gebhart/patrepeval huggingface dataset:
Genome-wide cell-free DNA fragmentation in patients with cancer (2019)

Cell-free DNA in the blood provides a non-invasive diagnostic avenue for patients with cancer<sup>1</sup>. However, characteristics of the origins and molecular features of cell-free DNA are poorly understood. Here we developed an approach to evaluate fragmentation patterns of cell-free DNA across the genome, and found that profiles of healthy individuals reflected nucleosomal patterns of white blood cells, whereas patients with cancer had altered fragmentation profiles. We used this method to analyse the fragmentation profiles of 236 patients with breast, colorectal, lung, ovarian, pancreatic, gastric or bile duct cancer and 245 healthy individuals. A machine learning model that incorporated genome-wide fragmentation features had sensitivities of detection ranging from 57% to more than 99% among the seven cancer types at 98% specificity, with an overall area under the curve value of 0.94. Fragmentation profiles could be used to identify the tissue of origin of the cancers to a limited number of sites in 75% of cases. Combining our approach with mutation-based cell-free DNA analyses detected 91% of patients with cancer. The results of these analyses highlight important properties of cell-free DNA and provide a proof-of-principle approach for the screening, early detection and monitoring of human cancer.
Evidence ofγ-Tocotrienol as an Apoptosis-Inducing, Invasion-Suppressing, and Chemotherapy Drug-Sensitizing Agent in Human Melanoma Cells (2009)

To date, the most effective cure for metastatic melanoma remains the surgical resection of the primary tumor. Recently, tocotrienol-rich-fraction has shown antiproliferative effect on cancer cells. To elucidate this anticancer property in malignant melanoma, this study aimed, first, to identify the most potent isomer for eliminating melanoma cells and second to decipher the molecular pathway responsible for its activity. Results showed that the inhibitory effect of gamma-tocotrienol was most potent, which resulted in induction of apoptosis as evidenced by activation of procaspases and the accumulation of sub-G1 cell population. Examination of the prosurvival genes revealed that the gamma-tocotrienol-induced cell death was associated with suppression of NF-kappaB, EGF-R, and Id family proteins. Meanwhile, gamma-tocotrienol treatment also resulted in induction of JNK signaling pathway, and inhibition of JNK activity by selective inhibitor was able to partially block the effect of gamma-tocotrienol. Interestingly, gamma-tocotrienol treatment led to suppression of mesenchymal markers and the restoration of E-cadherin and gamma-catenin expression, which was associated with suppression of cell invasion capability. Furthermore, synergistic effect was observed when cells were cotreated with gamma-tocotrienol and chemotherapy drugs. Together, our results demonstrated for the first time the anti-invasion and chemonsensitization effect of gamma-tocotrienol against human malignant melanoma cells.
The Streptomyces glaucescens TcmR protein represses transcription of the divergently oriented tcmR and tcmA genes by binding to an intergenic operator region (1992)

Preliminary evidence has been presented by Guilfoile and Hutchinson (J. Bacteriol. 174:3651-3658, 1992) suggesting that the Streptomyces glaucescens TcmR protein is a transcriptional repressor. Here, we extend that work by showing that transcription of the S. glaucescens tcmA gene is inducible by tetracenomycin C and that inactivation of the tcmR gene results in constitutive transcription of the tcmA gene. Gel retardation studies show that the TcmR protein binds to the tcmA-tcmR intergenic region in vitro and that this binding is inhibited by tetracenomycin C. Footprinting experiments demonstrate that the TcmR protein binds to an operator region that encompasses both the tcmA and the tcmR promoters. This genetic and biochemical evidence strongly supports the model of the TcmR protein acting as a repressor in inhibiting transcription of both the tcmA and the tcmR genes, in much the same way that TetR from Tn10 inhibits transcription of tetA and tetR.
Transseptal left heart catheterization: Usefulness of the intracavitary electrocardiogram in the localization of the fossa ovalis (1991)

One of the major difficulties in left heart catheterization through the interatrial septum is to ensure that the Brockenbrough needle tip is correctly laid on the fossa ovalis floor (FOF), which is the only area where the puncture must be done. The difficulties may be enhanced in patients with atrial enlargement and subsequent distortion of the anatomical structures. In order to reduce the hazards of the septal puncture, an electrocardiographic mapping of the right atrial endocardium was performed using the Brockenbrough needle as an exploratory electrode in a group of 20 patients. When the tip of the needle was laid against the FOF, the endoatrial electrocardiogram (EAE) registered a slight or no injury curve, even when the pressure was tight enough to perforate the septum. On the contrary, the pressure on any other area of the muscular septum or atrial walls elicited a bizarre monophasic injury curve. The peculiar electrocardiographic response of the FOF to the pressure exerted by the Brockenbrough needle tip was a valuable aid to identify the area where the transseptal puncture must be done. In addition, the sudden changes in the P wave morphology immediately after the septal perforation, provided the first clue that the left atrium has been reached.
Identifying and managing adverse environmental health effects: 3. Lead exposure. (2002)

Lead levels in North American children and adults have declined in the past 3 decades, but lead persists in the environment in lead paint, old plumbing and contaminated soil. There are also a number of occupations and hobbies that carry a high risk of lead exposure. There is no evidence for a threshold below which lead has no adverse health effects. Blood lead levels previously considered safe are now known to cause subtle, chronic health effects. The health effects of lead exposure include developmental neurotoxicity, reproductive dysfunction and toxicity to the kidneys, blood and endocrine systems. Most lead exposures are preventable, and diagnosing lead poisoning is relatively simple compared with diagnosing health effects of exposures to other environmental toxins. Accurate assessment of lead poisoning requires specific knowledge of the sources, high-risk groups and relevant laboratory tests. In this article we review the multiple, systemic toxic effects of lead and provide current information on groups at risk, prevention, diagnosis and clinical treatment. We illustrate how the CH2OPD2 mnemonic (Community, Home, Hobbies, Occupation, Personal habits, Diet and Drugs) and specific screening questions are useful tools for physicians to quickly obtain an environmental exposure history and identify patients at high risk of lead exposure. By applying effective primary prevention, case-finding and treatment interventions for lead exposure, both the individual patient and the larger community reap the benefits of better health.
Crown-shaped stacked-capacitor cell for 1.5-V operation 64-Mb DRAMs (1991)

A self-aligned stacked-capacitor cell called the CROWN cell (a crown-shaped stacked-capacitor cell), used for experimental 64-Mb-DRAMs operated at 1.5 V, has been developed using 0.3- mu m electron-beam lithography. This memory cell has an area of 1.28 mu m/sup 2/. The word-line pitch and sense-amplifier pitch of this cell are 0.8 and 1.6 mu m, respectively. In spite of this small cell area, the CROWN cell has a large capacitor surface area of 3.7 mu m/sup 2/ because (1) it has a crown-shaped capacitor electrode, (2) its capacitor is on the data line, and (3) it has a self-aligned memory cell fabrication process and structure. The large capacitor area and a Ta/sub 2/O/sub 5/ film equivalent to a 2.8-nm SiO/sub 2/ film ensure a large storage charge of 33 fC (storage capacitance equals 44 fF) for 1.5-V operation. A small CROWN cell array and a memory test circuit were successfully used to achieve a basic DRAM cell operation.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
De Novo Synthesis of Sphingolipids Is Required for Cell Survival by Down-Regulating c-Jun N-Terminal Kinase in Drosophila Imaginal Discs (1999)

Mitogen-activated protein kinase (MAPK) is a conserved eukaryotic signaling factor that mediates various signals, cumulating in the activation of transcription factors. Extracellular signal-regulated kinase (ERK), a MAPK, is activated through phosphorylation by the kinase MAPK/ERK kinase (MEK). To elucidate the extent of the involvement of ERK in various aspects of animal development, we searched for a Drosophila mutant which responds to elevated MEK activity and herein identified a lace mutant. Mutants with mild lace alleles grow to become adults with multiple aberrant morphologies in the appendages, compound eye, and bristles. These aberrations were suppressed by elevated MEK activity. Structural and transgenic analyses of the lace cDNA have revealed that the lace gene product is a membrane protein similar to the yeast protein LCB2, a subunit of serine palmitoyltransferase (SPT), which catalyzes the first step of sphingolipid biosynthesis. In fact, SPT activity in the fly expressing epitope-tagged Lace was absorbed by epitope-specific antibody. The number of dead cells in various imaginal discs of a lace hypomorph was considerably increased, thereby ectopically activating c-Jun N-terminal kinase (JNK), another MAPK. These results account for the adult phenotypes of the lace mutant and suppression of the phenotypes by elevated MEK activity: we hypothesize that mutation of lace causes decreased de novo synthesis of sphingolipid metabolites, some of which are signaling molecules, and one or more of these changes activates JNK to elicit apoptosis. The ERK pathway may be antagonistic to the JNK pathway in the control of cell survival.
On the Foundations of Modern Cryptography (2008)

It is possible to build a cabin with no foundations, but not a lasting building.Eng. Isidor Goldreich (1906–95)
Cooperation between Apoptotic and Viable Metacyclics Enhances the Pathogenesis of Leishmaniasis (2009)

Mimicking mammalian apoptotic cells by exposing phosphatidylserine (PS) is a strategy used by virus and parasitic protozoa to escape host protective inflammatory responses. With Leishmania amazonensis (La), apoptotic mimicry is a prerogative of the intramacrophagic amastigote form of the parasite and is modulated by the host. Now we show that differently from what happens with amastigotes, promastigotes exposing PS are non-viable, non-infective cells, undergoing apoptotic death. As part of the normal metacyclogenic process occurring in axenic cultures and in the gut of sand fly vectors, a sub-population of metacyclic promastigotes exposes PS. Apoptotic death of the purified PS-positive (PS(POS)) sub-population was confirmed by TUNEL staining and DNA laddering. Transmission electron microscopy revealed morphological alterations in PS(POS) metacyclics such as DNA condensation, cytoplasm degradation and mitochondrion and kinetoplast destruction, both in in vitro cultures and in sand fly guts. TUNEL(POS) promastigotes were detected only in the anterior midgut to foregut boundary of infected sand flies. Interestingly, caspase inhibitors modulated parasite death and PS exposure, when added to parasite cultures in a specific time window. Efficient in vitro macrophage infections and in vivo lesions only occur when PS(POS) and PS-negative (PS(NEG)) parasites were simultaneously added to the cell culture or inoculated in the mammalian host. The viable PS(NEG) promastigote was the infective form, as shown by following the fate of fluorescently labeled parasites, while the PS(POS) apoptotic sub-population inhibited host macrophage inflammatory response. PS exposure and macrophage inhibition by a subpopulation of promastigotes is a different mechanism than the one previously described with amastigotes, where the entire population exposes PS. Both mechanisms co-exist and play a role in the transmission and development of the disease in case of infection by La. Since both processes confer selective advantages to the infective microorganism they justify the occurrence of apoptotic features in a unicellular pathogen.
A smart camera application: DSP-based people detection and tracking (2000)

The <i>Journal of Electronic Imaging</i> (JEI), copublished bimonthly with the Society for Imaging Science and Technology, publishes peer-reviewed papers that cover research and applications in all areas of electronic imaging science and technology.
Minimal Requirement for a Lentivirus Vector Based on Human Immunodeficiency Virus Type 1 (1998)

The use of human immunodeficiency virus vectors for gene therapy is hampered by concern over their safety. This concern might be ameliorated, in part, if the viral accessory genes and proteins could be eliminated from the vector genomes and particles. Here we describe a minimal vector system that is capable of transducing nondividing cells and which does not contain tat, vif, vpr, vpu, and nef.
Intraluminal bypass of abdominal aortic aneurysm: feasibility study. (1992)

This study evaluated the feasibility of treatment of abdominal aortic aneurysm (AAA) by means of intraluminal bypass. Artificial aortic aneurysms with fusiform Dacron conduits were created at surgery , a weft-knit Dacron tube with balloon-expandable stents attached at both ends was inserted transfemorally through a 14-F introducer sheath and expanded at the aneurysmal level by means of inflation of a coaxial balloon. The transluminal bypass successfully excluded the aneurysmal lumen immediately after placement. In two dogs, a postplacement aortogram revealed torsion of the graft that caused early occlusion. The six other dogs had a patent bypass at 6 months follow-up. Four of these dogs had evidence of kinking of the graft as a result of shrinkage of the prosthetic aneurysm. Histopathologic studies revealed that endothelialization was complete on the stents and partial on the graft surface. It is concluded that transluminal bypass of AAA is feasible in the dog model.
Contributions of ATM mutations to familial breast and ovarian cancer. (2003)

This study addresses the prevalence of ATM mutations and the association with breast cancer in Austrian families selected for a history of breast or ovarian cancer or both [hereditary breast and ovarian cancer (HBOC)]. In 270 HBOC families previously screened for BRCA1 and BRCA2 mutations, 137 different sequence alterations of ATM were identified. Seven of these were mutations presumed to cause ataxia telangiectasia based on their effect on the ATM protein, including five that caused a protein truncation and two missense mutations in the catalytic kinase domain of the highly conserved COOH terminus of the protein. The seven mutations were found in 10 families (3.7%). In addition, one missense variant, L1420F, was observed in 13 HBOC families (4.8%) but was not observed in any of the 122 healthy volunteers with no history of breast cancer. In addition, the variant segregated with breast cancer in some of the families, suggesting that it may be pathogenic for breast cancer. Sixty-two additional variants of potential significance were observed in 65 HBOC families, but not in healthy controls. These variants included 24 sequence alterations with possible effects on splicing or protein-protein interactions. This study indicates that there is a significant prevalence of ATM mutations in breast and ovarian cancer families and adds to a growing body of evidence that ATM mutations confer increased susceptibility to breast cancer.
Enriched Multimodal Representations of Music Performances: Online Access and Visualization (2017)

The authors provide a first-person outlook on the technical challenges involved in the recording, analysis, archiving, and cloud-based interchange of multimodal string quartet performance data as part of a collaborative research project on ensemble music making. To facilitate the sharing of their own collection of multimodal recordings and extracted descriptors and annotations, they developed a hosting platform through which multimodal data (audio, video, motion capture, and derived signals) can be stored, visualized, annotated, and selectively retrieved via a web interface and a dedicated API. This article offers a twofold contribution: the authors open their collection of enriched multimodal recordings, the Quartet dataset, to the community, and they introduce and enable access to their multimodal data exchange platform and web application, the Repovizz system. This article is part of a special issue on multimedia technologies for enriched music.
Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine V. Unitarian theory of the origin of the four epithelial cell types (1974)

Abstract The previous articles of this series provided presumptive evidence that the four main differentiated cell types in the epithelium of the mouse small intestine: villus columnar, mucous, entero‐endocrine, and Paneth cells, originate from the same precursor, the crypt‐base columnar cell. In the present work, direct evidence was obtained in support of this view. It was first found that crypt‐base columnar cells phagocytose non‐viable cells in their vicinity, with the result that a large phagosome appears in the cytoplasm. Such phagosomes were then used as markers to follow the evolution of crypt‐base columnar cells. In normal control animals, a rare crypt‐base columnar cell includes a large phagosome containing Paneth cell remnants. By six hours after injection of two μCi 3 H‐thymidine per g body weight, a fair number of crypt‐base columnar cells include a different type of phagosome containing labeled nucleus and granulefree cytoplasm, which is attributed to phagocytosis of a labeled crypt‐base columnar cell killed by beta‐radiation from the incorporated 3 H‐thymidine. By 12 hours after 3 H‐thymidine injection, phagosomes have appeared in partly differentiated mid‐crypt columnar cells and oligomucous cells; by 18–24 hours, in fully differentiated columnar cells and in Paneth cells; and by 30 hours, in an entero‐endocrine cell. Since phagosomes are first found in crypt‐base columnar cells and only later in the four differentiated cell types, it is concluded that crypt‐base columnar cells transform into cells of these four types and, therefore, behave as the stem cells of the epithelium. The finding of rare epithelial cells containing two different types of secretory material (either mucous globules and entero‐endocrine granules, or mucous globules and Paneth cell granules) confirms that the stem cells are multipotential. These findings support the Unitarian Theory of epithelial cell formation in the small intestine.
Oral immunization with hepatitis B surface antigen expressed in transgenic plants (2001)

Oral immunogenicity of recombinant hepatitis B surface antigen (HBsAg) derived from yeast (purified product) or in transgenic potatoes (uncooked unprocessed sample) was compared. An oral adjuvant, cholera toxin, was used to increase immune responses. Transgenic plant material containing HBsAg was the superior means of both inducing a primary immune response and priming the mice to respond to a subsequent parenteral injection of HBsAg. Electron microscopy of transgenic plant samples revealed evidence that the HBsAg accumulated intracellularly; we conclude that natural bioencapsulation of the antigen may provide protection from degradation in the digestive tract until plant cell degradation occurs near an immune effector site in the gut. The correlate of protection from hepatitis B virus infection is serum antibody titers induced by vaccination; the protective level in humans is 10 milliunits/ml or greater. Mice fed HBsAg-transgenic potatoes produced HBsAg-specific serum antibodies that exceeded the protective level and, on parenteral boosting, generated a strong long-lasting secondary antibody response. We have also shown the effectiveness of oral delivery by using a parenteral prime-oral boost immunization schedule. The demonstrated success of oral immunization for hepatitis B virus with an "edible vaccine" provides a strategy for contributing a means to achieve global immunization for hepatitis B prevention and eradication.
Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor (2003)

Prostaglandin E 2 (PGE 2 ), a major COX metabolite, plays important roles in several facets of tumor biology.We characterized the contribution of the PGE 2 EP2 receptor to cancer-associated immune deficiency using EP2 -/-mice.EP2 -/-mice exhibited significantly attenuated tumor growth and longer survival times when challenged with MC26 or Lewis lung carcinoma cell lines as compared with their wild-type littermates.While no differences in T cell function were observed, PGE 2 suppressed differentiation of DCs from wild-type bone marrow progenitors, whereas EP2-null cells were refractory to this effect.Stimulation of cells in mixed lymphocyte reactions by wild-type DCs was suppressed by treatment with PGE 2 , while EP2 -/--derived DCs were resistant to this effect.In vivo, DCs, CD4 + , and CD8 + T cells were significantly more abundant in draining lymph nodes of tumor-bearing EP2 -/-mice than in tumor-bearing wild-type mice, and a significant antitumor cytotoxic T lymphocyte response could be observed only in the EP2 -/-animals.Our data demonstrate an important role for the EP2 receptor in PGE 2 -induced inhibition of DC differentiation and function and the diminished antitumor cellular immune responses in vivo.
Perceptual Learning Directs Auditory Cortical Map Reorganization through Top-Down Influences (2006)

The primary sensory cortex is positioned at a confluence of bottom-up dedicated sensory inputs and top-down inputs related to higher-order sensory features, attentional state, and behavioral reinforcement. We tested whether topographic map plasticity in the adult primary auditory cortex and a secondary auditory area, the suprarhinal auditory field, was controlled by the statistics of bottom-up sensory inputs or by top-down task-dependent influences. Rats were trained to attend to independent parameters, either frequency or intensity, within an identical set of auditory stimuli, allowing us to vary task demands while holding the bottom-up sensory inputs constant. We observed a clear double-dissociation in map plasticity in both cortical fields. Rats trained to attend to frequency cues exhibited an expanded representation of the target frequency range within the tonotopic map but no change in sound intensity encoding compared with controls. Rats trained to attend to intensity cues expressed an increased proportion of nonmonotonic intensity response profiles preferentially tuned to the target intensity range but no change in tonotopic map organization relative to controls. The degree of topographic map plasticity within the task-relevant stimulus dimension was correlated with the degree of perceptual learning for rats in both tasks. These data suggest that enduring receptive field plasticity in the adult auditory cortex may be shaped by task-specific top-down inputs that interact with bottom-up sensory inputs and reinforcement-based neuromodulator release. Top-down inputs might confer the selectivity necessary to modify a single feature representation without affecting other spatially organized feature representations embedded within the same neural circuitry.
Nonintrusive monitoring of electric loads (1999)

The authors describe how the Electric Power Research Institute (EPRI) commissioned an implementation and commercialization of a nonintrusive appliance load monitoring system (NIALMS) based on EPRI-developed intellectual property. The system determines the energy consumption of individual appliances being turned on and off within a whole building's electric load.