gebhart/patrepeval huggingface dataset:
Aberrant Splicing of tau Pre-mRNA Caused by Intronic Mutations Associated with the Inherited Dementia Frontotemporal Dementia with Parkinsonism Linked to Chromosome 17 (2000)

Frontotemporal dementia accounts for a significant fraction of dementia cases. Frontotemporal dementia with parkinsonism linked to chromosome 17 is associated with either exonic or intronic mutations in the tau gene. This highlights the involvement of aberrant pre-mRNA splicing in the pathogenesis of neurodegenerative disorders. Little is known about the molecular mechanisms of the splicing defects underlying these diseases. To establish a model system for studying the role of pre-mRNA splicing in neurodegenerative diseases, we have constructed a tau minigene that reproduces tau alternative splicing in both cultured cells and in vitro biochemical assays. We demonstrate that mutations in a nonconserved intronic region of the human tau gene lead to increased splicing between exon 10 and exon 11. Systematic biochemical analyses indicate the importance of U1 snRNP and, to a lesser extent, U6 snRNP in differentially recognizing wild-type versus intron mutant tau pre-mRNAs. Gel mobility shift assays with purified U1 snRNP and oligonucleotide-directed RNase H cleavage experiments support the idea that the intronic mutations destabilize a stem-loop structure that sequesters the 5' splice site downstream of exon 10 in tau pre-mRNA, leading to increases in U1 snRNP binding and in splicing between exon 10 and exon 11. Thus, mutations in nonconserved intronic regions that increase rather than decrease alternative splicing can be an important pathogenic mechanism for the development of human diseases.
Influence of dietary nucleotides on plasma immunoglobulin levels and lymphocyte subsets of preterm infants (1999)

We examined the effects of nucleotide supplementation to a preterm adapted milk formula on the lymphocyte subsets and plasma IgG, IgM and IgA levels in preterm infants for the first three months of life. Two groups of preterm infants received a milk formula or the same formula supplemented with CMP, AMP, UMP, GMP and IMP to mimic the concentration of acid-soluble nucleotides found in human milk. Blood samples were obtained at birth, 10 days, 20-30 days and 3 months of age. Preterm infants fed the nucleotide formula exhibited higher plasma levels of IgM in all postnatal study periods than neonates fed the standard formula; moreover, IgA was also higher at 3 months of age in nucleotide formula fed infants. No major differences were seen between groups for IgG levels and lymphocyte subsets. Thus, dietary nucleotides appear to exert actions on immature human neonate lymphocytes enhancing the in vivo production of Ig which may have a role in the defense capacity of neonates.
Durable Therapeutic Efficacy Utilizing Combinatorial Blockade against IDO, CTLA-4, and PD-L1 in Mice with Brain Tumors (2014)

Collectively, these data provide strong preclinical evidence that combinatorially targeting immunosuppression in malignant glioma is a strategy that has high potential value for future clinical trials in patients with GBM.
Feasibility of Automatic Error Detect-and-Undo System in Human Intracortical Brain–Computer Interfaces (2017)

These offline results suggest that it will be possible to improve the performance of clinical intracortical BCIs by incorporating a real-time error detect-and-undo system alongside the decoding of movement intention.
Dual-tracer background subtraction approach for fluorescent molecular tomography (2013)

Diffuse fluorescence tomography requires high contrast-to-background ratios to accurately reconstruct inclusions of interest. This is a problem when imaging the uptake of fluorescently labeled molecularly targeted tracers in tissue, which can result in high levels of heterogeneously distributed background uptake. We present a dual-tracer background subtraction approach, wherein signal from the uptake of an untargeted tracer is subtracted from targeted tracer signal prior to image reconstruction, resulting in maps of targeted tracer binding. The approach is demonstrated in simulations, a phantom study, and in a mouse glioma imaging study, demonstrating substantial improvement over conventional and homogenous background subtraction image reconstruction approaches.
IL-1 up-regulates the expression of cytokine receptors on a factor-dependent human hemopoietic cell line, TF-1 (1991)

A factor-dependent human hemopoietic cell line, TF-1, requires interleukin 3 (IL-3) or granulocyte/macrophage colony-stimulating factor (GM-CSF) for its long-term growth. We have found that IL-4, IL-5, and IL-6 also support the growth of TF-1 and that IL-1 enhances the proliferative effect of these cytokines. Augmentation by IL-1 is associated with up-regulation of the receptors for IL-3, IL-5, GM-CSF, and erythropoietin (Epo). IL-1 increased the number of binding sites for IL-3 and Epo without changing their affinities. In contrast, IL-1 increased the number of high affinity binding sites for GM-CSF and IL-5, whereas the total number of binding sites was unchanged. Chemical crosslinking experiments indicated that the receptors for IL-3, IL-5, and GM-CSF were composed of two components and that the molecular masses of the larger components of these cytokine receptors were quite similar (120 kd). The enhanced expression of the larger components of the IL-3, IL-5, and GM-CSF receptors by IL-1 may be responsible for IL-1-induced up-regulation of these receptors. These observations are consistent with the model that the receptors for IL-3 and GM-CSF share a common component.
Rescue from Cloned cDNAs and In Vivo Characterization of Recombinant Pathogenic Romero and Live-Attenuated Candid #1 Strains of Junin Virus, the Causative Agent of Argentine Hemorrhagic Fever Disease (2010)

The New World arenavirus Junin virus (JUNV) is the causative agent of Argentine hemorrhagic fever (AHF), which is associated with high morbidity and significant mortality. Several pathogenic strains of JUNV have been documented, and a highly attenuated vaccine strain (Candid #1) was generated and used to vaccinate the human population at risk. The identification and functional characterization of viral genetic determinants associated with AHF and Candid #1 attenuation would contribute to the elucidation of the mechanisms contributing to AHF and the development of better vaccines and therapeutics. To this end, we used reverse genetics to rescue the pathogenic Romero and the attenuated Candid #1 strains of JUNV from cloned cDNAs. Both recombinant Candid #1 (rCandid #1) and Romero (rRomero) had the same growth properties and phenotypic features in cultured cells and in vivo as their corresponding parental viruses. Infection with rRomero caused 100% lethality in guinea pigs, whereas rCandid #1 infection was asymptomatic and provided protection against a lethal challenge with Romero. Notably, Romero and Candid #1 trans-acting proteins, L and NP, required for virus RNA replication and gene expression were exchangeable in a minigenome rescue assay. These findings support the feasibility of studies aimed at determining the contribution of each viral gene to JUNV pathogenesis and attenuation. In addition, we rescued Candid #1 viruses with three segments that efficiently expressed foreign genes introduced into their genomes. This finding opens the way for the development of a safe multivalent arenavirus vaccine.
Retinoids and Interferons as Antiangiogenic Cancer Drugs (1999)

Retinoids are a class of chemical compounds that include active metabolites of vitamin A (retinol) as well as a diverse array of synthetic derivatives. Vitamin A is required for normal embryonic development, epithelial homeostasis, maintainance of reproductive capacity, and functioning of the visual cycle (1). Additionally, retinoids have been shown to modulate a wide variety of cellular processes, including proliferation, differentiation, homeostasis, and malignant transformation (for reviews see refs. 2–5). Retinoids also act pharmacologically to restore regulation of differentiation and growth in certain premalignant and malignant cells in vitro and in vivo (6, 7). Consequently, retinoids are under study as therapeutic and chemopreventive agents for a variety of cancers (see refs. 8–10 for reviews). Retinoids are also potent drugs for the treatment of severe cystic acne, psoriasis, and several other dermatologic disorders (11).
Loss of heterozygosity on the short arm of chromosome 3 in carcinoma of the uterine cervix. (1989)

Loss of genes at specific chromosomal loci is a common genetic alteration in human tumors and is thought to be critical for unmasking the recessive genetic changes for tumorigenesis. To learn whether such recessive mutations are involved in the development of carcinoma of the uterine cervix, 18 fresh tumors were analyzed by Southern blot hybridization using 34 polymorphic DNA markers covering 19 different chromosomes. We found loss of heterozygosity at the D3S2 locus on chromosome 3p in all nine patients who could be evaluated. Human papillomavirus type 16 and type 18 were present in seven and three of 18 tumors, respectively, while no amplification of 13 oncogenes, including c-myc and H-ras, was detected in these tumors. These results suggest that recessive genetic changes on chromosome 3p are one of the important genetic alterations for the development of carcinoma of the uterine cervix. Since this locus is also lost commonly in lung cancer and in renal cell carcinoma, it is possible that these three different types of adult tumors result from mutations of the same recessive gene on chromosome 3p.
Production of tumor necrosis factor and other proinflammatory cytokines by human mononuclear phagocytes stimulated with myelin P2 protein. (1993)

In this study we examined the effect of myelin P2 protein on some proinflammatory functions exerted by human mononuclear phagocytes. Northern blot analysis demonstrated that P2 protein selectively induced in monocytes and macrophages mRNA accumulation of tumor necrosis factor (TNF), interleukin 1 beta (IL-1 beta), and interleukin 8 (IL-8) in a time-dependent manner. Natural killer stimulating factor (IL-12) mRNA and protein secretion was strongly induced by lipopolysaccharide but not by P2 protein. Supernatants harvested from P2-stimulated monocytes contained significant amounts of TNF, IL-1 beta, and IL-8, whereas those from macrophages contained only TNF and IL-8. The effect of the P2 protein on TNF and IL-8 mRNA accumulation and secretion was not affected by polymyxin B, which, on the other hand, almost completely abolished the effect of lipopolysaccharide. Finally, P2 protein did not directly trigger hydrogen peroxide release but, through the induced release of TNF, potentiated monocyte respiratory burst capability. Since P2 protein is the antigen responsible for the induction of experimental allergic neuritis, these findings identify a potential mechanism involved in the inflammatory reaction and myelin damage during experimental allergic neuritis.
Residual serum monoclonal protein predicts progression‐free survival in patients with previously untreated multiple myeloma (2009)

The average residual M-protein reduction metric is promising and needs further validation. This exploratory analysis is the first step in the search for treatment-based trend metrics predictive of outcomes in MM.
Expression of fatty acid synthase (FAS) as a predictor of recurrence in stage I breast carcinoma patients (1996)

FAS is a reliable prognostic marker to predict DFS and OS in patients with early breast cancer.
Inhaled Nitric Oxide. A Bronchodilator in Mild Asthmatics With Methacholine-Induced Bronchospasm (1996)

Nitric oxide (NO) reduces airway tone in the methacholine-treated guinea pig. We examined whether low levels of inhaled NO gas would relax airway smooth muscle tone in patients with mild asthma subjected to methacholine-induced bronchospasm. Thirteen adult volunteers with mild asthma inspired increasing concentrations of methacholine until their baseline forced expiratory volume in one second (FEV1, 3.29 +/- 0.17 L, mean +/- SEM) decreased by > or = 20% (2.33 +/- 0.18 L, p < 0.01). Thereafter, they sequentially inhaled 100 parts per million (ppm) NO, 40% O2; 40% O2; and 100 ppm NO, 40% O2 while spirometry was performed. Subsequent inhalation of isoproterenol returned the FEV1 levels to baseline. Inhaling 100 ppm NO increased FEV1 to 2.66 +/- 0.18 L (p < 0.01), and this increase was maintained after NO was discontinued. FEV1 did not change during the second period of NO inhalation. Similar results were observed for vital capacity, but no significant effect was noted on forced expiratory flow at 25% of vital capacity or peak expiratory flow. Subjects were then divided into a responder subgroup, which showed a mean increase in FEV1 after initial NO inhalation of 560 +/- 150 ml, and a nonresponder subgroup, which showed a mean increase in FEV1 of 129 +/- 29 ml. Our data suggest that inhalation of nitric oxide by patients with mild asthma with methacholine-induced bronchospasm results in a minor but significant relaxation of airway tone.
End-column detection for capillary zone electrophoresis (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnd-column detection for capillary zone electrophoresisXiaohua. Huang, Richard N. Zare, Sandra. Sloss, and Andrew G. EwingCite this: Anal. Chem. 1991, 63, 2, 189–192Publication Date (Print):January 15, 1991Publication History Published online1 May 2002Published inissue 15 January 1991https://pubs.acs.org/doi/10.1021/ac00002a020https://doi.org/10.1021/ac00002a020research-articleACS PublicationsRequest reuse permissionsArticle Views427Altmetric-Citations164LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Anti-melanoma antibodies from melanoma patients immunized with genetically modified autologous tumor cells: selection of specific antibodies from single-chain Fv fusion phage libraries. (1995)

Fusion phage libraries expressing single-chain Fv antibodies were constructed from the peripheral blood lymphocytes of two melanoma patients who had been immunized with autologous melanoma cells transduced the gamma-interferon gene to enhance immunogenicity, in a trial conducted at another institution. Anti-melanoma antibodies were selected from each library by panning the phage against live cultures of the autologous tumor. After two or three rounds of panning, clones of the phage were tested by ELISA for binding to the autologous tumor cells; > 90% of the clones tested showed a strong ELISA reaction, demonstrating the effectiveness of the panning procedure for selecting antimelanoma antibodies. The panned phage population was extensively absorbed against normal melanocytes to enrich for antibodies that react with melanoma cells but not with melanocytes. The unabsorbed phage were cloned, and the specificities of the expressed antibodies were individually tested by ELISA with a panel of cultured human cells. The first tests were done with normal endothelial and fibroblast cells to identify antibodies that do not react, or react weakly, with two normal cell types, indicating some degree of specificity for melanoma cells. The proportion of phage clones expressing such antibodies was approximately 1%. Those phage were further tested by ELISA with melanocytes, several melanoma lines, and eight other tumor lines, including a glioma line derived from glial cells that share a common lineage with melanocytes. The ELISA tests identified three classes of anti-melanoma antibodies, as follows: (i) a melanoma-specific class that reacts almost exclusively with the melanoma lines; (ii) a tumor-specific class that reacts with melanoma and other tumor lines but does not react with the normal melanocyte, endothelial and fibroblast cells; and (iii) a lineage-specific class that reacts with the melanoma lines, melanocytes, and the glioma line but does not react with the other lines. These are rare classes from the immunized patients' repertoires of anti-melanoma antibodies, most of which are relatively nonspecific anti-self antibodies. The melanoma-specific class was isolated from one patient, and the lineage-specific class was isolated from the other patient, indicating that different patients can have markedly different responses to the same immunization protocol. The procedures described here can be used to screen the antibody repertoire of any person with cancer, providing access to an enormous untapped pool of human monoclonal anti-tumor antibodies with clinical and research potential.
Coating of carbon fiber‐reinforced polyetheretherketone implants with titanium to improve bone apposition (2012)

Carbon fiber-reinforced polyetheretherketone (CF/PEEK) is a thermoplastic composite biomaterial exhibiting properties suitable for load-bearing orthopedic implants. However, the hydrophobic surface of CF/PEEK implants induces the deposition of a peri-implant fibrous tissue capsule preventing bone apposition. However, if bone apposition was improved, the use of CF/PEEK in orthopedics could be increased as it has many advantages compared with metallic implants. In this study, CF/PEEK screws were coated with titanium (Ti) using two different techniques, namely vacuum plasma spraying (VPS) and physical vapor deposition (PVD) with uncoated screws as controls. These coatings were characterized and implanted in a loaded sheep tibia model. In the characterization of the screw surfaces using microscopy techniques, the uncoated screws were seen to have an irregular surface. The PVD coating appeared smooth and consistent, whereas the VPS coating appeared to be a rough coating with some inhomogeneities, which did not cover the entire surface area. Nevertheless, in the ex vivo analysis the VPS-coated screws had a screw removal torque which was statistically greater than uncoated and PVD-coated screws (p ≤ 0.002 for both comparisons). Additionally, the VPS-coated screws had a statistically higher bone contact area than the uncoated screws (p = 0.006), whereas no statistical difference was detected between VPS and PVD coating types (p = 0.11). Thereby illustrating that Ti coating of CF/PEEK screws significantly improve bone apposition and removal torque compared with uncoated CF/PEEK screws.
On-line Business-to-business Auction Platforms: Enhancing Buyer-Supplier Relationships (2006)

The authors examine the minimum design elements required for the development of effective business-to-business (B2B) auction platforms for public procurement and resource allocation. The benefits of a well-designed auction that is both ethical and efficient are described.
Applying a flexible microactuator to robotic mechanisms (1992)

A flexible microactuator (FMA) driven by an electropneumatic (or electrohydraulic) system has been developed. It has three degrees of freedom-pitch, yaw, and stretch-making it suitable for robotic mechanisms such as fingers, arms, or legs. It is made of fiber-reinforced rubber, and the mechanism is very simple, enabling miniature robots without conventional link mechanisms to be designed. Serially connected FMAs act as a miniature robot manipulator. The kinematics and control algorithm for this type of robot are presented. FMAs combined in parallel act as a multifingered robot hand, with each FMA representing a finger. An algorithm for the cooperative control for such FMAs, the stable region for holding, and its performance have been developed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The RADIANCE lighting simulation and rendering system (1994)

This paper describes a physically-based rendering system tailored to the demands of lighting design and architecture. The simulation uses a light-backwards ray-tracing method with extensions to efficiently solve the rendering equation under most conditions. This includes specular, diffuse and directional-diffuse reflection and transmission in any combination to any level in any environment, including complicated, curved geometries. The simulation blends deterministic and stochastic ray-tracing techniques to achieve the best balance between speed and accuracy in its local and global illumination methods. Some of the more interesting techniques are outlined, with references to more detailed descriptions elsewhere. Finally, examples are given of successful applications of this free software by others.
CCD arrays for readout of electrophotographic latent images (1991)

Arrays of charge sensing elements have been fabricated for nondestructive electronic readout of latent images on electrophotographic materials. The arrays are implemented in the form of a monolithic integrated circuit in which each sensing element is a 5- mu m *5- mu m MOS capacitor; 2048 such elements are arranged in a linear format with effective 5- mu m element-to-element pitch. On-chip circuitry allows for multiple sampling at each sensing site for enhancing signal-to-noise ratio. The resulting signals from the sense elements are multiplexed onto charge-coupled-device (CCD) shift registers for high-speed serial readout. To allow for the small sensor-to-film gap (on the order of 10 mu m) required for capacitive sensing, the chip's bond pads are recessed in deep grooves below the active array surface. The array is packaged within a hydrostatic air bearing which maintains a constant and uniform gap. The response of the array to targets of high spatial frequency recorded on various electrophotographic materials is in excellent agreement with analytical predictions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
LSECtin Expressed on Melanoma Cells Promotes Tumor Progression by Inhibiting Antitumor T-cell Responses (2014)

Therapeutic antibodies that target T-cell co-inhibitory molecules display potent antitumor effects in multiple types of cancer. LSECtin is a cell surface lectin of the DC-SIGN family expressed in dendritic cells that inhibits T-cell responses. LSECtin limits T-cell activity in infectious disease, but it has not been studied in cancer. Here we report the finding that LSECtin is expressed commonly in melanomas where it blunts tumor-specific T-cell responses. When expressed in B16 melanoma cells, LSECtin promoted tumor growth, whereas its blockade slowed tumor growth in either wild-type or LSECtin-deficient mice. The tumor-promoting effects of LSECtin were abrogated in Rag1(-/-) mice or in response to CD4(+) or CD8(+) T-cell depletion. Mechanistic investigations determined that LSECtin inhibited the proliferation of tumor-specific effector T cells by downregulating the cell cycle kinases CDK2, CDK4, and CDK6. Accordingly, as expressed in B16, tumor cells LSECtin inhibited tumor-specific T-cell responses relying upon proliferation in vitro and in vivo. Notably, LSECtin interacted with the co-regulatory molecule LAG-3, the blockade of which restored IFNγ secretion that was reduced by melanoma-derived expression of LSECtin. Together, our findings reveal that common expression of LSECtin in melanoma cells engenders a mechanism of immune escape, with implications for novel immunotherapeutic combination strategies.