gebhart/patrepeval huggingface dataset:
Isolation and characterization of a membrane protein from normal human erythrocytes that inhibits reactive lysis of the erythrocytes of paroxysmal nocturnal hemoglobinuria. (1989)

The observation that type III erythrocytes of paroxysmal nocturnal hemoglobinuria (PNH) are susceptible to hemolysis initiated by activated cobra venom factor complexes (CoFBb), whereas normal erythrocytes are resistant, implies that the PNH III cells are deficient in a membrane constituent that regulates this process. To isolate the inhibitory factor from normal erythrocytes, membrane proteins were first extracted with butanol and then subjected to sequential anion exchange, hydroxylapatite, and hydrophobic chromatography. Analysis by SDS-PAGE and silver stain of the inhibitory fractions showed a single band corresponding to a protein with an apparent Mr of 18 kD. PNH erythrocytes were incubated with incremental concentrations of the radiolabeled protein and then washed. In a dose-dependent fashion, the protein incorporated into the cell membrane and inhibited CoFBb-initiated lysis. This protein inhibitor functioned by restricting the assembly of the membrane attack complex at the level of C7 and C8 incorporation. By using a monospecific antibody to block the function of the inhibitor, it was shown that normal erythrocytes are rendered susceptible to CoFBb-initiated hemolysis. Analysis by Western blot of membrane proteins revealed that PNH III erythrocytes are deficient in the 18-kD protein. By virtue of its molecular weight and inhibitory activity, the 18-kD protein appears to be discrete from other previously described erythrocyte membrane proteins that regulate complement. These studies also indicate that the susceptibility of PNH III erythrocytes to reactive lysis is causally related to a deficiency of the 18-kD membrane inhibitor.
Aberrant cell cycle checkpoint function and early embryonic death in Chk1−/− mice (2000)

The recent discovery of checkpoint kinases has suggested the conservation of checkpoint mechanisms between yeast and mammals. In yeast, the protein kinase Chk1 is thought to mediate signaling associated with the DNA damage checkpoint of the cell cycle. However, the function of Chk1 in mammals has remained unknown. Targeted disruption of Chk1 in mice showed that Chk1(-/-) embryos exhibit gross morphologic abnormalities in nuclei as early as the blastocyst stage. In culture, Chk1(-/-) blastocysts showed a severe defect in outgrowth of the inner cell mass and died of apoptosis. DNA replication block and DNA damage failed to arrest the cell cycle before initiation of mitosis in Chk1(-/-) embryos. These results may indicate that Chk1 is indispensable for cell proliferation and survival through maintaining the G(2) checkpoint in mammals.
Protein-bound glycogen is linked to tyrosine residues (1985)

Tyrosine-glycogen obtained from retina proteoglycogen by exhaustive proteolytic digestion was radiolabelled with 125I. The 125I-labelled tyrosine-glycogen was degraded by amylolytic digestion to a very small radioactive product, which was identified as iodotyrosine by h.p.l.c. The amylolytic mixture used released glucose and maltose that were alpha-linked to the phenolic hydroxy group of p-nitrophenol. No free iodotyrosine was found before or after the intact [125I]iodotyrosine-glycogen was subjected to two cycles of the Edman degradation procedure. The linkage between protein and glycogen was alkali-stable. Therefore it is concluded that the protein-bound glycogen was O-glycosidically linked to the phenolic hydroxy group of tyrosine. The amino acid has not been heretofore found to be involved in the linkage of carbohydrates to proteins.
NMR studies of brain 13C-glucose uptake and metabolism: Present status (1995)

One of the common features of epilepsy is a change in glucose metabolism at the site of seizure activity during and between seizures. The noninvasive in situ study of glucose transport and metabolism by NMR can potentially provide detailed information about this phenomena. In this short review, we will discuss the principles of 13C-glucose NMR studies of the brain and compare the advantages and disadvantages of this method to those of 18F-deoxyglucose studies using positron emission tomography (PET).
Genetic association of NOS1 exon18, NOS1 exon29, ABCB1 1236C/T, and ABCB1 3435C/T polymorphisms with the risk of Parkinson's disease (2016)

The NOS1 exon18 and ABCB1 1236C/T variants might play a role in the risk of Parkinson's disease, whereas NOS1 exon29 and ABCB1 3435C/T polymorphisms might not contribute to PD susceptibility.
Regulation and actions of the insulin-like growth factor binding proteins (1994)

Six structurally distinct binding proteins for the insulin-like growth factors (IGFs) have been identified. The IGF binding proteins (IGFBPs), IGFBP-1 through IGFBP-6, modulate the Bioavailability and actions of IGFs in the circulation and the extracellular environment. IGFBP-1 is metabolically regulated and suppressed by insulin administration, except when hypoglycemia ensues. IGFBP-3 is the major IGF carrier in serum, where it is found complexed with an acid-labile glycoprotein. The roles of IGFBP-2 and other circulating IGFBPs are as yet poorly defined. Most cell types secrete IGFBPs, with fibrobiasts, hepatocytes, osteobiasts. and granulosa cells being particularly well-studied sources. The actions of IGFBPs in local IGF regulation are complex and are modified by limited proteolysis, phosphorylation, and other posttranslational events. The current intense research focus on the IGF-IGFBP axis will lead to a better understanding of the regulation of IGF action in ceil growth and metabolism and allow the therapeutic utility of the IGFs to be optimized.
The XPB and XPD DNA helicases are components of the p53-mediated apoptosis pathway. (1996)

The molecular pathway of p53-dependent apoptosis (programmed cell death) is poorly understood. Because p53 binds to the basal transcription-repair complex TFIIH and modulates its DNA helicase activities, we hypothesized that TFIIH DNA helicases XPB and XPD are members of the p53-mediated apoptotic pathway. Whereas transfer of a wild-type p53 expression vector by microinjection or retroviral infection into primary normal human fibroblasts resulted in apoptosis, primary fibroblasts from individuals with xeroderma pigmentosum (XP), who are deficient in DNA repair and have germ-line mutations in the XPB or XPD gene, but not in the XPA or XPC gene, have a deficiency in the apoptotic response. This deficiency can be rescued by transferring the wild-type XPB or XPD gene into the corresponding mutant cells. XP-D lymphocytes also have a decreased apoptotic response to DNA damage by adriamycin, indicating a physiologically relevant deficiency. The XP-B or XP-D mutant cells undergo a normal apoptotic response when microinjected with the Ich-L, and ICE genes. Analyses of p53 mutants and the effects of microinjected anti-p53 antibody, Pab421, indicate that the carboxyl terminus of p53 may be required for apoptosis. Direct microinjection of the p53 carboxy-terminal-derived peptide (amino acid residues 319-393) resulted in apoptosis of primary normal human fibroblasts. These results disclose a novel pathway of p53-induced apoptosis.
Oxazolines. IX. Synthesis of homologated acetic acids and esters (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxazolines. IX. Synthesis of homologated acetic acids and estersA. I. Meyers, Davis L. Temple, Robert L. Nolen, and Edward D. MihelichCite this: J. Org. Chem. 1974, 39, 18, 2778–2783Publication Date (Print):September 1, 1974Publication History Published online1 May 2002Published inissue 1 September 1974https://doi.org/10.1021/jo00932a022RIGHTS & PERMISSIONSArticle Views871Altmetric-Citations77LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (783 KB) Get e-Alerts Get e-Alerts
Nonlinear image processing for beautifying facial images (2005)

Summary form only given. A nonlinear image processing system is proposed for beautifying face images. The system is composed of a nonlinear filter bank using an e-filter, which is a nonlinear digital filter previously proposed by the author for removing small-amplitude and high-frequency noise added to a large-amplitude signal. By combining e-filters, a filter bank is obtained which separates signals considering not only the frequency, but also the amplitude. By applying this nonlinear filter bank to a face image, signal components in the face image can be obtained separately. Thus, by removing small-amplitude, relatively high-frequency components, which correspond to wrinkles and spots, the skin looks smooth and beautified. Moreover, by combining the filter bank with signal enhancement, a face image becomes sharp while keeping the skin smooth. Computer simulations verify its high performance.
A 96 Mbit/sec, 15.5 pJ/bit 16-QAM modulator for UHF backscatter communication (2012)

We describe a low power vector backscatter modulator capable of transmitting 16-QAM at a rate of 96 Mbps while consuming only 1.49 mW (15.5 pJ/bit). While designed around a center frequency of 915 MHz, the modulator is capable of operation over the worldwide 868-950 MHz UHF band. We present experimental results from the modulator operating in 4-QAM/4-PSK, 4-PAM, and 16-QAM modes. Achieved data rates are comparable to WiFi (IEEE 802.11) with a measured tag-side power consumption over 50 times lower than a WiFi chipset. Potential applications for low power, high bit rate modulators include biotelemetry, high-bandwidth data transfer from camera tags or audio tags, uplink from mass storage tags, and exchange of large amounts of encryption or authentication data. Given a +36 dBm EIRP transmitter operating at 915 MHz, the semi-passive (battery-assisted) prototype tag is return link limited and has a theoretical maximum operating range of 17.01 m at 96 Mbps or 21.25 m at 40 Mbps.
Efficacy of Intraoperative Cooling Methods (1997)

Bladder lavage provided only trivial cooling and gastric lavage provoked complications. Forced-air and circulating-water cooling transferred relatively little heat but are noninvasive and easy to implement. Forced-air or circulating-water cooling, perhaps combined with intravenous administration of refrigerated fluids, may be sufficient in some patients. When noninvasive methods prove insufficient for rapid cooling, ice-water immersion or peritoneal lavage probably should be the next lines of defense.
Toll receptors: an expanding role in our understanding of human disease (2000)

Toll receptor proteins in Drosophila are involved in establishing the dorsal-ventral axis in embryogenesis as well as participating in the innate immune response to invading pathogens. The basic mediators of this response show striking similarities in plants, insects, and vertebrates. The cytoplasmic signaling cascade is exemplified by the human interleukin-1 receptor complex (IL-1R), resulting in transcriptional activation of effector proteins through nuclear factor-kappaB (NF-kappaB). Six mammalian/human Toll-like receptors (TLR) have been described to date. The TLRs share the IL-1R cytoplasmic signaling cascade but are distinguished by their extracellular leucine-rich repeat (LRR) structure. The LRR superfamily comprises a diverse group of proteins, including a cohort involved in transmembrane signaling. Two of the human TLRs (TLR2, TLR4) have been shown to be involved in the innate response to bacterial pathogens and appear to provide a link between the innate and adaptive immune response. A better understanding of this response may provide improved therapeutic modalities in the treatment of bacterial and fungal sepsis, which continues to be a significant source of morbidity and mortality worldwide. In addition, similar to Drosophila, Toll receptors and related proteins in the LRR superfamily may also be involved in human development, as well as in noninfectious human disease.
In vivo chamber angiogenesis assay: An optimized Matrigel plug assay for fast assessment of anti-angiogenic activity (2003)

Efficient in vitro and in vivo angiogenesis assays, to assess and compare anti-angiogenic activity are a prerequisite for the discovery and characterization of anti-angiogenic targets. Here we describe an optimized Matrigel plug assay based on subcutaneously implanted chambers and two fast and reproducible measuring techniques. Plexiglas ring/nylon net filter-chambers (0.2 ml) containing growth factor-reduced Matrigel and 300 ng basic fibroblast growth factor (bFGF) were subcutaneously implanted into the right flank of rats. Chamber angiogenesis was scored on day 5 and day 10 post-implantation by computer image analysis of the chamber, and by optical density reading at 415 nm of a PBS solution of the chamber content. bFGF significantly induced chamber angiogenesis and histological examination confirmed that numerous blood vessels were present in the bFGF-induced chambers. The anti-angiogenic control compound TNP-470 (10 mg/kg/d s.c.) completely inhibited the bFGF-induced angiogenesis. In contrast, the anti-inflammatory or immuno-suppressive compounds cyclosporin A (15 mg/kg/d p.o.), indomethacin (1 mg/kg/d p.o.), and prednisolone (5 mg/kg/d p.o.) showed no anti-angiogenic activity, indicating that the bFGF-induced angiogenesis was not driven by an inflammatory response or by a foreign body reaction. Finally, two candidate anti-angiogenic compounds were tested in the assay. Continuous low-dose therapy with cyclophosphamide (25 mg/kg/d p.o.) significantly inhibited bFGF-induced angiogenesis, whereas 1alpha,25-dihydroxyvitamin D3 (0.5 micro g/kg/d p.o.) showed no significant anti-angiogenic activity. In conclusion, this in vivo chamber angiogenesis assay is a useful new tool for drug evaluation as well as research into anti-angiogenesis.
Mutational Analysis of the Yeast DEAH-Box Splicing Factor Prp16 (1998)

Abstract Prp16 is an essential yeast splicing factor that catalyzes RNA-dependent hydrolysis of nucleoside triphosphates. Prp16 is a member of the DEAH-box protein family, which is defined by six collinear sequence motifs. The importance of residues within four of the conserved motifs was assessed by alanine-scanning mutagenesis. Mutant alleles of PRP16 were tested for in vivo function by complementation of a Δprp16 null strain. In motif I (GETGSGKT), alanine substitutions at Gly-378, Lys-379, and Thr-380 were lethal, whereas replacement of the amino acids in positions 373–377 were viable. In the signature DEAH-box (motif II), Asp-473 and Glu-474 were essential, whereas the H476A mutant was viable. The S505A and T507A mutants in motif III (SAT) were viable. In motif VI (QRSGRAGRTAPG), mutants Q685A, R686A, G688A, R689A, and R692A were lethal, whereas G691A, P695A, and G696A supported growth. Instructive structure-function relationships were established by conservative substitutions at essential residues identified by alanine scan. Overexpression of nonviable alleles impaired the growth of wild-type PRP16 cells. Deletion analysis of the 1071-amino-acid Prp16 protein revealed that the N-terminal 204 amino acids and the C-terminal 100 residues were dispensable for PRP16 function in vivo. These studies provide an instructive framework for functional analysis of other DEAH-box splicing factors.
Persistent generation of thrombin after acute myocardial infarction. (1992)

During the acute phase of myocardial infarction, the generation of thrombin is reflected in the sudden rise of fibrinopeptide A (FPA) and the thrombin-antithrombin III (TAT) complex in blood. We have systematically determined the FPA and TAT plasma concentrations over a period of 14 days after acute myocardial infarction in 100 patients. Mean levels of both thrombin markers were the highest on admission, remained elevated over the following few days, and then gradually declined after day 5. Still, by the end of the first week two thirds of the patients had distinctly elevated TAT and FPA levels, and by the end of the second week such an abnormality was present in half of them. Continuous intravenous heparin infusion at a dose of 20,000 units/day, administered for 1 week to patients who had either received (n = 21) or not received (n = 17) streptokinase, led to a significant depression (p less than 0.05) of thrombin markers over the first 48 hours, an effect that did not persist over the subsequent days of treatment. In patients not assigned to heparin treatment, those in heart failure had significantly (p less than 0.05) higher mean TAT and FPA values on days 3, 5, and 7 compared with patients in whom heart failure was absent. Infarct extension, pulmonary embolism, and death were also associated with a rise in one or both thrombin markers, often preceding the onset of clinical symptoms. Thrombinogenesis was not accompanied by changes in mean plasma concentrations of prothrombin, antithrombin III, or alpha 2-macroglobulin.(ABSTRACT TRUNCATED AT 250 WORDS)
Technology evaluation: transgenic alpha-1-antitrypsin (AAT), PPL therapeutics. (2000)

PPL Therapeutics is developing transgenic alpha-1-antitrypsin for the treatment of cystic fibrosis lung disease and other conditions in which connective tissue is broken down irreversibly. AAT is a plasma protein that inhibits elastase, a key player in the inflammatory response that, unchecked, will lead to excessive tissue destruction. PPL has taken transgenic alpha-1-antitrypsin through phase II clinical trials in the cystic fibrosis lung, delivering it in aerosol form to assess its safety and efficacy [315887]. Although early results are not statistically relevant with respect to clinical benefit, they do show some promise, especially given the low numbers of patients studied and the complex phenotypes and severities associated with cystic fibrosis.
Potent CD4+ T cell-associated antitumor memory responses induced by trifunctional bispecific antibodies in combination with immune checkpoint inhibition (2016)

Combinatorial approaches of immunotherapy hold great promise for the treatment of malignant disease. Here, we examined the potential of combining an immune checkpoint inhibitor and trifunctional bispecific antibodies (trAbs) in a preclinical melanoma mouse model using surrogate antibodies of Ipilimumab and Catumaxomab, both of which have already been approved for clinical use. The specific binding arms of trAbs redirect T cells to tumor cells and trigger direct cytotoxicity, while the Fc region activates accessory cells eventually giving rise to a long-lasting immunologic memory. We show here that T cells redirected to tumor cells by trAbs strongly upregulate CTLA-4 expression in vitro and in vivo. This suggested that blocking of CTLA-4 in combination with trAb treatment enhances T-cell activation in a tumor-selective manner. However, when mice were challenged with melanoma cells and subsequently treated with antibodies, there was only a moderate beneficial effect of the combinatorial approach in vivo with regard to direct tumor destruction in comparison to trAb therapy alone. By contrast, a significantly improved vaccination effect was obtained by CTLA-4 blocking during trAb-dependent immunization. This resulted in enhanced rejection of melanoma cells given after pre-immunization. The improved immunologic memory induced by the combinatorial approach correlated with an increased humoral antitumor response as measured in the sera and an expansion of CD4+ memory T cells found in the spleens.
Impact of coma on CD control for multiphase PSM designs (1998)

Alternating PSM applied selectively to transistor regions on the poly gate mask is one way to achieve smaller gate CDs and tighter CD control. When using multiphase PSMs we have observed, experimentally, a difference between the CDs of isolated lines when the phase shifter is on the right side compared to the left side (we have called this effect the PSM right-left effect). The effect is shown to correlate with lens coma and the magnitude of the effect is also a strong function of defocus. In this paper we present experimental data showing the magnitude of the effect and how it can be minimized by choosing optimum values of numerical aperture (NA) and partial coherence ((sigma) ). The magnitude of the effect within the stepper field is shown to correlate with measured coma values. The sensitivity of the effect to defocus was calculated. Aerial Image simulation was performed and found to predict the experimental behavior to within a factor of two. Variations in PSM design were explored using simulation. In general, the effect is reduced if the PSM layout is symmetrical. By comparing the sensitivity to coma of various PSM designs with the sensitivity of line pair structures on binary masks we were able to determine which designs had acceptable coma sensitivity.
DARPins: a true alternative to antibodies. (2007)

Designed ankyrin repeat proteins (DARPins) are a promising class of non-immunoglobulin proteins that can offer advantages over antibodies for target binding in drug discovery and drug development. DARPins have been successfully used, for example, for the inhibition of kinases, proteases and drug-exporting membrane proteins. DARPins specifically targeting the cancer marker HER2 have also been generated and were shown to function in both in vitro diagnostics and in vivo tumor targeting. DARPins are ideally suited for in vivo imaging or delivery of toxins or other therapeutic payloads because of their favorable molecular properties, including small size and high stability. The low-cost production in bacteria and the rapid generation of many target-specific DARPins make the DARPin approach useful for drug discovery. Additionally, DARPins can be easily generated in multispecific formats, offering the potential to target an effector DARPin to a specific organ or to target multiple receptors with one molecule composed of several DARPins.