gebhart/patrepeval huggingface dataset:
Clinical Relevance of BCL2, BCL6, and MYC Rearrangements in Diffuse Large B-Cell Lymphoma (1998)

Diffuse large B-cell lymphoma (DLCL) is characterized by a marked degree of morphologic and clinical heterogeneity. We studied 156 patients with de novo DLCL for rearrangements of the BCL2, BCL6, and MYC oncogenes by Southern blot analysis and BCL2 protein expression. We related these data to the primary site of presentation, disease stage, and other clinical risk factors. Structural alterations of BCL2, BCL6, and MYC were detected in 25 of 156, 36 of 116, and 10 of 151 patients, respectively. Three cases showed a combination of BCL2 and BCL6 rearrangements, and two cases had a combination of BCL6 and MYC rearrangements. BCL2 rearrangement was found more often in extensive (39%) and primary nodal (17%) lymphomas than in extranodal cases (4%) (P = .003). BCL2 rearrangement was present in none of 40 patients with stage I disease, but in 22% of patients with stage II to IV (P = .006). The presence of BCL2 rearrangements did not significantly affect overall survival (OS) or disease-free survival (DFS). In contrast, high BCL2 protein expression adversely affected both OS (P = .008) and DFS (P = .01). BCL2 protein expression was poorly correlated with BCL2 rearrangement: only 52% of BCL2-rearranged lymphomas and 37% of BCL2-unrearranged cases had high BCL2 protein expression. Rearrangement of BCL6 was found more often in patients with extranodal (36%) and extensive (39%) presentation versus primary nodal disease (28%). No significant correlation was found with disease stage, lymphadenopathy, or bone marrow involvement. DFS and OS were not influenced by BCL6 rearrangements. MYC rearrangements were found in 16% of primary extranodal lymphomas, versus 2% of primary nodal cases (P = .02). In particular, gastrointestinal (GI) lymphomas (5 of 18 cases, 28%) were affected by MYC rearrangements. The distinct biologic behavior of these extranodal lymphomas was reflected by a high complete remission (CR) rate: 7 of 10 patients with MYC rearrangement attained complete remission and 6 responders remained alive for more than 4 years, resulting in a trend for better DFS (P = .07). These data show the complex nature of molecular events in DLCL, which is a reflection of the morphologic and clinical heterogeneity of these lymphomas. However, thus far, these genetic rearrangements fail as prognostic markers.
Application of tyramide signal amplification system to immunohistochemistry: A potent method to localize antigens that are not detectable by ordinary method (1999)

Tyramide signal amplification-avidin-biotin complex (TSA-ABC) method is a powerful technique used to detect antigens that are not detectable by ordinary immunohistochemistry. It is worth trying in cases where localization of antigens by the conventional method has failed and antibodies are precious.
Inter- and Intragenus Structural Variations in Caliciviruses and Their Functional Implications (2004)

The family Caliciviridae is divided into four genera and consists of single-stranded RNA viruses with hosts ranging from humans to a wide variety of animals. Human caliciviruses are the major cause of outbreaks of acute nonbacterial gastroenteritis, whereas animal caliciviruses cause various host-dependent illnesses with a documented potential for zoonoses. To investigate inter- and intragenus structural variations and to provide a better understanding of the structural basis of host specificity and strain diversity, we performed structural studies of the recombinant capsid of Grimsby virus, the recombinant capsid of Parkville virus, and San Miguel sea lion virus serotype 4 (SMSV4), which are representative of the genera Norovirus (genogroup 2), Sapovirus, and Vesivirus, respectively. A comparative analysis of these structures was performed with that of the recombinant capsid of Norwalk virus, a prototype member of Norovirus genogroup 1. Although these capsids share a common architectural framework of 90 dimers of the capsid protein arranged on a T=3 icosahedral lattice with a modular domain organization of the subunit consisting of a shell (S) domain and a protrusion (P) domain, they exhibit distinct differences. The distally located P2 subdomain of P shows the most prominent differences both in shape and in size, in accordance with the observed sequence variability. Another major difference is in the relative orientation between the S and P domains, particularly between those of noroviruses and other caliciviruses. Despite being a human pathogen, the Parkville virus capsid shows more structural similarity to SMSV4, an animal calicivirus, suggesting a closer relationship between sapoviruses and animal caliciviruses. These comparative structural studies of caliciviruses provide a functional rationale for the unique modular domain organization of the capsid protein with an embedded flexibility reminiscent of an antibody structure. The highly conserved S domain functions to provide an icosahedral scaffold; the hypervariable P2 subdomain may function as a replaceable module to confer host specificity and strain diversity; and the P1 subdomain, located between S and P2, provides additional fine-tuning to position the P2 subdomain.
Lithium divertor concept and results of supporting experiments (2002)

The ITER project development has shown that considerable difficulties are encountered when already known engineering solutions and materials are used for divertor and divertor plates for tokamaks of such a scale. We offer to use a Li capillary-pore system (CPS) as a plasma facing material for tokamak divertor. Evaporated Li serves as a gas target and redistributes thermal load. The heat flux from the plasma is transported to the first wall by Li radiation in the plasma periphery. This allows the divertor plate to reduce the heat flux. A solid CPS filled with liquid lithium has a high resistance to surface damage in the stationary mode and during plasma transitions (disruptions, ELMs, VDEs, runaways) to assure normal operation of the divertor target plates. These materials are not the sources of impurities giving rise to Zeff and they will not be collected as dust in the divertor area and in ducts. Experiments with lithium CPS in a steady-state mode (up to 25 MW m-2) and in plasma disruption simulation conditions (~5 MJ m-2, ~0.5 ms) have been performed. High stability of these systems have been shown. Li limiter tests on T-11M tokamak have revealed the lithium CPS compatibility with the edge plasma for energy loads of up to 10 MW m-2. In a stable discharge mode at lithium limiter temperature of 20-600°C, no Li abnormal erosion and injection to plasma have been detected. A high sorption of D+ and H+ ions on the vessel walls was the main substantial result of the replacement of a graphite limiter by lithium one. He and D sorption was terminated by wall heating up to 50-100°C and above 350°C, respectively. T-11 tests on helium discharge allowed to reduce limiter heat load by a factor of two due to lithium radiation. All the experimental results have shown considerable progress in the development of lithium divertor.
So‐Called Cellulite: An Invented Disease (1978)

The anatomic basis of so-called cellulite, the hormonal basis for the clinical condition, the prevalence of it, the essential normality and inevitability of it in women, the supervention of it in hormonally feminized men, and the near futility of treating the non-disease are explored in this paper.
Human MHC Class I Transgenic Mice Deficient for H2 Class I Expression Facilitate Identification and Characterization of New HLA Class I-Restricted Viral T Cell Epitopes (2002)

Although mice transgenic (Tg) for human MHC (HLA) class I alleles could provide an important model for characterizing HLA-restricted viral and tumor Ag CTL epitopes, the extent to which Tg mouse T cells become HLA restricted in the presence of endogenous H2 class I and recognize the same peptides as in HLA allele-matched humans is not clear. We previously described Tg mice carrying the HLA-B27, HLA-B7, or HLA-A2 alleles expressed as fully native (HLA(nat)) (with human beta(2)-microglobulin) and as hybrid human/mouse (HLA(hyb)) molecules on the H2(b) background. To eliminate the influence of H2(b) class I, each HLA Tg strain was bred with a H2-K(b)/H2-D(b)-double knockout (DKO) strain to generate mice in which the only classical class I expression was the human molecule. Expression of each HLA(hyb) molecule and HLA-B27(nat)/human beta(2)-microglobulin led to peripheral CD8(+) T cell levels comparable with that for mice expressing a single H2-K(b) or H2-D(b) gene. Influenza A infection of Tg HLA-B27(hyb)/DKO generated a strong CD8(+) T cell response directed at the same peptide (flu nucleoprotein NP383-391) recognized by CTLs from flu-infected B27(+) humans. As HLA-B7/flu epitopes were not known from human studies, we used flu-infected Tg HLA-B7(hyb)/DKO mice to examine the CTL response to candidate peptides identified based on the B7 binding motif. We have identified flu NP418-426 as a major HLA-B7-restricted flu CTL epitope. In summary, the HLA class I Tg/H2-K/H2-D DKO mouse model described in this study provides a sensitive and specific approach for identifying and characterizing HLA-restricted CTL epitopes for a variety of human disease-associated Ags.
Functional interactions between matrix metalloproteinases and glycosaminoglycans (2013)

Similar to most proteinases, matrix metalloproteinases ( MMP ) do not recognize a consensus cleavage site. Thus, it is not surprising that, in a defined in vitro reaction, most MMP s can act on a wide range of proteins, including many extracellular matrix proteins. However, the findings obtained from in vivo studies with genetic models have demonstrated that individual MMP s act on just a few extracellular protein substrates, typically not matrix proteins. The limited, precise functions of an MMP imply that mechanisms have evolved to control the specificity of proteinase:substrate interactions. We discuss the possibility that interactions with the glycosaminoglycan chains of proteoglycans may function as allosteric regulators or accessory factors directing MMP catalysis to specific substrates. We propose that understanding how the activity of specific MMP s is confined to discreet compartments and targeted to defined substrates via interactions with other macromolecules may provide a means of blocking potentially deleterious MMP ‐mediated processes at the same time as sparing any beneficial functions.
A self-assembled hierarchical nanostructure comprising carbon spheres and graphene nanosheets for enhanced supercapacitor performance (2011)

A self-assembly approach is used to fabricate a hierarchical nanostructure using functionalized carbon spheres as nano-spacers to separate graphene nanosheets. The nanostructure significantly enhances capacitance of a graphene supercapacitor by more than 70%, while providing a universal method to self-assembling various carbons into hierarchical structures for energy conversion/storage systems.
Tomographic mammography using a limited number of low‐dose cone‐beam projection images (2003)

A method is described for using a limited number (typically 10-50) of low-dose radiographs to reconstruct the three-dimensional (3D) distribution of x-ray attenuation in the breast. The method uses x-ray cone-beam imaging, an electronic digital detector, and constrained nonlinear iterative computational techniques. Images are reconstructed with high resolution in two dimensions and lower resolution in the third dimension. The 3D distribution of attenuation that is projected into one image in conventional mammography can be separated into many layers (typically 30-80 1-mm-thick layers, depending on breast thickness), increasing the conspicuity of features that are often obscured by overlapping structure in a single-projection view. Schemes that record breast images at nonuniform angular increments, nonuniform image exposure, and nonuniform detector resolution are investigated in order to reduce the total x-ray exposure necessary to obtain diagnostically useful 3D reconstructions, and to improve the quality of the reconstructed images for a given exposure. The total patient radiation dose can be comparable to that used for a standard two-view mammogram. The method is illustrated with images from mastectomy specimens, a phantom, and human volunteers. The results show how image quality is affected by various data-collection protocols.
An updated two‐dimensional gel database of rat liver proteins useful in gene regulation and drug effect studies (1995)

We have improved upon the reference two-dimensional (2-D) electrophoretic map of rat liver proteins originally published in 1991 (N. L. Anderson et al., Electrophoresis 1991, 12, 907-930). A total of 53 proteins (102 spots) are now identified, many by microsequencing. In most cases, spots cut from wet, Coomassie Blue stained 2-D gels were submitted to internal tryptic digestion [2], and individual peptides, separated by high-performance liquid chromatography (HPLC), were sequenced using a Perkin-Elmer 477A sequenator. Additional spots were identified using specific antibodies.
A refined solution structure of hen lysozyme determined using residual dipolar coupling data (2001)

A high resolution NMR structure of hen lysozyme has been determined using 209 residual 1H-15N dipolar coupling restraints from measurements made in two different dilute liquid crystalline phases (bicelles) in conjunction with a data set of 1632 NOE distance restraints, 110 torsion angle restraints, and 60 hydrogen bond restraints. The ensemble of 50 low-energy calculated structures has an average backbone RMSD of 0.50+/-0.13A to the mean structure and of 1.49+/-0.10A to the crystal structure of hen lysozyme. To assess the importance of the dipolar coupling data in the structure determination, the final structures are compared with an ensemble calculated using an identical protocol but excluding the dipolar coupling restraints. The comparison shows that structures calculated with the dipolar coupling data are more similar to the crystal structure than those calculated without, and have better stereochemical quality. The structures also show improved quality factors when compared with additional dipolar coupling data that were not included in the structure calculations, with orientation-dependent 15N chemical shift changes measured in the bicelle solutions, and with T1/T2 values obtained from 15N relaxation measurements. Analysis of the ensemble of NMR structures and comparisons with crystal structures, 15N relaxation data, and molecular dynamics simulations of hen lysozyme provides a detailed description of the solution structure of this protein and insights into its dynamical behavior.
Targeted degradation of ENaC in response to PKC activation of the ERK1/2 cascade (2003)

Renal A6 epithelial cells were used to determine the mechanism by which protein kinase C (PKC) decreases epithelial Na(+) channel (ENaC) activity. Activation of PKC reduced relative Na(+) reabsorption to <20% within 60 min. This decrease was sustained over the next 24-48 h. In response to PKC signaling, alpha-, beta-, and gamma-ENaC levels were 0.97, 0.36, and 0.39, respectively, after 24 h, with the levels of the latter two subunits being significantly decreased. The PKC-mediated decreases in beta- and gamma-ENaC were significantly reversed by simultaneous addition of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase-1/2 inhibitors U-0126 and PD-98059. These inhibitors, in addition, protected Na(+) reabsorption from PKC, demonstrating that the MAPK1/2 cascade, in some instances, plays a central role in downregulation of ENaC activity. The effects of PKC on beta- and gamma-ENaC levels were additive with those of inhibitors of transcription (actinomycin D) and translation (emetine and cycloheximide), suggesting that PKC promotes subunit degradation and does not affect subunit synthesis. The bulk of whole cell gamma-ENaC was degraded within 1 h after treatment with inhibitors of synthesis; however, a significant pool was "protected" from inhibitors for up to 12 h. PKC affected this protected pool of gamma-ENaC. Moreover, proteosome inhibitors (MG-132 and lactacystin) reversed PKC effects on this protected pool of gamma-ENaC. Thus PKC signaling via MAPK1/2 cascade activation in A6 cells promotes degradation of gamma-ENaC.
90Y and 177Lu Labeling of a DOTA-Conjugated Vitronectin Receptor Antagonist Useful for Tumor Therapy (2001)

The (90)Y and (177)Lu complexes (RP697 and RP688, respectively) of a DOTA-conjugated vitronectin receptor antagonist (SU015: 2-(1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-1-cyclododecyl)acetyl-Glu(cyclo[Lys-Arg-Gly-Asp-D-Phe])-cyclo[Lys-Arg-Gly-Asp-D-Phe]) were prepared by reacting SU015 with the radiometal chloride in ammonium acetate buffer (pH > 7.2) in the presence of an antioxidant (sodium gentisate, GA). Through a series of radiolabeling experiments, it was found that there are many factors influencing the rate of (90)Y chelation and the radiolabeling efficiency of SU015. These include the purity of SU015, the pH, reaction temperature, and heating time, as well as the presence of trace metal contaminants, such as Ca(2+), Fe(3+), and Zn(2+). The chelation of (90)Y by SU015 is slow, so that heating at elevated temperatures (50-100 degrees C) is needed to complete the (90)Y-labeling. The rate of (90)Y chelation is also dependent on the pH of the reaction mixture. Under optimized radiolabeling conditions (pH 7.2-7.8 and heating at 50-100 degrees C for 5-10 min), the minimum amount of SU015 required to achieve 95% RCP for RP697 is approximately 25 microg for 20 mCi of (90)YCl(3) corresponding to a SU015:(90)Y ratio of approximately 30:1.
안지오텐신 II에 의한 Apoptosis와 그 조절인자의 신장 특이적 변화에 관한 연구 (1999)

Angiotensin II plays an important role in the regulation of systemic and renal hemodynamics, and functions as a growth factor in various tissues. To determine whether ANG II are related to renal-specific stimulation of apoptosis, 36 adult male Sprague-Dawley rats were infused with ANG II at 50 ng/min(low ANG group), 100 ng/min(high ANG group), or vehicle(control group) for 1 week using osmotic minipump(Model 1007D, Alza Co, USA) inserted into the interscapular area of the back. Blood pressure and serum aldosterone level were measured. To detect apoptosis of the kidney, TUNEL(Terminal deoxynucleotidyl Transferase dUTP Nick End Labelling) technique was introduced. Cellular proliferation was detected with PCNA immune histochemical staining. To know the expression of Bcl-2 protein and mRNA, immune histochemical staining, Western blot assay and RT-PCR were done. Results were as follows: 1) There were no differences in body weight or organ weight/body weight among 3 groups. 2) Mean blood pressure between control and low ANG group were not changed throughtout the study. But mean blood pressure was increased at th day 3 and 7 in high ANG group(P<0.05). Serum aldosterone level increased at the day 7 in high ANG group only(P<0.05). 3) PCNA positive cells were increased significantly in the the low ANG groups compared with the control group(P<0.05) and they were decreased significantly in the .high ANG group compared with the the low ANG group(P<0.05). However, they were not different between control and high ANG groups. 4) Apoptosis of renal medulla was increased significantly in the low and high ANG groups compared with the control group(P<0.05). 5) Expression of bcl-2 protein was decreased significantly in the low and high ANG groups compared with the control group(P<0.05). In this study, ANG II infusion induced renal apoptosis and changed expression of PCNA but decreased expression of bcl-2 in the kidney of the Sprague-Dawley rat. In conclusion, histologic changes of the kidney may be controlled by ANG II regardless of systemic hypertension.
Ubiquitin Is a Component of Paired Helical Filaments in Alzheimer's Disease (1987)

Paired helical filaments (PHF), which constitute a distinct type of pathological neuronal fiber, are the principal constituent of neurofibrillary tangles that occur in the brain of patients with Alzheimer's disease. Their insolubility in sodium dodecyl sulfate and urea has prevented the analysis of their subunit composition by gel electrophoresis. A monoclonal antibody (DF2) was isolated that specifically labeled PHF at both the light and electron microscopic levels. It labeled a small polypeptide (5 kilodaltons) that was shown to be ubiquitin in immunoblots of the soluble fraction of brain homogenates. To obtain direct evidence that ubiquitin is a component of PHF, PHF were treated with concentrated formic acid and digested with lysylendopeptidase; ubiquitin-derived peptides were then identified by reversed-phase high-performance liquid chromatography. Two fragments in the PHF digest were identified as derived from ubiquitin by protein sequencing. This procedure should make possible definitive identification of other PHF components.
Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant (2021)

Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations. (Funded by Public Health England.).
Six- vs Seven-Membered Ring Formation from the 1-Bicyclo[4.1.0]heptanylmethyl Radical:  Synthetic and ab Initio Studies (1998)

The viability of utilizing 1-bicyclo[4.1.0]heptanylmethyl radical (3) to serve as a progenitor of seven-membered carbocycles was examined. Rate constants for the rearrangement of this radical to 3-methylenecycloheptyl radical (4) and 2-methylenecyclohexyl-1-methyl radical (6) were measured using the competition method of 3 with thiophenol over the temperature range of −75 to 59 °C. Arrhenius functions were calculated for the conversions of 3 to 4 and 3 to 6 and found to be log(k/s-1) = (12.38 ± 0.20) − (5.63 ± 0.23)/θ and log(k/s-1) = (11.54 ± 0.32) − (5.26 ± 0.37)/θ, respectively. The rate constants for these conversions at 25 °C are 1.86 × 108 s-1 and 5.11 × 107 s-1, respectively. Hence, the seven-membered ring-expanded carbocycle is formed 3.6 times faster at 25 °C than the nonexpanded species. This suggests that the 1-bicyclo[4.1.0]heptanylmethyl radical system may be synthetically useful in seven-membered ring-forming methodology. Preliminary theoretical examination of this radical system qualitatively predicted the experimentally determined energies of activation: PMP4/6-31G*//HF/6-31G* ΔEa (3 → 6 − 3 → 4) = 3.0 kcal/mol with zero point energy correction. The HF/6-31G* optimized reaction coordinate stationary points suggest cyclopropyl substituent eclipsing interactions play an important role in determining the kinetic outcome of these rearrangements.
Melanoma-infiltrating dendritic cells (2012)

The infiltration of melanoma lesions by dendritic cells (DCs) has been suggested to play a tumorigenic role due to the capacity of DCs to induce tumor tolerance and promote angiogenesis as well as metastasis. However, it has also been shown that tumor-infiltrating DCs (TIDCs) induce antitumor responses and hence may be targeted in cost-effective therapeutic approaches to obtain patient-specific DCs that present relevant tumor antigens, without the need for ex vivo DC expansion or tumor antigen identification. Unfortunately, little is known about the composition, nature and function of TIDCs found in human melanoma. The development of mouse melanoma models has greatly contributed to the molecular understanding of melanoma immunology in mice, but many questions on TIDCs remain unanswered. Here, we discuss current knowledge about melanoma TIDCs in various mouse models with regard to their translational potential and clinical relevance.