gebhart/patrepeval huggingface dataset:
The first antibody therapy for cancer: a personal experience (2013)

More than 100 years ago, Paul Ehrlich proposed that antibodies could be used for therapeutic purposes. Little progress was achieved until Köhler and Milstein developed hybridoma technology in the 1970s. In 1997, rituximab, the first antibody for the treatment of cancer, was approved. Its development (laboratory and clinical) broke records, provided proof of concept for antibodies as anticancer agents and opened the floodgates for research in the area. Rituximab, in combination with cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone chemotherapy, was proven to increase the cure rate for patients with diffuse large cell lymphoma. Hopefully, over the next decades, we will find additional indications where antibodies in combination with other agents result in making patients cancer free, provide long-term survival and cures.
Engineering of a Cold-Adapted Protease by Sequential Random Mutagenesis and a Screening System (1998)

A cold-adapted protease subtilisin was successfully isolated by evolutionary engineering based on sequential in vitro random mutagenesis and an improved method of screening (H. Kano, S. Taguchi, and H. Momose, Appl. Microbiol. Biotechnol. 47:46-51, 1997). The mutant subtilisin, termed m-63, exhibited a catalytic efficiency (expressed as the kcat/Km value) 100% higher than that of the wild type at 10 degrees C when N-succinyl-L-Ala-L-Ala-L-Pro-L-Phe-p-nitroanilide was used as a synthetic substrate. This cold adaptation was achieved with three mutations, Val to Ile at position 72 (V72I), Ala to Thr at position 92 (A92T), and Gly to Asp at position 131 (G131D), and it was found that an increase in substrate affinity (i.e., a decreased Km value) was mostly responsible for the increased activity. Analysis of kinetic parameters revealed that the V72I mutation contributed negatively to the activity but that the other two mutations, A92T and G131D, overcame the negative contribution to confer the 100% increase in activity. Besides suppression of the activity-negative mutation (V72I) by A92T and G131D, suppression of structural stability was observed in measurements of activity retention at 60 degrees C and circular dichroism spectra at 10 degrees C.
An autosomal recessive DNASE1L3 -related autoimmune disease with unusual clinical presentation mimicking systemic lupus erythematosus (2016)

We describe the third family in the world, after Arabian and Turkish ones, displaying an autosomal recessive autoimmune disease (AID), mimicking systemic lupus erythematosus (SLE), with unusual manifestations due to a homozygous frame-shift variant in DNASE1L3. SLE is a complex AID characterized by multiple organ involvement. Genetic risk variants identified account for only 15% of SLE heritability. Rare Mendelian forms have been reported, including DNASE1L3-related SLE. Through specific genetic tests we identified a homozygous 2 bp-deletion c.289_290delAC (NM_004944.2) in DNASE1L3, predicting frameshift and premature truncation (p.Thr97Ilefs*2). The same mutation was previously reported in three sisters, born from consanguineous parents and affected with hypocomplementemic urticarial vasculitis syndrome (HUVS). As approximately 50% of individuals affected with HUVS develop SLE, it is still unclear whether it is a SLE sub-phenotype or a separate condition.
Performance Analysis of TCP Congestion Control Algorithms (2008)

Abstract — The demand for fast transfer of large volumes of data, and the deployment of the network infrastructures is ever increasing. However, the dominant transport protocol of today, TCP, does not meet this demand because it favors reliability over timeliness and fails to fully utilize the network capacity due to limitations of its conservative congestion control algorithm. The slow response of TCP in fast long distance networks leaves sizeable unused bandwidth in such networks. A large variety of TCP variants have been proposed to improve the connection’s throughput by adopting more aggressive congestion control algorithms. Some of the flavors of TCP congestion control are loss-based, high-speed TCP congestion control algorithms that uses packet losses as an indication of congestion; delay-based TCP congestion control that emphasizes packet delay rather than packet loss as a signal to determine the rate at which to send packets. Some efforts combine the features of loss-based and delay-based algorithms to achieve fair bandwidth allocation and fairness among flows. A comparative analysis between different flavors of TCP congestion control namely Standard TCP congestion control (TCP Reno), loss-based TCP congestion control (HighSpeed TCP, Scalable TCP, CUBIC TCP), delay-based TCP congestion control (TCP Vegas) and mixed loss-delay based TCP congestion control (Compound TCP) is presented here in terns of congestion window verses elapsed time after the connection is established.
Optical Hough And Fourier Processors For Product Inspection (1988)

Coherent optical processors for product inspection are discussed, and data from a case study are presented. An optical processor that produces both Fourier and Hough transform data is presented. The Fourier transform data are wedge/ring sampled to produce in-plane distortion-invariant features to determine the product's attribute (good or defective) and its orientation. Hough transform data are used for new quantitative mensuration information on good products. In one case, optical Hough transforms are quantitatively shown to yield more consistent results than do digital realizations.
New I-line Lens for Half-Micron Lithography. (1991)

In the last few years, i-line lithography has made remarkable progress. It is based on the development of high-contrast i-line resists and of high-NA lenses owing to improvement of the transmittance of glass for i-line. It is generally assumed that i-line steppers will play a major role in the production of 16 Mbit DRAMs. For half-micron production, CANON has developed a new i-line lens with a high NA of 0.52 and a wide image field 28.28 mm in diameter. This paper first reports on the image performance of this lens for half-micron, and then describes the distortion characteristics and magnification stability of the lens. In the last section, the possibility of i-line lithography of sub-half-micron referring to the experimental results on 0.4 micrometers L/S applications are discussed.© (1991) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Diverse taxa of cyanobacteria produce β- N -methylamino- l -alanine, a neurotoxic amino acid (2005)

Cyanobacteria can generate molecules hazardous to human health, but production of the known cyanotoxins is taxonomically sporadic. For example, members of a few genera produce hepatotoxic microcystins, whereas production of hepatotoxic nodularins appears to be limited to a single genus. Production of known neurotoxins has also been considered phylogenetically unpredictable. We report here that a single neurotoxin, beta-N-methylamino-L-alanine, may be produced by all known groups of cyanobacteria, including cyanobacterial symbionts and free-living cyanobacteria. The ubiquity of cyanobacteria in terrestrial, as well as freshwater, brackish, and marine environments, suggests a potential for wide-spread human exposure.
Estrogen and the endometrium: lessons learned from gene expression profiling in rodents and human (2007)

To date, research into the biological processes and molecular mechanisms associated with endometrial receptivity and embryo implantation has been a focus of attention, whereas the complex events that occur in the human endometrium during the menstrual and proliferative phase under the influence of estrogen have received little attention. The objective of this review is to provide an update of our current understanding of the actions of estrogen on both human and rodent endometrium, with special emphasis on the regulation of uterine growth and cell proliferation, and the value of global gene expression analysis, in increasing understanding of these processes.
Role of Brca1 in Nonhomologous DNA End Joining (2004)

Abstract : To examine the possible role of the breast cancer susceptibility factor BRCA1 in the nonhomologous end joining pathway of DNA double-strand break repair, an assay to detect both accurate and inaccurate end joining events in intact cells was devised. A fusion gene of green fluorescent protein (EGFP) and neomycin resistance (nec) was constructed with a linker containing cleavage sites for the enzymes BcgI and 1-Scel. EcgI induces two simultaneous breaks, excising a 34-bp segment of DNA. Accurate repair of such a break would be detected as a 34-bp deletion that would put neo back in-frame and confer G4l8 resistance. Inaccurate repair events of both BcgI- and 1-Scel-induced breaks would similarly be detected. A lentivirus vector was constructed to introduce the fusion gene into human cells, and transductants of MCF-7 breast tumor cells were isolated. Although development of the assay system is not yet complete, proof-of-principle experiments showed that deletions could indeed be generated by 1-Scel-induced cleavage and detected as reactivation of the neo gene. Intracellular DNA cleavage by BcgI, introduced into cells by electroporation was also demonstrated, although it remains to be determined whether such cleavage will be sufficient to detect repair and assess repair accuracy.
Intrusion tolerance in distributed computing systems (2002)

An intrusion-tolerant distributed system is a system which is designed so that any intrusion into a part of the system will not endanger confidentiality, integrity and availability. This approach is suitable for distributed systems, because distribution enables isolation of elements so that an intrusion gives physical access to only a part of the system. In particular, the intrusion-tolerant authentication and authorization servers enable a consistent security policy to be implemented on a set of heterogeneous, untrusted sites, administered by untrusted (but nonconspiring) people. The authors describe how some functions of distributed systems can be designed to tolerate intrusions. A prototype of the persistent file server presented has been successfully developed and implemented as part of the Delta-4 project of the European ESPRIT program.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Development of New and Selective Trypanosoma cruzi trans‐Sialidase Inhibitors from Sulfonamide Chalcones and Their Derivatives (2009)

A series of sulfonamide-containing hydroxylated chalcone (4-7) and quinolinone (8, 9) derivatives was synthesised and tested for inhibition of the trans-sialidase from Trypanosoma cruzi (TcTS). IC(50) values for these inhibitors ranged from 0.6 to 7.3 microM, with the dihydroxylated (catechol) derivatives being the tightest binders. Full kinetic analyses of inhibition were performed for these catechol derivatives, both for the transglycosylation reaction in the presence of lactose and for the hydrolysis reaction in its absence. Competitive inhibition was seen in each case with K(i) values for 5, 7 and 9 of 2.0, 2.2 and 0.2 microM, respectively, in the absence of lactose, and 4.6, 3.7 and 0.4 microM in its presence. None of the compounds tested showed any significant inhibition of the human sialidase Neu2, at concentrations up to 200 microM.
Vimentin–ERK Signaling Uncouples Slug Gene Regulatory Function (2015)

Epithelial-mesenchymal transition (EMT) in cells is a developmental process adopted during tumorigenesis that promotes metastatic capacity. In this study, we advance understanding of EMT control in cancer cells with the description of a novel vimentin-ERK axis that regulates the transcriptional activity of Slug (SNAI2). Vimentin, ERK, and Slug exhibited overlapping subcellular localization in clinical specimens of triple-negative breast carcinoma. RNAi-mediated ablation of these gene products inhibited cancer cell migration and cell invasion through a laminin-rich matrix. Biochemical analyses demonstrated direct interaction of vimentin and ERK, which promoted ERK activation and enhanced vimentin transcription. Consistent with its role as an intermediate filament, vimentin acted as a scaffold to recruit Slug to ERK and promote Slug phosphorylation at serine-87. Site-directed mutagenesis established a requirement for ERK-mediated Slug phosphorylation in EMT initiation. Together, these findings identified a pivotal step in controlling the ability of Slug to organize hallmarks of EMT.
Steroid-Dependent Crohn’s Disease (2000)

Placebo controlled trials have demonstrated that a tapering course of corticosteroids is an effective therapy for active Crohn's disease. A population-based study of 109 patients with Crohn's disease undergoing their first course of corticosteroids showed that, at the end of one year, 44% of patients were steroid responsive, 36% were steroid dependent and 20% were steroid refractory. Side effects occur frequently during a four-month tapering course of corticosteroids, including moon face, acne, infection, ecchymoses, hypertension, hirsutism, petechial bleeding and striae. More serious side effects occur with long term use, including hypertension, diabetes, infection, osteonecrosis, osteoporosis, myopathy, cataracts, glaucoma and psychosis. Low dose corticosteroids, alternate-day corticosteroids and mesalamine (5-aminosalicylate) are not effective steroid-sparing agents in patients with Crohn's disease. Controlled ileal release budesonide, 6 mg/day, is an effective steroid-sparing agent, but it does result in some decrease in adrenal function. Azathioprine, 6-mercaptopurine and methotrexate are all effective steroid-sparing agents, as is the humanized, anti-tumour necrosis factor monoclonal antibody, CDP571. A preliminary, uncontrolled study has suggested that the mouse/human chimeric monoclonal antibody infliximab may also be steroid sparing. Surgical resection is an effective strategy to reduce steroid use in the short to intermediate term, but postoperative reoccurrence of Crohn's disease occurs frequently. Given the morbidity associated with prolonged corticosteroid use, medical and surgical treatment strategies to reduce steroid use should be employed routinely.
Targeted Lysosome Disruptive Elements for Improvement of Parenchymal Liver Cell-specific Gene Delivery (2002)

The transfection ability of nonviral gene therapy vehicles is generally hampered by untimely lysosomal degradation of internalized DNA. In this study we describe the development of a targeted lysosome disruptive element to facilitate the escape of DNA from the lysosomal compartment, thus enhancing the transfection efficacy, in a cell-specific fashion. Two peptides (INF7 and JTS-1) were tested for their capacity to disrupt liposomes. In contrast to JTS-1, INF7 induced rapid cholesterol-independent leakage (EC(50), 1.3 microm). INF7 was therefore selected for coupling to a high affinity ligand for the asialoglycoprotein receptor (ASGPr), K(GalNAc)(2), to im- prove its uptake by parenchymal liver cells. Although the parent peptide disrupted both cholesterol-rich and -poor liposomes, the conjugate, INF7-K(GalNAc)(2), only induced leakage of cholesterol-poor liposomes. Given that endosomal membranes of eukaryotic cells contain <5% cholesterol, this implies that the conjugate will display a higher selectivity toward endosomal membranes. Although both INF7 and INF7-K(GalNAc)(2) were found to increase the transfection efficiency on polyplex-mediated gene transfer to parenchymal liver cells by 30-fold, only INF7-K(GalNAc)(2) appeared to do so in an ASGPr-specific manner. In mice, INF7-K(GalNAc)(2) was specifically targeted to the liver, whereas INF7 was distributed evenly over various organs. In summary, we have prepared a nontoxic cell-specific lysosome disruptive element that improves gene delivery to parenchymal liver cells via the ASGPr. Its high cell specificity and preference to lyse intracellular membranes make this conjugate a promising lead in hepatocyte-specific drug/gene delivery protocols.
WiSLAM: Improving FootSLAM with WiFi (2011)

We address Simultaneous Localization and Mapping (SLAM) for pedestrians by means of WiFi signal strength measurements. In our system odometric data from foot mounted Inertial Measurements Units are fused with received signal strength (RSS) measurements of IEEE 802.11. To do this, we assign a probabilistic model to RSS measurements, and adopt the Bayesian framework on which FootSLAM and PlaceSLAM are based. Computational aspects are also accounted in order to provide a practical implementation of the algorithm. Simulative and experimental examples of WiSLAM are shown to underline the effectiveness of our proposal.
The Word Tree, an Interactive Visual Concordance (2008)

We introduce the Word Tree, a new visualization and information-retrieval technique aimed at text documents. A word tree is a graphical version of the traditional "keyword-in-context" method, and enables rapid querying and exploration of bodies of text. In this paper we describe the design of the technique, along with some of the technical issues that arise in its implementation. In addition, we discuss the results of several months of public deployment of word trees on Many Eyes, which provides a window onto the ways in which users obtain value from the visualization.
Global approaches to quantitative analysis of gene-expression patterns observed by use of two-dimensional gel electrophoresis. (1984)

A major difficulty in the use of two-dimensional protein maps to identify and classify cell types is the problem of acquiring, selecting, and analyzing quantitative data on hundreds of protein spots. Here we use methods of multivariate statistics to analyze the differences among a panel of human cell lines, in some cases involving quantitative data on more than 250 proteins. Principal-component and cluster-analysis techniques show that the lines can be easily distinguished, even by using the subset of proteins present in all cells. A preliminary analysis of the protein changes brought about by phorbol ester-induced differentiation of the line U937 is included.
The gene encoding the biotin-apoprotein ligase ofSaccharomyces cerevisiae (1995)

We report the isolation, genomic mapping, and DNA sequence of the BPL1 gene encoding the biotin-apoprotein ligase of Saccharomyces cerevisiae. The gene was isolated by complementation of an Escherichia coli birA (biotin-apoprotein ligase) mutant indicating that the expressed yeast protein modified the essential biotinated protein of the bacterial host. The BPL1 gene encodes a protein of 690 residues (M(r) 76.4 kDa) with strong sequence similarities to the E. coli and human biotin-apoprotein ligases. BPL1 was mapped to chromosome IV, is allelic to the previously described ACC2 gene, and encodes the major (if not the only) biotin-apoprotein ligase activity of S. cerevisiae.
PIG3 plays an oncogenic role in papillary thyroid cancer by activating the PI3K/AKT/PTEN pathway (2015)

The p53-inducible gene 3 (PIG3 or TP53I3) is a downstream gene of p53, which can be involved in the process of apoptosis induced by p53 via the production of reactive oxygen species (ROS). However, the functional significance of PIG3 in cancer remains to be determined. This aim of this study was to examine the mRNA and protein expression of PIG3 in papillary thyroid carcinoma (PTC) and normal thyroid tissues, assess the relationship between PIG3 expression and clinicopathological parameters in PTC and examine its role in the proliferation of PTC cell lines. The results showed that PIG3 was aberrantly overexpressed in the majority of specimens of PTC while the expression of p53 was lower in PTC compared with normal thyroid tissues. Anti-PIG3 immuno-reactivity positively correlated with TNM grade. In the PTC cell lines, PIG3 silencing using small interfering RNA (siRNAs) impaired their ability of proliferation and decreased the activity of the PI3K/AKT/PTEN pathway. The results suggested that PIG3 plays an oncogenic role in PTC via the regulation of the PI3K/AKT/PTEN pathway and support the exploration of PIG3 as a novel biomarker for patients with PTC.
Off-Label Use of Bone Morphogenetic Proteins in the United States Using Administrative Data (2010)

At least 85% of principal procedures using BMP were for off-label applications. With uncertainty regarding the risks of using BMP in certain off-label applications, further research will be needed to better define the appropriate indications. Our study also demonstrates that disparities in the differential rates of BMP use exist in the spine fusion population.
Pathophysiology of lumbar disc degeneration: a review of the literature (2002)

Lumbar disc degeneration occurs because of a variety of factors and results in a multitude of conditions. Alterations in the vertebral endplate cause loss of disc nutrition and disc degeneration. Aging, apoptosis, abnormalities in collagen, vascular ingrowth, loads placed on the disc, and abnormal proteoglycan all contribute to disc degeneration. Some forms of disc degeneration lead to loss of height of the motion segment with concomitant changes in biomechanics of the segment. Disc herniation with radiculopathy and chronic discogenic pain are the result of this degenerative process.
Recurrence of the Acute HIV Syndrome after Interruption of Antiretroviral Therapy in a Patient with Chronic HIV Infection: A Case Report (2000)

Therapeutic interruption may be associated with profound viral rebound and recurrence of the acute HIV syndrome.
The amidase activity of human tissue kallikrein is significantly higher in the urine of patients with either type 1 or gestational diabetes mellitus (2010)

The levels of tissue kallikrein are reduced in humans with hypertension, cardiovascular and renal diseases. There is little information on the participation of human tissue (renal/urinary) kallikrein (hK1) in type 1 diabetes mellitus (DM), and, no information concerning the role of hK1 was reported in gestational diabetes mellitus (GDM). The present study evaluated the roles of insulin and hyperglycemia on urinary hK1 activity in type 1 DM and in GDM. Forty three type 1 DM patients (535 years, disease duration  5 years, receiving insulin, HbA1c &amp;gt; 7.6%) were selected. Forty three healthy individuals, paired according to gender and age, were used as controls. Thirty GDM patients (18−42 years, between the 24th and 37th weeks of pregnancy, recently diagnosed, not under insulin therapy) were also selected. Thirty healthy pregnant and thirty healthy non−pregnant women (18−42 years) were selected as controls. A random midstream urine was used. hK1 amidase activity was estimated with D-Val-Leu-Arg-Nan substrate. Albumin was determined with Coomassie Brilliant Blue reagent. Creatinine was determined by Jaffe's method. hK1 specific amidase activity was expressed as μM/(min/mg creatinine to correct for differences in urine flow rate. hK1 specific amidase activity was significantly higher in the urine of type 1 DM and GDM patients, respectively, than in controls. These findings suggest that hyperglycemia rather insulin is involved in the mechanism of increased hK1 specific amidase activity in the urine of both type 1 DM and GDM patients. Albumin/creatinine ratio was increased in type 1 DM, GDM and healthy pregnant women.