gebhart/patrepeval huggingface dataset:
Development of Cleaning-in-Place Procedures for Protein A Chromatography Resins using Design of Experiments and High Throughput Screening Technologies (2008)

Robust and efficient cleaning procedures for protein A chromatography resins used for production of monoclonal antibody based biopharmaceuticals are crucial for safe and cost efficient processes. In this master thesis the effect of different cleaning regimes with respect to ligand stability of two protein A derived media, MabSelectTM and MabSelect SuReTM, has been investigated. A 96-well format has been used for preliminary screening of different cleaning agents, contact times and temperatures. NaCl as a ligand stabilizer during cleaning-in-place (CIP) was also included as a parameter. For optimal throughput and efficiency of screening, Rectangular Experimental Design for Multi-Unit Platforms; RED-MUP, and TECAN robotic platform have been utilized. For verification of screening, selected conditions were run in column format using the parallel chromatography system ÄKTAxpressTM. In the efficiency study, where a manual preparation of CIP solutions was compared with an automated mode performed in TECAN, the total process time ended up at eight hours versus three days respectively. However, the time measured included the learning process for the TECAN platform and for further preparations the automated mode is the superior choice. The study confirmed the higher alkaline stability of MabSelect SuRe compared to MabSelect. After exposure to 0.55 M NaOH during 24h MabSelect SuRe still retained 90% of the initial capacity. In contrast MabSelect had 60% of the initial binding capacity. When CIP with 10 mM NaOH was performed at 40 °C MabSelect reduced its capacity by half while MabSelect SuRe still had a binding capacity of 80%. The 96-well screening showed that an addition of NaCl during CIP had a significant positive effect on the stability of MabSelect, but needs to be verified on column format. The correlation between results from screening in 96-well filter plate and column format was good.
Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels (2013)

Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of adverse outcomes. These findings may inform the discussion about the potential risks of testosterone therapy.
A lymphocyte cell surface heat shock protein homologous to the endoplasmic reticulum chaperone, immunoglobulin heavy chain binding protein BIP (1997)

BE2 is a cell surface monomeric 78-kDa protein (BE2-78) expressed on the malignant lymphocytes of cutaneous T-cell lymphoma and adult T-cell leukemia, on some lymphocytes from patients with acquired immunodeficiency syndrome and on Epstein-Barr virus-transformed B cells. BE2-78 positivity of cutaneous T-cell lymphoma tumor cells is a useful diagnostic and prognostic determinant in evaluating patients with that disorder. The BE2-78 protein was isolated from Epstein Barr virus-transformed B cells, purified by 1- and 2-dimensional electrophoresis and then sequenced. The sequence of 4 isolated peptide fragments was highly homologous with the 78-kDa heat shock protein, BiP, an endoplasmic reticulum chaperone. The similarity between BiP and BE2-78 was supported by the demonstration that BE2-78, like BiP, avidly binds to ATP. However, polyclonal and monoclonal reagents that recognize cytoplasmic 70- and 78-kDa heat shock proteins do not detect the BE2-78 antigen on the cell surface of cutaneous T-cell lymphoma or Epstein Barr virus-transformed lymphocytes, and peptide mapping demonstrates sequence divergence, suggesting that either they are distinct or conformationally different molecules. Our results indicate that BE2-78 is a cell surface heat shock protein. The possibility that malignant or transformed lymphocytes may express cell surface molecules with the capacity to bind a spectrum of exogenous or endogenous peptides has potential implications for tumor immunology.
A new endoscopic technique to decompress lumbar nerve roots affected by spondylolysis (2003)

The authors describe a new endoscopic technique to decompress lumbar nerve roots affected by spondylolysis. Short-term clinical outcome was evaluated. Surgery-related indications were: 1) radiculopathy without low-back pain; 2) no spinal instability demonstrated on dynamic radiographs; and 3) age older than 40 years. Seven patients, four men and three women, fulfilled these criteria and underwent endoscopic decompressive surgery. Their mean age was 60.9 years (range 42-70 years). No subluxation was present in four patients, whereas Meyerding Grade I slippage was demonstrated in three. For endoscopic decompression, a skin incision of 16 to 18 mm in length was made, and fenestration was performed to identify the affected nerve root. The proximal stump of the ragged edge of the spondylotic lesion, and the fibrocartilaginous mass compressing the nerve root were removed. The follow-up period ranged from 6 to 22 months (mean 11.7 months). Clinical outcome was evaluated using Gill criteria; in three patients the outcome was excellent, and in four it was good. This new endoscopic technique was useful in the decompression of nerve roots affected by spondylolysis, the technique was minimally invasive, and the clinical results were acceptable.
Best of both worlds (2010)

Gmail's filing system for email conversations is based around labels, which are more flexible and powerful than folders. With its original user interface, many users did not discover labels, and wondered why Gmail had no folders. The Gmail team redesigned the user interface for labeling to make it more discoverable and understandable, and to add the most useful functionality of folders. The new design works for the simple use case (a conversation with only one label), while still making the more complex use case (multiple labels) easily available. It has been launched to millions of users worldwide and has resulted in much higher adoption of labels, especially by new users of Gmail.
CX, an algorithm that identifies protruding atoms in proteins (2002)

The algorithm is implemented in a standalone program written in C and its source is freely available at ftp.icgeb.trieste.it/pub/CX or on request from the authors.
Expression and Regulation of Latent TGF-β Binding Protein-1 Transcripts and Their Splice Variants in Human Glomerular Endothelial Cells (2005)

Latent transforming growth factor (TGF)-beta-binding protein (LTBP) is required for the assembly, secretion, matrix association, and activation of latent TGF-beta complex. To elucidate the cell specific expression of the genes of LTBP-1 and their splice variants and the factors that regulate the gene expression, we cultured primary human glomerular endothelial cells (HGEC) under different conditions. Basal expression of LTBP-1 mRNA was suppressed in HGEC compared to WI-38 human embryonic lung fibroblasts. High glucose, H(2)O(2), and TGF-beta1 upregulated and vascular endothelial growth factor (VEGF) further downregulated LTBP-1 mRNA in HGEC. RT-PCR with a primer set for LTBP-1S produced many clones but no clone was gained with a primer set for LTBP-1L. Of 12 clones selected randomly, Sca I mapping and DNA sequencing revealed that only one was LTBP-1S and all the others were LTBP-1Sdelta53. TGF-beta1, but not high glucose, H(2)O(2) or VEGF, tended to increase LTBP-1Sdelta53 mRNA. In conclusion, HGEC express LTBP-1 mRNA which is suppressed at basal state but upregulated by high glucose, H(2)O(2), and TGF-beta1 and downregulated by VEGF. Major splice variant of LTBP-1 in HGEC was LTBP-1S 53. Modification of LTBP-1S 53 gene in HGEC may abrogate fibrotic action of TGF-beta1 but this requires confirmation.
O cão que nem sempre late: o Grupo Globo e a cobertura das eleições presidenciais de 2014 e 1998 (2016)

Os estudos da mídia brasileira em períodos eleitorais têm consistentemente encontrado um viés contrapolíticos e partidos de esquerda, particularmente contra o Partido dos Trabalhadores. O presente trabalhoé uma contribuição a essa literatura. Trata-se de uma comparação entre as coberturas eleitorais do JornalNacional e das capas do jornal impresso O Globo, ambos pertencentes ao Grupo Globo durante o períodoeleitoral de 2014. Queremos, primeiramente, testar a hipótese da continuidade do comportamento dasmídias desta empresa. Uma vez confirmada essa hipótese, partiremos para o exame da hipótese do papelde “cão de guarda”. Para tal, comparamos os resultados das análises das eleições de 2014 e de 1998:duas campanhas para reeleição, com os mesmos partidos em competição, PT e PSDB, mas ocupandolugares opostos dos polos situação e oposição. Nossos resultados confirmam a tese da continuidade doviés antipetista e rejeitam o papel de cão de guarda. A metodologia utilizada para a análise das coberturasdas três eleições é a análise de valências das notícias.
The int-1 proto-oncogene is transcriptionally activated during neuroectodermal differentiation of P19 mouse embryonal carcinoma cells. (1989)

We have used the P19 line of mouse embryonal carcinoma (EC) cells to initiate studies on the putative role of the int-1 proto-oncogene during neuronal differentiation. P19 cells are induced to differentiate into neurons, astrocytes and fibroblast-like cells following exposure to retinoic acid (RA). Treatment of the same P19 cells with dimethyl sulfoxide (DMSO) leads to differentiation into mesodermal derivatives, including skeletal and cardiac muscle. Northern blot analysis showed that int-1 RNA was not present in the EC cells but appeared 48 h after RA exposure and could be detected for at least the next 8 days. No int-1 RNA was detected in P19 cells induced to differentiate with DMSO. Nuclear run-on transcription assays showed that int-1 expression in RA-treated P19 cells was induced at the transcriptional level. Immunofluorescent staining with an antibody directed against an int-1 peptide identified immunoreactive material in cytoplasmic granules of fibroblast-like cells in RA-treated P19 cultures. Thus the P19 cell line is a suitable experimental system to study int-1 gene expression and function during neuroectodermal development.
Purification and molecular cloning of prostacyclin-stimulating factor from serum-free conditioned medium of human diploid fibroblast cells (1994)

We attempted to identify the factor that stimulated prostacyclin (PGI2) production using conditioned medium from cultured human diploid fibroblast cells subjected to a series of purification steps using h.p.l.c. on DEAE-5PW, Heparin-5PW, Protein-Pak 300, and an insulin-like growth factor-1 ligand affinity column. The purified prostacyclin-stimulating factor (PSF) ran as a single band with a molecular mass of 31 kDa by SDS/PAGE. Analysis of the purified PSF by C4 reversed-phase h.p.l.c. showed a single sharp peak in 31% (v/v) acetonitrile. The material was purified 8000-fold with an overall yield of about 18%. The purified PSF stimulated PGI2 production by cultured bovine aortic endothelial cells at a concentration of about 10 ng/ml; maximal stimulation was achieved at a concentration of 25 ng/ml. A cDNA coding for PSF was cloned and sequenced, revealing an apparently novel protein with no obvious sequence similarity to known proteins.
Medium (DMEM/F12)‐containing chitosan hydrogel as adhesive and dressing in autologous skin grafts and accelerator in the healing process (2006)

Autologous skin grafts are considered necessary for the treatment of extensive skin defects. However, skin graft by suturing is a time-consuming medical handling and rather stressful event for recipients. To that end, tissue adhesives have been suggested in skin grafts. Chitosan hydrogel is well known as a wound dressing and tissue adhesive material showing biocompatibility, anti-infective activity, and the ability to accelerate wound healing. In this report, we evaluated the application of the chitosan hydrogel as a tissue adhesive in skin grafts. Although chitosan hydrogel shortened the operation time and resulted in a high graft absorption rate in comparison with suturing, wound epithelization was rather retarded. On the other hand, chitosan hydrogel was found more biocompatible than the commonly used tissue adhesive octyl-2-cyanoacrylate. When the chitosan hydrogel was premixed with a serum-free tissue culture medium DMEM/F12, it was found to easily degrade and promote wound epithelization. Histological examination revealed that the medium (DMEM/F12)-containing chitosan hydrogel was associated with the accumulation of polymorphonuclear leukocytes and neovascularization. In addition, immunohistochemical staining showed that the vascular endothelial growth factor (VEGF) was localized in the chitosan hydrogel degraded matrices. And infiltration of leukocytes determined the degradation activity with the D-glucose in the medium (DMEM/F12) suggested to play a central role in chitosan hydrogel degradation. Therefore, the medium (DMEM/F12)-containing chitosan hydrogel may become commonly accepted as a beneficial wound dressing and tissue adhesive in extensive wound management and skin grafts.
Development of an siRNA-based method for repressing specific genes in renal organ culture and its use to show that the Wt1 tumour suppressor is required for nephron differentiation (2003)

Wt1 is a tumour suppressor gene, mutation of which is a cause of Wilms' tumour, a childhood renal nephroblastoma. Wt1 is expressed in a rich pattern during renal development suggesting that it acts at three stages: determination of the kidney area, the differentiation of nephrons and maturation of glomeruli. Wt1-/- mice confirm that Wt1 is essential for the inception of kidney development; cells that ought to form kidneys die by apoptosis instead. Specific human WT1 mutations cause defects of glomerular maturation (Denys-Drash and Frasier syndromes), providing circumstantial evidence for action of Wt1 during glomerular maturation. There is, however, no genetic evidence for a function during nephron differentiation because this stage is never reached in Wt1-/- mice. We have therefore developed a novel technique, based on small interfering RNA (siRNA), to repress the expression of Wt1 and other specific genes at different stages of kidney development in culture. We find that early repression of Wt1 phenocopies the Wt1-/- mouse, but later repression prevents cells differentiating into nephrons and causes them instead to proliferate abnormally, possibly mimicking aspects of Wilms' tumour. In line with established hypotheses about genetic pathways that control kidney development, we find that repressing Pax2 using siRNAs represses Wt1 expression and blocks both bud growth and nephron differentiation, but that repressing Wnt4 blocks nephron differentiation without affecting Wt1 expression. As well as illuminating previously inaccessible aspects of Wt1 biology, our results suggest that siRNA in organ culture will be a powerful method for analyzing other developmental pathways and testing the effects of stage-specific loss of tumour suppressor genes.
Synthesis of Macroporous Minerals with Highly Ordered Three-Dimensional Arrays of Spheroidal Voids (1998)

Titania, zirconia, and alumina samples with periodic three-dimensional arrays of macropores were synthesized from the corresponding metal alkoxides, using latex spheres as templates. In a fast, single-step reaction, the monomeric alkoxide precursors permeate the array of bulk polystyrene spheres and condense in air at room temperature. Close packed, open-pore structures with 320- to 360-nanometer voids are obtained after calcination of the organic component at 575 degreesC. The examples presented demonstrate the compositional diversity possible with this technique. The resulting highly structured ceramics could have applications in areas ranging from quantum electronics to photocatalysis to battery materials.
The Thrombospondin Motif of Aggrecanase-1 (ADAMTS-4) Is Critical for Aggrecan Substrate Recognition and Cleavage (2000)

Aggrecanase-1 (ADAMTS-4) is a member of the a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) protein family that was recently identified. Aggrecanase-1 is one of two ADAMTS cartilage-degrading enzymes purified from interleukin-1-stimulated bovine nasal cartilage (Tortorella, M. D., Burn, T. C., Pratta, M. A. , Abbaszade, I., Hollis, J. M., Liu, R., Rosenfeld, S. A., Copeland, R. A., Decicco, C. P., Wynn, R., Rockwell, A., Yang, F., Duke, J. L., Solomon, K., George, H., Bruckner, R., Nagase, H., Itoh, Y., Ellis, D. M., Ross, H., Wiswall, B. H., Murphy, K., Hillman, M. C., Jr., Hollis, G. F., and Arner, E.C. (1999) Science 284, 1664-1666; 2 Abbaszade, I., Liu, R. Q., Yang, F., Rosenfeld, S. A., Ross, O. H., Link, J. R., Ellis, D. M., Tortorella, M. D., Pratta, M. A., Hollis, J. M., Wynn, R., Duke, J. L., George, H. J., Hillman, M. C., Jr., Murphy, K., Wiswall, B. H., Copeland, R. A., Decicco, C. P., Bruckner, R., Nagase, H., Itoh, Y., Newton, R. C., Magolda, R. L., Trzaskos, J. M., and Burn, T. C. (1999) J. Biol. Chem. 274, 23443-23450). The aggrecan products generated by this enzyme are found in cartilage cultures stimulated with cytokines and in synovial fluid from patients with arthritis, suggesting that aggrecanase-1 may be important in diseases involving cartilage destruction. Here we demonstrate that the thrombospondin type-1 (TSP-1) motif located within the C terminus of aggrecanase-1 binds to the glycosaminoglycans of aggrecan. Data from several studies indicate that this binding of aggrecanase-1 to aggrecan through the TSP-1 motif is necessary for enzymatic cleavage of aggrecan. 1) A truncated form of aggrecanase-1 lacking the TSP-1 motif was not effective in cleaving aggrecan. 2) Several peptides representing different regions of the TSP-1 motif effectively blocked aggrecanase-1 cleavage of aggrecan by preventing the enzyme from binding to the substrate. 3) Aggrecanase-1 was not effective in cleaving glycosaminoglycan-free aggrecan. Taken together, these data suggest that the TSP-1 motif of aggrecanase-1 is critical for substrate recognition and cleavage.
The Army Research Laboratory (ARL) synchronous impulse reconstruction (SIRE) forward-looking radar (2007)

The Army Research Laboratory (ARL) has designed and fabricated a forward-looking, impulse-based, ultra-wideband (UWB) imaging radar for detection of concealed targets. This system employs a physical array of 16 receive antennas to provide the necessary aperture for sufficient cross-range resolution in the forward-looking geometry. Each antenna feeds a base-band receiver/digitizer that integrates the data from a number of radar pulses before passing it on to the personal computer (PC) based operator's console and display. The innovative ARL receiver design uses commercially available integrated circuits to provide a low-cost, lightweight digitizing scheme with an effective sampling rate of approximately 8 GHz. The design is extensible to allow for growth in the number of channels used and improvements in integrated circuit performance to eventually meet the expected unmanned ground vehicle combat pace. Down-range resolution is provided by the bandwidth of the transmitted pulse which occupies 300-3000 MHz. Range coverage is designed to be 25 meters with an adjustable start point forward of the vehicle. Modeling studies have shown that a pair of transmitters situated at the two ends of the receive array provides best performance in cross-range resolution. Radar data is continuously collected so that a horizontal two-dimensional synthetic aperture is formed for 3-D image formation. This allows focusing of the data to yield estimates of target height as well as position to tag potential obstacles as being negative (e.g. holes, ditches) or positive (e.g. tree stumps). The forward motion also improves the cross range resolution to targets as their aspect changes.
Inhibition of metallo-beta-lactamases by a series of mercaptoacetic acid thiol ester derivatives (1997)

A series of mercaptoacetic acid thiol esters have been identified as metallo-beta-lactamase inhibitors. Electrospray mass spectrometry (ESMS) has shown that irreversible inhibition of the Bacillus cereus II metallo-beta-lactamase by SB214751, SB214752, and SB213079 was concomitant with a 90-Da increase in mass of the enzyme. Tryptic digestion of the B. cereus II inhibited with SB214751 illustrated that the peptide fragment, containing the only cysteine of the enzyme, had undergone a mass increment of 90 Da. It was further demonstrated that B. cereus II hydrolyzed this type of compound across the thiol ester bond to yield mercaptoacetic acid. Mercaptoacetic acid is the only molecular fragment common to SB214751, SB214752, and SB213079, and free mercaptoacetic acid does not bind covalently to B. cereus II. Therefore, it is concluded that these compounds inhibit B. cereus II by the mechanism-based delivery of mercaptoacetic acid, forming a disulfide linkage with the active sites cysteine (predicted mass shift = +90 Da) under the aerobic conditions of the assay. The different thiol esters examined had a broad range of potencies against the metallo-beta-lactamases tested. For example SB214751, SB214752, and SB213079 all had 50% inhibitory concentrations of < 10 and > 1,000 microM for the Stenotrophomonas maltophilia L-1 and Bacteroides fragilis CfiA enzymes, respectively. SB216968 was particularly active against the Aeromonas hydrophila CphA metallo-beta-lactamase and was found to be an uncompetitive inhibitor of this enzyme (Ki = 3.9 microM), whereas it exhibited irreversible inhibition of the L-1 enzyme. These observations with this series of compounds have revealed subtle differences between the active sites of different metallo-beta-lactamases. Finally, a novel application for isothermal titration calorimetry for assessing the zinc chelating activity of candidate inhibitors is also presented.
α‐Regioselective Aqueous Mukaiyama Aldol Reaction of 2‐(Trimethylsilyloxy)furan with Pyruvates (2016)

A procedure that enables access to α‐(hydroxyalkyl)butenolides from 2‐(trimethylsilyloxy)furan and keto esters with excellent regiocontrol is reported. Despite their synthetic significance, there is a general lack of catalytic methodology for the α‐regioselective Mukaiyama‐type aldol reaction of O ‐silylated dienolates. We demonstrate that the challenging competition between the α and γ positions of the nucleophilic dienolate can be controlled by the use of aqueous solvent. This phenomenon, which is observed for 2‐(trimethylsilyloxy)furan, can be further extended to the reaction of 2‐(trimethylsilyloxy)thiophene and, less efficiently, to 2‐(trimethylsilyloxy)pyrrole. Moreover, initial application of water‐compatible chiral zinc complexes composed of ( R , R )‐diphenylethylenediamine‐based ligands affords enantiomerically enriched α‐addition products in good yields (up to 72 %) and with good enantioselectivity (up to 55 % ee ).