gebhart/patrepeval huggingface dataset:
Molecular cloning of unintegrated closed circular DNA of porcine retrovirus (1986)

Viral DNA of unintegrated closed circular form was isolated from a swine kidney cell line (SKL) which was infected with a porcine retrovirus Tsukuba-1 (PRetV) produced from a swine malignant lymphoma-derived cell line. Shimozuma-1 and cloned using a lambda phage vector, Charon 21A. One of ten independent clones contained the 8.3 kb DNA fragment as an insert, which was thought to be a full length of viral DNA molecule carrying a long terminal repeat (LTR) sequence. We have analyzed this insert by mapping the recognition sites of some restriction endonucleases by Southern blot hybridization with appropriate probes.
Patterns of Resistance and Cross-Resistance to Human Immunodeficiency Virus Type 1 Reverse Transcriptase Inhibitors in Patients Treated with the Nonnucleoside Reverse Transcriptase Inhibitor Loviride (1998)

Human immunodeficiency virus type 1 (HIV-1) strains resistant to nonnucleoside reverse transcriptase inhibitors (NNRTIs) may easily be selected for in vitro and in vivo under a suboptimal therapy regimen. Although cross-resistance is extensive within this class of compounds, newer NNRTIs were reported to retain activity against laboratory strains containing defined resistance-associated mutations. We have characterized HIV-1 resistance to loviride and the extent of cross-resistance to nevirapine, delavirdine, efavirenz, HBY-097, and tivirapine in a set of 24 clinical samples from patients treated with long-term loviride monotherapy by using a recombinant virus assay. Genotypic changes associated with resistance were analyzed by population sequencing. Overall, phenotypic resistance to loviride ranged from 0.04 to 3.47 log10-fold. Resistance was observed in samples from patients who had discontinued loviride for up to 27 months. Cross-resistance to the other compounds was extensive; however, fold resistance to efavirenz was significantly lower than fold resistance to nevirapine. No genotypic changes were detected in three samples; these were sensitive to all of the NNRTIs tested. The most common genotypic change was the K103N substitution. The range of phenotypic resistance in samples containing the K103N substitution could not be predicted from a genotypic analysis of known NNRTI resistance-associated mutations. The Y181C substitution was detected in one isolate which was resistant to loviride and delavirdine but sensitive to efavirenz, HBY-097, and tivirapine. Our data indicate that the available newer NNRTIs which retain activity against some HIV-1 strains selected by other compounds of this class in vitro may have compromised clinical efficacy in some patients pretreated with NNRTI.
Unmasking antigens for immunohistochemistry. (2001)

Preservation of tissue by fixation in a formalin solution, followed by dehydration and paraffin-wax embedding remains the predominant method of preparation for microscopic analysis of morphology. Whilst this may be optimal for morphological assessment, this technique has major disadvantages for subsequent immunohistochemical study as a result of the structural alteration of antigens that occurs during the processing procedure. However, the introduction of a range of antigen unmasking procedures has revolutionised immunohistochemistry, establishing the technique as a powerful tool in diagnostic pathology. Here, the development of enzymatic, non-enzymatic and heat-based antigen retrieval techniques is reviewed, and the methods in use currently are appraised.
Topical negative pressure in wound management (2000)

TNP can, in some circumstances, promote rapid secondary wound healing. A further randomised trial of TNP versus more traditional wound management modalities is justified.
Dynamic 3D models with local and global deformations: deformable superquadrics (1991)

The authors present a physically based approach to fitting complex three-dimensional shapes using a novel class of dynamic models that can deform both locally and globally. They formulate the deformable superquadrics which incorporate the global shape parameters of a conventional superellipsoid with the local degrees of freedom of a spline. The model's six global deformational degrees of freedom capture gross shape features from visual data and provide salient part descriptors for efficient indexing into a database of stored models. The local deformation parameters reconstruct the details of complex shapes that the global abstraction misses. The equations of motion which govern the behavior of deformable superquadrics make them responsive to externally applied forces. The authors fit models to visual data by transforming the data into forces and simulating the equations of motion through time to adjust the translational, rotational, and deformational degrees of freedom of the models. Model fitting experiments involving 2D monocular image data and 3D range data are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
PROGRESSIVE FRACTURE MODELING OF THE FAILURE WAVE IN IMPACTED GLASS (2006)

失败波浪被观察了在自从 1991，装载的影响下面在玻璃里宣传。是一个连续破裂地区可以在冲击波的繁殖期间与损坏累积过程被联系。一个进步破裂模型被建议就它的 heterogeneousmeso 结构而言在震惊的玻璃里描述失败波浪形成和繁殖。原版并且。当装载的吃惊在 Hugoniot 有弹性的限制下面时，起核心作用的微裂缝将与伴随物膨胀沿着毛孔和另外的缺点膨胀。失败波浪的 Thegoverning 方程被无弹性的体积紧张与材料损坏和骨折描绘。并且无弹性的体积紧张从原来的毛孔的倒塌从微裂缝和压缩紧张的成核和扩大由膨胀紧张组成。免费表面速度的 Numericalsimulation 在设计物理的中国学院在对 K9 玻璃的平面影响实验的好同意被执行并且发现。并且纵的、侧面的 ands 听说在失败波浪的到达之上的应力历史被预言，它介绍减少砍在没有通过的层的强度和失去的裂片强度。
Timing jitter and pulse energy fluctuations in a passively mode-locked two-section quantum-well laser coupled to an external cavity (1991)

Stability of pulse energy and timing in a passively mode-locked two-section quantum-well laser is measured. Spectral analysis of the 546-MHz pulse train reveals rms timing jitter of 5.5 ps above 50 Hz and rms pulse energy fluctuations of &amp;lt;0.52% above 200 Hz.
Mechanistic Insights into the Enhancement of Adeno-Associated Virus Transduction by Proteasome Inhibitors (2013)

Proteasome inhibitors (e.g., bortezomib, MG132) are known to enhance adeno-associated virus (AAV) transduction; however, whether this results from pleotropic proteasome inhibition or off-target serine and/or cysteine protease inhibition remains unresolved. Here, we examined recombinant AAV (rAAV) effects of a new proteasome inhibitor, carfilzomib, which specifically inhibits chymotrypsin-like proteasome activity and no other proteases. We determined that proteasome inhibitors act on rAAV through proteasome inhibition and not serine or cysteine protease inhibition, likely through positive changes late in transduction.
Evidence for the involvement of interleukin 6 in experimental cancer cachexia. (1992)

In this report we describe an experimental model of cachexia that fulfills the criteria of an early effect with a small tumor mass not related to the growth rate of the tumor, and progressive wasting of muscle and fat without a detectable loss of appetite. C-26.IVX is a cell line derived from murine colon-26 adenocarcinoma which retains the transplantability of the original tumor and induces true cachexia in syngeneic hosts. Evidence is presented to support a role for interleukin (IL-6) as a cachectic factor in the development of cancer cachexia in this model system. Thus, increasing levels of IL-6 in C-26.IVX-bearing mice correlate with the development of cachexia. If the primary tumors were resected, mice gained weight and the levels of IL-6 in the serum were reduced significantly. Moreover, monoclonal antibody to murine IL-6 (but not anti-tumor necrosis factor antibody) was able to significantly suppress the development of key parameters of cachexia in tumor bearing mice.
[Expression of EYA2 in non-small cell lang cancer]. (2009)

The results of this study suggest that expression of EYA2 in lung adenocarcinoma is augmented. EYA2 is likely participating in the development of lung adenocarcinoma as a transcriptional activator.
Cytotoxic T cell immunity against telomerase reverse transcriptase in humans (2000)

Telomerase is a ribonucleoprotein enzyme which has been linked to malignant transformation in human cells. Telomerase activity is increased in the vast majority of human tumors, making its gene product the first molecule common to all human tumors. The generation of endogenously processed telomerase peptides bound to Class I MHC molecules could therefore target cytotoxic T lymphocytes (CTL) to tumors of different origins. This could advance vaccine therapy against cancer provided that precursor CTL recognizing telomerase peptides in normal adults and cancer patients can be expanded through immunization. We demonstrate here that the majority of normal individuals and patients with prostate cancer immunized in vitro against two HLA-A2.1 restricted peptides from telomerase reverse transcriptase (hTRT) develop hTRT-specific CTL. This suggests the existence of precursor CTL for hTRT in the repertoire of normal individuals and in cancer patients. Most importantly, the CTL of cancer patients specifically lysed a variety of HLA-A2(+) cancer cell lines, demonstrating immunological recognition of endogenously processed hTRT peptides. Moreover, in vivo immunization of HLA-A2.1 transgenic mice generated a specific CTL response against both hTRT peptides. Based on the induction of CTL responses in vitro and in vivo, and the susceptibility to lysis of tumor cells of various origins by hTRT CTL, we suggest that hTRT could serve as a universal cancer vaccine for humans.
Clozapine: a comparison with other novel antipsychotics. (1999)

Clinical studies with clozapine have clearly demonstrated its superior efficacy over that of conventional antipsychotics in treatment-resistant schizophrenic patients. In comparative trials with these drugs, considerably more patients respond to treatment with clozapine than to conventional antipsychotic medication. Recently, new antipsychotics, such as olanzapine, quetiapine, risperidone, sertindole, and zotepine, have been introduced, but extensive data on their effects in treatment-resistant patients are not yet available. Published studies have drawn criticism in terms of inappropriate titration schedules, nonequivalent dosing between treatment groups, short treatment duration, and inadequate sample sizes. Further research will be needed to determine whether novel antipsychotics may substitute for clozapine in the future or whether clozapine will retain its unique role in the management of patients suffering from difficult-to-treat schizophrenic disorders.
The Immune Diversity in a Test Tube - Non-Immunised Antibody Libraries and Functional Variability in Defined Protein Scaffolds (2001)

Technologies to develop and evolve the function of proteins and, in particular, antibodies have developed rapidly since the introduction of phage display. Importantly, it has become possible to identify molecules with binding properties that cannot be found by other means. A range of different approaches to create general libraries that are useful for the selection of such molecules specific for essentially any kind of target have emerged. We herein review some of the most prominent approaches in the field and in particular discuss specific features related to the development of antibody libraries based on single antibody framework scaffolds. This approach not only permits identification of a range of specific binders, but also facilitates further evolution of initially derived molecules into molecules with optimised functions.
Amine-Reactive Biodegradable Diblock Copolymers (2001)

A new class of diblock copolymers was synthesized from biodegradable poly(lactic acid) and poly(ethylene glycol)minus signmonoamine. These polymers were activated by covalently attaching linkers such as disuccinimidyl tartrate or disuccinimidyl succinate to the hydrophilic polymer chain. The polymers were characterized by (1)H NMR spectroscopy, (13)C NMR spectroscopy and gel permeation chromatography (GPC). These investigations indicated that the polymers were obtained with the correct composition, in high purities, and the expected molecular weight. By using dyes containing primary amine groups such as 5-aminoeosin as model substrates, it was possible to show that the polymers are able to bind such compounds covalently. The diblock copolymers were developed to suppress unspecific protein adsorption and allow the binding of bioactive molecules by instant surface modification. The polymers are intended to be used for tissue engineering applications where surface immobilized cell adhesion peptides or growth factors are needed to control cell behavior.
3D line imaging on a clinical magnetic particle imaging demonstrator (2015)

A clinical MPI demonstrator system is being built [1] that will enable fast 3D imaging with 3D drive field excitation and rapid 3D focus fields. To date, all components have been realized only once, i.e., a 1D drive field coil (x direction), a 1D fast focus field (y direction), and a 1D selection and focus field (z direction). To test the respective components, a 3D image is acquired using a linear drive field trajectory.
Results of decitabine (5‐aza‐2′deoxycytidine) therapy in 130 patients with chronic myelogenous leukemia (2003)

Decitabine appears to have significant anti-CML activity. Future studies should evaluate lower-dose, longer-exposure decitabine schedules alone in imatinib-resistant CML, as well as combinations of decitabine and imatinib in different CML phases.
Studies of the aggregation of mutant proteins in vitro provide insights into the genetics of amyloid diseases (2002)

Protein aggregation and the formation of highly insoluble amyloid structures is associated with a range of debilitating human conditions, which include Alzheimer's disease, Parkinson's disease, and the Creutzfeldt-Jakob disease. Muscle acylphosphatase (AcP) has already provided significant insights into mutational changes that modulate amyloid formation. In the present paper, we have used this system to investigate the effects of mutations that modify the charge state of a protein without affecting significantly the hydrophobicity or secondary structural propensities of the polypeptide chain. A highly significant inverse correlation was found to exist between the rates of aggregation of the protein variants under denaturing conditions and their overall net charge. This result indicates that aggregation is generally favored by mutations that bring the net charge of the protein closer to neutrality. In light of this finding, we have analyzed natural mutations associated with familial forms of amyloid diseases that involve alteration of the net charge of the proteins or protein fragments associated with the diseases. Sixteen mutations have been identified for which the mechanism of action that causes the pathological condition is not yet known or fully understood. Remarkably, 14 of these 16 mutations cause the net charge of the corresponding peptide or protein that converts into amyloid deposits to be reduced. This result suggests that charge has been a key parameter in molecular evolution to ensure the avoidance of protein aggregation and identifies reduction of the net charge as an important determinant in at least some forms of protein deposition diseases.
Review: cytokines and the pathogenesis of multiple sclerosis (1996)

Perivascular accumulation of mononuclear cells (MNCs) in the central nervous system (CNS) and high levels of myelin autoantigen-reactive T cells in blood and further enriched in cerebrospinal fluid (CSF) are characteristic for multiple sclerosis (MS) and suggest a role for immunoregulatory cytokines in MS pathogenesis. The difficulties inherent to measurements of cytokine concentrations in body fluids have been partly overcome by adopting techniques allowing cytokine determinations on cellular level. MS is associated with the parallel up-regulation of proinflammatory [interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), lymphotoxin-alpha, and interleukin (IL)-12] and immune response-down-regulating [transforming growth factor-beta (TGF-beta), IL-10] cytokines systemically. A preferential up-modulation of TNF-alpha and lymphotoxin-alpha is observed in clinical exacerbations and of TGF-beta and IL-10 in remissions. The B cell-stimulating IL-4 and IL-6 are also up-regulated in MS, as is the cytolysis-promoting perforin. Cytokine production is elevated to an even higher degree in the CSF than systemically, underlining the autonomy of the immune responses in the CSF. All cytokine abnormalities are demonstrable already in very early MS, manifested by acute unilateral optic neuritis associated with more than two MS-like lesions on brain magnetic resonance imaging and oligoclonal IgG bands in CSF. The cytokine abnormalities hitherto observed are not MS specific, because they can be found in other inflammatory CNS diseases, e.g., aseptic meningitis and even noninflammatory neurological diseases like stroke. The influence on cytokine profiles, e.g., suppressing proinflammatory cytokines and promoting TGF-beta and IL-10, could be an important way to identify new and promising treatments of MS.
Paradoxical activation and RAF inhibitor resistance of BRAF protein kinase fusions characterizing pediatric astrocytomas (2013)

Astrocytomas are the most common type of brain tumors in children. Activated BRAF protein kinase mutations are characteristic of pediatric astrocytomas with KIAA1549-BRAF fusion genes typifying low-grade astrocytomas and (V600E)BRAF alterations characterizing distinct or higher-grade tumors. Recently, BRAF-targeted therapies, such as vemurafenib, have shown great promise in treating V600E-dependent melanomas. Like (V600E)BRAF, BRAF fusion kinases activate MAPK signaling and are sufficient for malignant transformation; however, here we characterized the distinct mechanisms of action of KIAA1549-BRAF and its differential responsiveness to PLX4720, a first-generation BRAF inhibitor and research analog of vemurafenib. We found that in cells expressing KIAA1549-BRAF, the fusion kinase functions as a homodimer that is resistant to PLX4720 and accordingly is associated with CRAF-independent paradoxical activation of MAPK signaling. Mutagenesis studies demonstrated that KIAA1549-BRAF fusion-mediated signaling is diminished with disruption of the BRAF kinase dimer interface. In addition, the KIAA1549-BRAF fusion displays increased binding affinity to kinase suppressor of RAS (KSR), an RAF relative recently demonstrated to facilitate MEK phosphorylation by BRAF. Despite its resistance to PLX4720, the KIAA1549-BRAF fusion is responsive to a second-generation selective BRAF inhibitor that, unlike vemurafenib, does not induce activation of wild-type BRAF. Our data support the development of targeted treatment paradigms for BRAF-altered pediatric astrocytomas and also demonstrate that therapies must be tailored to the specific mutational context and distinct mechanisms of action of the mutant kinase.
Monoclonal Antibody Therapy for B-Cell Non-Hodgkin's Lymphoma (2008)

Treatment of B-cell non-Hodgkin's lymphoma has become more successful, largely owing to the availability of therapeutic monoclonal antibodies, which may avoid the toxic effects of chemotherapy, improve the outcomes when combined with chemotherapy, and provide options for patients with refractory disease. This article reviews the current uses of monoclonal antibodies in B-cell non-Hodgkin's lymphoma.
Phase I and pharmacologic studies of the camptothecin analog irinotecan administered every 3 weeks in cancer patients. (1995)

The MTD of CPT-11 administered as a 30-minute IV infusion every 3 weeks is 600 mg/m2, with granulocytopenia being dose-limiting. At 350 mg/m2, diarrhea appeared dose-limiting, but high-dose loperamide reduced this toxicity and allowed dose escalation. For safety reasons, the recommended dose is presently 350 mg/m2 every 3 weeks; more experience must be gained to establish the feasibility of a higher dose in large multicentric phase II studies. However, when careful monitoring of gastrointestinal toxicities is possible, a higher dose of 500 mg/m2 could be recommended in good-risk patients. The activity of this agent in 5-FU-refractory colorectal carcinoma makes it unique and mandates expedited phase II testing.
Branched Polymer−Protein Conjugates Made From Mid-Chain-Functional P(HPMA) (2009)

A novel midchain-functional chain transfer agent was synthesized and used as a reversible addition-fragmentation chain transfer polymerization agent to prepare branched poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA). The P(HPMA) contained a thio-reactive group, namely, pyridyldisulfide midchain. The synthesized polymers were fully analyzed by (1)H NMR, GPC, and hydrolysis, confirming well-defined structures (predesigned molecular weights, narrow polydispersities, and high functionalization efficiencies). These midfunctionalized polymers were incubated with bovine serum albumin to generate protein-polymer conjugates. This straightforward methodology for the synthesis of branched midfunctionalized polymers for protein conjugation has the potential to enhance the properties of polymer-protein conjugates by improving biomolecule stability and enhancing circulation time.
Early Clinical PET Imaging Results with the Novel PHF-Tau Radioligand [F-18]-T807 (2013)

Aggregates of hyperphosphorylated tau (PHF-tau), such as neurofibrillary tangles, are linked to the degree of cognitive impairment in Alzheimer's disease. We have developed a novel PHF-tau targeting positron emission tomography imaging agent, [F-18]-T807, which may be useful for imaging Alzheimer's disease and other tauopathies. Here in, we describe the first human brain images with [F-18]-T807.
Absorbable pins of self-reinforced poly-L-lactic acid for fixation of fractures and osteotomies (1992)

We reviewed 27 patients with small-fragment fractures or osteotomies treated by internal fixation with absorbable self-reinforced poly-L-lactide pins. The follow-up time ranged from eight to 37 months. The two most common indications were chevron osteotomy of the first metatarsal bone for hallux valgus and displaced fracture of the radial head. No redisplacements occurred, and there were no signs of inflammatory foreign-body reaction. Biopsy in two patients 20 and 37 months after implantation showed that no polymeric material remained.
Variation in Epidermal Morphology in Human Skin at Different Body Sites as Measured by Reflectance Confocal Microscopy (2010)

Two methods of estimating stratum corneum thickness using reflectance confocal microscopy were examined, and epidermal thickness measurements at multiple body sites were compared. Measurements of stratum corneum thickness were made using the derivative method, which is based on the rate of change of image intensity as a proxy for keratin concentration, and simple visual analysis of confocal images. To compare epidermal thickness we collected 1491 z-axis stacks of confocal images from 10 body sites in 39 subjects. An artefact associated with the imaging process interfered with the derivative method for stratum corneum thickness, and simple visual analysis is to be preferred. Although some epidermal properties varied by site, the most striking finding was the degree of within-site variation, which accounted for between 50% and 74% of the total variation observed. The majority of this variation was not due to measurement error, and represents genuine topographical irregularity. This fine-scale variation limits the ease of use of reflectance confocal microscopy for quantitative studies of the epidermis and stratum corneum.