gebhart/patrepeval huggingface dataset:
Altered transfer RNA methylase patterns in Marek's disease tumors. (1971)

The in vitro tRNA methylase activities in liver and kidney homogenates from chicks infected with Marek's disease virus were elevated up to 3-fold compared to those in noninfected control animals. Increased enzyme activity was observed after the development of discrete tumors and was highest in isolated tumor nodules when separated from normal adjacent tissue. Organs with no visible tumor foci (lung, heart, spleen) did not possess elevated methylase activities. While extracts from both control and tumorous liver methylated heterologous methyl-deficient tRNA from Escherichia coli K-12 W-6 (tRNAMe-), only extracts from tumor-bearing livers possess methylases for the synthesis of N 7-methylguanosine, 3-methylcytidine, and 5-methyluridine. When control chick liver tRNA was the substrate, a similar pattern of results was obtained but at a lower methyl acceptance capacity. tRNA prepared from tumorous liver was approximately one-fourth as effective as control liver tRNA as a substrate for E. coli methylases.
THE CHOLINERGIC LIMBIC SYSTEM: PROJECTIONS TO HIPPOCAMPAL FORMATION, MEDIAL CORTEX, NUCLEI OF THE ASCENDING CHOLINERGIC RETICULAR SYSTEM, AND THE SUBFORNICAL ORGAN AND SUPRA-OPTIC CREST (1967)

Journal Article THE CHOLINERGIC LIMBIC SYSTEM: PROJECTIONS TO HIPPOCAMPAL FORMATION, MEDIAL CORTEX, NUCLEI OF THE ASCENDING CHOLINERGIC RETICULAR SYSTEM, AND THE SUBFORNICAL ORGAN AND SUPRA-OPTIC CREST Get access P. R. LEWIS, P. R. LEWIS From the Anatomy School, University of Cambridge Search for other works by this author on: Oxford Academic PubMed Google Scholar C. C. D. SHUTE C. C. D. SHUTE From the Anatomy School, University of Cambridge Search for other works by this author on: Oxford Academic PubMed Google Scholar Brain, Volume 90, Issue 3, September 1967, Pages 521–540, https://doi.org/10.1093/brain/90.3.521 Published: 01 September 1967
Production of a Monoclonal Antibody That Recognizes the Lipopolysaccharide of a Campylobacter‐Like Organism (1992)

A monoclonal antibody was produced to a Campylobacter-like organism (RMIT 32A) which was isolated from the terminal ileum of a pig with proliferative enteritis. Isotyping of the antibody revealed that it was an IgG2a with kappa light chains. Immunoblots using the antibody against proteinase-K-treated whole cell lysates of RMIT 32A, a selection of Campylobacter species and other enteric bacteria showed that the antibody was specific for RMIT 32A and was directed against the lipopolysaccharide. This antibody can be used for the specific detection of RMIT 32A.
Case 12-1990 (1990)

Case Records of the Massachusetts General Hospital from The New England Journal of Medicine — Case 12-1990 — A 21-Year-Old Man with Progressive Gastrointestinal Stasis, Hepatomegaly, and a Neurologic Disorder
Relocation of the catalytic carboxylate group in class A β-lactamase: the structure and function of the mutant enzyme Glu166→Gln:Asn170→Asp (1999)

The hydrolysis of beta-lactam antibiotics by the serine-beta-lactamases proceeds via an acyl-enzyme intermediate. In the class A enzymes, a key catalytic residue, Glu166, activates a water molecule for nucleophilic attack on the acyl-enzyme intermediate. The active site architecture raises the possibility that the location of the catalytic carboxylate group may be shifted while still maintaining close proximity to the hydrolytic water molecule. A double mutant of the Staphylococcus aureus PC1 beta-lactamase, E166Q:N170D, was produced, with the carboxylate group shifted to position 170 of the polypeptide chain. A mutant protein, E166Q, without a carboxylate group and with abolished deacylation, was produced as a control. The kinetics of the two mutant proteins have been analyzed and the crystal structure of the double mutant protein has been determined. The kinetic data confirmed that deacylation was restored in E166Q:N170D beta-lactamase, albeit not to the level of the wild-type enzyme. In addition, the kinetics of the double mutant enzyme follows progressive inactivation, characterized by initial fast rates and final slower rates. The addition of ammonium sulfate increases the size of the initial burst, consistent with stabilization of the active form of the enzyme by salt. The crystal structure reveals that the overall fold of the E166Q:N170D enzyme is similar to that of native beta-lactamase. However, high crystallographic temperature factors are associated with the ohm-loop region and some of the side chains, including Asp170, are partially or completely disordered. The structure provides a rationale for the progressive inactivation of the Asp170-containing mutant, suggesting that the flexible ohm-loop may be readily perturbed by the substrate such that Asp170's carboxylate group is not always poised to facilitate hydrolysis.
Comparison of an Established Simple Office-Based Immunological FOBT With Fecal Tumor Pyruvate Kinase Type M2 (M2-PK) for Colorectal Cancer Screening: Prospective Multicenter Study (2008)

This office-based IFOBT was found to have significantly higher specificity, PPV, and positive LR as compared with M2-PK. IFOBT proved to be a convenient, noncumbersome, quick, and cheap tool in patients with above-average risk for detection of CRN.
Genomic analysis of field pennycress (Thlaspi arvense) provides insights into mechanisms of adaptation to high elevation (2021)

Our results provide a genome-wide perspective of how plants adapt to distinct environmental conditions across extreme elevation differences and the potential for further follow-up research with extensive data from additional populations and species.
Structure reveals function of the dual variable domain immunoglobulin (DVD-Ig™) molecule (2013)

Several bispecific antibody-based formats have been developed over the past 25 years in an effort to produce a new generation of immunotherapeutics that target two or more disease mechanisms simultaneously. One such format, the dual-variable domain immunoglobulin (DVD-Ig™), combines the target binding domains of two monoclonal antibodies via flexible naturally occurring linkers, which yields a tetravalent IgG - like molecule. We report the structure of an interleukin (IL)12-IL18 DVD-Ig™ Fab (DFab) fragment with IL18 bound to the inner variable domain (VD) that reveals the remarkable flexibility of the DVD-Ig™ molecule and how the DVD-Ig™ format can function to bind four antigens simultaneously. An understanding of how the inner variable domain retains function is of critical importance for designing DVD-Ig™ molecules, and for better understanding of the flexibility of immunoglobulin variable domains and linkers, which may aid in the design of improved bi- and multi-specific biologics in general.
Telomere length measurements using digital fluorescence microscopy (1999)

We demonstrate that accurate and repeatable fluorescence intensity measurements can be made from Q-FISH images that provide information on the length of telomere repeats at individual chromosomes from limited number of cells.
A phase I study of AGRO100 in advanced cancer (2004)

3112 Background: AGRO100 is an oligonucleotide that functions as an aptamer and binds to nucleolin, a protein found intranuclear in all cells, but uniquely expressed on the surface of tumor cells. Such binding leads to internalization of the complex, and a strong anti-proliferative response in the tumor cell. Methods: Objectives are toxicity, pharmacokinetics and preliminary responses. AGRO100 was administered as continuous intravenous infusion over 96 hours in the hospital. Dose level 1 was 1 mg/kg/day. Patients were enrolled in cohorts of 3. If no toxicity was observed 28 days after therapy, the dose of AGRO100 was doubled. Toxicity was graded by the NCI CTCAE v3.0. Responses were assessed every 28 days by using the RECIST guidelines. Results: From September 2003 through December 2003, 9 patients with advanced cancer were enrolled. Prior to AGRO100 treatment, all patients had objective documentation of progressive metastatic disease after multiple therapies. Patient characteristics: 9 patients are evaluable for toxicity and 6 for response. 13 cycles of AGRO100 have been administered (1–2 cycles/patient). 4/6 patients had stable disease after 1 treatment and received a second course. 2/6 patients progressed after 1 cycle. No toxicity of any type has been observed. AGRO100 was present in the serum during the entire infusion and the concentration was related to the dose. Further dose escalation is ongoing. Conclusions: AGRO100 is the first nucleic acid aptamer ever tested for the treatment of cancer in humans. This non-toxic targeted cancer therapy achieved stable disease in 67% of the patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aptamera, Inc. Aptamera, Inc.
A new liquid, intravenous immunoglobulin product (IGIV 10%) highly purified by a state‐of‐the‐art process (2006)

The new manufacturing process enables the production of a highly purified IgG preparation for intravenous administration. The product has an IgG subclass distribution similar to plasma and contains a broad spectrum of functionally intact antibodies. Preclinical studies demonstrate that the liquid IGIV 10% combines excellent qualities of efficacy, safety and tolerability.
The execution pipeline of the Intel i486 CPU (2002)

The integer instruction execution pipeline of the Intel i486 processor is described. The performance of the i486 CPU in a system is related to several systems based on competitive reduced-instruction-set-computer (RISC) processors. The instruction pipeline was designed to execute instructions at a sustained rate of 1 clock per instruction. A key to achieving this rate was the integration of the cache into the pipeline. Another key was pipelining the instruction decoder into two stages to provide a sustained throughput of 1 instruction per clock, while decoding the complex instruction formats of the Intel 386 family architecture. An overview of the pipeline is provided by giving a brief description of each pipeline stage. Then several multiple instruction examples are given to illustrate some key properties of the pipeline.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Digital alloy AlAsSb/AlGaAsSb distributed Braggreflectors lattice matched to InP for 1.3 – 1.55µm wavelength range (1995)

The authors report a distributed Bragg reflector (DBR) consisting of 15.5 periods of AlAsSb and AlGaAsSb digital alloy with a peak reflectivity &gt;95% at 1.46 µm. The DBR is grown by molecular beam epitaxy on an InP substrate.
Migraine as an inflammatory disorder (2005)

Inflammation is a localized response designed to protect tissues against infection, injury, or disease. The inflammatory response acts to destroy, dilute, or wall off (sequester) both the injurious agent and the injured area. The production and release of chemical agents by cells in the affected tissue result in the four well-known signs of Celsus: pain (dolor), heat (calor), redness (rubor), and swelling (tumor), to which Galen later added loss of function (functio laesa). Histologically, inflammation is characterized by a complex series of events. These include the following: dilatation of arterioles, capillaries, and venules, with increased permeability and blood flow; exudation of fluids, including plasma proteins; and leukocyte migration into the inflammatory focus.

Although pain and inflammation usually go hand in hand, migraine has not classically been considered an inflammatory disease, possibly because it is not obviously associated with heat, redness, and swelling. Instead, a vascular etiology was proposed on the basis of a report that ergotamine tartrate alleviates pain and reduces the amplitude of temporal artery pulsation in migraineurs,1 a small but significantly increased risk for strokes,2 association with vascular malformations,3 and genetic disorders such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).4 For most of the twentieth century, the prevailing theory of migraine held that pain results from an abnormal dilatation of intracranial blood vessels, leading to mechanical excitation of sensory fibers that innervate these vessels. This “vascular” theory, however, has never been validated. No differences in blood flow velocity exist in vertebral and middle cerebral arteries during and outside migraine attacks,5 and a consistent relationship between vessel caliber, cerebral blood flow, and headache has not been established.6

In recent years, accumulating evidence has shifted the emphasis away from vascular smooth muscle and toward mechanisms related to inflammation within cephalic …
Theoretical model for diffusion bonding (1982)

AbstractDespite successful applications of diffusion bonding, there is uncertainty as to the dominant mechanisms which operate when the two surfaces to be joined are brought together under an applied pressure at an elevated temperature. This paper describes a theoretical model for solid-state diffusion bonding, the aim of which is to understand how the various competing mechanisms operating at the bond interface are affected both by process variables (time, temperature, pressure) and by the properties of the materials being joined. Thus in the model the rate-controlling mechanisms governing the elimination of the interface between the two surfaces are identified, their relative kinetics predicted, and their individual importance in the various stages of diffusion bonding assessed. The approach adopted bears some similarity with that used when modelling the pressure sintering of powders, although the geometry at the interface of a diffusion bond results in differences.
Photosensitivity and Scanning of Silicon Image Detector Arrays (1969)

The first part of this paper deals with the basic photodiode unit, its principle of operation, and the factors that affect the photodiode and array sensitivity. Experimental results of the planar Si p/sup +/-n photodiode are presented. Design and layout considerations including the integration time are also given. The second part of this paper deals with scanning of photodiode arrays. Detail design considerations are given for a static MOST ring counter. A dynamic shift register with clocked loads for integral scanning is also considered. Design considerations of a realized photosensing matrix with integral scanning are given. Finally, scanning problems of large arrays are briefly considered.
Low-fidelity Venezuelan equine encephalitis virus polymerase mutants to improve live-attenuated vaccine safety and efficacy (2018)

During RNA virus replication, there is the potential to incorporate mutations that affect virulence or pathogenesis. For live-attenuated vaccines, this has implications for stability, as replication may result in mutations that either restore the wild-type phenotype via reversion or compensate for the attenuating mutations by increasing virulence (pseudoreversion). Recent studies have demonstrated that altering the mutation rate of an RNA virus is an effective attenuation tool. To validate the safety of low-fidelity mutations to increase vaccine attenuation, several mutations in the RNA-dependent RNA-polymerase (RdRp) were tested in the live-attenuated Venezuelan equine encephalitis virus vaccine strain, TC-83. Next generation sequencing after passage in the presence of mutagens revealed a mutant containing three mutations in the RdRp, TC-83 3x, to have decreased replication fidelity, while a second mutant, TC-83 4x displayed no change in fidelity, but shared many phenotypic characteristics with TC-83 3x. Both mutants exhibited increased, albeit inconsistent attenuation in an infant mouse model, as well as increased immunogenicity and complete protection against lethal challenge of an adult murine model compared with the parent TC-83. During serial passaging in a highly permissive model, the mutants increased in virulence but remained less virulent than the parent TC-83. These results suggest that the incorporation of low-fidelity mutations into the RdRp of live-attenuated vaccines for RNA viruses can confer increased immunogenicity whilst showing some evidence of increased attenuation. However, while in theory such constructs may result in more effective vaccines, the instability of the vaccine phenotype decreases the likelihood of this being an effective vaccine strategy.
Idiotype vaccination of multiple myeloma patients using monocyte-derived dendritic cells. (2003)

Serum-free DC vaccines induce Id-specific T-cell responses in MM patients.
High‐affinity binding sites for human 26‐kDa protein (interleukin 6, B cell stimulatory factor‐2, human hybridoma plasmacytoma growth factor, interferon‐β2), different from those of type I interferon (α,β), on lymphoblastoid cells (1987)

The human 26-kDa glycoprotein (26K) is a cytokine produced by lymphoid as well as nonlymphoid cells. So far it is active as (a) a potent hybridoma and plasmacytoma growth factor on mouse cells, (b) a B cell differentiating factor on human cells, and (c) (for some authors) an interferon (IFN). Internally labeled recombinant human 26K, obtained by translation of mRNA in Xenopus oocytes, was used to investigate the presence of specific receptors for this new cytokine and to analyze its binding to responsive cells. The results indicate that (a) the 26K-responsive human lymphoblastoid CESS cells express about 1500 high-affinity (Kd = 30 pM) binding sites for this cytokine, (b) this binding is not competed for by interleukin (IL)1, IL2, tumor necrosis factor (TNF), IFN-alpha 2, IFN-beta or IFN-gamma, and (c) these 26K-binding sites are different from the classical type I (alpha-beta) IFN receptors by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
Characterization of Cu surface cleaning by hydrogen plasma (2001)

When a Cu surface is exposed to a clean room ambient, a surface layer containing Cu2O, CuO, Cu(OH)2, and CuCO3 is formed. Thermal treatment in a vacuum combined with hydrogen plasma can remove this layer. Water and carbon dioxide desorb during the thermal treatment and the hydrogen plasma reduces the remaining Cu oxide. Ellipsometric, x-ray photoelectron spectroscopy, and time-of-flight secondary ion mass spectroscopy analyses indicate that the mechanism of interaction of the H2 plasma with this layer depends on temperature. When the temperature is below 150 °C, H2 plasma cannot completely reduce Cu oxide. Hydrogen diffuses through the oxide and hydrogenation of the Cu layer is observed. The hydrogenated Cu surface has a higher resistance than a nontreated Cu layer. The hydrogen plasma efficiently cleans the Cu surface when the substrate temperature is higher than 150 °C. In this case, hydrogen atoms have enough activation energy to reduce Cu oxide and adsorbed water forms as a byproduct of Cu oxide reduction. When the wafer temperature is higher than 350 °C, the interaction of the Cu film with hydrogen and residual oxygen is observed.
Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas and epithelial cancers. (1994)

Analysis of the cellular origin of carcinomas of different organs indicates that there is in each instance, a determined stem cell required for tissue renewal that is the cell of origin for carcinomas. The normal tissue-determined stem cells are the result of differentiation in the embryo and are little changed, if at all, from the embryonic cells. Malignant stem cells are derived from these normal stem cells of adult tissues. The resultant tumors are caricatures of the normal process of tissue renewal with many stem cells and imperfect differentiation (14). This imparts an undifferentiated appearance to the tumors, not a dedifferentiated one. Study of the regulation of normal stem cells in the embryo should lead to rational therapies for malignant ones, and conversely, study of secretions and regulation of malignant stem cells will provide insights into normal regulation. The cancer-derived differentiated cells are benign (12, 74) if not normal (39, 53) leading to the conclusion that attempts to direct normal differentiation of malignant stem cells might serve as an alternative to cytotoxic therapy. Attempts to develop such therapies are currently underway (208). The degree of differentiation of a carcinoma depends on the proportion of undifferentiated tumor stem cells, the stage of maturation arrest of the majority of cells in the tumor, and on the ability of some cells to escape arrest and to differentiate (Fig. 1). These concepts of the stem cell contribution to tumors originated largely from studies of teratocarcinoma (209) and were not widely accepted because many considered the lessons learned were unique to teratocarcinomas and would not apply to other tissues. On the basis of the concepts covered in this review, it is clear that teratocarcinomas are unique only in the potential of their stem cells. Other stem cells have more limited potential. The balance of expression of the differentiated histiotype of the tumor cell lineage and the undifferentiated phenotype of the tumor stem cells determine the morphology of the tumor. Normal tissue renewal of epithelial organs is also from stem cells or their differentiating progeny. The cellular events during liver development and regeneration and the changes that precede the development of liver cancer during hepatocarcinogenesis are similar to the cellular response in pancreas, prostate, breast, lung, and gut. In liver, as in the leukopoietic system, the primitive tissue-specific stem cell is not primarily involved in renewal because that would be too slow a process; individuals would die before generation of sufficient replacement cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Inhibition of Polymorphonuclear Leukocyte 5-Lipoxygenase and Platelet Cyclooxygenase by α-(3,5-Di-Tert-Butyl-4-Hydroxybenzylidene)-γ-Butyrolactone (KME-4), a New Anti-Inflammatory Drug (1985)

The effect of alpha-(3,5-di-tert-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), a new anti-inflammatory compound, on arachidonate lipoxygenase and cyclooxygenase was investigated. KME-4 showed a dose-dependent inhibition of 5-lipoxygenase activity in both the cytosol (IC50: 0.85 microM) and ionophore A23187-stimulated cells (IC50: 11.5 microM) of guinea pig peritoneal polymorphonuclear leukocytes. KME-4 was also found to inhibit rabbit platelet cyclooxygenase (IC50: 0.44 microM), but had no inhibitory effect on platelet 12-lipoxygenase at concentrations up to 100 microM, whereas BW755C inhibited both enzymes in the same range of concentrations. The results indicate that KME-4 is a dual 5-lipoxygenase and cyclooxygenase inhibitor which is different from BW755C in affecting 12-lipoxygenase. These effects may provide information for understanding the pharmacological activity of KME-4.
Synthesis and Antitumor Activity of Novel Dolastatin 10 Analogs. (1995)

Dolastatin 10 (1) is a potent antineoplastic pentapeptide. Novel dolastatin 10 analogs each modified at one of the constituent amino acid derivatives, were synthesized and their antitumor activity was evaluated against P388 leukemia in mice. The structural requirements for antitumor activity are discussed. Some of the analogs, 31c, 35c, 38b, and 50c showed excellent activity in vivo. Highly active 50c, which lacks the thiazole group of 1, was selected for further development as an antitumor agent.