gebhart/patrepeval huggingface dataset:
An anti-CD30 single-chain Fv selected by phage display and fused to Pseudomonas exotoxin A (Ki-4(scFv)-ETA’) is a potent immunotoxin against a Hodgkin-derived cell line (1999)

The human CD30 receptor is highly overexpressed on the surface of Hodgkin Reed-Sternberg cells and has been shown to be an excellent target for selective immunotherapy using monoclonal antibody-based agents such as immunotoxins. To construct a new recombinant immunotoxin for possible clinical use in patients with Hodgkin's lymphoma, we have chosen the murine anti-CD30 hybridoma Ki-4 to generate a high-affinity Ki-4 single-chain variable fragment (scFv). Hybridoma V-genes were polymerase chain reaction-amplified, assembled, cloned and expressed as a mini-library for display on filamentous phage. Functional Ki-4 scFv were obtained by selection of binding phage on the Hodgkin lymphoma-derived, CD30-expressing cell line L540Cy. The selected recombinant Ki-4 scFv was shown to specifically bind to an overlapping epitope on the CD30 antigen with binding kinetics similar to those of the original antibody. The Ki-4 scFv was subsequently fused to a deletion mutant of Pseudomonas exotoxin A (ETA'). The resulting immunotoxin Ki-4(scFv)-ETA' specifically binds to CD30+ L540Cy cells and inhibits the protein synthesis by 50% at a concentration (IC50) of 43 pM. This recombinant immunotoxin is a promising candidate for further clinical evaluation in patients with Hodgkin's lymphoma or other CD30+ malignancies.
Improving Power Output for Vibration-Based Energy Scavengers (2005)

Pervasive networks of wireless sensor and communication nodes have the potential to significantly impact society and create large market opportunities. For such networks to achieve their full potential, however, we must develop practical solutions for self-powering these autonomous electronic devices. We've modeled, designed, and built small cantilever-based devices using piezoelectric materials that can scavenge power from low-level ambient vibration sources. Given appropriate power conditioning and capacitive storage, the resulting power source is sufficient to support networks of ultra-low-power, peer-to-peer wireless nodes. These devices have a fixed geometry and - to maximize power output - we've individually designed them to operate as close as possible to the frequency of the driving surface on which they're mounted. In this paper, we describe these devices and present some new designs that can be tuned to the frequency of the host surface, thereby expanding the method's flexibility. We also discuss piezoelectric designs that use new geometries, some of which are microscale (approximately hundreds of microns).
Densification, Microstructure, and Behavior of Hydroxyapatite Ceramics Sintered by Using Spark Plasma Sintering (2008)

This paper discusses the dependence of the mechanical properties and microstructure of sintered hydroxyapatite (HA) on the sintering temperature and pressure. A set of specimens was prepared from as-received HA powder and sintered by using a spark plasma sintering (SPS) process. The sintering pressures were set at 22.3MPa, 44.6MPa, and 66.9MPa, and sintering was performed in the temperature range from 800°Cto1000°C at each pressure. Mechanisms underlying the interrelated temperature-mechanical and pressure-mechanical properties of dense HA were investigated. The effects of temperature and pressure on the flexural strength, Young’s modulus, fracture toughness, relative density, activation energy, phase stability, and microstructure were assessed. The relative density and grain size increased with an increase in the temperature. The flexural strength and Young’s modulus increased with an increase in the temperature, giving maximum values of 131.5MPa and 75.6GPa, respectively, at a critical temperature of 950°C and 44.6MPa, and the fracture toughness was 1.4MPam1∕2 at 1000°C at 44.6MPa. Increasing the sintering pressure led to acceleration of the densification of HA.
Discovery of Potent Nonpeptide Inhibitors of Stromelysin Using SAR by NMR (1997)

With the use of an NMR-based method, potent (IC50 < 25 nM) nonpeptide inhibitors of the matrix metalloproteinase stromelysin (MMP-3) were discovered. The method, called SAR by NMR (for structure−activity relationships by nuclear magnetic resonance), involves the identification, optimization, and linking of compounds that bind to proximal sites on a protein. Using this technique, two ligands that bind weakly to stromelysin (acetohydroxamic acid, KD = 17 mM; 3-(cyanomethyl)-4‘-hydroxybiphenyl, KD = 0.02 mM) were identified. On the basis of NMR-derived structural information, the two fragments were connected to produce a 15 nM inhibitor of this enzyme. This compound was rapidly discovered (less than 6 months) and required only a minimal amount of chemical synthesis. These studies indicate that the SAR by NMR method can be effectively applied to enzymes to yield potent lead inhibitorsan important part of the drug discovery process.
Bevacizumab plus irinotecan/5-FU/leucovorin for treatment of metastatic colorectal cancer results in survival benefit in all pre-specified patient subgroups (2004)

3617 Background. Bevacizumab [Avastin (BV)], a recombinant, humanized monoclonal antibody against VEGF, has demonstrated efficacy and safety when added to irinotecan/5-fluorouracil/leucovorin (IFL) chemotherapy as first-line therapy for metastatic colorectal cancer (CRC). The results of the primary analysis of a randomized phase III trial demonstrated that the addition of BV to IFL resulted in significant improvement in survival compared with IFL alone (p=0.00004; median survival increased from 15.61 to 20.34 months). Additional sub-group analyses were performed to evaluate the effects of baseline risk factors on survival. Methods. The effects of demographic and baseline prognostic characteristics and selected baseline laboratory values on duration of survival, PFS, and objective response rate were examined. Patient characteristics included baseline ECOG performance status, number of organ sites with metastases, site of primary tumor, age, sex, race, prior adjuvant chemotherapy, prior radiotherapy, duration of metastatic disease, years since diagnosis of CRC, baseline sum of longest diameters of target lesions, baseline levels of albumin, alkaline phosphatase, and LDH. Descriptive summaries of duration of survival and PFS were produced for each level of the categorical variables listed above for each treatment arm. These descriptive summaries consisted of the hazard ratio from unstratified Cox regression and Kaplan-Meier estimates of median time to the event. Results. 815 patients were randomized to receive either IFL + placebo or IFL + BV. A survival benefit in the IFL/BV arm was seen across all patient subgroups compared with the IFL/placebo arm (see table). Conclusion. The addition of Bevacizumab to IFL chemotherapy results in prolonged survival in multiple sub-groups. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Genentech Genentech Genentech
Evaluation of the antitumor activity of gemcitabine (2',2'-difluoro-2'-deoxycytidine). (1990)

A new pyrimidine antimetabolite, 2',2'-difluorodeoxycytidine, Gemcitabine (LY188011, dFdCyd) has been synthesized and evaluated in experimental tumor models. dFdCyd is a very potent and specific deoxycytidine analogue. The concentration required for 50% inhibition of growth is 1 ng/ml in the CCRF-CEM human leukemia cell culture assay. Concurrent addition of deoxycytidine to the cell culture system provides about a 1000-fold decrease in biological activity. The inhibition of growth of human leukemia cells in culture led to the in vivo evaluation of this compound as a potential oncolytic agent. Maximal activity in vivo was seen with dFdCyd when administered on an every third day schedule. 1-beta-D-Arabinofuranosylcytosine, administered on a daily for 10-day schedule, was directly compared to dFdCyd in this evaluation. dFdCyd demonstrated good to excellent antitumor activity in eight of the eight murine tumor models evaluated. 1-beta-D-Arabinofuranosylcytosine was substantially less active or had no activity in these same tumor models. This in vivo activity against murine solid tumors supports the conclusion that dFdCyd is an excellent candidate for clinical trials in the treatment of cancer.
Processen med utformning av nationella farmakologiska riktlinjer i samband med tonsilloperation (2013)

Processen med utformning av nationella farmakologiska riktlinjer i samband med tonsilloperation
Repression of Transcription by WT1-BASP1 Requires the Myristoylation of BASP1 and the PIP2-Dependent Recruitment of Histone Deacetylase (2012)

The Wilms' tumor 1 protein WT1 is a transcriptional regulator that is involved in cell growth and differentiation. The transcriptional corepressor BASP1 interacts with WT1 and converts WT1 from a transcriptional activator to a repressor. Here, we demonstrate that the N-terminal myristoylation of BASP1 is required in order to elicit transcriptional repression at WT1 target genes. We show that myristoylated BASP1 binds to nuclear PIP2, which leads to the recruitment of PIP2 to the promoter regions of WT1-dependent target genes. BASP1's myristoylation and association with PIP2 are required for the interaction of BASP1 with HDAC1, which mediates the recruitment of HDAC1 to the promoter and elicits transcriptional repression. Our findings uncover a role for myristoylation in transcription, as well as a critical function for PIP2 in gene-specific transcriptional repression through the recruitment of histone deacetylase.
Neutrophil margination, sequestration, and emigration in the lungs of L-selectin-deficient mice. (1997)

These studies tested the hypothesis that L-selectin plays a role in neutrophil traffic in the lungs, particularly in neutrophil margination, sequestration, and emigration, using L-selectin-deficient mice. No defect in neutrophil margination within either capillaries or arterioles and venules was observed in uninflamed lungs of L-selectin-deficient mice. The initial rapid sequestration of neutrophils within the pulmonary capillaries 1 min after intravascular injection of complement fragments was not prevented. In contrast, L-selectin did contribute to the prolonged neutrophil sequestration (> or = 5 min). Interestingly, neutrophil accumulation within noncapillary microvessels required L-selectin at both 1 and 5 min after complement injection. During bacterial pneumonias, L-selectin played a role in neutrophil accumulation within noncapillary microvessels in response to either Escherichia coli or Streptococcus pneumoniae and within capillaries in response to E. coli but not S. pneumoniae. However, L-selectin was not required for emigration of neutrophils or edema in response to either organism. These studies demonstrate a role for L-selectin in the prolonged sequestration of neutrophils in response to intravascular complement fragments, in the intracapillary accumulation of neutrophils during E. coli-induced pneumonia, and in the accumulation of neutrophils within noncapillary microvessels when induced by either intravascular complement fragments or
C5L2 Is a Functional Receptor for Acylation-stimulating Protein (2005)

C5L2 binds acylation-stimulating protein (ASP) with high affinity and is expressed in ASP-responsive cells. Functionality of C5L2 has not yet been demonstrated. Here we show that C5L2 is expressed in human subcutaneous and omental adipose tissue in both preadipocytes and adipocytes. In mice, C5L2 is expressed in all adipose tissues, at levels comparable with other tissues. Stable transfection of human C5L2 cDNA into HEK293 cells results in ASP stimulation of triglyceride synthesis (TGS) (193 +/- 33%, 5 microM ASP, p < 0.001, where basal = 100%) and glucose transport (168 +/- 21%, 10 microM ASP, p < 0.001). C3a similarly stimulates TGS (163 +/- 12%, p < 0.001), but C5a and C5a des-Arg have no effect. The ASP mechanism is to increase Vmax of glucose transport (149%) and triglyceride (TG) synthesis activity (165%) through increased diacylglycerolacyltransferase activity (200%). Antisense oligonucleotide down-regulation of C5L2 in human skin fibroblasts decreases cell surface C5L2 (down to 54 +/- 4% of control, p < 0.001, comparable with nonimmune background). ASP response is coordinately lost (basal TGS = 14.6 +/- 1.6, with ASP = 21.0 +/- 1.4 (144%), with ASP + oligonucleotides = 11.0 +/- 0.8 pmol of TG/mg of cell protein, p < 0.001). In mouse 3T3-L1 preadipocytes, antisense oligonucleotides decrease C5L2 expression to 69.5 +/- 0.5% of control, p < 0.001 (comparable with nonimmune) with a loss of ASP stimulation (basal TGS = 22.4 +/- 2.9, with ASP = 39.6 +/- 8.8 (177%), with ASP + oligonucleotides = 25.3 +/- 3.0 pmol of TG/mg of cell protein, p < 0.001). C5L2 down-regulation and decreased ASP response correlate (r = 0.761, p < 0.0001 for HSF and r = 0.451, p < 0.05 for 3T3-L1). In HEK-hC5L2 expressing fluorescently tagged beta-arrestin, ASP induced beta-arrestin translocation to the plasma membrane and formation of endocytic complexes concurrently with increased phosphorylation of C5L2. This is the first demonstration that C5L2 is a functional receptor, mediating ASP triglyceride stimulation.
Fibronectin binding to a Streptococcus pyogenes strain (1984)

In previous studies, Staphylococcus aureus has been shown to bind fibronectin (P. Kuusela, Nature (London) 276:718-720, 1978), an interaction that may be important in bacterial attachment and opsonization. Recently some strains of streptococci of serological groups A, C, and G were also found to bind fibronectin. The binding to one selected strain of Streptococcus pyogenes has been characterized here. The binding of [125I]fibronectin to streptococcal cells resembles that to staphylococcal cells and was found to be time dependent, functionally irreversible, and specific in the sense that unlabeled proteins other than fibronectin did not block binding. Bacteria incubated with proteases largely lost their ability to bind fibronectin, and material released from the streptococci by a brief trypsin digestion contained active fibronectin receptors. This material inhibited the binding of [125I]fibronectin to the streptococci. The inhibitory activity was adsorbed on a column of fibronectin-Sepharose but not on a column of unsubstituted Sepharose 4B or egg albumin Sepharose. The receptor appeared to be a protein nature since the inhibitory activity of the trypsinate was destroyed by papain and was not absorbed on a column containing monoclonal antibodies directed against lipoteichoic acid bound to protein A-Sepharose. Binding sites in fibronectin for streptococci and staphylococci, respectively, were localized by analyzing the ability of isolated fragments to inhibit [125I]fibronectin binding to bacteria and by adsorbing 125I-labeled tryptic fragments with staphylococcal and streptococcal cells. Both species of bacteria appeared to preferentially bind a fragment (Mr = approximately 25,000) originating from the N-terminal region of the protein. In addition, streptococci also bound a slightly smaller fragment (Mr = approximately 23,000). Fibronectin receptors solubilized from either streptococci or staphylococci inhibited the binding of fibronectin to both species of bacteria.
ChemInform Abstract: CHARACTERIZATION OF SUPPORTED MOLYBDATE CATALYSTS DURING PREPARATION USING LASER RAMAN SPECTROSCOPY (1980)

Abstract Co‐Mo‐Hydrodesulfurierungskatalysatoren werden durch Imprägnieren von 7‐Al 2 O 3 ‐, SiO 2 ‐ oder α‐Al 2 O 3 ‐Trägern mit (NH4)5Mo‐,O24‐H2O‐ und Co(NO 3 ) 2 ·6H 2 O‐Lösungen und Trocknung sowie Calcinierung hergestellt und Änderungen der Herstellungsbedingungen wie Beladung, Imprägnierungsreihenfolge, pH der Imprägnierungslösungen sowie Trocknungs‐ und Calcinierungsbedingungen Laser‐Raman‐spektroskopisch in situ untersucht.
Minimizing the communication cost for continuous skyline maintenance (2009)

Existing work in the skyline literature focuses on optimizing the processing cost. This paper aims at minimization of the communication overhead in client-server architectures, where a server continuously maintains the skyline of dynamic objects. Our first contribution is a Filter method that avoids transmission of updates from objects that cannot influence the skyline. Specifically, each object is assigned a filter so that it needs to issue an update only if it violates its filter. Filter achieves significant savings over the naive approach of transmitting all updates. Going one step further, we introduce the concept of frequent skyline query over a sliding window(FSQW). The motivation is that snapshot skylines are not very useful in streaming environments because they keep changing over time. Instead, FSQW reports the objects that appear in the skylines of at least θ ⋅ s of the s most recent timestamps (0 < θ ≤ 1). Filter can be easily adapted to FSQW processing, however, with potentially high overhead for large and frequently updated datasets. To further reduce the communication cost, we propose a Sampling method, which returns approximate FSQW results without computing each snapshot skyline. Finally, we integrate Filter and Sampling in a Hybrid approach that combines their individual advantages.
Recent Developments in the Culture and Regeneration of Plant Protoplasts (1983)

During the last fifteen years, workers from various disciplines of plant biology have recognized the potential which protoplasts offer as an experimental system. Currently, such isolated cells see application in basic morphological and physiological studies, in plant propagation, and in the production of somatic hybrids, cybrids, and genetically transformed cells and plants. Fundamental to all these approaches is the requirement to obtain consistently high yields of viable protoplasts, which, in most long-term investigations should be capable of wall regeneration, division, and preferably plant regeneration. Although many aspects of basic protoplast technology have been reviewed at length (Davey and Kumar, 1983), a fully comprehensive discussion of this field is difficult, and probably impossible, to achieve.
Phase II Trial of Doxorubicin and Docetaxel Plus Granulocyte Colony-Stimulating Factor in Metastatic Breast Cancer: Eastern Cooperative Oncology Group Study E1196 (2000)

PURPOSE: The purpose of this multi-institutional phase II trial was to evaluate the efficacy and toxicity of doxorubicin and docetaxel plus granulocyte colony-stimulating factor (G-CSF) in patients with metastatic breast cancer. The primary objective was to determine whether the combination produced a response rate of at least 50%. PATIENTS AND METHODS: Fifty-four patients with metastatic breast cancer received doxorubicin (60 mg/m 2 by intravenous [IV] injection) followed 1 hour later by docetaxel (60 mg/m 2 by IV infusion over 1 hour) every 3 weeks for up to eight cycles. All patients also received G-CSF. RESULTS: Objective response occurred in 29 (57%) of 51 eligible patients (95% confidence interval [CI], 42% to 70%), including three patients who had a complete response (6%; 95% CI, 1% to 16%). The median response duration was 7 months (95% CI, 6.0 to 15.0 months), median time to treatment failure was 7.6 months (95% CI, 6.2 to 9.9 months), and the median survival was 27.5 months (95% CI, 21.5 months to upper limit not reached). The median cumulative doxorubicin dose was 395 mg/m 2 (range, 60 to 480 mg/m 2 ). Fifteen patients (28%) were documented to have a decrease in the left ventricular ejection fraction below normal, and three patients (6%; 95% CI, 1% to 15%) developed congestive heart failure. CONCLUSION: Using criteria that we had defined a priori, the doxorubicin-docetaxel regimen as used in this study was sufficiently active and tolerable to justify a phase III comparison with doxorubicin-cyclophosphamide in early-stage breast cancer.
Evolutionary families of peptidases (1993)

The available amino acid sequences of peptidases have been examined, and the enzymes have been allocated to evolutionary families. Some of the families can be grouped together in 'clans' that show signs of distant relationship, but nevertheless, it appears that there may be as many as 60 evolutionary lines of peptidases with separate origins. Some of these contain members with quite diverse peptidase activities, and yet there are some striking examples of convergence. We suggest that the classification by families could be used as an extension of the current classification by catalytic type.
Proteasome Inhibition as a New Therapeutic Principle in Hematological Malignancies (2006)

The intracellular concentration of proteins in both normal and tumor cells are regulated by the balance between the rates of protein synthesis vs. degradation. The ubiquitin-proteasome pathway is the main intracellular cascade for controlled degradation of proteins and has attracted in recent years major interest not only because of its biochemical complexity and the intricate regulation of its function, but also because diverse cell cycle regulators and modulators of apoptosis are subject to regulation by proteasome function, and can therefore be significantly affected by small molecule inhibitors of the proteolytic activity of the proteasome. In fact, bortezomib, the prototypic member of this class of agents, was recently approved by the U.S. Food and Drug Administration for the treatment of advanced multiple myeloma patients. This review article focuses on the exciting recent progress in the use of proteasome inhibitors, with emphasis on the bench-to-bedside research effort which provided the foundation for clinical development of bortezomib for the treatment of multiple myeloma, as well as other hematologic malignancies, such as mantle cell lymphoma.
Can we alter survival in patients with congestive heart failure? (1992)

<h3>Objective.</h3> —To assess the efficacy of pharmacologic therapy in improving survival in patients with congestive heart failure (CHF) in the context of recent investigational studies having mortality as an end point. <h3>Data Sources.</h3> —Data were obtained from English-language articles that reported both randomized and retrospective studies assessing the efficacy of pharmacologic therapy in the treatment of patients with CHF. The review included articles indexed under the terms<i>congestive heart failure and drug therapy</i>in the National Library of Medicine's MEDLINE database. <h3>Study Selection.</h3> —Studies selected for detailed review were those having mortality as a primary or secondary end point. <h3>Data Extraction.</h3> —Guidelines for assessing data quality and validity included study size, double-blind and randomized design, the number of end points, the sensitivity and specificity of objective measurements, and the validity of the statistical analysis. <h3>Data Synthesis.</h3> —Review of the existing literature demonstrates that pharmacologic agents that improve resting hemodynamics or exercise duration in patients with CHF may not necessarily prolong survival. However, recent studies demonstrate that angiotensin-converting enzyme inhibitors prolong survival in patients with symptomatic CHF, while at the same time improving exercise capacity and left ventricular performance. Although less well tolerated, the combination of hydralazine hydrochloride and isosorbide dinitrate therapy also improves survival, but to a lesser degree. New agents show promise, but definitive assessment requires the results of large, randomized and double-blind studies having mortality as an end point. <h3>Conclusions.</h3> —Mortality is an important end point in assessing the efficacy of drugs for the treatment of CHF. (<i>JAMA</i>. 1992;267:1956-1961)