gebhart/patrepeval huggingface dataset:
Systemic Messenger RNA Therapy as a Treatment for Methylmalonic Acidemia (2017)

Isolated methylmalonic acidemia/aciduria (MMA) is a devastating metabolic disorder with poor outcomes despite current medical treatments. Like other mitochondrial enzymopathies, enzyme replacement therapy (ERT) is not available, and although promising, AAV gene therapy can be limited by pre-existing immunity and has been associated with genotoxicity in mice. To develop a new class of therapy for MMA, we generated a pseudoU-modified codon-optimized mRNA encoding human methylmalonyl-CoA mutase (hMUT), the enzyme most frequently mutated in MMA, and encapsulated it into biodegradable lipid nanoparticles (LNPs). Intravenous (i.v.) administration of hMUT mRNA in two different mouse models of MMA resulted in a 75%-85% reduction in plasma methylmalonic acid and was associated with increased hMUT protein expression and activity in liver. Repeat dosing of hMUT mRNA reduced circulating metabolites and dramatically improved survival and weight gain. Additionally, repeat i.v. dosing did not increase markers of liver toxicity or inflammation in heterozygote MMA mice.
New long-wavelength Nd:YAG laser at 1.44 µm: effect on brain (1989)

A wavelength-shifted Nd:YAG laser, tuned to coincide with the infrared absorption peak of water at 1.44 microns, was used to make lesions in normal rabbit brain. A total of 48 lesions were made with power up to 20 W, with energy up to 40 joules, and with two different spot sizes. These lesions were compared to lesions made with 1.06 microns radiation from an Nd:YAG laser under identical operating conditions. Measurements of blood-brain barrier damage and width, depth, and volume of tissue affected were obtained 30 minutes after placement of the lesions. It was found that 1.44-microns lesions produced photoevaporative tissue loss at the highest intensities used. The layer of coagulated tissue remaining after photovaporization had a mean thickness of 0.6 mm irrespective of the volume of tissue removed. There was no photovaporization in the 1.06-microns lesions. In addition, the amount of peripheral edema per unit volume of tissue coagulated was approximately half at the 1.44-microns wavelength. These findings suggest that the 1.44-microns Nd:YAG laser may be a useful surgical instrument since it combines the photoevaporative effect of the CO2 laser while maintaining the advantages of the conventional Nd:YAG laser (quartz fiber delivery and effective hemostasis).
CTLA-4 and the genetic predisposition to autoimmunity. (2005)

Due to the wide spectrum of clinical manifestations and their epidemiological dimensions, autoimmune diseases represent an important medical issue. They are the consequence of the loss of immune tolerance to autoantigens, which in turn is a result of the interaction of environmental, as well as genetic factors. The predisposing role of HLA antigens is widely accepted; nonetheless, it does not fully explain the occurrence of autoimmune disorders. In this topical review, we present the current knowledge on the role of some non-HLA genes (ICOS, CD28 and CTLA-4 in particular) in the development of autoimmunity. (Fig. 1, Ref: 106.)
Highly Polarized Photoluminescence and Photodetection from Single Indium Phosphide Nanowires (2001)

We have characterized the fundamental photoluminescence (PL) properties of individual, isolated indium phosphide (InP) nanowires to define their potential for optoelectronics. Polarization-sensitive measurements reveal a striking anisotropy in the PL intensity recorded parallel and perpendicular to the long axis of a nanowire. The order-of-magnitude polarization anisotropy was quantitatively explained in terms of the large dielectric contrast between these free-standing nanowires and surrounding environment, as opposed to quantum confinement effects. This intrinsic anisotropy was used to create polarization-sensitive nanoscale photodetectors that may prove useful in integrated photonic circuits, optical switches and interconnects, near-field imaging, and high-resolution detectors.
Construction of a genome-length cDNA clone for human astrovirus serotype 1 and synthesis of infectious RNA transcripts (1997)

We have constructed a genome-length cDNA clone for human astrovirus serotype 1. When a human colon cancer-derived cell line, CaCo-2, is transfected with RNA transcribed in vitro from this cDNA clone, infectious virus is produced at titers close to those observed after infection with intact astrovirus. A rodent cell line, BHK, which is largely refractory to astrovirus infection, was found to support efficient growth of the virus if transfected with viral RNA. The high transfection efficiency seen in the BHK cells allows studies of the viral replication in the transfected cells and thus should prove useful for the characterization of noninfectious astroviral mutants.
Menopausal and Reproductive Factors and Risk of Age-Related Macular Degeneration (2008)

Although PMH and OC use were associated with a lower risk of neovascular AMD, no benefit was observed for early AMD. Factors influencing lifetime exposure to estrogens were not consistently associated with the disease.
Lignin Impact on Fiber Degradation. 3. Reversal of Inhibition of Enzymatic Hydrolysis by Chemical Modification of Lignin and by Additives (1997)

The impact of lignins of various origins on filter paper hydrolysis by fungal cellulase was evaluated. Powdered lignins were added to enzyme incubations, either as isolated or after thorough hydroxypropylation of phenolic sites. Extent of cellulose hydrolysis was reduced by 14−60% by the addition of up to 15% lignin to the substrate. Unmodified lignins were more detrimental to cellulose hydrolysis than hydroxypropylated lignins. The inhibitory effect of lignin addition was only partially overcome by a 10-fold increase in cellulase activity, suggesting inhibitory lignin interactions with both substrate and enzyme. Preincubation of cellulase with underivatized lignins resulted in reduced enzyme activity and soluble protein concentration in the supernatant, suggesting protein precipitation with lignin rather than reduced activity of a lignin−enzyme complex as the inhibitory mechanism. Two further experiments showed that the negative impact of lignin on cellulose hydrolysis can be counteracted by addition of various N compounds and by ammoniation. Keywords: Lignin; cellulose degradation; cellulase inhibition; free phenolic group; ammoniation; PEG; PVP; N compounds
Integrative Genome Comparison of Primary and Metastatic Melanomas (2010)

A cardinal feature of malignant melanoma is its metastatic propensity. An incomplete view of the genetic events driving metastatic progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. In this study, we conducted global genomic characterization of primary and metastatic melanomas to examine the genomic landscape associated with metastatic progression. In addition to uncovering three genomic subclasses of metastastic melanomas, we delineated 39 focal and recurrent regions of amplification and deletions, many of which encompassed resident genes that have not been implicated in cancer or metastasis. To identify progressionassociated metastasis gene candidates, we applied a statistical approach, Integrative Genome Comparison (IGC), to define 32 genomic regions of interest that were significantly altered in metastatic relative to primary melanomas, encompassing 30 resident genes with statistically significant expression deregulation. Functional assays on a subset of these candidates, including MET, ASPM, AKAP9, IMP3, PRKCA, RPA3, and SCAP2, validated their pro-invasion activities in human melanoma cells. Validity of the IGC approach was further reinforced by tissue microarray analysis of Survivin showing significant increased protein expression in thick versus thin primary cutaneous melanomas, and a progression correlation with lymph node metastases. Together, these functional validation results and correlative analysis of human tissues support the thesis that integrated genomic and pathological analyses of staged melanomas provide a productive entry point for discovery of melanoma metastases genes.
SAGE analysis of neuroblastoma reveals a high expression of the human homologue of theDrosophila Delta gene (2000)

Our data therefore suggest a role for the Delta-Notch pathway in neuroblast differentiation.
Charge storage in InAlAs/InGaAs/InP floating gate heterostructures (1990)

Charge retention in floating gate InAlAs/InGaAs/InP field effect transistors is limited by lateral electron motion along the storage channel, a different direction for motion than found for AlAs/GaAs devices. Storage times as a function of temperature for the InP based alloy devices are reported and compared with similar AlAs/GaAs devices by using Poisson equation models.
Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention (1999)

Angiogenesis is the process in which new vessels emerge from existing endothelial lined vessels. This is distinct from the process of vasculogenesis in that the endothelial cells arise by proliferation from existing vessels rather than differentiating from stem cells. Angiogenesis is an invasive process that requires proteolysis of the extracellular matrix and, proliferation and migration of endothelial cells, as well as synthesis of new matrix components. During embryonic development, both vasculogenesis and angiogenesis contribute to formation of the circulatory system. In the adult, with the single exception of the reproductive cycle in women, angiogenesis is initiated only in response to a pathologic condition, such as inflammation or hypoxia. The angiogenic response is critical for progression of wound healing and rheumatoid arthritis. Angiogenesis is also a prerequisite for tumor growth and metastasis formation. Therefore, understanding the cellular events involved in angiogenesis and the molecular regulation of these events has enormous clinical implications. This understanding is providing novel therapeutic targets for the treatment of a variety of diseases, including cancer.
Regulation of phagocytic leukocyte activities by C-reactive protein (2000)

The classic acute phase reactant C-reactive protein (CRP) is classified as an effector of innate host resistance because it activates the classical complement cascade and is opsonic. The latter action occurs via specific CRP receptors (CRP-R) that have recently been identified as both FcgammaRI and FcgammaRII on human phagocytic leukocytes. New findings also suggest an anti-inflammatory role for CRP because it modulates endotoxin shock and inhibits chemotaxis and the respiratory burst of neutrophils. CRP inhibited phorbol myristate acetate-induced superoxide (O2-) production more efficiently than the fMLP-triggered response. An examination of the inhibition of the protein kinase C (PKC)-dependent assembly of the NADPH oxidase complex revealed that both phosphorylation and translocation of PKC-beta2 to the membrane were inhibited by a threshold acute phase dose of approximately 50 microg/mL CRP. Translocation to the membrane and serine-phosphorylation of the major cytosolic p47-phox component of the NADPH oxidase complex was inhibited by CRP. CRP also inhibited membrane localization of activated Rac2, the small G protein regulator of the assembly of the oxidase components in activated neutrophils as well as the cytoskeleton during chemotactic movement. CRP-mediated regulation occurs via the CRP-R because an IgM mouse mAb to the human CRP-R mimicked CRP-induced inhibition of O2- production and chemotaxis. CRP may serve as an antiinflammatory regulator of activities at sites of tissue damage where it selectively accumulates and thus influences neutrophil infiltration and polymorphonuclear neutrophil activities. By contrast, CRP activates cells of the monocyte/macrophage lineage, suggesting differential regulation of these two leukocyte populations at the level of signaling. CRP appears to be a multifunctional protein with the capability of exerting both effector functions for innate host resistance, as well as exerting specific anti-inflammatory effects.
Syndecan-1 mediates cell spreading in transfected human lymphoblastoid (Raji) cells. (1996)

Syndecan-1 is a cell surface proteoglycan containing a highly conserved transmembrane and cytoplasmic domain, and an extracellular domain bearing heparan sulfate glycosaminoglycans. Through these domains, syndecan-1 is proposed to have roles in growth factor action, extracellular matrix adhesion, and cytoskeletal organization that controls cell morphology. To study the role of syndecan-1 in cell adhesion and cytoskeleton reorganization, mouse syndecan-1 cDNA was transfected into human Raji cells, a lymphoblastoid cell line that grows as suspended cells and exhibits little or no endogenous cell surface heparan sulfate. High expressing transfectants (Raji-Sl cells) bind to and spread on immobilized thrombospondin or fibronectin, which are ligands for the heparan sulfate chains of the proteoglycan. This binding and spreading as not dependent on the cytoplasmic domain of the core protein, is mutants expressing core proteins with cytoplasmic deletions maintain the ability to spread. The spreading is mediated through engagement of the syndecan-1 core protein, as the Raji-S 1 cells also bind to and spread on immobilized mAb 281.2, an antibody specific for the ectodomain of the syndecan-1 core protein. Spreading on the antibody is independent of the heparan sulfate glycosaminoglycan chains and can be inhibited by competition with soluble mAb 281.2. The spreading can be inhibited by treatment with cytochalasin D or colchicine. These data suggest that the core protein of syndecan-1 mediates spreading through the formation of a multimolecular signaling complex at the cell surface that signals cytoskeleton reorganization. This complex may form via intramembrane or extracellular interactions with the syndecan core protein.
Molecular mechanisms of crown gall tumorigenesis (1991)

Abstract Crown gall is a neoplastic tumor disease of many types of plants. The etiological agent of this economically important disease is Agrobacterium tumefaciens, a soil‐bome, Gram‐negative, rod‐shaped bacterium commonly associated with the roots of plants. The precise mechanism of crown gall tumorigenesis is not thoroughly understood. Studies over the past 10 years have shown that there are oncogenic genes carried on a large extrachromosomal element known as the Ti (for tumor‐inducing) plasmid. These genes are transferred to the plant by a novel mechanism carried out during infection (i.e., during the interaction between bacterial and host plant cells). The precise mechanism of this gene transfer remains unclear. Furthermore, how these genes are regulated and function in the transformed plant cell is not well understood. It is known, however, that these genes are directly involved in plant‐growth hormore synthesis and represent the oncogenic genes that operate in the host plant. A deregulatory effect also occurs when part of the Ti plasmid, known as the T‐DNA, is. incorporated into the plant genome as a static “transposable”; element. The stepwise stages leading to crown gall transformation are categorically described in this review.
PML in a Patient Treated with Dimethyl Fumarate from a Compounding Pharmacy (2013)

Two cases of progressive multifocal leukoencephalopathy (PML) are reported in patients with psoriasis who were treated with fumarates, one with Fumaderm and the other with a compound containing dimethyl fumarate. The manufacturer of Fumaderm comments on the reports.
Optimizing Flexion After Total Knee Arthroplasty (2003)

The clinical results with most modern total knee arthroplasty (TKA) designs are highly satisfactory regarding pain relief and improving walking ability. However, one problem that has not been addressed fully by most current designs is the ability to consistently achieve flexion greater than 120 degrees. Although the human knee is capable of flexion of more than 150 degrees, an analysis of the results of contemporary TKA reveals that on average, patients rarely flex beyond 120 degrees. Key factors influencing range of flexion after TKA include preoperative knee motion, surgical technique, prosthetic design, and rehabilitation. The success of any total knee system may in part be linked to its ability to optimally restore normal kinematic function. Some arthroplasty designs currently are available that incorporate modifications aimed at improving range of flexion, but limited data currently are available on their function and potential advantages. Currently, an in vitro experimental model incorporating robotics is being used to investigate the kinematics of the native knee and various TKA designs at flexion angles beyond 120 degrees. This robotic model in conjunction with clinical studies may provide an understanding of the limitations of contemporary knee designs regarding achieving higher degrees of knee flexion. This may lead to the refinement of existing designs and development of newer prostheses that may enhance the range of flexion that is achievable after TKA.
Accurate Information Extraction from Research Papers using Conditional Random Fields (2004)

With the increasing use of research paper search engines, such as CiteSeer, for both literature search and hiring decisions, the accuracy of such systems is of paramount importance. This paper employs Conditional Random Fields (CRFs) for the task of extracting various common fields from the headers and citation of research papers. The basic theory of CRFs is becoming well-understood, but best-practices for applying them to real-world data require additional exploration. This paper makes an empirical exploration of several factors, including variations on Gaussian, exponential and hyperbolic-L1 priors for improved regularization, and several classes of features and Markov order. On a standard benchmark data set, we achieve new state-of-the-art performance, reducing error in average F1 by 36%, and word error rate by 78% in comparison with the previous best SVM results. Accuracy compares even more favorably against HMMs.
Irinotecan in the management of patients with pancreatic cancer. (2000)

Synergy with no overlapping toxicities has been demonstrated for the combination of irinotecan (Camptosar, CPT-11) and gemcitabine (Gemzar) in vitro. Results of a single-institution phase I study in which patients with previously untreated pancreatic cancer were given irinotecan and gemcitabine were promising, with two of three patients achieving a partial response. Because of the favorable outcome of the phase I study, a multicenter phase II trial was undertaken in previously untreated patients with pancreatic carcinoma. Data from other sites entering patients in this phase II study have been analyzed, and a multicenter phase III trial of single-agent gemcitabine vs the irinotecan combination in first-line treatment of patients with locally advanced or metastatic pancreatic cancer is underway.
Deferring updates in a relational data base system (1981)

Deferred updating in a relational data base is a technique which delays the application of updates until a request is made for the value. In general we do not know, a priori, which of the updated values will be retrieved; therefore, it is beneficial to defer the access and computation. This technique promotes an 'update-by-need' policy. The method uses generalization, property inheritance, and procedural attachment for dynamically maintaining the update and query processes. The use of these representational concepts aids in maintaining the structure of the relational model, yet provides opportunities to extend the semantic power of the model. (Author)
Cellular immune response to the hepatitis C virus (1999)

Hepatitis C virus (HCV) infection is most often clinically inapparent and rarely associated with symptoms of acute hepatitis. Most patients, however, fail to resolve the acute infection and proceed to develop chronic hepatitis with the risk of liver cirrhosis and hepatocellular carcinoma later in life. Since the kinetics of the earliest events of virus-host interaction are likely to determine the outcome of infection, research has focused on the characterization of the strength and kinetics of the antiviral immune response in different stages of disease. The identification of the immunological correlates of viral clearance is pivotal for the development of vaccines and efficient therapies.
The Baxα:Bcl-2 ratio modulates the response to dexamethasone in leukaemic cells and is highly variable in childhood acute leukaemia (1997)

Bcl-2 over-expression has been shown to inhibit apoptosis induced by a variety of stimuli, whereas a predominance of Bax alpha to Bcl-2 accelerates apoptosis upon apoptotic stimuli. We sought to study the relevance of these apoptotic regulating gene products in leukaemia. In a panel of leukaemia and lymphoma cell lines (HL60, DoHH2, CEM C7, L1210 and S49), the Bax alpha-to-Bcl-2 ratio as assessed by Western-blot analysis correlated with sensitivity to dexamethasone treatment. In addition, in HAbax alpha-transfected CEM C7 clones, a similar correlation was found for dexamethasone and thapsigargin sensitivity. In bone-marrow aspirates from patients with childhood acute lymphoblastic or myelocytic leukaemia (ALL, n = 48; AML, n = 8), the Bcl-2 and Bax alpha levels were highly variable, but well within the range found in the Bax alpha transfectants and in the established cell lines. Bcl-2 levels were lower in T- than in B-lineage ALL, which could be ascribed to simultaneous inverse relation between Bcl-2 and WBC. By contrast, Bax alpha:Bcl-2 was independent of any presenting feature and was largely dependent on Bax alpha levels. Results suggest that Bax alpha:Bcl-2, rather than Bcl-2 alone is important for the survival of drug-induced apoptosis in leukemic cell lines and ALL.
A Faster Way to Shut Down Genes (2001)

When scientists say a new technique ranks up there with the polymerase chain reaction (PCR), you know it's big. That's how at least one researcher is viewing a report this week of a new method for shutting off specific genes in mammalian cells. Although still in its infancy, the approach, known as RNA interference (RNAi), makes a currently arduous process much faster, much as PCR did for copying segments of DNA.
Highly Conserved Neisseria meningitidis Surface Protein Confers Protection against Experimental Infection (1997)

A new surface protein, named NspA, which is distinct from the previously described Neisseria meningitidis outer membrane proteins was identified. An NspA-specific mAb, named Me-1, reacted with 99% of the meningococcal strains tested indicating that the epitope recognized by this particular mAb is widely distributed and highly conserved. Western immunoblotting experiments indicated that mAb Me-1 is directed against a protein band with an approximate molecular mass of 22,000, but also recognized a minor protein band with an approximate molecular mass of 18,000. This mAb exhibited bactericidal activity against four meningococcal strains, two isolates of serogroup B, and one isolate from each serogroup A and C, and passively protected mice against an experimental infection. To further characterize the NspA protein and to evaluate the protective potential of recombinant NspA protein, the nspA gene was identified and cloned into a low copy expression vector. Nucleotide sequencing of the meningococcal insert revealed an ORF of 525 nucleotides coding for a polypeptide of 174 amino acid residues, with a predicted molecular weight of 18,404 and a isoelectric point of 9.93. Three injections of either 10 or 20 microg of the affinity-purified recombinant NspA protein efficiently protected 80% of the mice against a meningococcal deadly challenge comparatively to the 20% observed in the control groups. The fact that the NspA protein can elicit the production of bactericidal and protective antibodies emphasize its potential as a vaccine candidate.