gebhart/patrepeval huggingface dataset:
Abstract 5263: An RNAi screen of the protein kinome identifies CHEK1 as a therapeutic target in neuroblastoma (2010)

Abstract Background High-risk neuroblastoma is a pediatric cancer that is often fatal despite intense multimodality therapy associated with significant late effects for those who survive. Therefore, patients will benefit from treatment strategies that rationally exploit signaling pathways for which a tumor cell is selectively dependent. In an effort to identify novel therapeutic targets, we performed a comprehensive loss of function screen of the protein kinome in neuroblastoma cell models. Methods Using a validated siRNA library which targets the human protein kinome, we transiently transfected individual kinase siRNAs into four neuroblastoma cell lines and measured substrate adherent growth. We then ranked the top 100 most potent kinase siRNAs per cell line and integrated the lists to identify kinases with inhibition in multiple lines. Results Thirty targets emerged as potent in at least three of the four neuroblastoma cell lines. They were enriched for kinases involved in the cell cycle and mitosis. This select group was tested with an independent set of more specific siRNA pools in an expanded panel of eight neuroblastoma cell lines. The strikingly most potent to emerge from the secondary screen was the cell cycle checkpoint kinase CHEK1. CHEK1 knockdown appeared cytotoxic, often by 24 hours, coinciding with complete CHEK1 protein knockdown and an emergence of a substantial apoptotic fraction. As further validation of the siRNA results, pharmacologic inhibition with SB21807, a relatively specific CHEK1 inhibitor, showed cytotoxicity in 7 of 8 neuroblastoma cell lines with a median IC50 of 430 nM (range 62-677 nM), while the non-neuroblastoma lines RPE-1, DOAY and MCF7 cells were resistant with a median IC50 of 2609 nM (1066 - 2898 nM). The mechanism of selective inhibition in neuroblastoma is unclear as we did not identify mutations in the coding exons of CHEK1. Western blotting revealed, however, that CHEK1 is constitutively phosphorylated at the Ser 296 residue in 8/8 neuroblastoma cell lines and 10/16 primary tumors samples, but not in controls. Conclusion We have identified CHEK1 as a potential therapeutic target in neuroblastoma and are currently extending our work to understand the mechanism of this tumor's apparent selective sensitivity to CHEK1 inhibition. As CHEK1 inhibitors are currently in phase I/II clinical trials as chemosensitizers, we are also focused on determining the in vivo efficacy of combination CHEK1 inhibition with chemotherapy in neuroblastoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5263.
The kis and kid genes of the parD maintenance system of plasmid R1 form an operon that is autoregulated at the level of transcription by the co‐ordinated action of the Kis and Kid proteins (1991)

Stability mediated by the parD system of plasmid R1 is modulated by a killer protein, Kid, and by an antagonist of this function, Kis. Determination of the 5' ends of ParD transcripts, revealed that the genes coding for these proteins are transcribed from a single promoter. Analysis of the 3' end of the ParD RNAs indicated the existence of two transcripts: one of them coding for the Kis and Kid proteins, and the other coding only for Kis. Analysis of the effects of parD+ and kis+ recombinants on the beta-galactosidase levels expressed by different transcriptional and translational parD-lacZ fusions, and on the ParD RNA levels determined by a derepressed parD mutant, indicated that the Kis and Kid proteins repress coordinately the parD system at the transcriptional level. We discuss the relevance of these results in terms of the activities of the Kis and Kid proteins and in the context of the stabilization mediated by parD.
BENEFICIAL EFFECTS OF PLURONIC F-68 AND ARTIFICIAL OXYGEN CARRIERS ON THE POST-THAW RECOVERY OF CRYOPRESERVED PLANT CELLS (2001)

The storage of prokaryotic and eukaryotic cells at ultra-low temperature in liquid nitrogen (-196 degrees C) is a procedure that has assumed an increasingly important role in underpinning many aspects of biotechnology. For eukaryotic cells, the transition from a cryopreserved state to physiologically normal temperatures and oxygen tensions, induces respiratory imbalances that may stimulate the production of toxic oxygen radicals causing impaired cellular functions. Novel treatments, that focus specifically on enhancing oxygen delivery to cells, are important in maximising post-thaw recovery. Recently, several approaches have been evaluated with suspension cultured plant cells as a model, yet biotechnologically-important, totipotent eukaryotic cell system. Such treatments include non-ionic surfactants, primarily Pluronic F-68, and artificial oxygen carriers, the latter based on inert perfluorochemical liquids or chemically-modifed haemoglobin, as supplements to culture medium used during the post-thaw recovery phase of cell growth. When used either alone or in combination, such novel treatments stimulate significantly the post-thaw viability and biomass production of cultured plant cells. Many of these technologies will be exploitable in cryopreservation protocols for eukaryotic cells in general.
A large-area, flexible pressure sensor matrix with organic field-effect transistors for artificial skin applications (2004)

It is now widely accepted that skin sensitivity will be very important for future robots used by humans in daily life for housekeeping and entertainment purposes. Despite this fact, relatively little progress has been made in the field of pressure recognition compared to the areas of sight and voice recognition, mainly because good artificial "electronic skin" with a large area and mechanical flexibility is not yet available. The fabrication of a sensitive skin consisting of thousands of pressure sensors would require a flexible switching matrix that cannot be realized with present silicon-based electronics. Organic field-effect transistors can substitute for such conventional electronics because organic circuits are inherently flexible and potentially ultralow in cost even for a large area. Thus, integration of organic transistors and rubber pressure sensors, both of which can be produced by low-cost processing technology such as large-area printing technology, will provide an ideal solution to realize a practical artificial skin, whose feasibility has been demonstrated in this paper. Pressure images have been taken by flexible active matrix drivers with organic transistors whose mobility reaches as high as 1.4 cm(2)/V.s. The device is electrically functional even when it is wrapped around a cylindrical bar with a 2-mm radius.
Role of polyamines in arginine‐dependent colon carcinogenesis in ApcMin/+ mice (2006)

We evaluated the role of polyamines in arginine-dependent intestinal tumorigenesis in Apc(Min) (/+) mice. Arginine is a substrate for ornithine synthesis and thus can influence polyamine production. Supplementing the diet with arginine increased intestinal and colonic polyamine levels and colonic carcinogenesis. Inhibiting polyamine synthesis with D,L-alpha-diflouromethylornithine (DFMO) decreased small intestinal and colonic polyamine pools. In mice provided basal diet, but not when supplemented with arginine, DFMO decreased small intestinal tumor number and burden, and increased intestinal apoptosis. In mice provided supplemental arginine in the diet, DFMO induced late apoptosis and decreased tumorigenesis in the colon. DFMO slightly reduced tumor incidence, number, and size while significantly decreasing tumor burden and grade. These changes in colon tumorigenesis did not occur in mice not provided supplemental arginine. Our study indicates that polyamines play unique roles in intestinal and colonic carcinogenesis in Apc(Min) (/+) mice. Inhibition of polyamine synthesis suppresses the arginine-dependent risk of colon tumorigenesis, resulting in apoptosis induction and decreased tumorigenesis, in this murine model.
Note: Phylogenetic status of Anaerobacter polyendosporus, an anaerobic, polysporogenic bacterium (1999)

The almost complete sequence of the 16S rRNA gene of the Gram-positive polysporogenic bacterium Anaerobacter polyendosporus was determined. This allowed phylogenetic analysis of A. polyendosporus by comparing sequences of the 16S rRNA gene of this bacterium to similar genes of other Gram-positive bacteria. It was shown that this polysporogenic bacterium belongs to the Clostridium cluster I, subcluster A. Phylogenetically, A. polyendosporus is distantly related to another polysporogenic, but non-cultivatable, bacterium, 'Metabacterium polyspora' and can be satisfactorily clustered within the saccharolytic clostridia with a low DNA G+C content grouped in subcluster A. A. polyendosporus was most closely related to Clostridium intestinale (94.8% identity of 16S rRNA genes) and Clostridium fallax (93.1%). Like other members of the Clostridium cluster I, subcluster A, A. polyendosporus possesses such common phenotypic features as a Gram-positive cell wall structure, anaerobiosis, derivation of energy from carbohydrate fermentation yielding butyric acid among other organic acids and the capacity for endogenous spore-formation. However, the scale of evolutionary change in the 16S rRNA gene between A. polyendosporus and phylogenetically related Clostridium species does not correspond to the profound changes in the phenotype of A. polyendosporus. Distinctive phenotypic features of the latter are large cell size, polysporogenesis (up to seven spores per cell), alternative modes of development and an unusual membrane ultrastructure.
Rapidly adapting machine vision for automated vehicle steering (1996)

The Ralph vision system helps automobile drivers steer, by sampling an image, assessing the road curvature, and determining the lateral offset of the vehicle relative to the lane center. Ralph has performed well under extensive tests, including a coast-to-coast, 2,850-mile drive.
Update in Medical Therapy of Ulcerative Colitis (2002)

The bewildering array of medications in the therapy of inflammatory bowel disease (IBD) often confounds the clinician in the choice of specific agents regarding the balance between safety and efficacy. This review surveys and evaluates currently available IBD therapies as well as those used in clinical trials of ulcerative colitis. The primary purpose is to provide the busy clinician with a practical guide to the use of established and newly emerging medical therapies of IBD.
Pyrolysis and combustion of cellulose. VII. Thermal analysis of the phosphorylation of cellulose and model carbohydrates during pyrolsis in the presence of aromatic phosphates and phosphoramides (1980)

Abstract Thermal gravimetric analysis, differential scanning calorimetry, and derivative thermal gravimetric analysis were utilized to characterize the thermal interactions between cellulose, 1‐6, anhydro β‐D‐glucopyranoside, and D‐glucose and model phosphate and phosphoramide flame retardants. The phosphoramides induced higher char yields than the phosphates during the pyrolysis of the mixtures of carbohydrates and organophosphorus compounds. Exothermic reactions attributed to phosphorylation and char formation were observed with each of the phosphoramide/carbohydrate mixtures and were absent with the phosphates. The individual phosphorus compounds studied showed similar thermal behavior with each of the carbohydrates indicating that the mode of interaction for these mixtures was similar. Isothermal gravimetric analysis of the organophosphorus/carbohydrate mixtures was used to measure the rate of decomposition weight loss from isothermal conditions. This weight loss was used as an indication of rate of fuel formation. The kinetics observed for these measurements indicated that the phosphoramide mixtures underwent a rapid weight loss to a final char with an effective E act of about 55 kcal/mol while the phosphate mixtures exhibited effective E act ′s for decomposition lower than those observed for the pure carbohydrates. Mixtures of glucose with selcted arylphosphoramide esters were pyrolysed in order to determine the effect of lability of the leaving group on char formation. Gas chromatographic analysis of the pyrolysis products indicated that phenol was the favored leaving group in comparison with aniline units, but char promotion appeared to be dependent on the number of P‐N bonds present in the original phosphoramide. Electron spectroscopy for chemical analysis indicated that chemically similar chars were obtained from the different organophosphorus/carbohydrate combinations.
Recombinant Adeno-Associated Viral Integration and Genotoxicity: Insights from Animal Models (2017)

Currently, clinical gene therapy is experiencing a renaissance, with new products for clinical use approved in Europe and clinical trials for multiple diseases reporting positive results, especially those using recombinant adeno-associated viral (rAAV) vectors. Amid this new success, it is prudent to recall that the field of gene therapy experienced tragic setbacks in 1999 and 2002 because of the serious adverse events related to retroviral and adenoviral gene delivery in two clinical trials that resulted in the death of two patients. In both cases, the toxicity observed in humans had been documented to occur in animal models. However, these toxicities were either undetected or underappreciated before they arose in humans. rAAVs have been tested extensively in animals and animal models of disease, largely without adverse events, except for transient elevation in liver enzymes in some patients. However, a small but growing number of murine studies have documented that adeno-associated viral gene delivery can result in insertional mutagenesis. Herein, the aggregate data are reviewed from multiple murine studies where genotoxicity associated with rAAV treatment has been observed. The data emphasize the need for a proactive position to evaluate the potential risks and possible solutions associated with AAV-mediated gene therapy.
Toxicity of Seven Monoterpenoids to Tracheal Mites (Acari: Tarsonemidae) and Their Honey Bee (Hymenoptera: Apidae) Hosts When Applied as Fumigants (1997)

Journal Article Toxicity of Seven Monoterpenoids to Tracheal Mites (Acari: Tarsonemidae) and Their Honey Bee (Hymenoptera: Apidae) Hosts When Applied as Fumigants Get access Marion D. Ellis, Marion D. Ellis Department of Entomology, University of Nebraska, 202 Plant Industries Building, Lincoln, NE 68583-0816 Search for other works by this author on: Oxford Academic PubMed Google Scholar Frederick P. Baxendale Frederick P. Baxendale Department of Entomology, University of Nebraska, 202 Plant Industries Building, Lincoln, NE 68583-0816 Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Economic Entomology, Volume 90, Issue 5, 1 October 1997, Pages 1087–1091, https://doi.org/10.1093/jee/90.5.1087 Published: 01 October 1997 Article history Received: 25 October 1996 Accepted: 19 May 1997 Published: 01 October 1997
Increased in vivo immunological potency of HB-110, a novel therapeutic HBV DNA vaccine, by electroporation (2008)

Pulse-induced permeabilization of cellular membranes, generally referred to as electroporation (EP), has been used for years as a tool to increase macromolecule uptake in tissues, including nucleic acids, for gene therapeutic applications, and this technique has been shown to result in improved immunogenicity. In this study, we assessed the utility of EP as a tool to improve the efficacy of HB-110, a novel therapeutic DNA vaccine against chronic hepatitis B, now in phase 1 of clinical study in South Korea. The potency of HB-110 in mice was shown to be improved by EP. The rapid onset of antigen expression and higher magnitude of humoral and cellular responses in electric pulse-treated mice revealed that EP may enable a substantial reduction in the dosage of DNA vaccine required to elicit a response similar in magnitude to that achievable via conventional administration. This study also showed that EP-based vaccination at 4-week-intervals elicited a cellular immune response which was about two-fold higher than the response elicited by conventional vaccination at 2-week intervals. These results may provide a rationale to reduce the clinical dose and increase the interval between the doses in the multidose vaccination schedule. Electric pulsing also elicited a more balanced immune response against four antigens expressed by HB-110: S, preS, Core, and Pol.
A Preliminary Study of Human Amniotic Membrane as a Potential Chondrocyte Carrier (2009)

Purpose: To investigate the feasibility of using processed human amniotic membrane (HAM) to support the attachment and proliferation of chondrocytes in vitro which in turn can be utilised as a cell delivery vehicle in tissue engineering applications. Methods: Fresh HAM obtained from patients undergoing routine elective caesarean sections was harvested, processed and dried using either freeze drying (FD) or air drying (AD) methods prior to sterilisation by gamma irradiation. Isolated, processed and characterised rabbit autologous chondrocytes were seeded on processed HAM and cultured for up to three weeks. Cell attachment and proliferation were examined qualitatively using inverted brightfield microscopy. Results: Processed HAM appeared to allow cell attachment when implanted with chondrocytes. Although cells seeded on AD and FD HAM did not appear to attach as strongly as those seeded on glycerol preserved intact human amniotic membrane, these cells to be proliferated in cell culture conditions. Conclusion: Preliminary results show that processed HAM promotes chondrocyte attachment and proliferation.
CT Findings of Small Bowel Metastases From Primary Lung Cancer (2002)

Purpose: To evaluate the CT findings of small bowel metastases from primary lung cancer. Materials and Methods: Of the 1468 patients with primary lung cancer between 1990 and 2000, 13 patients who had metastasis to the small intestine were collected. Of these 13 patients, nine who underwent CT scan were included for analysis. The pathologic diagnoses of primary lung cancer in these nine patients were squamous cell carcinoma in six, adenocarcinoma in two, and large cell carcinoma in one. CT scans were analyzed with regard to the site and patterns (intraluminal mass/bowel wall thickening/bowel implants) of metastatic masses, and the presence or absence of complication such as intussusception, obstruction, or perforation of the small bowel. The medical records of the patients were also reviewed retrospectively for evaluation of presenting abdominal symptom and time interval of metastases from initial diagnosis of lung cancer. Results: Metastatic lesions were distributed throughout the small intestine: the duodenum in five, the jejunum in four, the ileum in six, and both jejunum and ileum in one patient. The size of metastatic masses of small bowel ranged from 1.3 cm to 5.0 cm (mean size, 2.6 cm) On CT, the small bowel was involved with intraluminal masses (mean size, 3.4 cm) in eight patients, diffuse wall thickening (mean thickness, 1.6 cm) in five, and bowel implants (mean size, 2.2 cm) in two. Complications occurred in seven patients, including intussusceptions without obstruction in two patients and with obstruction in two, obstruction without intussusceptions in two, and bowel perforation in one. Of 9 patients, 6 had at least one symptom referable to the small bowel including abdominal pain in 4, anemia in 3, vomiting in 1, and jaundice in 1. Lung cancer and small bowel lesions were detected simultaneously in four patients and the time interval of metastases from initial diagnosis of lung cancer ranged from 10 days to 30 months (median interval, 54 days) in 5 patients. Conclusion: CT helps in defining the extent and pattern of small bowel metastases as well as in demonstrating their complication.
Static versus dynamic teboroxime myocardial perfusion SPECT in canines (2000)

Tc-99m-teboroxime is a perfusion tracer with high myocardial extraction, fast washin and washout kinetics, and excellent imaging properties. The fast kinetics pose some problems for static imaging, but they also allow for back-to-back stress / rest studies to be performed very quickly. Furthermore, such fast kinetics are ideally suited for dynamic imaging. We have compared static versus dynamic myocardial perfusion SPECT with teboroxime in canines using microsphere-derived flow values as the gold standard. Dynamic data were successfully acquired at rest and under adenosine stress in seven dogs using a fast serial scanning protocol. The data were analyzed in two ways: summing timeframes to create a single, static dataset with consistent projections; and 4D reconstruction and kinetic parameter estimation for a two compartment model. In both cases imaging data (voxel intensity or washin rate parameter) were correlated with flow values measured by microspheres. The static summing procedure that produced the best correlation with flow consisted of summing the projection data acquired from 60 to 180 seconds post-injection. The washin rate parameter was found to provide better correlation with flow than static image intensity in six of seven animals. When the data were pooled over all studies, washin provided significantly better correlation with flow than static imaging (p<0.01). We conclude that dynamic imaging of teboroxime with compartmental modeling provides a better measure of flow than can be obtained from static imaging techniques.
Adoptive Immunotherapy for EBV-associated Malignancies (2004)

Latent Epstein-Barr virus (EBV) infection is associated with a diverse group of malignancies including Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma (NPC), and lymphoproliferative disease (LPD). EBV proteins expressed in these malignancies provide targets for the adoptive immunotherapy with antigen-specific cytotoxic T cells (CTL) and EBV-specific CTL have been used successfully for the prophylaxis and treatment of EBV-LPD post hematopoietic stem cell transplantation (HSCT). The clinical experience with EBV-specific CTL for other EBV-associated malignancies such as Hodgkin's disease and NPC is limited and the results obtained so far indicate that EBV-specific CTL are less effective than for EBV-LPD post HSCT. Decreased CTL efficacy most likely reflect immune evasion strategies by tumor cells such as down regulation of immunodominant EBV proteins and secretion of inhibitory cytokines. To overcome these immune evasion strategies a number of approaches have been developed including targeting CTL to subdominant EBV antigens and genetically modifying CTL to increase their potency.
Pure Red-Cell Aplasia of 10 Years' Duration Due to Persistent Parvovirus B19 Infection and Its Cure with Immunoglobulin Therapy (1989)

PARVOVIRUS B19 is the etiologic agent of transient aplastic crisis, an acute episode of bone marrow failure in persons with underlying hemolysis.1 , 2 In tissue-culture studies, parvovirus B19 infects3 and replicates4 in erythroid progenitor cells. The pathophysiologic basis of acute marrow failure in patients is viral tropism and cytotoxicity for erythroid progenitor cells.5 , 6 In experimental7 and natural8 infections, the infection is terminated with the development of specific antibodies, which neutralize the activity of the virus in vitro.9 In the immunocompromised host who is unable to produce neutralizing antibody,10 an infection with parvovirus B19 can persist and cause chronic bone marrow failure, . . .