gebhart/patrepeval huggingface dataset:
TNF-α-Converting Enzyme Cleaves the Macrophage Colony-Stimulating Factor Receptor in Macrophages Undergoing Activation (2001)

We previously reported that macrophage activators such as LPS, IL-2, and IL-4 down-modulate the M-CSFR via a mechanism involving protein kinase C and phospholipase C. In this study, we showed that M-CSFR is shed from macrophage surface and identified the protease responsible for M-CSFR cleavage and down-modulation. The shedding of M-CSFR elicited by phorbol esters (tetradecanoylphorbol myristate acetate (TPA)) or LPS in murine BAC.1-2F5 macrophages was prevented by cation chelators, as well as hydroxamate-based competitive inhibitors of metalloproteases. We found that the protease cleaving M-CSFR is a transmembrane enzyme and that its expression is controlled by furin-like serine endoproteases, which selectively process transmembrane metalloproteases. M-CSFR down-modulation was inhibited by treating cells in vivo, before TPA stimulation, with an Ab raised against the extracellular, catalytic domain of proTNF-converting enzyme (TACE). TACE expression was confirmed in BAC.1-2F5 cells and found inhibited after blocking furin-dependent processing. Using TACE-negative murine Dexter-ras-myc cell monocytes, we found that in these cells TPA is unable to down-modulate M-CSFR expression. These data indicated that TACE is required for the TPA-induced M-CSFR cleavage. The possibility that the cleavage is indirectly driven by TACE via the release of TNF was excluded by treating cells in vivo with anti-TNF Ab. Thus, we concluded that TACE is the protease responsible for M-CSFR shedding and down-modulation in mononuclear phagocytes undergoing activation. The possible physiological relevance of this mechanism is discussed.
Diverse expression of cytosolic phospholipase A2, 5‐lipoxygenase and prostaglandin H synthase 2 in acute pre‐B‐lymphocytic leukaemia cells (1995)

Several lines of evidence suggest that phospholipases A2, leukotrienes and prostaglandins play a role in the proliferation of haemopoietic cells. The expression of genes involved in the biosynthesis of leukotrienes and prostaglandins was investigated in peripheral B lymphoblasts, isolated from eight patients with acute pre-B-lymphocytic leukaemia (pre B-ALL). RT-PCR analysis demonstrated that four of the investigated pre-B-ALL clones expressed the gene coding for cytosolic phospholipase A2 (cPLA2), but not the gene coding for 5-lipoxygenase. In contrast, the remaining four pre-B-ALL clones expressed 5-lipoxygenase but not cPLA2, suggesting that the transcriptional regulation of these two genes are different and that their cellular functions are not linked to each other. The capacity of pre B-ALL cells to produce LTB4 and to express the 5-lipoxygenase protein, correlated with the expression of 5-lipoxygenase mRNA. All pre-B-ALL clones expressed genes coding for 5-lipoxygenase activating protein (FLAP), leukotriene A4 hydrolase and prostaglandin (PG)H synthase 1. Seven of the eight pre B-ALL clones expressed PGH synthase 2. In comparison, normal tonsillar B cells did not express cPLA2 or PGH synthase 2.
Why minimally invasive skin sampling techniques? A bright scientific future (2010)

There is strong interest in finding methods to access internal biochemical, molecular, and genetic processes through noninvasive and minimally invasive external means. Minimally invasive techniques include the widely used skin tape stripping, the abrasion method that includes scraping and detergent, and reverse iontophoresis. The first 2 methods harvest largely the stratum corneum. Hair root sampling (material deeper than the epidermis), buccal smear, shave biopsy, punch biopsy, and suction blistering are also methods used to obtain cellular material for analysis, but involve some degree of increased invasiveness and thus are only briefly mentioned. Existing and new sampling methods are being refined and validated, offering exciting, different noninvasive means of quickly and efficiently obtaining molecular material with which to monitor bodily functions and responses, assess drug levels, and follow disease processes without subjecting patients to unnecessary discomfort and risk.
Affinity Analysis of a Protein−Aptamer Complex Using Nonequilibrium Capillary Electrophoresis of Equilibrium Mixtures (2003)

We propose a new method that allows the use of low-affinity aptamers as affinity probes in quantitative analyses of proteins. The method is based on nonequilibrium capillary electrophoresis of the equilibrium mixture (NECEEM) of a protein with its fluorescently labeled aptamer. In general, NECEEM of a protein with a fluorescently labeled aptamer generates an electropherogram with three characteristic features: two peaks and an exponential curve. Two peaks correspond to (i) the equilibrium amount of free aptamer in the equilibrium mixture and (ii) the amount of the protein-aptamer complex that remains intact at the time of detection. The exponential part is ascribed to the complex decaying during separation under nonequilibrium conditions. Simple analysis of the three features in experiments with known concentrations of the protein can be used for the determination of the equilibrium dissociation constant, Kd, of the aptamer-protein complex. Similar analysis of the three features in the experiment with unknown concentration of the protein and known Kd value allows the determination of the protein concentration. In this proof-of-principle work, the NECEEM method was applied to the analysis of thrombin using a fluorescein-labeled aptamer under the conditions at which the protein-aptamer complex completely decayed during the separation. We demonstrated that, despite the decay, as few as 4 x 10(6) molecules of the protein could be detected with NECEEM without sacrificing the accuracy. This sensitivity is comparable with that reported by others for the aptamer-based equilibrium method. Thus, the proposed NECEEM-based method allows the use of aptamers for highly sensitive affinity analysis of proteins even when protein-aptamer complexes are unstable.
Development of new multivalent-bispecific agents for pretargeting tumor localization and therapy. (2003)

These results indicate that BS1.5 and BS1.5H are promising candidates for use in a variety of pretargeting applications, including tumor therapy with radionuclides and drugs. BS6 and BS8 may be even more attractive because of their potential to achieve higher levels of tumor uptake because of divalent carcinoembryonic antigen binding.
Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH 2 -terminal kinase (1997)

The c-Jun NH2-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases is activated by phosphorylation on Thr and Tyr. Here we report the molecular cloning of a new member of the mammalian MAP kinase kinase group (MKK7) that functions as an activator of JNK. In vitro protein kinase assays demonstrate that MKK7 phosphorylates and activates JNK, but not the p38 or extracellular signal-regulated kinase groups of MAP kinase. Expression of MKK7 in cultured cells causes activation of the JNK signal transduction pathway. MKK7 is therefore established to be a novel component of the JNK signal transduction pathway.
Nitrogen assimilation and growth of wheat under elevated carbon dioxide (2002)

Simultaneous measurements of CO(2) and O(2) fluxes from wheat (Triticum aestivum) shoots indicated that short-term exposures to elevated CO(2) concentrations diverted photosynthetic reductant from NO(3)(-) or NO(2)(-) reduction to CO(2) fixation. With longer exposures to elevated CO(2), wheat leaves showed a diminished capacity for NO(3)(-) photoassimilation at any CO(2) concentration. Moreover, high bicarbonate levels impeded NO(2)(-) translocation into chloroplasts isolated from wheat or pea leaves. These results support the hypothesis that elevated CO(2) inhibits NO(3)(-) photoassimilation. Accordingly, when wheat plants received NO(3)(-) rather than NH(4)(+) as a nitrogen source, CO(2) enhancement of shoot growth halved and CO(2) inhibition of shoot protein doubled. This result will likely have major implications for the ability of wheat to use NO(3)(-) as a nitrogen source under elevated CO(2).
Phage Display Evolution of a Peptide Substrate for Yeast Biotin Ligase and Application to Two-Color Quantum Dot Labeling of Cell Surface Proteins (2007)

Site-specific protein labeling with Escherichia coli biotin ligase (BirA) has been used to introduce fluorophores, quantum dots (QDs), and photocross-linkers onto recombinant proteins fused to a 15-amino acid acceptor peptide (AP) substrate for BirA and expressed on the surface of living mammalian cells. Here, we used phage display to engineer a new and orthogonal biotin ligase-AP pair for site-specific protein labeling. Yeast biotin ligase (yBL) does not recognize the AP, but we discovered a new 15-amino acid substrate for yBL called the yeast acceptor peptide (yAP), using two generations of phage display selection from 15-mer peptide libraries. The yAP is not recognized by BirA, and thus, we were able to specifically label AP and yAP fusion proteins coexpressed in the same cell with differently colored QDs. We fused the yAP to a variety of recombinant proteins and demonstrated biotinylation by yBL at the N-terminus, C-terminus, and within a flexible internal region. yBL is extremely sequence-specific, as endogenous proteins on the surface of yeast and HeLa cells are not biotinylated. This new methodology expands the scope of biotin ligase labeling to two-color imaging and yeast-based applications.
Compound heterozygous mutations in severe factor VII deficiency including a novel nonsense mutation (2008)

A 26-year-old man who had a history of recurrent spontaneous nasal bleeding was admitted to our hospital with uncontrolled traumatic subdural hemorrhage. His plasma factor VII activity was less than 10% of normal. DNA sequence analysis revealed that the proband had a compound heterozygote for a novel nonsense mutation (F7 NM_000131.2 c.345C > A; p.Cys115X) in exon 4 encoding the EGF1 domain and a known missense mutation (F7 NM_000131.2 c.1027G > A; p.Gly343Ser) in exon 8 encoding the serine protease domain of F7. The same F7 Gly343Ser mutation was present in the asymptomatic father, who exhibited a modest reduction in the plasma level of factor VII activity (48%).
Instrumented posterior arthrodesis of the lumbar spine in patients with diabetes mellitus. (2000)

The existence of diabetes mellitus has been postulated to have a deleterious effect on the outcome following lumbar spine surgery. We retrospectively examined the records and radiographs of 32 diabetic patients (mean age, 60 years) who underwent posterior lumbar fusions using transpedicular instrumentation and iliac crest autograft. Ten patients were insulin-dependent and 22 required oral hypoglycemic agents for at least 1 year prior to surgery. The minimum follow-up time was 2 years after surgery (mean, 2.5 years). Surgical indications included herniated lumbar disk, lumbar spinal stenosis, thoracolumbar trauma, and lumbar pseudarthrosis. Clinical results were evaluated by chart review and/or interview by using Odom's criteria. At follow-up, 75% of patients were graded as excellent or good, and 25% as fair or poor. Twenty-five of 32 patients (78%) had improvement of back pain. Twenty of 27 (74%) patients had improvement of leg pain. Eight of 15 (53%) patients had improvement in motor strength, and 6 of 11 (54%) had improvement in light-touch sensation. Insulin dependence and the presence of polyneuropathy were associated with a poorer outcome. The average time to radiographic fusion was 5 months. Twenty-nine of 32 patients (91%) developed solid fusion by strict radiographic criteria. The three patients with a pseudarthrosis had persistent back pain and a poor result. Ten of 32 (31%) of the patients experienced perioperative complications, including prolonged wound drainage (n = 5), deep wound infection (n = 1), superficial wound infection (n = 1), atrial fibrillation (n = 1), ruptured cerebral aneurysm (n = 1), and ulnar nerve neuropathy (n = 1). We conclude that posterolateral lumbar spinal fusion with internal fixation in diabetic patients yields clinical results comparable to those of nondiabetic patients, with similar risks of perioperative complications.
Recovering 3D human body configurations using shape contexts (2006)

The problem we consider in this paper is to take a single two-dimensional image containing a human figure, locate the joint positions, and use these to estimate the body configuration and pose in three-dimensional space. The basic approach is to store a number of exemplar 2D views of the human body in a variety of different configurations and viewpoints with respect to the camera. On each of these stored views, the locations of the body joints (left elbow, right knee, etc.) are manually marked and labeled for future use. The input image is then matched to each stored view, using the technique of shape context matching in conjunction with a kinematic chain-based deformation model. Assuming that there is a stored view sufficiently similar in configuration and pose, the correspondence process will succeed. The locations of the body joints are then transferred from the exemplar view to the test shape. Given the 2D joint locations, the 3D body configuration and pose are then estimated using an existing algorithm. We can apply this technique to video by treating each frame independently--tracking just becomes repeated recognition. We present results on a variety of data sets.
A recursive MISD architecture for pattern matching (2004)

Many applications require searching for multiple patterns in large data streams for which there is no preprocessed index to rely on for efficient lookups. An multiple instruction stream-single data stream (MISD) VLSI architecture that is based on a recursive divide and conquer approach to pattern matching is proposed. This architecture allows searching for multiple patterns simultaneously. The patterns can be constructed much like regular expressions, and add features such as requiring subpatterns to match in a specific order with some fuzzy distance between them, and the ability to allow errors according to prescribed thresholds, or ranges of such. The current implementation permits up to 127 simultaneous patterns at a clock frequency of 100 MHz, and does 1.024/spl times/10/sup 11/ character comparisons per second.
Windows 95 Uncut (1995)

Geared to new and experienced Windows users, this book explains new Windows features and provides tips and techniques for simplified access to frequently used resources. Includes tutorial vignettes that are organized by type of task. The CD-ROM features hundreds of time-saving Windows 95 utilities and accessories.
Selective Treatment of Cancer: Synthesis, Biological Evaluation and Structural Elucidation of Novel Analogues of the Antibiotic CC‐1065 and the Duocarmycins (2007)

Novel diastereomerically pure beta-D-galactosidic prodrugs (+)-12 a-e of the cytotoxic antibiotics CC-1065 and the duocarmycins were prepared for an antibody directed enzyme prodrug therapy (ADEPT) using 4 as a substrate via a radical cyclization to give rac-5 and rac-6 followed by a chromatographic resolution of the enantiomers of rac-5, glycosidation and linkage to the DNA-binding units 10 a-e. These only slightly toxic compounds can be toxified enzymatically by an antibody-beta-D-galactosidase conjugate at the surface of malignant cells to give the cytotoxic drugs, which then alkylate DNA. The new prodrugs were tested in in vitro cytotoxicity assays showing excellent QIC(50) values of 4800 and 4300 for (+)-12 a and (+)-12 b, respectively. The absolute configuration of precursor (+)-5 was determined by comparison of the experimental CD spectrum with the theoretically predicted CD spectra and by X-ray structure analysis.
Efficient in vitro affinity maturation of phage antibodies using BIAcore guided selections (1996)

Selection of higher affinity mutant phage antibodies has proven less than straightforward due to sequence dependent differences in phage antibody expression, toxicity to Escherichia coli, and difficulty in eluting the highest affinity phage. These differences lead to selection for increased levels of expression or decreased toxicity rather than for higher affinity. In this work, we demonstrate how surface plasmon resonance as employed in the BIAcore can be used to increase the efficiency of phage antibody selections, yielding greater increments in affinity from a single library. A mutant phage antibody library was created by randomizing nine amino acids located in the V(L) CDR3 of C6.5, a human scFv which binds the tumor antigen c-erbB-2 with a Kd of 1.6 x 10-8 M. The library was subjected to five rounds of selection in solution using decreasing concentrations of biotinylated c-erbB-2. After each round of selection, polyclonal phage were prepared and the rate of binding to c-erbB-2 determined in a BIAcore under mass transport limited conditions. Determination of the rate of binding permitted calculation of the concentration, and hence percent, of binding phage present. Results were used to select the antigen concentration for the next round of selection. To determine the optimal eluent, polyclonal phage was injected in a BIAcore and eluted using one of five different solutions (10 mM HCl, 50 mM HCl, 100 mM HCl, 100 mM triethylamine, 2.6 M MgCl2). Differences were observed in eluent efficacy, which was reflected in significant differences in the affinities of phage antibodies isolated from the library after a round of selection using the different eluents. Use of the BIAcore to determine the optimal eluent and guide the antigen concentration used for selection yielded a C6.5 mutant with a 16 fold reduction in Kd (Kd = 1.0 x 10-9 M). This represents at least a twofold greater increment in affinity than previously obtained from a single library of phage antibodies which bind antigens.
CHROMOSOME DOUBLING OF BARLEY HAPLOIDS BY NITROUS OXIDE AND COLCHICINE TREATMENTS (1975)

Hybridization of Hordeum vulgare L. (2n = 14) with H. bulbosum L. (2n = 14) results in a high frequency of haploids of H. vulgare through selective elimination of H. bulbosum chromosomes. Doubled haploids were produced by nitrous oxide (N 2 O) or 0.1% colchicine with and without dimethyl sulfoxide (DMSO) treatments. Pollinated florets (vulgare × bulbosum) were treated with N 2 O under 21.1 × 10 −3 to 42.2 × 10 −3 kg/m 2 pressure (30 to 60 psi) and the frequency of doubled haploids ranged from 0 to 100%, depending upon pressure and duration of exposure. However, the frequency of seedlings from the most effective N 2 O doubling treatment was very low (0.5%) whereas 17% of the florets pollinated in the controls resulted in seedlings. Of the haploid seedlings treated with either 0.1% colchicine or colchicine plus DMSO, doubled sectors occurred in 37.4 and 55.8% respectively. Seed was also obtained from 3% of the untreated plants indicating a low frequency of natural chromosome doubling. The proportion of doubled tillers per plant was 61.6% in colchicine plus DMSO treatments and 30.8% in the colchicine treatments. Colchicine plus DMSO was the most efficient treatment for doubling barley haploids during early stages of development.
Solid-State Structures of Zinc(II) Benzoate Complexes. Catalyst Precursors for the Coupling of Carbon Dioxide and Epoxides (2002)

Zinc complexes derived from benzoic acids containing electron-withdrawing substituents have been synthesized from Zn(II)(bis-trimethylsilyl amide)(2) and the corresponding carboxylic acid (2,6-X(2)C(6)H(3)COOH, where X = F, Cl, or OMe) in THF and structurally characterized via X-ray crystallography. The 2,6-difluorobenzoate complex crystallizes from THF or CH(3)CN as a seven membered zinc aggregate, where the metal atoms are interconnected by a combination of 10 mu-benzoates and mu(4)-oxo ligands, that is, [(2,6-difluorobenzoate)(10)O(2)Zn(7)](solvent)(2), solvent = THF (1) and CH(3)CN (1a). On the other hand, the 2,6-dichlorobenzoate zinc derivative crystallizes from THF as a dimer, [(2,6-dichlorobenzoate)(4)Zn(2)](THF)(3) (2), where the two zinc centers are bridged by three benzoate ligand. One of the zinc centers possesses a tetrahedral ligand environment where the fourth ligand is a unidentate benzoate, and the other zinc center has an octahedral arrangement of ligands which is accomplished by the additional binding of three THF molecules. Upon dissolution of complex 1 or 2 in the strongly binding pyridine solvent, disruption of these zinc carboxylates occurs with concomitant formation of mononuclear zinc bis-benzoates with three pyridine ligands in the metal coordination sphere. Complexes 1 and 2 were found to be effective catalysts for the copolymerization of cyclohexene oxide and carbon dioxide to afford polycarbonates devoid of polyether linkages, that is, completely alternating copolymers. Although these catalysts or catalyst precursors in the presence of CO(2)/propylene oxide afforded mostly propylene carbonate, they did serve as efficient catalysts for the terpolymerization of carbon dioxide/cyclohexene oxide/propylene oxide. The reactivities of these zinc carboxylates were very similar to those previously reported analogous complexes which have not been structurally characterized. Hence, it is suggested here that all of these zinc carboxylates provide similar catalytic sites for CO(2)/epoxide coupling processes.
Gene copy number variation and common human disease (2009)

Variation in gene copy number is increasingly recognized as a common, heritable source of inter-individual differences in genomic sequence. The role of copy number variation is well established in the pathogenesis of rare genomic disorders. More recently, germline and somatic copy number variation have been shown to be important pathogenic factors in a range of common diseases, including infectious, autoimmune and neuropsychiatric diseases and cancer. In this review, we describe the range of methods available for measuring copy number variants (CNVs) in individuals and populations, including the limitations of presently available assays, and highlight some key examples of common diseases in which CNVs have been shown clearly to have a pathogenic role. Although there has been major progress in this field in the last 5 years, understanding the full contribution of CNVs to the genetic basis of common diseases will require further studies, with more accurate CNV assays and larger cohorts than have presently been completed.