gebhart/patrepeval huggingface dataset:
Erk Is Essential for Growth, Differentiation, Integrin Expression, and Cell Function in Human Osteoblastic Cells (2001)

Extracellular signal-regulated kinases (Erks), members of the mitogen-activated protein kinase superfamily, play an important role in cell proliferation and differentiation. In this study we employed a dominant negative approach to determine the role of Erks in the regulation of human osteoblastic cell function. Human osteoblastic cells were transduced with a pseudotyped retrovirus encoding either a mutated Erk1 protein with a dominant negative action against both Erk1 and Erk2 (Erk1DN cells) or the LacZ protein (LacZ cells) as a control. Both basal and growth factor-stimulated MAPK activity and cell proliferation were inhibited in Erk1DN cells. Expression of Erk1DN protein suppressed both osteoblast differentiation and matrix mineralization by decreasing alkaline phosphatase activity and the deposition of bone matrix proteins. Cell adhesion to collagen, osteopontin, and vitronectin was decreased in Erk1DN cells as compared with LacZ cells. Cell spreading and migration on these matrices were also inhibited. In Erk1DN cells, expression of alphabeta(1), alpha(v)beta(3), and alpha(v)beta(5) integrins on the surface was decreased. Metabolic labeling indicated that the synthesis of these integrins was inhibited in Erk1DN cells. These data suggest that Erks are not only essential for the growth and differentiation of osteoblasts but also are important for osteoblast adhesion, spreading, migration, and integrin expression.
Experimental neurobiology of central nervous system trauma. (1993)

Traumatic injuries to the brain or spinal cord cause irreversible tissue damage by at least three mechanisms: through consequences of mechanical disruption of neurons or their projections; through biochemical or metabolic changes that are initiated by the trauma; and through reactive inflammatory or gliotic changes. During the past decade, considerable data have been accumulated regarding cellular and biochemical events associated with posttraumatic tissue damage. This has led to the application of pharmacological strategies to limit secondary injury and subsequent neurological deficits. Such research has resulted in the first effective treatment of human spinal cord injury, with other promising treatments in late preclinical or early clinical development.
Introduction (1977)

It is a useful first stage in a market research project to decide what it is that you are trying to do, so that at the end you can decide whether you have done it successfully. The same principle can be applied to writing a book, and this book will therefore start with three definitions, namely: what is meant by market research; what sort of reader the book is aimed at; what the reader should be able to do in the field of market research, by reference to this book.
Cis-acting determinants of asymmetric, cytoplasmic RNA transport (2007)

Asymmetric subcellular distribution of RNA is used by many organisms to establish cell polarity, differences in cell fate, or to sequester protein activity. Accurate localization of RNA requires specific sequence and/or structural elements in the localized RNA, as well as proteins that recognize these elements and link the RNA to the appropriate molecular motors. Recent advances in biochemistry, molecular biology, and cell imaging have enabled the identification of many RNA localization elements, or "zipcodes," from a variety of systems. This review focuses on the mechanisms by which various zipcodes direct RNA transport and on the known sequence/structural requirements for their recognition by transport complexes. Computational and experimental methods for predicting and identifying zipcodes are also discussed.
Conserved catalytic machinery and the prediction of a common fold for several families of glycosyl hydrolases. (1995)

The regions surrounding the catalytic amino acids previously identified in a few "retaining" O-glycosyl hydrolases (EC 3.2.1) have been analyzed by hydrophobic cluster analysis and have been used to define sequence motifs. These motifs have been found in more than 150 glycosyl hydrolase sequences representing at least eight established protein families that act on a large variety of substrates. This allows the localization and the precise role of the catalytic residues (nucleophile and acid catalyst) to be predicted for each of these enzymes, including several lysosomal glycosidases. An identical arrangement of the catalytic nucleophile was also found for S-glycosyl hydrolases (myrosinases; EC 3.2.3.1) for which the acid catalyst is lacking. A (beta/alpha)8 barrel structure has been reported for two of the eight families of proteins that have been grouped. It is suggested that the six other families also share this fold at their catalytic domain. These enzymes illustrate how evolutionary events led to a wide diversification of substrate specificity with a similar disposition of identical catalytic residues onto the same ancestral (beta/alpha)8 barrel structure.
Integrating alternative splicing detection into gene prediction (2005)

This automatic combination of experimental data analysis and ab initio gene finding offers an ideal integration of alternatively spliced gene prediction inside a single annotation pipeline.
Daedalus: a robust, turnkey platform for rapid production of decigram quantities of active recombinant proteins in human cell lines using novel lentiviral vectors (2011)

A key challenge for the academic and biopharmaceutical communities is the rapid and scalable production of recombinant proteins for supporting downstream applications ranging from therapeutic trials to structural genomics efforts. Here, we describe a novel system for the production of recombinant mammalian proteins, including immune receptors, cytokines and antibodies, in a human cell line culture system, often requiring <3 weeks to achieve stable, high-level expression: Daedalus. The inclusion of minimized ubiquitous chromatin opening elements in the transduction vectors is key for preventing genomic silencing and maintaining the stability of decigram levels of expression. This system can bypass the tedious and time-consuming steps of conventional protein production methods by employing the secretion pathway of serum-free adapted human suspension cell lines, such as 293 Freestyle. Using optimized lentiviral vectors, yields of 20-100 mg/l of correctly folded and post-translationally modified, endotoxin-free protein of up to ~70 kDa in size, can be achieved in conventional, small-scale (100 ml) culture. At these yields, most proteins can be purified using a single size-exclusion chromatography step, immediately appropriate for use in structural, biophysical or therapeutic applications.
Synthesis, antilipidemic and platelet antiaggregatory activity of 2-aminobenzimidazole amide derivatives. (1989)

The synthesis and preliminary pharmacological evaluation of 2-aminobenzimidazole amide derivatives are reported. None of these compounds showed antilipidemic or platelet antiaggregatory activity comparable to that of drugs used in therapy.
Controlling Annual Bluegrass (Poa annua L.) Summer Patch Disease with Faeriefungin (1993)

Faeriefungin, an antibiotic produced by the actinomycete Streptomyces griseus var. autotrophicus MSU-32058/ATCC 53668, was tested in field trials on golf course fairways to determine if it could control annual bluegrass (Poa annua L.) summer patch effectively. Test sites with a history of severe summer patch outbreaks caused by Magnaporthe poae Landschoot and Jackson were chosen for study. Faeriefungin, when applied as a drench at 0.74 kg·ha -1 , effectively controlled summer patch and was not significantly different than the fungicide fenarimol in three of four field trials. Faeriefungin may be an alternative to chemically controlling summer patch disease.
Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus. (1988)

Single-copy sequences can be enzymatically amplified from genomic DNA by the polymerase chain reaction. By using unequal molar amounts of the two amplification primers, it is possible in a single step to amplify a single-copy gene and produce an excess of single-stranded DNA of a chosen strand for direct sequencing or for use as a hybridization probe. Further, individual alleles in a heterozygote can be sequenced directly by using allele-specific oligonucleotides either in the amplification reaction or as sequencing primers. By using these methods, we have studied the allelic diversity at the HLA-DQA locus and its association with the serologically defined HLA-DR and -DQ types. This analysis has revealed a total of eight alleles and three additional haplotypes. This procedure has wide applications in screening for mutations in human genes and facilitates the linking of enzymatic amplification of genes to automated sequencing.
A critical role of TRPM channel‐kinase for human magnesium transport (2005)

Hereditary disorders of magnesium homeostasis comprise a heterogenous group of diseases mainly affecting the renal conservation of magnesium. In the past few years, genetic studies in affected individuals disclosed the first molecular components of epithelial magnesium transport: the tight junction protein paracellin-1 (claudin-16) was discovered as a key player in paracellular magnesium and calcium reabsorption in the thick ascending limb of Henle's loop and the gamma-subunit was identified as a component of renal Na+ -K+ -ATPase critical for transcellular magnesium reabsorption in the distal convoluted tubule. However, the molecular identity of proteins directly involved in cellular magnesium transport remained largely unknown until a series of recent studies highlighted the critical role of two members of the transient receptor potential (TRP) family, for body magnesium homeostasis. TRPM6 and TRPM7 belong to the melastatin-related TRPM subfamily of TRP channels whose eight members exhibit a significant diversity in domain structure as well as cation selectivity and activation mechanisms. Both proteins share the unique feature of an atypical kinase domain at their C-terminus for which they have been termed 'chanzymes' (channels plus enzymes). Whereas electrophysiological and biochemical analyses identified TRPM7 as an important player in cellular magnesium homeostasis, the critical role of TRPM6 for epithelial magnesium transport emerged from the discovery of loss-of-function mutations in patients with a severe form of hereditary hypomagnesaemia called primary hypomagnesaemia with secondary hypocalcaemia or HSH. The aim of this review is to summarize the data emerging from molecular genetic, biochemical and electrophysiological studies on these fascinating two new proteins combining ion channel and enzyme functions/properties.
Lack of Acidification in Mycobacterium Phagosomes Produced by Exclusion of the Vesicular Proton-ATPase (1994)

The success of Mycobacterium species as pathogens depends on their ability to maintain an infection inside the phagocytic vacuole of the macrophage. Although the bacteria are reported to modulate maturation of their intracellular vacuoles, the nature of such modifications is unknown. In this study, vacuoles formed around Mycobacterium avium failed to acidify below pH 6.3 to 6.5. Immunoelectron microscopy of infected macrophages and immunoblotting of isolated phagosomes showed that Mycobacterium vacuoles acquire the lysosomal membrane protein LAMP-1, but not the vesicular proton-adenosine triphosphatase (ATPase) responsible for phagosomal acidification. This suggests either a selective inhibition of fusion with proton-ATPase-containing vesicles or a rapid removal of the complex from Mycobacterium phagosomes.
Antiproliferatiye effects of recombinant human bone morphogenetic protein-2 on human tumor colony-forming units (1998)

Bone morphogenetic protein-2 (BMP-2) is a differentiation factor for normal osteoblasts. BMP-2 is structurally related to transforming growth factor-beta which inhibits cell proliferation and enhances apoptosis. A recent study has shown the presence of BMP-2 receptors on several cancer cell lines. In this study, we attempted to determine if recombinant human BMP-2 (rhBMP-2) can modulate the proliferation of human tumor colony-forming units taken from 113 patients. Tumor cells were cultured in soft agar and continuously exposed to three concentrations of rhBMP-2 (10, 100 and 1000 ng/ml) for 14 days in the capillary cloning system. There were 65 evaluable specimens, including 17 breast cancers, 15 ovarian cancers, 14 non-small cell lung cancers and five prostate cancers. Importantly, rhBMP-2 did not stimulate the tumor cell proliferation. A significant inhibition (50% or less survival of tumor colony-forming units) was seen in 16 of 65 specimens (24.6%) at 1000 ng/ml, including five of 14 non-small cell lung cancers, five of 17 breast tumors and two of 15 ovarian tumors. A concentration-response relationship was observed (p<0.001 by Mantel-extension test). The results of this study encourage further evaluation of the antiproliferative effects of rhBMP-2 against human cancers.
Indoor SDMA capacity using a smart antenna base station (2002)

In this paper we consider the capacity of a set of portable stations sharing a single indoor radio channel. The stations communicate with a base station which is equipped with a smart antenna operating in multibeam SDMA/FDMA mode, Both theoretical models and measured data from an experimental testbed are presented. The experimental system operates at 1.86 GHz and uses an 8 element circular antenna array. This system was built at the Communications Research Laboratory at McMaster University. The paper focuses on the static TDMA network capacity of this system. In particular, we explore the value of performing dynamic slot assignment when constructing the SDMA/TDMA frames. Slot assignment algorithms are introduced which are capable of increasing static system capacity under non-ideal propagation situations. In all cases, optimal SINR beamforming is used to determine the performance of the system. The results presented give clear insights into the network capacity possible in such systems and indicate the value of dynamic slot assignment under time division duplex operation. The results can also be used to motivate the design of media access protocols for these types of networks.
High‐frequency homologous recombination in plants mediated by zinc‐finger nucleases (2005)

Homologous recombination offers great promise for plant genome engineering. This promise has not been realized, however, because when DNA enters plant cells homologous recombination occurs infrequently and random integration predominates. Using a tobacco test system, we demonstrate that chromosome breaks created by zinc-finger nucleases greatly enhance the frequency of localized recombination. Homologous recombination was measured by restoring function to a defective GUS:NPTII reporter gene integrated at various chromosomal sites in 10 different transgenic tobacco lines. The reporter gene carried a recognition site for a zinc-finger nuclease, and protoplasts from each tobacco line were electroporated with both DNA encoding the nuclease and donor DNA to effect repair of the reporter. Homologous recombination occurred in more than 10% of the transformed protoplasts regardless of the reporter's chromosomal position. Approximately 20% of the GUS:NPTII reporter genes were repaired solely by homologous recombination, whereas the remainder had associated DNA insertions or deletions consistent with repair by both homologous recombination and non-homologous end joining. The DNA-binding domain encoded by zinc-finger nucleases can be engineered to recognize a variety of chromosomal target sequences. This flexibility, coupled with the enhancement in homologous recombination conferred by double-strand breaks, suggests that plant genome engineering through homologous recombination can now be reliably accomplished using zinc-finger nucleases.
Allergen impermeable covers appear clinically ineffective in the management of adult asthma patients (2003)

▴ Woodcock A, Forster L, Mattehews E, et al. Control of exposure to mite allergen and allergen-impermeable bed covers for adults with asthma. N Engl J Med2003;349:3[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] This double blind, randomised study compared allergen impermeable … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.aulast%253DLangford%26rft.auinit1%253DC.%2BA.%26rft.volume%253D349%26rft.issue%253D1%26rft.spage%253D3%26rft.epage%253D4%26rft.atitle%253DTreatment%2Bof%2BANCA-Associated%2BVasculitis%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMp030047%26rft_id%253Dinfo%253Apmid%252F12840085%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMp030047&link_type=DOI [3]: /lookup/external-ref?access_num=12840085&link_type=MED&atom=%2Fthoraxjnl%2F58%2F10%2F854.atom [4]: /lookup/external-ref?access_num=000183896100001&link_type=ISI
Tumor necrosis factor alpha-induced leukocyte adhesion in normal and tumor vessels: effect of tumor type, transplantation site, and host strain. (1995)

Tumor necrosis factor alpha (TNF-alpha) can lead to tumor regression when injected locally or when used in an isolated limb perfusion, and it can enhance the tumoricidal effect of various therapies. TNF-alpha can also up-regulate adhesion molecules, and thus, facilitate the binding of leukocytes to normal vessels. The present study was designed to investigate the extent to which the host leukocytes roll and adhere to vessels of different tumors (MCaIV, a murine mammary adenocarcinoma; HGL21, a human malignant astrocytoma) at a given site or to the same tumor at different sites (dorsal skin and cranium), in different mouse strains [C3H and severe combined immunodeficient (SCID)], both with and without TNF-alpha-activation. There was no significant difference in hemodynamic parameters such as RBC velocity, diameter, or shear rate between PBS-treated control groups and corresponding TNF-alpha-treated groups. Under PBS control conditions, the leukocyte rolling count in MCaIV tumor vessels in the dorsal chamber in C3H and SCID mice and in the cranial window in C3H mice was significantly lower than that in normal vessels (P < 0.05), but stable cell adhesion was similar between normal and tumor vessels. TNF-alpha led to an increase (P < 0.05) in leukocyte-endothelial interaction in vessels in the following cases: normal tissue regardless of sites and strains, MCaIV tumor in the cranial window in C3H mice, and HGL21 tumor in the cranial window in SCID mice. However, the increase in rolling and adhesion in the MCaIV tumor in response to TNF-alpha was significantly lower than in the corresponding normal vessels (P < 0.05) in the dorsal chamber in C3H and SCID mice and in the cranial window in C3H mice. The HGL21 tumor in the cranial window in SCID mice showed leukocyte rolling and adhesion comparable to that in normal pial vessels. These findings suggest that (a) in general, basal leukocyte rolling is lower in tumor vessels than in normal vessels; (b) leukocyte rolling and adhesion in tumors can be enhanced by TNF-alpha-mediated activation; and (c) the TNF-alpha response is dependent on tumor type, transplantation site, and host strain. These results have significant implications in the gene therapy of cancer using TNF-alpha-gene-transfected cancer cells or lymphocytes.
On Quantifying Surprise: The Variation of Event‐Related Potentials With Subjective Probability (1977)

ABSTRACT Two factors are known to determine the waveform of event‐related potentials (ERP) elicited by task‐relevant stimuli: the a priori probability of the stimuli and the sequence of immediately preceding stimuli. The relative contribution of these factors to the ERP waveform was assessed at nine levels of a priori probability (from .10 to .90). Random sequences of high (1500 Hz) and low (1000 Hz) tones were presented to 10 male subjects at each level of probability, both when the events were task‐relevant and when the subjects were performing an alternate task to which the tones were irrelevant. The EEG was recorded from five midline electrode sites referred to linked mastoids. The amplitude of the P300 and Slow Wave components was inversely proportional to the a priori probability of task‐relevant events. At every level of a priori probability, the magnitude of the P300 complex (N200‐P300‐Slow Wave) was diminished when the eliciting tone repeated the preceding tone, and was enhanced when it was preceded by the other tone. Thus, a priori probability and sequential structure appear to be independent determinants of the P300 complex.
Nonenzymatic cleavage of proteins by reactive oxygen species generated by dithiothreitol and iron. (1985)

Many enzymes, represented by yeast glutamine synthetase, are inactivated and degraded in the presence of dithiothreitol (DTT), oxygen, and catalytic amounts of iron salts. The roles of DTT and iron can be replaced by ascorbate and copper, respectively. Experimental data suggest that reactive oxygen species, likely hydroxyl radicals, are generated locally around irons bound at specific sites on enzymes, and these species are responsible for the inactivation and degradation. Since many biochemicals are contaminated with metal salts in quantities sufficient for some hydroxyl radical formation to occur, the possibility of oxidative modification and degradation should be considered when an enzyme is exposed to DTT.
Inhibition of oncogene-mediated transformation by ectopic expression of p21Waf1 in NIH3T3 cells. (1996)

The p53-regulated p21Waf1 protein is a universal inhibitor of cyclin-dependent kinases (CDKs). To study the potential tumor-suppressive properties of CDK inhibitors, the ability of p21Waf1 to interfere with oncogene-mediated cellular transformation was analysed in the NIH3T3 cell system. Cotransfection of waf1 together with activated ras or several other oncogenes into NIH3T3 cells potently inhibited the formation of transformed foci in a dose-dependent manner. Expression of the CDK-binding N-terminal half of p21Waf1 (N-p21Waf1) was necessary and sufficient to inhibit Ras-induced focus formation. In contrast, expression of the C-terminal domain (C-p21Waf1) had no effect on Ras-induced focus formation. Immunofluorescence analysis revealed that ectopically expressed p21Waf1 and C-p21Waf1 were localized in the nucleus, while N-p21Waf1 was found in the cytoplasm, with the tendency to accumulate around the nuclear membrane. Surprisingly, stable NIH3T3 transfectants expressing ectopic p21Waf1 grew at the same rate and displayed similar cell cycle distribution as NIH3T3 cells transfected with the same vector containing no insert. However, ectopic p21Waf1 expression did inhibit Ras-mediated anchorage-independent colony formation, indicating that p21Waf1 can selectively interfere with oncogene-mediated transformation without affecting NIH3T3 cell growth, at least at the levels of p21Waf1 expression achieved in these experiments. Transient transfection of waf1 into NIH3T3 cells inhibited Ras-induced transcription from a E2F-responsive element but not from a serum-responsive element, indicating that p21Waf1 acts downstream of early transcriptional events induced by Ras but upstream of E2F-controlled gene transcription. These results provide evidence that p21Waf1 potently suppresses oncogene-mediated cellular transformation of NIH3T3 cells and that it may do so by inhibiting E2F-driven transcription of S phase genes.