, which lead to differentiation and specialized function. Model intestinal genes should possess a number of characteristics: They should be expressed in the adult small bowel, there should be a characteristic temporal-and spatial-specific pattern of gene expression that coincides with developmental changes in the gut, and re-expression of these small bowel genes should also occur with certain neoplastic states (such as certain colon cancers) suggesting a reversion to a fetal pattern of expression. The author has been interested in analyzing the regulation of the gene encoding the gut hormone neurotensin (NT), which possesses many of the characteristics of a model intestinal gene.
Global Phosphoproteomics Reveals Crosstalk Between Bcr-Abl and Negative Feedback Mechanisms Controlling Src Signaling (2011)

In subtypes and late stages of leukemias driven by the tyrosine kinase fusion protein Bcr-Abl, signaling by the Src family kinases (SFKs) critically contributes to the leukemic phenotype. We performed global tyrosine phosphoprofiling by quantitative mass spectrometry of Bcr-Abl-transformed cells in which the activities of the SFKs were perturbed to build a detailed context-dependent network of cancer signaling. Perturbation of the SFKs Lyn and Hck with genetics or inhibitors revealed Bcr-Abl downstream phosphorylation events either mediated by or independent of SFKs. We identified multiple negative feedback mechanisms within the network of signaling events affected by Bcr-Abl and SFKs and found that Bcr-Abl attenuated these inhibitory mechanisms. The C-terminal Src kinase (Csk)-binding protein Pag1 (also known as Cbp) and the tyrosine phosphatase Ptpn18 both mediated negative feedback to SFKs. We observed Bcr-Abl-mediated phosphorylation of the phosphatase Shp2 (Ptpn11), and this may contribute to the suppression of these negative feedback mechanisms to promote Bcr-Abl-activated SFK signaling. Csk and a kinase-deficient Csk mutant both produced similar globally repressive signaling consequences, suggesting a critical role for the adaptor protein function of Csk in its inhibition of Bcr-Abl and SFK signaling. The identified Bcr-Abl-activated SFK regulatory mechanisms are candidates for dysregulation during leukemia progression and acquisition of SFK-mediated drug resistance.
LGG-50. Human induced pluripotent stem cell engineering establishes a humanized mouse platform for pediatric low-grade glioma modeling (2022)

Abstract A major obstacle to identifying improved treatments for pediatric low-grade brain tumors (gliomas) is the inability to reproducibly generate human xenografts. To surmount this barrier, we leveraged human induced pluripotent stem cell (hiPSC) engineering to generate low-grade glioma (LGG) lesions representing the two most common pediatric pilocytic astrocytoma-associated molecular alterations, NF1 loss and KIAA1549:BRAF fusion. Using hiPSCs, we identified the susceptible cells of origin for these tumors, and demonstrated that the resulting tumors retain LGG histologic features for at least 6 months in vivo. Finally, this platform enabled the successful long-term growth of patient-derived pLGGs in vivo. Taken together, these avatars establish tractable experimental humanized platforms to elucidate the pathogenesis of childhood brain tumors.
Security Guards for the Future Web (2004)

This report documents research efforts for the FY03 and FY04 Mission Oriented Investigation and Experimentation (MOIE) project "Security Guards for the Future Web." Traditionally, computer security guards have been used to control what information flows between security domains. Guard technology needs to keep pace with the evolving Web environment. The authors conjectured that a family of security guard services would be needed to provide the full range of functionality necessary to support the future Web. They structured their research into three segments: the browser-based environment, the Web Services environment and the Semantic Web. Their objectives were to investigate how the content and format of data would change in the various Web environments and how mechanisms designed to enforce cross-domain information sharing rules would have to evolve to match that changing content. Their research for the browser-based environment included a requirements analysis and an analysis of alternative architectures for cross-domain information exchanges. Their research for the Web Services and Semantic Web environments focused on two aspects of guards: the type of data that the guard can transfer and the method used to check the content of items. They decided to focus their Web Services and Semantic Web research on highly structured XML data and guards that would automatically check the content using machine-interpretable information sharing rules. They chose to explore guard designs that supported a wide range of security policies and the ability to easily replace or update the information sharing rules. Their approach entailed three steps: (1) creating an operational scenario for use in their experiment, (2) building a prototype for experimentation, and (3) conducting tests with the prototype using the generated scenario and capturing the lessons learned.
Electron Microscopic Evaluation of Bone Cells in Pigs with Experimentally Induced Bordetella Rhinitis (Turbinate Osteoporosis) (1975)

SUMMARY The development of osseous lesions in the nasal turbinates of pigs with experimentally induced Bordetella rhinitis, occurring 2 to 6 weeks after inoculation with Bordetella bronchiseptica strain B, was evaluated ultrastructurally, and comparisons were made with controls. Progressive degenerative changes were seen in osteoblasts and osteocytes of diseased pigs. These changes included swollen mitochondria, distention of cisternae of endoplasmic reticulum, and lysis of some cells. Bacterial organisms, believed to be B bronchiseptica , were observed in the cytoplasm of osteoblasts and in close proximity to bone surfaces in diseased pigs. Although osteoclasts occasionally had degenerative changes in the brush border, most osteoclasts were similar to those of control pigs. Resorption of bone adjacent to degenerative osteoblasts and osteocytes may have contributed to the development of turbinate osteoporosis when combined with the normal cellular resorptive processes. These ultrastructural changes were similar to those previously reported in bone cells of the nasal turbinates of pigs with experimentally induced and naturally occurring atrophic rhinitis.
Initial Evaluation ofN,N-Diethyl-m-toluamide and Permethrin Absorption in Human Volunteers under Stress Conditions (2006)

It is possible to blind subjects with respect to DEET and permethrin. Permethrin on clothing does not enter the bloodstream at appreciable levels. Combat videotapes and mental arithmetic can be stressful.
RECRYSTALLIZATION OF BERYLLIUM OXIDE BODIES AT 2000°C.* (1949)

A bstract Recrystallization is an important factor in the preparation of very dense pure oxide ceramic bodies. The work described in this paper shows the effect of the original particle size on the degree of recrystallization of beryllium oxide bodies. A water elutriator for particle‐size separation in the subsieve range and an oxyacetylene furnace with zirconia refractories for operation at 2000°C. are described. The microscopic examination of prepared thin sections and the X‐ray diffraction back‐reflection method are used to determine particle sizes and the degree of recrystallization. Shrinkage during firing is found to be approximately constant for all particle sizes originally below 10 microns and decreases in a regular manner with increasing particle size. The recrystallization factor for beryllium oxide is found to vary from 40 for 1.25‐micron particles to 2.5 for 10‐micron particles.
Boundary stacking interactions enable cross-TAD enhancer-promoter communication during limb development (2023)

Abstract While long-range enhancers and their target promoters are frequently contained within a TAD, many developmentally important genes have their promoter and enhancers within different TADs. Hypotheses about molecular mechanisms enabling such cross-TAD interactions remain to be assessed. To test these hypotheses, we use Optical Reconstruction of Chromatin Architecture (ORCA) to characterize the conformations of the Pitx1 locus on thousands of single chromosomes in developing mouse limbs. Our data supports a model in which neighboring boundaries are stacked with each other as a result of loop-extrusion, bringing boundary-proximal cis -elements into contact. This stacking interaction also explains the appearance of architectural stripes in the population average maps (e.g. Hi-C data). Through molecular dynamics simulations, we further propose that increasing boundary strengths facilitates the formation of the stacked boundary conformation, counter-intuitively facilitating border bypass. This work provides a revised view of the TAD borders’ function, both facilitating as well as preventing cis -regulatory interactions, and introduces a framework to distinguish border-crossing from border-respecting enhancer-promoter pairs.
Activated hepatic stellate cells promote hepatocellular carcinoma cell migration and invasion via the activation of FAK-MMP9 signaling (2013)

Activated hepatic stellate cells (HSCs) are the major subtype of stromal cells in the liver tumor microenvironment which can promote the growth and migration of hepatocellular carcinoma (HCC) cells. However, the underlying mechanisms by which activated HSCs exert their oncogenic effects are not fully understood to date. In the present study, we investigated the number of activated HSCs and its clinicopathological significance in HCC and uncovered its correlation with focal adhesion kinase (FAK)-MMP9 signaling. A higher number of activated HSCs was associated with tumor invasion of the portal vein, advanced TNM stage and poorer tumor differentiation. The number of activated HSCs was positively correlated with the expression levels of p-FAK and MMP9 in HCC. Furthermore, we studied the effects of activated HSCs on the migration and invasion of HCC cells in vitro. Conditioned medium (CM) from activated HSCs or co-culture with activated HSCs significantly induced the migration and invasion of HCC cells. In addition, activation of FAK-MMP9 signaling in HCC was demonstrated in the presence of activated HSC-CM and of co-culture. Inhibition of FAK-MMP9 signaling in HCC cells with FAK short hairpin RNA (shRNA) abrogated the effects of activated HSCs on HCC cells. Taken together, our data suggest that activated HSCs in the tumor microenvironment promote HCC cell migration and invasion via activation of FAK-MMP9 signaling.
Practical Assessment of Energy-Based Sensing through Software Defined Radio Devices (2014)

The Cognitive Radio is a solution proposed for the increasing demand of radio spectrum. Usually cognitive radios are adopted by the non-license wireless users, which have a certain degree of cognition in order to only access to a given frequency band when the band is sensed idle. However, these bands and their use must be assessed, to avoid interfering with licensed users (primary users). The way to assess band’s occupancy is by discerning between just noise or noise plus signal. In this paper, energy-based sensing (EBS) is considered through the use of a classical energy detector. The work proposes and describes an implementation of an energy detector using a software defined radio (SDR) testbed and, after computing the probability of detection and false alarm from a real set of samples obtained with the SDR devices, we successfully validate a theoretical model for the probabilities. EBS’ performance is validated for several points of operation, i.e. for different signal-to-noise-ratio (SNR) values. These findings may be useful for building an EBS detector that defines its own decision threshold in real time given the target probabilities, since the formal probabilities are successfully validated. Moreover, our contribution also includes a detailed description of the implemented blocks using GNU Radio’s open-source software development toolkit.
ChemInform Abstract: Selective Reactions of Isocyanatocarboxylic Chlorides with Silylated Alcohols and Amines: A Simple Synthesis of Isocyanatocarboxylic Acid Esters and Amides. (1987)

Abstract The trimethylsilyl ethers (III), prepared from the alcohols (I), react with the isocyanates (IV) to give the isocyanato esters (V).
Sinusoidal Shape of a Papillary Line Crosscut (2007)

This paper deals with a new approach for the fingerprint image quality testing. Some metrics for such purpose are well known - e.g. contrast differences or the average value of grayscale information in an image. These methods are shortly mentioned at the beginning, but the main goal of this article is to present a new method for the evaluation of fingerprint image which can indicate whether an image is suitable for further processing or not. The method tests whether the crosscut of some papillary line differs from the ideal case of papillary line (a sinusoidal curve).
An experimental study of an audio indexing system for the web (2000)

We have developed a speech recognition based audio search engine for indexing spoken documents found on the World Wide Web. Our site (http://www.compaq.com/speechbot) indexes around 20 news and talk radio shows covering a wide range of topics, speaking styles and acoustic conditions from a selection of public Web sites with multimedia archives. In this paper, we describe our system and its performance, focusing on the speech recognition and retrieval aspects. We describe our training procedure in some detail and report our historical error rate since the site launch. We also investigate the impact of Out Of Vocabulary (OOV) words. Finally we report the results of retrieval experiments which demonstrate that our system can index effectively.
Multi-kernel construction of polar codes (2017)

We propose a generalized construction for binary polar codes based on mixing multiple kernels of different sizes in order to construct polar codes of block lengths that are not only powers of integers. This results in a multi-kernel polar code with very good performance while the encoding complexity remains low and the decoding follows the same general structure as for the original Arikan polar codes. The construction provides numerous practical advantages as more code lengths can be achieved without puncturing or shortening. We observe numerically that the error-rate performance of our construction outperforms state-of-the-art constructions using puncturing methods.
Performance Evaluation of In-network Packet Retransmissions using Markov Chains (2020)

We consider the retransmission of packets inside the network on a segment of an end-to-end path. Using a Markov chain formulation of the problem, we evaluate the effect of the loss probability in the network segment that is responsible for retransmission as well as the ratio between the local RTT and the end-to-end timeout. We also obtain the optimal cache size required for retransmission depending on the packet loss and cache blocking probabilities. Our study reveals that the local RTT of the path segment for retransmission as a function of the end-to-end timeout significantly influences the packet caching time. We also observe that a small increment in the packet loss probability above a threshold can severely affect the percentage of cache filling irrespective of the cache size. Use cases to which our findings apply include a recent IETF proposal called “LOOPS”, recursive network architectures and proposals that use hop-by-hop retransmissions in special network scenarios, e.g. for Information-Centric Networking (ICN).
Insect sex attractant pheromones, a tool for reducing insecticide contamination in the environment† (1972)

The great reproductivity of many insect species can be ascribed in part to the ability of the sexes to find one another for mating and propagation. This process is frequently mediated by sex attractant pheromones, chemicals emitted by one sex to attract one or both sexes for mating. In recent years, researchers have isolated, identified, and synthesized a number of these substances. Procedures used in their isolation and identification are discussed, and the sex attractants found are listed. Secondary chemicals and volatility regulators can augment pheromone action and are required for maximum effectiveness. Because sex attractants are utilized by many species of economic importance, attention is now being directed toward means of using these chemicals to combat insect pests. Sex pheromones that attract insects in the field have been effective in detecting infestations; their direct use in control is now being explored because these compounds can minimize the amount of insecticide needed for insect control, they can make the use of insecticides more selective in their attack, and in some instances they hold forth the possibility of eradication of highly injurious insect pests. In one approach sex‐lure‐baited traps ensnare insects before they can mate. In another, the atmosphere is permeated with sex lure; with attractant everywhere the insects cannot locate mates. Either approach is apt to lessen the disruptive effects of insecticides on the environment. Insect sex pheromones are expected to play an increasingly important role in future pest control strategy.
Mammalian DNA (Cytosine-5-)-methyltransferase Expressed in Escherichia coli, Purified and Characterized (1995)

Besides modulating specific DNA-protein interactions, methylated cytosine, frequently referred to as the fifth base of the genome, also influences DNA structure, recombination, transposition, repair, transcription, imprinting, and mutagenesis. DNA (cytosine-5-)-methyltransferase catalyzes cytosine methylation in eukaryotes. We have cloned and expressed this enzyme in Escherichia coli, purified it to apparent homogeneity, characterized its properties, and we have shown that it hemimethylates DNA. The cDNA for murine maintenance methyltransferase was reconstructed and cloned for direct expression in native form. Immunoblotting revealed a unique protein (M(r) = 190,000) not present in control cells. The mostly soluble overexpressed protein was purified by DEAE, Sephadex, and DNA cellulose chromatography. Peak methylating activity correlated with methyltransferase immunoblots. The purified enzyme preferentially transferred radioactive methyl moieties to hemimethylated DNA in assays and on autoradiograms. All of the examined properties of the purified recombinant DNA methyltransferase are consistent with the enzyme purified from mammalian cells. Further characterization revealed enhanced in vitro methylation of premethylated oligodeoxynucleotides. The cloning of hemimethyltransferase in E. coli should allow facilitated structure-function mutational analysis of this enzyme, studies of its biological effects in prokaryotes, and potential large scale methyltransferase production for crystallography, and it may have broad applications in maintaining the native methylated state of cloned DNA.
Cardiovascular Genetics and Genomics for the Cardiologist (2007)

Contributors. Foreword. Introduction. 1 The gene in the twenty-first century. Choong-Chin Liew, Victor J. Dzau. Part I: Cardiovascular single gene disorders. 2 Monogenic hypercholesterolemia. Ruth McPherson. 3 Hypertrophic cardiomyopathy. Ali J. Marian. 4 Dilated cardiomyopathy and other cardiomyopathies. Mitra Esfandiarei, Robert Yanagawa, Bruce M. McManus. 5 The long QT syndrome. Sabina Kupershmidt, Kamilla Kelemen, Tadashi Nakajima. Part II: Cardiovascular polygenic disorders. 6 Atherosclerosis. Paivi Pajukanta, Kiat Tsong Tan, Choong-Chin Liew. 7 Heart failure. Markus Meyer, Peter VanBuren. 8 The implications of genes on the pathogenesis, diagnosis and therapeutics of hypertension. Kiat Tsong Tan, Choong-Chin Liew. Part III: Therapies and applications. 9 Gene therapy for cardiovascular disease: inserting new genes, regulating the expression of native genes, and correcting genetic defects. Ion S. Jovin, Frank J. Giordano. 10 Stem cell therapy for cardiovascular disease. Emerson C. Perin, Guilherme V. Silva. 11 Pharmacogenetics and personalized medicine. Julie A. Johnson, Issam Zineh. 12 The potential of blood-based gene profiling for disease assessment. Steve Mohr, Choong-Chin Liew. Index. Colour plates
Off-Clamp versus On-Clamp Robotic Partial Nephrectomy: A Multicenter Match-Paired Case-Control Study (2017)

Off-clamp RPN is feasible for a small subgroup of renal tumors without increased risk of postoperative complications but at the cost of higher estimated blood loss and increased risk of conversion to radical nephrectomy.