gebhart/patrepeval huggingface dataset:
Adenovirus E1A gene induction of susceptibility to lysis by natural killer cells and activated macrophages in infected rodent cells (1987)

Rodent cells immortalized by the E1A gene of nononcogenic adenoviruses are susceptible to lysis by natural killer (NK) cells and activated macrophages. This cytolysis-susceptible phenotype may contribute to the rejection of adenovirus-transformed cells by immunocompetent animals. Such increased cytolytic susceptibility has also been observed with infected rodent cells. This infection model provided a means to study the role of E1A gene products in induction of cytolytic susceptibility without cell selection during transformation. Deletion mutations outside of the E1A gene had no effect on adenovirus type 2 (Ad2) or Ad5 induction of cytolytic susceptibility in infected hamster cells, while E1A-minus mutant viruses could not induce this phenotype. E1A mutant viruses that induced expression of either E1A 12S or 13S mRNA in infected cells were competent to induce cytolytic susceptibility. Furthermore, there was a correlation between the accumulation of E1A gene products in Ad5-infected cells and the level of susceptibility of such target cells to lysis by NK cells. The results of coinfection studies indicated that the E1A gene products of highly oncogenic Ad12 could not complement the lack of induction of cytolytic susceptibility by E1A-minus Ad5 virus in infected cells and also could not block induction of this infected-cell phenotype by Ad5. These data suggest that expression of the E1A gene of nononcogenic adenoviruses may cause the elimination of infected cells by the immunologically nonspecific host inflammatory cell response prior to cellular transformation. The lack of induction of this cytolysis-susceptible phenotype by Ad12 E1A may result in an increased persistence of Ad12-infected cells in vivo and may lead to an increased Ad12-transformed cell burden for the host.
Observations on the Use of the Avian Chorioallantoic Membrane (CAM) Model in Investigations into Angiogenesis (2003)

The chorioallantoic membrane (CAM) is widely used as a model to examine angiogenesis, and anti-angiogenesis. Its advantages over mammalian systems include low cost, and ease of preparation, as well as the absence of a mature immune system. Although the use of this model presents a major opportunity to compare data generated in different laboratories, thereby expediting the evaluation of new drugs, angiogenic potential of cells and tissues, and body fluids, as well as to provide meaningful information concerning the molecular mechanisms involved, the wide range of methodologies used, especially in the quantification of the response, make any comparison essentially invalid. In this review, the major methodologies for all aspects of the use of the CAM in angiogenesis-related studies have been described. These include the source of the CAM, the methods for culture, and methods for evaluation of normal growth and of the response to an intervention. Methods for applying an intervention, the age for intervention and the duration of an intervention are documented. The structure and growth characteristics, the nature of possible responses to stimulation and inhibition of angiogenesis, and the complications of non-specific reactions have been examined. The need for a standardized approach to the use of the CAM model is obvious. One set of possible parameters is suggested.
Receptor‐associated protein: a specialized chaperone and antagonist for members of the LDL receptor gene family (1998)

Members of the LDL receptor gene family mediate cellular uptake of various extracellular ligands, including lipoprotein particles. Ligand interactions with these receptors can be antagonized by a 39 kDa receptor-associated protein. Recent biochemical, cellular, and genetic studies have shown that receptor-associated protein is a molecular chaperone/escort protein for LDL receptor-related protein, a member of the LDL receptor gene family that binds multiple ligands. These studies indicate that receptor-associated protein interacts with LDL receptor-related protein at multiple sites and assists the proper folding and disulfide bond formation of LDL receptor-related protein within the endoplasmic reticulum. Following the completion of folding, receptor-associated protein remains associated with the receptor during its subsequent trafficking along the early secretory pathway, thereby preventing premature ligand interaction with the receptor. The ability of receptor-associated protein to universally inhibit ligand interactions with members of the LDL receptor gene family underscores the use of this protein as a tool in the study of ligand-receptor interactions.
Old Silks Endowed with New Properties (2009)

High-performance regenerated silkworm Bombyx mori silk fibers with new properties that mimic those of spider silk can be produced through a wet spinning process modified with an immersion postspinning drawing (IPSD) step. IPSD fibers show the ability to recover from irreversible deformation, and their tensile behavior can be tailored repeatedly, features solely exhibited until now by natural spider silk. It is further shown that the new properties emerge from a microstructure that is closer to that of spider than to natural silkworm silk. This work demonstrates that processing plays a role at least comparable to that of the amino acid sequence in the final properties of the material. The spinning process does not only modify the mechanical parameters of the fiber but also can even prompt the emergence of new properties, opening a wide range of new applications for regenerated silk fibers. It also represents a significant change of the paradigm in the field of biomimetics, given that it relaxes the condition of copying the natural protein sequences as close as possible to recover the outstanding properties of the natural materials.
Urokinase in the management of traumatic hyphaema. (1971)

There is no general agreement in the literature on the correct management of traumatic hyphaema*-even about such minor points as whether to pad the injured eye only or to pad both eyes, and whether to use a miotic or mydriatic or not. It was therefore decided in I966 to treat a controlled series of cases of traumatic hyphaema with various pre- selected regimes.
Cryptosporidium infection in an adult mouse model. Independent roles for IFN-gamma and CD4+ T lymphocytes in protective immunity (1991)

Cryptosporidium is a protozoan parasite that can cause chronic life-threatening diarrhea in immunocompromised persons. Host immune responses are poorly understood, an impediment to development of effective therapy. In mice, normal adult BALB/c animals resist infection whereas chronic symptomatic cryptosporidiosis develops in adult nude mice and in neonatally infected BALB/c mice treated with anti-CD4 mAb. To define further the immune defects that allow mice to be infected with Cryptosporidium, adult BALB/c mice were treated with cytolytic anti-CD4 or anti-CD8 or with neutralizing anti-IFN-gamma or anti-IL-2 mAb. Chronic infection, manifested by continuous shedding of sparse but statistically significant numbers of oocysts, occurred with anti-CD4 +/- anti-CD8 mAb treatment although anti-CD8 mAb treatment alone did not allow infection. Treatment with anti-IFN-gamma mAb greatly enhanced oocyst shedding but infection was self-limited. Treatment with a combination of anti-CD4 and anti-IFN-gamma mAb permitted both chronic infection and shedding of large numbers of oocysts. Furthermore mice treated initially with anti-CD4 mAb showed a substantial increase in oocyst shedding when later treated with anti-IFN-gamma mAb; and mice treated initially with both mAbs showed a decline in oocyst shedding when anti-IFN-gamma mAb was stopped. Anti-IFN-gamma mAb treatment of congenitally athymic adult BALB/c mice led to an approximately a 75-fold increase in oocyst shedding. Treatment of adult BALB/c mice with anti-IL-2 mAb did not permit Cryptosporidium infection. These results suggest that redundant immunologic mechanisms limit Cryptosporidium infection such that both CD4+ cells and IFN-gamma are required to prevent initiation of infection whereas either alone can limit the extent (IFN-gamma) or duration (CD4+ T cells) of infection. They also suggest that production of IFN-gamma by a non-T cell contributes to host immunity.
Calcium Does Not Protect against Colorectal Neoplasia (1996)

Calcium could decrease risk of colorectal neoplasia by binding bowel-irritating compounds and diminishing mucosal proliferation. This study quantitatively summarizes epidemiologic studies addressing this hypothesis and aims to explain heterogeneity between studies. Twenty-four articles reported 43 measures of relative risks (RRs). The weighted mean, according to a random effects model, did not indicate substantial protection by calcium [RR = 0.89; 95% confidence interval (CI) = 0.79-1.01]. Results from different studies showed substantial heterogeneity, with the "true" underlying RRs ranging from about 0.50 to 1.60. Summary RRs for cohort and case-control studies were 0.90 and 0.88, respectively. For adenomas and carcinomas, RRs were 1.13 (95% CI = 0.91-1.39) and 0.86 (95% CI = 0.74-0.98), respectively, both falling within the range of between study heterogeneity. With respect to subsites, lower RRs were observed for estimates that included proximal colon as one of the subsites (RR = 0.67), whereas the RR was close to 1.0 for distal (RR = 0.97) and rectal subsites (RR = 0.99). Stratification on study characteristics and weighted regression analysis yielded RRs slightly below 1.0, with considerable heterogeneity. These results do not support the hypothesis that calcium prevents colorectal neoplasia.
Disulfide bridges in human complement component C3b (1993)

The disulfide bridges of human complement component C3b, derived from C3 by removal of the 77‐residue C3a, have been determined. The 10 bridges are Cys 537 ‐Cys 794 , Cys 605 ‐Cys 640 , Cys 851 ‐Cys 1491 , Cys 1079 ‐Cys 1169 , Cys 1336 ‐Cys 1467 , Cys 1367 ‐Cys 1436 , Cys 1448 ‐Cys 1489 , Cys 1496 ‐Cys 1568 , Cys 1515 ‐Cys 1639 , and Cys 1615 ‐Cys 1624 . Including the 3 bridges in C3a (Cys 670 ‐Cys 698 , Cys 672 ‐Cys 705 , and Cys 685 ‐Cys 706 ) previously determined by high‐resolution X‐ray crystallography [Hoppe‐Seyler's Z. Physiol. Chem. 361 (1980) 1389‐1399] all disulfide bridges of C3 are localized. C3 and the strongly related C4 and C5 are members of the α 2 ‐macroglobulin superfamily. The predicted bridge patterns of C4 and C5 are discussed and compared with that of α 2 ‐macroglobulin.
Expression of -gal epitopes on HeLa cells transduced with adenovirus containing 1,3galactosyltransferase cDNA (2002)

Alpha1,3galactosyltransferase (alpha1,3GT) synthesizes alpha-gal epitopes (Gal(alpha)1-3Galbeta1-4GlcNAc-R) on glycoconjugates in nonprimate mammals but not in humans. Transduction of alpha1,3GT gene into human HeLa cells by an adenovirus vector allowed for accurate kinetics studies on the appearance of alpha1,3GT and of its product, the alpha-gal epitope, in the transduced cells. Mouse alpha1,3GT cDNA was inserted into a replication-defective adenovirus vector. This viral vector, designated Ad(alpha)GT, could be propagated in human 293 cells that have the viral E1 complementing gene. Transduction of HeLa cells resulted in immediate penetration of approximately 20 Ad(alpha)GT copies into each cell and the appearance of alpha1,3GT mRNA after 4h. Catalytic activity of alpha1,3GT was first detected in the cells after 6 h. The initial appearance of alpha-gal epitopes (approximately 6 x 10(4)/cell) on cell surface glycoconjugates was detected 10 h posttransduction, whereas 24 h posttransduction each cell expressed 2 x 10(6) epitopes. The activity of alpha1,3GT in cells transduced with approximately two copies of Ad(alpha)GT was eightfold lower than that in cells transduced with approximately 20 Ad(alpha)GT copies; however, the number of alpha-gal epitopes/cell remained closely similar. This implies that increased alpha1,3GT activity above a certain saturation level does not result in a corresponding increase in the carbohydrate product, possibly because of competing glycosyltransferases.
MUC16: molecular analysis and its functional implications in benign and malignant conditions (2014)

MUC16 is a high-molecular-weight glycoprotein that is expressed by the various epithelial cell surfaces of the human body to protect the cell layer from a myriad of insults. It is the largest mucin known to date, with an ∼22,152 aa sequence. Structurally, MUC16 is characterized into 3 distinct domains: the amino terminal, the tandem repeat, and the carboxyl terminal domain, with each domain having unique attributes. The extracellular portion of MUC16 is shed into the bloodstream and serves as a biomarker for diagnosing and monitoring patients with cancer; however, its functional role in cancer is yet to be elucidated. Several factors contribute to this challenge, which include the large protein size; the extensive glycosylation that the protein undergoes, which confers functional heterogeneity; lack of specific antibodies that detect the unique domains of MUC16; and the existence of splicing variants. Despite these limitations, MUC16 has been established as a molecule of significant application in cancer. Hence, in this review, we discuss the various aspects of MUC16, which include its discovery, structure, and biological significance both in benign and malignant conditions with an attempt to dissect its functional relevance
Brief Report: Analysis of 4070A Envelope Levels in Retroviral Preparations and Effect on Target Cell Transduction Efficiency (2000)

A number of stable producer cell lines for high-titer Mo-MuLV vectors have been constructed. Development has previously centered on increasing end-point titers by producing maximal levels of Mo-MuLV Gag/Pol, envelope glycoproteins, and retroviral RNA genomes. We describe the production yields and transduction efficiency characteristics of two Mo-MuLV packaging cell lines, FLYA13 and TEFLYA. Although they both produce 4070A-pseudotyped retroviral vectors reproducibly at >1 x 10(6) LFU ml(-1), the transduction efficiency of unconcentrated and concentrated virus from FLYA13 lines is poor compared with vector preparations from TEFLYA lines. A powerful inhibitor of retroviral transduction is secreted by FLYA13 packaging cells. We show that the inhibitory factor does not affect transduction of target cells by RD114-pseudotyped vectors. This suggests that the inhibitory factor functions at the level of envelope-receptor interactions. Phosphate starvation of target cells shows a two-fold increase in Pit2 receptor mRNA and causes some improvement in FLYA13 virus transduction efficiency. Western blots show that FLYA13 viral samples contain an eight-fold higher ratio of 4070A envelope to p30gag than that of virus produced by TEFLYA producer cell lines. This study correlates overexpression of 4070A envelope glycoprotein in retroviral preparations with a reduction of transduction efficiency at high multiplicities of infection. We suggest that TEFLYA packaging cells express preferable levels of 4070A compared with FLYA13, which not only enables high-titer stocks to be generated, but also facilitates a high efficiency of transduction of target cells.
Reasoning about evidence in causal explanations (1988)

Causal models can provide richly-detailed knowledge bases for producing explanations about behaviors in many domains, a task often termed interpretation or diagnosis. However, producing a causal explanation from the model can be time-consuming. This paper describes a system that solves a new problem by recalling a previous, similar problem and modifying its solution to fit the current problem. Because it is unlikely that any new problem will exactly match a previous one, the system evaluates differences between the problems using a set of evidence principles that allow the system to reason about such concepts as alternate lines of evidence, additional supporting evidence, and inconsistent evidence. If all differences between the new situation and the remembered situation are found to be insignificant, the previous causal explanation is adapted to fit the new case. This technique results in the same solution, but with an average of two orders of magnitude less effort. The evidence principles are domain independent, and the information necessary to apply them to other domain models is described.
Nuclear factors are involved in hepatitis C virus RNA replication (2007)

Unraveling the molecular basis of the life cycle of hepatitis C virus (HCV), a prevalent agent of human liver disease, entails the identification of cell-encoded factors that participate in the replication of the viral RNA genome. This study provides evidence that the so-called NF/NFAR proteins, namely, NF90/NFAR-1, NF110/NFAR-2, NF45, and RNA helicase A (RHA), which mostly belong to the dsRBM protein family, are involved in the HCV RNA replication process. NF/NFAR proteins were shown to specifically bind to replication signals in the HCV genomic 5' and 3' termini and to promote the formation of a looplike structure of the viral RNA. In cells containing replicating HCV RNA, the generally nuclear NF/NFAR proteins accumulate in the cytoplasmic viral replication complexes, and the prototype NFAR protein, NF90/NFAR-1, stably interacts with a viral protein. HCV replication was inhibited in cells where RNAi depleted RHA from the cytoplasm. Likewise, HCV replication was hindered in cells that contained another NF/NFAR protein recruiting virus. The recruitment of NF/NFAR proteins by HCV is assumed to serve two major purposes: to support 5'-3' interactions of the viral RNA for the coordination of viral protein and RNA synthesis and to weaken host-defense mechanisms.
Assessment of Opioid Dependence with Naloxone (1988)

Summary The reliability and validity of a naloxone rating scale (CINA) for assessing opioid dependence were studied in 75 opiate‐abusing patients. Patients received 0.4 mg naloxone IV, and the naloxone‐precipitated withdrawal effects were systematically measured at three five minute intervals using the 13‐item CINA scale. The reliability coefficient alpha of the total withdrawal score was 0.81. The item scores and total score were correlated well except for nasal congestion, abdominal pain, and muscle pain. The inter‐rater reliability of the total scores for the two raters was 0.93. The final methadone dose used in the treatment of individual patients was regressed on the CINA score. The simple regression equation was: METHADONE DOSE=11.2+ 0.72 CINA SCORE. This equation accounted for 69% of the variance of the final dose. By including a quadratic term, the prediction of the final methadone dose was improved by 3% (or a total of 72% of the variance); the regression equation was: METHADONE DOSE=4.36+1.26 CINA SCORE—0.01 CINA SCORE. 2 The relatively large correlation (above 0.83) between CINA and the final methadone dose may be taken as an indication of the validity of the CINA score.
Reservoir management -- as conceived and applied on the Palinpinon reservoir, Phillipines (1988)

Advances in recombinant DNA manufacturing technology have now made possible the production of a highly purified and active recombinant factor IX (rFIX) product. Recombinant factor IX was developed by (1) stable insertion of the genes for both factor IX and PACE-SOL (a truncated, soluble serine protease needed to enhance the capacity of cells to remove the amino-terminal propeptide from rFIX) into Chinese hamster ovary cells; (2) selection of a cell line that was capable of expressing high amounts of active rFIX while growing in bioreactors containing a completely defined culture medium that does not contain blood or plasma products; and (3) inclusion of four independent chromatography steps, none of which require monoclonal antibodies. Furthermore, rFIX has been extensively tested to demonstrate similarity to plasma-derived factor IX and has been shown to be a consistent, high-purity product. For example, a high-specific-activity product (276+/-23 IU/mg) has been consistently produced throughout 65 consecutive batches from five consecutive manufacturing campaigns. Thus, rFIX offers a consistent and high-purity source of factor IX treatment for patients with hemophilia B.
Combining Atom Transfer Radical Polymerization and Disulfide/Thiol Redox Chemistry:  A Route to Well-Defined (Bio)degradable Polymeric Materials (2005)

Linear well-defined degradable polymethacrylates with internal disulfide link were prepared by atom transfer radical polymerization (ATRP) of methyl, tert-butyl, and benzyl methacrylate using bis[2-(2-bromoisobutyryloxy)ethyl] disulfide as the initiator and CuBr/2,2‘-bipyridine as the catalyst at 50 °C. The disulfide bond was cleaved to thiol by reduction with tributylphosphine, yielding polymers of half the molecular weight of the starting materials. Degradable gels were prepared by the copolymerization of methyl methacrylate and a disulfide-containing difunctional methacrylate, bis(2-methacryloyloxyethyl) disulfide, using similar reaction conditions. The produced gels were reduced with tributylphosphine to form soluble, low molecular weight linear poly(methyl methacrylate) fragments containing thiol groups at the chain end and along the backbone, originating from the disulfide difunctional initiator and monomer, respectively. The disulfide-cross-linked gels were further used as “supermacroinitiators” for the bulk ATRP of styrene at 90 °C, employing CuBr/N,N,N‘,N‘ ‘,N‘ ‘-pentamethyldiethylenetriamine as the catalyst. The length of the polystyrene pendant chains could be controlled by varying the reaction time. The prepared gels with segmented structure swelled more than the starting polymethacrylate gels in both THF and toluene. Degradation experiments confirmed the high degree of chain-end bromine functionalization of the “supermacroinitiators”.
The Role of Complement Inhibition in PNH (2008)

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, debilitating, acquired disorder that most frequently presents in early adulthood and usually continues throughout the life of a patient. PNH results in the death of approximately half of affected individuals, mainly through thrombotic complications, and until recently had no specific therapy. In 2007 eculizumab, an anti-complement antibody targeting the C5 complement component was approved for PNH by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA). Eculizumab is very effective in the treatment of intravascular hemolysis and all its sequelae, which include most of the symptoms and complications of PNH. Eculizumab has revolutionized our approach to hemolytic PNH and as it markedly reduces the principal complications of PNH, namely thrombosis and renal failure, should have a significant impact on survival. However, the development of eculizumab presents new challenges in PNH, such as how to avoid complications of therapy, how to overcome some of the problems associated with treatment and who to select for treatment, as only a proportion of patients with a PNH clone will benefit. This article will review the evidence behind the use of eculizumab in PNH, the effect it will have on the complications of the disease, the most appropriate selection of patients for therapy, the optimal management and the potential complications of the therapy.