gebhart/patrepeval huggingface dataset:
Up‐regulated Proteins in the Fluid Bathing the Tumour Cell Microenvironment as Potential Serological Markers for Early Detection of Cancer of the Breast (2009)

Breast cancer is by far the most common diagnosed form of cancer and the leading cause of cancer death in women today. Clinically useful biomarkers for early detection of breast cancer could lead to a significant reduction in mortality. Here we describe a detailed analysis using gel-based proteomics in combination with mass spectrometry and immunohistochemistry (IHC) of the tumour interstitial fluids (TIF) and normal interstitial fluids (NIF) collected from 69 prospective breast cancer patients. The goal of this study was to identify abundant cancer up-regulated proteins that are externalised by cells in the tumour microenvironment of most if not all these lesions. To this end, we applied a phased biomarker discovery research strategy to the analysis of these samples rather than comparing all samples among each other, with inherent inter and intra-sample variability problems. To this end, we chose to use samples derived from a single tumour/benign tissue pair (patient 46, triple negative tumour), for which we had well-matched samples in terms of epithelial cell numbers, to generate the initial dataset. In this first phase we found 110 proteins that were up-regulated by a factor of 2 or more in the TIF, some of which were confirmed by IHC. In the second phase, we carried out a systematic computer assisted analysis of the 2D gels of the remaining 68 TIF samples in order to identify TIF 46 up-regulated proteins that were deregulated in 90% or more of all the available TIFs, thus representing common breast cancer markers. This second phase singled out a set of 26 breast cancer markers, most of which were also identified by a complementary analysis using LC-MS/MS. The expression of calreticulin, cellular retinoic acid-binding protein II, chloride intracellular channel protein 1, EF-1-beta, galectin 1, peroxiredoxin-2, platelet-derived endothelial cell growth factor, protein disulfide isomerase and ubiquitin carboxyl-terminal hydrolase 5 were further validated using a tissue microarray containing 70 malignant breast carcinomas of various grades of atypia. A significant number of these proteins have already been detected in the blood/plasma/secretome by others. The next steps, which include biomarker prioritization based on the hierarchal evaluation of these markers, antibody and antigen development, assay development, analytical validation, and preliminary testing in the blood of healthy and breast cancer patients, are discussed.
Dysregulated gene expression networks in human acute myelogenous leukemia stem cells (2009)

We performed the first genome-wide expression analysis directly comparing the expression profile of highly enriched normal human hematopoietic stem cells (HSC) and leukemic stem cells (LSC) from patients with acute myeloid leukemia (AML). Comparing the expression signature of normal HSC to that of LSC, we identified 3,005 differentially expressed genes. Using 2 independent analyses, we identified multiple pathways that are aberrantly regulated in leukemic stem cells compared with normal HSC. Several pathways, including Wnt signaling, MAP Kinase signaling, and Adherens Junction, are well known for their role in cancer development and stem cell biology. Other pathways have not been previously implicated in the regulation of cancer stem cell functions, including Ribosome and T Cell Receptor Signaling pathway. This study demonstrates that combining global gene expression analysis with detailed annotated pathway resources applied to highly enriched normal and malignant stem cell populations, can yield an understanding of the critical pathways regulating cancer stem cells.
Systemin transiently depolarizes the tomato mesophyll cell membrane and antagonizes fusicoccin‐induced extracellular acidification of mesophyll tissue (1996)

ABSTRACT The plant polypeptide signal systemin induces proteinase inhibitor synthesis in tomato leaves. We show here that systemin elicits a transient depolarization of the tomato mesophyll cell membrane. Furthermore it triggers a transient decrease in the external pH of the mesophyll tissue which is followed by a sustained pH increase. In the presence of fusicoccin (which has been shown to antagonize the synthesis of proteinase inhibitors) the depolarization and transient H + efflux are attenuated whereas the slower phase of the sustained electroneutral H + influx persists. These results suggest that systemin‐induced changes in ion transport play a role in the early phases of systemin signal transduction.
Prevention of growth of leukemia cells in mice by monoclonal antibodies directed against Thy 1.1 antigen disulfide linked to two ribosomal inhibitors:pokeweed antiviral protein or ricin A chain. (1984)

Pokeweed antiviral protein (PAP) and ricin A chain are potent inhibitors of protein synthesis that inactivate eukaryotic 60S ribosomal subunits. Immunotoxins were prepared by linking monoclonal anti-Thy 1.1 antibodies to PAP and ricin A chain through a disulfide bond. Both the conjugates were shown earlier to specifically inhibit protein synthesis of Thy 1.1-positive target leukemic cells (AKR SL3). In the present study, the efficacy of the immunotoxins to prevent the growth of AKR SL3 cell-induced tumor was checked in vivo in a model system. Injection of AKR SL3 cells s.c. into AKR/Cum (Thy 1.2-positive) mice developed into a solid tumor which was fatal. Administration of 31-E6:PAP and 31-E6:ricin A chain suppressed tumor growth. Suppression was specific, as similar treatment could not prevent the growth of a nontarget Thy 1.2-positive leukemia cell line (AKR SL1) derived from a congenic mouse. Unconjugated anti-Thy 1.1 immunoglobulin antibodies also showed significant tumor protection; however, administration of F(ab')2 fragment could not prevent the tumor growth. Injection of F(ab')2:PAP efficiently protected mice from AKR SL3-induced tumor. All the conjugate-treated mice showed antibody response against the toxin polypeptide. Anti-toxin antibody response was found as early as 26 days after the initiation of therapy and lasted as long as 179 days of observation. Further studies indicate that the presence of anti-toxin antibodies blocked completely the inhibitory ability of the respective immunotoxin in vitro. Anti-ricin antibodies neutralized the activity of 31-E6:ricin A chain conjugate but not OX-7:PAP immunotoxin, and similarly, anti-PAP antibodies inhibited the activity of the latter and not the activity of 31-E6:ricin A chain conjugate. These observations indicate that the use of alternate immunotoxins having an immunologically distinct toxin polypeptide may be necessary for tumor therapy during relapse, as exposure to the conjugates results in the formation of specific neutralizing anti-toxin antibodies. The anti-toxin antibodies did not prevent the binding of immunotoxin to target cells. Nevertheless, preincubation of conjugate with anti-toxin antibodies specifically blocked the respective conjugate-induced inhibition of polyuridylic acid translation in a cell-free assay system.
Investigation of Cross-Coupling in Piezoelectric Transducer Arrays and Correction (2019)

Cross-coupling in piezoelectric transducer arrays is an undesirable phenomenon which decreases the performance of these devices. Indeed, when one element of a transducer is driven, it generates parasitic displacement fields at the radiating surfaces of the neighboring elements, which changes the directivity of the array. The objective of this paper is to investigate the cross-coupling effects on the piezoelectric transducer arrays performance and to propose solutions to reduce this parasitic phenomenon. In this context, it is demonstrated that a filling material having high mechanical losses contributes to the reduction of cross-coupling. In addition to this, a procedure of active cancellation of cross-coupling is successfully tested in the case of two transducer arrays vibrating in the transverse mode for the first prototype and thickness mode for the second one. Finally, the ability of the method is demonstrated even when the displacement at the radiating surface of the transducer array is not uniform.
Angiotensin-(1-7)-induced plasticity changes in the lateral amygdala are mediated by COX-2 and NO (2007)

It is known from studies outside the brain that upon binding to its receptor, angiotensin-(1-7) elicits the release of prostanoids and nitric oxide (NO). Cyclooxygenase (COX) is a key enzyme that converts arachidonic acid to prostaglandins. Since there are no data available so far on the role of COX-2 in the amygdala, in a first step we demonstrated that the selective COX-2 inhibitor NS-398 significantly reduced the probability of long-term potentiation (LTP) induction in the lateral nucleus of the amygdala. Similarly, in COX-2(-/-) mice, LTP induced by external capsule (EC) stimulation was impaired. Second, we evaluated the action of angiotensin-(1-7) in the amygdala. In wild-type mice, angiotensin-(1-7) increased LTP. This LTP-enhancing effect of Ang-(1-7) was not observed in COX-2(+/-) mice. However, in COX-2(-/-) mice, Ang-(1-7) caused an enhancement of LTP similar to that in wild-type mice. The NO synthetase inhibitor L-NAME blocked this angiotensin-(1-7)-induced increase in LTP in COX-2(-/-) mice. Low-frequency stimulation of external capsule fibers did not cause long-term depression (LTD) in drug-free and angiotensin-(1-7)-treated brain slices in wild-type mice. In contrast, in COX-2(-/-) mice, angiotensin-(1-7) caused stable LTD. Increasing NO concentration by the NO-donor SNAP also caused LTD in wild-type mice. Our study shows for the first time that LTP in the amygdala is dependent on COX-2 activity. Moreover, COX-2 is involved in the mediation of angiotensin-(1-7) effects on LTP. Finally, it is recognized that there is a molecular cross-talk between COX-2 and NO that may regulate synaptic plasticity.
A novel engineered VEGF blocker with an excellent pharmacokinetic profile and robust anti-tumor activity (2015)

HB-002.1 is a strong angiogenesis inhibitor that has the potential to be a novel promising drug for angiogenesis-related diseases such as tumor neoplasms and age-related macular degeneration.
Bacterial endotoxin : chemical, biological, and clinical aspects (1984)

Lipid A: Structure and Synthetic Approach Endotoxic Activities of Lipid A and Synthetic Analogues Action of Endotoxin on Tumors and Related Aspects Endotoxemia: Clinical Aspects Limulus Test, Endotoxin Standard Preparation.
A comparative evaluation of analgo‐sedative effects of oral dexmedetomidine and ketamine: a triple‐blind, randomized study (2014)

Given by oral route, the novel sedative dexmedetomidine provides dose-dependent effective analgo-sedation, comparable to ketamine, with less adverse effects.
Arthritis induced in rats with non‐immunogenic adjuvants as models for rheumatoid arthritis (2001)

Rat models are useful for studies of the pathogenesis of rheumatoid arthritis (RA) since rats are extraordinarily sensitive to induction of arthritis with adjuvants. Injection of not only the classical complete Freund's adjuvant but also mineral oil without mycobacteria and pure adjuvants such as pristane and squalene, induce severe arthritis in many rat strains. Models like pristane-induced arthritis in rats are optimal models for RA since they fulfill the RA criteria including a chronic relapsing disease course. Arthritogenic adjuvants like pristane, avridine, squalene and mineral oil are not immunogenic since they do not contain major histocompatibility complex (MHC) binding peptides. Nevertheless, the diseases are MHC-associated and dependent on the activation of alphabetaTCR (T-cell receptor)-expressing T cells. However, it has not been possible to link the immune response to joint antigens or other endogenous components although immunization with various cartilage proteins induce arthritis but with different pathogeneses. To unravel the mechanisms behind adjuvant-induced arthritis, a disease-oriented genetic approach is optimal. Several loci that control onset of arthritis, severity and chronicity of the disease have been identified in genetic crosses and most of these have been confirmed in congenic strains. In addition, many of these loci are found in other autoimmune models in the rat as well as associated with arthritis in mice and humans.
Improving monoclonal antibody pharmacokinetics via chemical modification. (1998)

The aim of radioimmunotherapy in treating solid tumors is to target tumor sites while sparing normal tissues. This can best be achieved by using a monoclonal antibody (MAb) with high tumor uptake and rapid clearance. Because MAbs are basic, positively charged proteins, and mammalian cells are negatively charged, the electrostatic interactions between the two can create higher levels of background binding resulting in low tumor to normal organ ratios. To overcome this effect, investigators have attempted to improve MAb clearance by using various methods such as secondary agents as well as chemical and charge modifications of the MAb itself. The use of a second agent to remove the MAb involves using a biotinylated MAb followed by treatments with a molecule like avidin. Charge modification can be accomplished by conjugating a chemical moiety with a positive, negative or neutral charge to residues exposed on the surface of MAbs. Experimental results demonstrate that the lowering of the isoelectric point by this method correlates with a decreased clearance time and improved tumor targeting. Altering the pharmacokinetic characteristics of intact MAbs with charge modification can improve their clearance times to rates similar to those of MAb fragments. Several groups have reported on the effects of chemical modification using molecules such as dextran, PEG, lactose and biotin. Some of these modified MAbs retain the antigen binding specificity of the parent molecule and have improved clearance characteristics from blood and other organs. Hence, these methods can be used to improve both the diagnostic and therapeutic potential of MAbs by improving the signal to noise ratio and the absolute tumor accretion of MAb, respectively.
Solid-phase polymerizations at high pressures (1970)

The following compounds have been found to polymerize spontaneously in the solid state at pressures in the range 10-50 kbar, at temperatures between 20 and 200°C: acrylamide, p-phenylstyrene, potassium p-styrenesulphonate, itaconic anhydride, maleic anhydride, maleimide, 1,2,3,6-tetrahydrophthalic acid, 1,2,3,6-tetrahydrophthalic anhydride, acenaphthylene, p-benzoquinone, N,N' -p-phenylene-dimaleimide, sulpholene, diphenylacetylene, 8-trioxan. The pressure-temperature requirements for polymerization have been determined in a high-pressure "squeezer" apparatus and in a diamond optical cell which permits infrared spectral analysis of a specimen while it is under compression. Apart from diphenylacetylene and trioxan, the compounds that polymerized were either monosubstituted ethylenes or cyclic 1,2-disubstituted ethylenes. Non-cyclic 1,2-disubstituted ethylenes and tri-substituted and tetra-substituted ethylenes failed to polymerize. There is evidence that shearing stresses played a part in some of the reactions. 1-Allyl-2-thiourea did not polymerize, but transformed from its stable crystal form I to the unstable modification 11.
Biomechanical Consequences of Replacement of the Anterior Cruciate Ligament with a Patellar Ligament Allograft. Part I (1996)

Nineteen fresh-frozen knee specimens from cadavera were tested for anterior-posterior laxity with 200 newtons of force applied to the tibia. A cylindrical cap of subchondral bone containing the tibial insertion of the anterior cruciate ligament was isolated with a coring cutter and was potted in acrylic. A thin wire was connected to the undersurface of the cap, and relative displacement between the cap and the tibia was measured with an isometer as the knee was extended. The cap of bone was connected to a load-cell that recorded force in the intact ligament during anterior-posterior testing with the tibia locked in neutral, internal rotation, and external rotation. The anterior cruciate ligament was then resected, and a femoral tunnel was drilled at the site where the isometer readings from the wire were the same as those obtained for the intact anterior cruciate ligament. A bone-patellar ligament-bone graft was used to reconstruct the anterior cruciate ligament, and the isometer measurements were repeated with the graft in place. The graft was pre-tensioned at 30 degrees of flexion to restore normal anterior-posterior laxity. Anterior-posterior laxity tests were repeated at this level of pre-tension (laxity-matched pre-tension) as well as at a level that was forty-five newtons greater (over-tension). The moment required to extend the knee was measured before and after insertion of the graft at both levels of pre-tension. When the tibia was locked in positions of internal and external rotation, the anterior-posterior laxities and the forces in the anterior cruciate ligament (generated by an anterior force applied to the tibia) were significantly less than the corresponding values with the tibia in neutral rotation at 20, 30, and 45 degrees of flexion (p < or = 0.05). Isometer readings for the intact anterior cruciate ligament indicated that the cap of bone retracted into the joint a mean and standard deviation of 3.1 +/- 0.8 millimeters as the knee was extended from 30 degrees of flexion to full extension. For each specimen, the isometer measurements for the trial wire and for the graft were within 1.5 millimeters of those for the intact anterior cruciate ligament. At laxity-matched pre-tension (mean, 28.2 +/- 16.8 newtons), the mean anterior-posterior laxities of the reconstructed knees were within 1.0 millimeter of the corresponding means for the intact knees between 0 and 45 degrees of flexion. Over-tensioning of the graft by forty-five newtons decreased the anterior-posterior laxity a mean of 1.2 millimeters at 30 degrees of flexion. Over-tensioning of the graft did not change the moment required to bring the knee to full extension.
Clay Functionalization and Organization for Delamination of the Silicate Tactoids in Poly(L‐lactide) Matrix (2005)

Abstract Summary: Three kinds of organoclay, i.e., Cloisite15A® (C15A), Cloisite20A® (C20A), and Cloisite30B® (C30B) were modified with silane to prepare twice functionalized organoclay (TFC). The pristine Cloisite® clays and the TFC were melt compounded with poly( L ‐lactide) (PLLA) and morphology of the composites was observed to elucidate the effects of the d 001 gallery distance, the epoxy content of TFC, and the compatibility between the organic ammonium surfactant and PLLA on the degree of exfoliation of the clay layers. Plots of I TFC / I Cloisite versus epoxy content for PLLA composites with (a) Cloisite15A® (C15A), (b) Cloisite20A® (C20A), (c) Cloisite30B® (C30B). magnified image Plots of I TFC / I Cloisite versus epoxy content for PLLA composites with (a) Cloisite15A® (C15A), (b) Cloisite20A® (C20A), (c) Cloisite30B® (C30B).
Antioxidants attenuate the plasma cytokine response to exercise in humans (2003)

Exercise increases plasma TNF-alpha, IL-1beta, and IL-6, yet the stimuli and sources of TNF-alpha and IL-1beta remain largely unknown. We tested the role of oxidative stress and the potential contribution of monocytes in this cytokine (especially IL-1beta) response in previously untrained individuals. Six healthy nonathletes performed two 45-min bicycle exercise sessions at 70% of Vo(2 max) before and after a combination of antioxidants (vitamins E, A, and C for 60 days; allopurinol for 15 days; and N-acetylcysteine for 3 days). Blood was drawn at baseline, end-exercise, and 30 and 120 min postexercise. Plasma cytokines were determined by ELISA and monocyte intracellular cytokine level by flow cytometry. Before antioxidants, TNF-alpha increased by 60%, IL-1beta by threefold, and IL-6 by sixfold secondary to exercise (P < 0.05). After antioxidants, plasma IL-1beta became undetectable, the TNF-alpha response to exercise was abolished, and the IL-6 response was significantly blunted (P < 0.05). Exercise did not increase the percentage of monocytes producing the cytokines or their mean fluorescence intensity. We conclude that in untrained humans oxidative stress is a major stimulus for exercise-induced cytokine production and that monocytes play no role in this process.
Crystal structure of core streptavidin determined from multiwavelength anomalous diffraction of synchrotron radiation. (1989)

A three-dimensional crystal structure of the biotin-binding core of streptavidin has been determined at 3.1-A resolution. The structure was analyzed from diffraction data measured at three wavelengths from a single crystal of the selenobiotinyl complex with streptavidin. Streptavidin is a tetramer with subunits arrayed in D2 symmetry. Each protomer is an 8-stranded beta-barrel with simple up-down topology. Biotin molecules are bound at one end of each barrel. This study demonstrates the effectiveness of multiwavelength anomalous diffraction (MAD) procedures for macromolecular crystallography and provides a basis for detailed study of biotin-avidin interactions.
Electrospray Quadrupole Mass Spectrometry Analysis of Model Oligonucleotides and Polymerase Chain Reaction Products:  Determination of Base Substitutions, Nucleotide Additions/Deletions, and Chemical Modifications (1999)

ESI FTICR mass spectrometry is the only technique currently used for accurate molecular weight analysis of PCR products above 100 bp in size. This is important in demonstrating the potential for MS in making major contributions in the molecular biology and genomics areas. In the near future, it is more likely that less expensive, more user friendly MS techniques will be used for high-throughput analyses (including MALDI TOF and ESI quadrupole). There have been numerous reports on the use of MALDI TOF. The current report is to the first to evaluate the use of ESI-quadrupole analysis of PCR products. Synthetic oligonucleotides (30 and 89 mers) and polymerase chain reaction products of varying molecular weight (62, 88, 89, and 114 bp) were analyzed by ESI using a quadrupole MS. The mass accuracy for nucleic acids in the 30-62 bp range was shown to allow determination of nucleotide substitutions and additions/deletions. For higher molecular weight PCR products (88-114 bp), the mass accuracy of ESI-MS distinguishes single or multiple nucleotide insertions/deletions. In addition, ESI quadrupole MS allows determination of molecular weight of both strands of higher molecular weight ds PCR products and can distinguish nucleotide modifications (e.g., with biotin). In conclusion, it is demonstrated that ESI-MS occupies an intermediate position (as compared to MALDI TOF and ESI FTICR) with regard to mass accuracy and resolution in analysis of nucleic acids.