gebhart/patrepeval huggingface dataset:
The Incidence of Concurrent Osteitis in Patients with Chronic Rhinosinusitis: A Clinicopathological Study (2006)

Concurrent osteitis can be found in 36-53% of patients with CRS, using both radiographic and pathological criteria, respectively. Although a causal relationship between osteitis and CRS can not be inferred from this data, these clinical findings correlate well with previous evidence of bone involvement in CRS found in animal models, further reaffirming the association between underlying osteitis and the pathogenesis of CRS.
Identifying behavior models for process plants (2011)

The increasing complexity of today's production systems and the variety of model-based approaches to their monitoring, diagnosis and testing emphasize the importance of the modeling step. Modeling is mostly done manually, in a costly and time-consuming way. In this paper, an alternative that comes from the learning theory is given: an automated procedure for identifying behavior models from recorded observations. Assuming the system's structure is known, the algorithm presented here is capable of learning behavior models for its components. The algorithm accounts for probabilistic, timing, discrete and continuous aspects of the given system, using the modeling formalism of hybrid automata. The practical usability of identified models is demonstrated using an anomaly detection application for a real production system.
Dorsal midline fate in Drosophila embryos requires twisted gastrulation, a gene encoding a secreted protein related to human connective tissue growth factor. (1994)

The twisted gastrulation (tsg) gene is one of seven known zygotic genes that specify the fate of dorsal cells in Drosophila embryos. Mutations in these genes cause at least some of the cells on the dorsal half of the embryo to adopt more ventral cell fates leading to the proposal that most of these genes participate in establishing, maintaining, or modulating a gradient of a single signaling molecule DECAPENTAPLEGIC (DPP). We have examined the effects of tsg mutations on the development of cuticule elements, expression of a region specific enhancer trap, and patterns of mitotic domains. Mutations of tsg only affect the fate of a narrow strip of dorsal midline cells and do not affect dorsal ectoderm cells. However, the pattern of tsg expression is not coincident with the territories affected by tsg mutations. Structural analysis of the tsg gene reveals features of a secreted protein suggesting an extracellular site of action. The TSG protein bears a weak resemblance to human connective tissue growth factor (CTGF), a TGF-beta-induced protein. We propose that dorsal midline cell fate is specified by the combination of both a TSG and a DPP signal to which the dorsal midline cells are uniquely competent to respond.
The A-Z Reference book of syndromes and inherited disorders Gilbert P The A-Z Reference book of syndromes and inherited disorders Chapman and Hall £15.99 012-64120-8 012641208 (1997)

This clearly presented book provides an invaluable reference for health professionals working with children. The incidence, characteristics and appropriate management of 90 syndromes and inherited disorders are included, along with the addresses of parent support groups.
Visualization and analysis of multi-variate data: a technique for all fields (1991)

Scientific Visualization has been driven by the need to visualize data sets that involve a large number of points and/or many dimensions or variables. However, many, or, perhaps all, fields of endeavor that use numeric data (including, finance, market research, management, manufacturing, process control, risk analysis, social services, health sciences, social sciences, physical sciences, computer science, applied mathematics, the engineering disciplines, and a host of other fields) deal with data sets of this type. Asking who can benefit from data visualization is like asking who can benefit from math or statistics. We present a hierarchical technique for visualizing truly multi-dimensional data that can be applied to any or all of these fields. The emphasis will be on visual statistical analysis of either discrete variables or continuous variables that have been sampled on, or binned to, a regular n-dimensional lattice.
RASAL2 down-regulation in ovarian cancer promotes epithelial-mesenchymal transition and metastasis (2014)

Ovarian cancer is the most lethal gynecologic malignancy, and transcoelomic metastasis is responsible for the greatest disease mortality. Although intensive efforts have been made, the mechanism behind this process remains unclear. RASAL2 is a GTPase activating proteins (GAPs) which was recently reported as a tumor suppressor in breast cancer. In this study, we identified RASAL2 as a regulator of epithelial-mesenchymal transition (EMT) and metastasis in ovarian cancer. RASAL2 was down-regulated in ovarian cancer samples compared with normal tissue samples, especially in advanced stages and grades. RASAL2 knockdown in ovarian cancer cell lines promoted in vitro anchorage-independent growth, cell migration and invasion and in vivo tumor formation. Moreover, we observed EMT in RASAL2-depleted cells. E-cadherin-mediated cell-cell adhesion was attenuated, and mesenchymal markers were up-regulated. Further investigation revealed that the oncogenic role of RASAL2 down-regulation was mediated by the Ras-ERK pathway. RASAL2 knockdown activated the Ras-ERK pathway, and inhibition of the pathway reversed the functional effects of RASAL2 depletion. Together, our results implicate RASAL2 as an EMT regulator and tumor suppressor in ovarian cancer, and down-regulation of RASAL2 promotes ovarian cancer progression.
LMO2 (LIM domain only 2) is expressed in a subset of acute myeloid leukaemia and correlates with normal karyotype (2013)

LMO2 is expressed in a subset of AML patients and is associated with normal karyotype, which is different from T-ALL, where specific translocation (11p13) mediates protein expression.
Telomere-mediated plasmid segregation in Saccharomyces cerevisiae involves gene products required for transcriptional repression at silencers and telomeres. (1993)

Plasmids that contain Saccharomyces cerevisiae TG1-3 telomere repeat sequences (TRS plasmids) segregate efficiently during mitosis. Mutations in histone H4 reduce the efficiency of TRS-mediated plasmid segregation, suggesting that chromatin structure is involved in this process. Sir2, Sir3 and Sir4 are required for the transcriptional repression of genes located at the silent mating type loci (HML and HMR) and at telomeres (telomere position effect) and are also involved in the segregation of TRS plasmids, indicating that TRS-mediated plasmid segregation involves factors that act at chromosomal telomeres. TRS plasmid segregation differes from the segregation of plasmids carrying the HMR E silencing region: HMR E plasmid segregation function is completely dependent upon Sir2, Sir3 and Sir4, involves Sir1 and is not influenced by mutations in RAP 1 that eliminate TRS plasmid segregation. Mutations in SIR1, SIN1, TOP1, TEL1 and TEL2 do not influence TRS plasmid segregation. Unlike transcriptional repression at telomeres, TRS plasmids retain partial segregation function in sir2, sir3, sir4, nat1 and ard1 mutant strains. Thus it is likely that TRS plasmid segregation involves additional factors that are not involved in telomere position effect.
Intratumoral chemotherapy with cisplatin in oily emulsion in horses (1993)

Twenty horses with 30 lesions were studied to evaluate the effects of intratumoral chemotherapy with cisplatin in sesame oil on equine sarcoids (n = 19), squamous cell carcinomas (n = 7), and squamous cell papillomas (n = 4). Treatment consisted of 4 sessions of intratumoral cisplatin chemotherapy at 2-week intervals. A controlled-release formulation of cisplatin in sesame oil was used to limit drug egress from the injection site. Mean dosage per session was 0.97 (+/- 0.17, SEM) mg of cisplatin/cm3 of tumor tissue treated for tumor volumes ranging from 10 to 20 cm3. Dosage tended to be slightly higher for smaller tumors and slightly lower for larger tumors. Tumor regression was observed in all horses. Complete response was observed in 18 of the sarcoids, 5 of the squamous cell carcinomas, and 4 of the squamous cell papillomas. The mean relapse-free interval was 21.6 and 14 months in horses with sarcoid and carcinoma/papilloma, respectively. The 1-year relapse-free rates were 87 and 65% for equine sarcoid and carcinoma/papilloma, respectively. In horses with relapse, 70% had tumor recurrence outside the treated field. Cisplatin-related local toxicosis was minimal. Intratumoral cisplatin chemotherapy was found to be a practical and effective treatment of sarcoid and squamous cell carcinoma/papilloma in horses.
Gene Transfer to the Nonhuman Primate Retina with Recombinant Feline Immunodeficiency Virus Vectors (2002)

We hypothesize that recombinant feline immunodeficiency viral (rFIV) vectors may be useful for gene transfer to the nonhuman primate retina. We performed vitrectomies and subretinal injections in the right eyes of 11 cynomolgus monkeys. Vesicular stomatitis virus glycoprotein-pseudotyped rFIV that expressed the Escherichia coli beta-galactosidase gene was injected into eight eyes. Sham vehicle or lactose buffer injections were also performed in two of these eight study eyes. rFIV pseudotyped with an amphotropic envelope was used in two eyes, and in one animal injections of lactose buffer only were given. After surgery the animals were clinically evaluated by retinal photography and electroretinography. beta-Galactosidase expression was evaluated, at a final end point, in histological sections. We found photoreceptor and Müller cells to have the greatest transgene expression. Focal inflammatory responses localized to the injection site were seen histologically in all eyes. No difference in transduction efficiency was seen between injections near the macula and more peripheral injections. Visual function as assessed by electroretinography was not significantly affected by vector or vehicle injections. We conclude that rFIV vectors administered beneath the retina can transduce a variety of retinal cells in the nonhuman primate retina. rFIV vectors have therapeutic potential and could be exploited to develop gene therapy for the human eye.
Retinal Vessel Changes in Galactose-Fed Dogs (1998)

These results confirm that galactosemic dogs are an appropriate and suitable animal model for investigating human diabetic retinopathy.
Rodent malaria parasites : genome organization & comparative genomics (2006)

The aim of the studies described in this thesis was to investigate the genome organization of rodent malaria parasites (RMPs) and compare the organization and gene content of the genomes of RMPs and the human malaria parasite P. falciparum. The release of the complete genome sequence of P. falciparum and partial genome sequences of three RMPs (Plasmodium yoelii - Chapter 3; Plasmodium berghei and Plasmodium chabaudi - Chapter 4) enabled us to expand the analysis to a genome-wide survey. By aligning the RMP contigs against the P. falciparum genome, a composite RMP genome was constructed, which was subsequently compared in detail with the P. falciparum genome (Chapter 5). These comparative analyses showed high levels of conservation in both genome organization and gene content (~85%), supporting the use of RMPs as models for human malaria infection. P. falciparum-specific genes located in both subtelomeric and core regions of the chromosomes were also found and included many genes involved in host-parasite interactions, such as host cell invasion and evasion of the human immune response. Finally, reverse genetics approaches were used to study the function of certain genes that are conserved between the rodent and human malaria parasites (Chapters 6 & 7).
Selective targeting of IL-2 to NKG2D bearing cells for improved immunotherapy (2016)

Despite over 20 years of clinical use, IL-2 has not fulfilled expectations as a safe and effective form of tumour immunotherapy. Expression of the high affinity IL-2Rα chain on regulatory T cells mitigates the anti-tumour immune response and its expression on vascular endothelium is responsible for life threatening complications such as diffuse capillary leak and pulmonary oedema. Here we describe the development of a recombinant fusion protein comprised of a cowpox virus encoded NKG2D binding protein (OMCP) and a mutated form of IL-2 with poor affinity for IL-2Rα. This fusion protein (OMCP-mutIL-2) potently and selectively activates IL-2 signalling only on NKG2D-bearing cells, such as natural killer (NK) cells, without broadly activating IL-2Rα-bearing cells. OMCP-mutIL-2 provides superior tumour control in several mouse models of malignancy and is not limited by mouse strain-specific variability of NK function. In addition, OMCP-mutIL-2 lacks the toxicity and vascular complications associated with parental wild-type IL-2.
Expression of GDNF mRNA in Rat and Human Nervous Tissue (1994)

A recently cloned neurotrophic factor, termed glial cell line-derived neurotrophic factor (GDNF), has been reported to exhibit selective neurotrophic properties on ventral mesencephalon dopaminergic neurons, which degenerate in patients with Parkinson's disease. In the present study, we used reverse transcriptase followed by polymerase chain reaction (PCR) and in situ hybridization to study the expression of GDNF messenger RNA (mRNA) in the adult rat and human central nervous system (CNS). GDNF transcripts were identified using PCR in all regions of the rat CNS analyzed including striatum, hippocampus, cortex, cerebellum, and spinal cord. Interestingly, the rat hippocampal formation contained two transcripts, i.e., a larger form in addition to the amplified GDNF cDNA found in all other areas analyzed. GDNF PCR products also were observed in human striatum, hippocampus, cortex, and spinal cord, but not cerebellum, and both the striatum and hippocampal formation contained two GDNF transcripts. Finally, GDNF transcripts were detected in a rat Schwann cell line previously shown to secrete a factor that exerts a neurotrophic effect on dopaminergic neurons. In situ hybridization experiments using a cRNA probe hybridized to adult rat brain sections demonstrated no positive GDNF mRNA signal. However, intense GDNF mRNA hybridization signal was found to be associated with dorsal root ganglia in Postnatal Day 1 rats. These findings provide evidence that GDNF is detectable using PCR in a number of nervous system structures and, in some areas, GDNF is expressed in more than one form.
Systemic delivery of blood–brain barrier-targeted polymeric nanoparticles enhances delivery to brain tissue (2015)

Delivery of therapeutic agents to the central nervous system is a significant challenge, hindering progress in the treatment of diseases such as glioblastoma. Due to the presence of the blood-brain barrier (BBB), therapeutic agents do not readily transverse the brain endothelium to enter the parenchyma. Previous reports suggest that surface modification of polymer nanoparticles (NPs) can improve their ability to cross the BBB, but it is unclear whether the observed enhancements in transport are large enough to enhance therapy. In this study, we synthesized two degradable polymer NP systems surface-modified with ligands previously suggested to improve BBB transport, and tested their ability to cross the BBB after intravenous injection in mice. All the NP preparations were able to cross the BBB, although generally in low amounts (<0.5% of the injected dose), which was consistent with prior reports. One NP produced significantly higher brain uptake (∼0.8% of the injected dose): a block copolymer of polylactic acid and hyperbranched polyglycerol, surface modified with adenosine (PLA-HPG-Ad). PLA-HPG-Ad NPs provided controlled release of camptothecin, killing U87 glioma cells in culture. When administered intravenously in mice with intracranial U87 tumors, they failed to increase survival. These results suggest that enhancing NP transport across the BBB does not necessarily yield proportional pharmacological effects.
Magnetic Switch of Permeability for Polyelectrolyte Microcapsules Embedded with Co@Au Nanoparticles (2005)

We explored using a magnetic field to modulate the permeability of polyelectrolyte microcapsules prepared by layer-by-layer self-assembly. Ferromagnetic gold-coated cobalt (Co@Au) nanoparticles (3 nm diameter) were embedded inside the capsule walls. The final 5 mum diameter microcapsules had wall structures consisting of 4 bilayers of poly(sodium styrene sulfonate)/poly(allylamine hydrochloride) (PSS/PAH), 1 layer of Co@Au, and 5 bilayers of PSS/PAH. External alternating magnetic fields of 100-300 Hz and 1200 Oe were applied to rotate the embedded Co@Au nanoparticles, which subsequently disturbed and distorted the capsule wall and drastically increased its permeability to macromolecules like FITC-labeled dextran. The capsule permeability change was estimated by taking the capsule interior and exterior fluorescent intensity ratio using confocal laser scanning microscopy. Capsules with 1 layer of Co@Au nanoparticles and 10 polyelectrolyte bilayers are optimal for magnetically controlling permeability. A theoretical explanation was proposed for the permeability control mechanisms. "Switching on" of these microcapsules using a magnetic field makes this method a good candidate for controlled drug delivery in biomedical applications.
Discovery of INCB9471, a Potent, Selective, and Orally Bioavailable CCR5 Antagonist with Potent Anti-HIV-1 Activity (2010)

To identify a CCR5 antagonist as an HIV-1 entry inhibitor, we designed a novel series of indane derivatives based on conformational considerations. Modification on the indane ring led to the discovery of compound 22a (INCB9471) that exhibited high affinity for CCR5, potent anti-HIV-1 activity, high receptor selectivity, excellent oral bioavailability, and a tolerated safety profile. INCB9471 has entered human clinical trials.
Carbon Uptake and the Metabolism and Transport of Lipids in an Arbuscular Mycorrhiza1 (1999)

Both the plant and the fungus benefit nutritionally in the arbuscular mycorrhizal symbiosis: The host plant enjoys enhanced mineral uptake and the fungus receives fixed carbon. In this exchange the uptake, metabolism, and translocation of carbon by the fungal partner are poorly understood. We therefore analyzed the fate of isotopically labeled substrates in an arbuscular mycorrhiza (in vitro cultures of Ri T-DNA-transformed carrot [Daucus carota] roots colonized by Glomus intraradices) using nuclear magnetic resonance spectroscopy. Labeling patterns observed in lipids and carbohydrates after substrates were supplied to the mycorrhizal roots or the extraradical mycelium indicated that: (a) 13C-labeled glucose and fructose (but not mannitol or succinate) are effectively taken up by the fungus within the root and are metabolized to yield labeled carbohydrates and lipids; (b) the extraradical mycelium does not use exogenous sugars for catabolism, storage, or transfer to the host; (c) the fungus converts sugars taken up in the root compartment into lipids that are then translocated to the extraradical mycelium (there being little or no lipid synthesis in the external mycelium); and (d) hexose in fungal tissue undergoes substantially higher fluxes through an oxidative pentose phosphate pathway than does hexose in the host plant.
Chronic alcohol intake reduces retinoic acid concentration and enhances AP-1 (c-Jun and c-Fos) expression in rat liver† (1998)

Chronic ethanol intake may interfere with retinoid signal transduction by inhibiting retinoic acid synthesis and by enhancing activator protein-1 (AP-1) (c-Jun and c-Fos) expression, thereby contributing to malignant transformation. To determine the effect of ethanol on hepatic retinoid levels, retinoic acid receptors (RARs) and AP-1 (c-Jun and c-Fos) gene expression, chronic ethanol (36% of total calorie intake) pair-feeding was conducted on rats for a 1-month period. Retinoic acid, retinol, and retinyl ester concentrations in both liver and plasma were examined by using high-performance liquid chromatography (HPLC). Both retinoic acid receptor (alpha, beta, gamma) and AP-1 (c-Jun and c-Fos) expression in the rat liver were examined by using Western blot analysis. Treatment with high-dose ethanol led to a significant reduction of retinoic acid concentration in both the liver and the plasma (11- and 8.5-fold reduction, respectively), as compared with animals pair-fed an isocaloric control diet containing the same amount of vitamin A. Similar to the retinoic acid reductions, both retinol and retinyl palmitate levels in the livers of the alcohol-fed group decreased significantly, but in smaller fold reduction (6.5- and 2.6-fold reduction, respectively). Ethanol did not modulate the expression of RARalpha, -beta, and -gamma genes in the liver. However, chronic alcohol feeding enhanced AP-1 (c-Jun and c-Fos) expression by 7- to 8-fold, as compared with the control group. These data suggest that functional downregulation of RARs by inhibiting biosynthesis of retinoic acid and up-regulation of AP-1 gene expression may be important mechanisms for causing malignant transformation by ethanol.
Interaction of AP-1-, AP-2-, and Sp1-like proteins with two distinct sites in the upstream regulatory region of the plasminogen activator inhibitor-1 gene mediates the phorbol 12-myristate 13-acetate response. (1992)

Phorbol 12-myristate 13-acetate induces a 3- and 10-fold induction of chloramphenicol acetyltransferase (CAT) activity in HT1080 and HeLa cells, respectively, following transient transfection of a 336-base pair plasminogen activator inhibitor-1 (PAI-1) promoter fragment linked to a CAT reporter gene. Substitution mutations in the regions encompassing nucleotides -78 to -69 (TGGGTGGGGC) or -61 to -54 (TGAGTTCA), but not in the regions -155 to -149 (TGCCTCA) or -84 to -76 (AGTGAGTGG) reduced this induction. Gel electrophoresis of double-stranded -65 to -50 oligonucleotides of the PAI-1 promoter region and nuclear extracts from Hela cells produced a gel shift pattern similar to that obtained with a AP-1 consensus oligomer, and excess unlabeled AP-1 oligomer reverted binding, suggesting that this region of the PAI-1 promoter is an AP-1-like binding site. Gel electrophoresis of double-stranded -82 to -65 oligonucleotides with HeLa nuclear extracts revealed a gel shift pattern of three bands; Sp1 consensus oligomer competed with the binding to two of these bands and AP-2 consensus sequence oligomer with the binding to the third band. The -82 to -65 oligomer also bound to purified AP-2 and Sp1 proteins. Southwestern blotting of HeLa nuclear extracts revealed that the labeled oligomer spanning region -82 to -65 bound to proteins with molecular masses of 52 and 72 kDa. Consensus AP-2 oligonucleotides competed for binding of the labeled -82 to -65 oligonucleotide to the 52-kDa protein, but consensus Sp-1 oligonucleotides did not compete for binding to the 72-kDa compound. The 72-kDa component binding to the -82 to -65 region may represent a new protein involved in transcriptional regulation.