gebhart/patrepeval huggingface dataset:
Kir6.2 is required for adaptation to stress (2002)

Reaction to stress requires feedback adaptation of cellular functions to secure a response without distress, but the molecular order of this process is only partially understood. Here, we report a previously unrecognized regulatory element in the general adaptation syndrome. Kir6.2, the ion-conducting subunit of the metabolically responsive ATP-sensitive potassium (K(ATP)) channel, was mandatory for optimal adaptation capacity under stress. Genetic deletion of Kir6.2 disrupted K(ATP) channel-dependent adjustment of membrane excitability and calcium handling, compromising the enhancement of cardiac performance driven by sympathetic stimulation, a key mediator of the adaptation response. In the absence of Kir6.2, vigorous sympathetic challenge caused arrhythmia and sudden death, preventable by calcium-channel blockade. Thus, this vital function identifies a physiological role for K(ATP) channels in the heart.
Sacral nerve stimulation lead implantation using the o-arm (2013)

To our knowledge, this is the first published tined lead implantation which was guided based on the surgical navigation and intraoperative O-arm images. In this case, the applied method was useful and helped the surgeon to demarcate the region of surgical interest. The method is slightly more invasive than the formal technique but could be an option in anatomically challenging cases and reoperations. However, further evaluation with larger patient series is required before definitive recommendations can be made.
Spectroscopic and redox properties of amine-functionalized K2[OsII(bpy)(CN)4] complexes (2011)

We report the first examples of amine-functionalized K(2)[Os(II)(bpy)(CN)(4)] (bpy = 2,2'-bipyridine) complexes. The tetracyanoosmate complexes were prepared by UV irradiation (λ = 254 nm) of K(4)[Os(II)(CN)(6)] and primary amine-functionalized bpy ligands in acidic aqueous media. The aqueous solution pH dependences of the spectroscopic and redox properties of 4,4'- and 5,5'-substituted complexes have been investigated. The pendant amine functional groups and coordinated cyanide ligands are basic sites that can be sequentially protonated, thereby allowing systematic tuning of electrochemical and optical spectroscopic properties.
ChemInform Abstract: Lithium Triethylborohydride‐Promoted Hydroboration of Alkenes with Dialkoxyboranes. (1992)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A case for avoiding security-enhanced HTTP tools to improve security for Web-based applications (1996)

This paper describes some of the general weaknesses of the current popular Hypertext Transmission Protocol (HTTP) security standards and products in an effort to show that these standards are not appealing for many applications. The author will then show how one can treat HTTP browsers and servers as untrusted elements in the network so that one can rely on other mechanisms to achieve better overall security than can be attained through today`s security-enhanced HTTP tools.
The multidrug resistance (mdr1) gene product functions as an ATP channel. (1993)

The multidrug resistance (mdr1) gene product, P-glycoprotein, is responsible for the ATP-dependent extrusion of a variety of compounds, including chemotherapeutic drugs, from cells. The data presented here show that cells with increased levels of the P-glycoprotein release ATP to the medium in proportion to the concentration of the protein in their plasma membrane. Furthermore, measurements of whole-cell and single-channel currents with patch-clamp electrodes indicate that the P-glycoprotein serves as an ATP-conducting channel in the plasma membrane. These findings suggest an unusual role for the P-glycoprotein.
Inhibition of leucocyte elastase by heparin and its derivatives (1988)

Leucocyte proteinases, e.g. leucocyte elastase and cathepsin G, are inhibited by heparin. The activities of pig pancreatic and Pseudomonas aeruginosa elastases are unaffected by this polysaccharide. Heparin derivatives of known Mr and degree of sulphation were isolated. The inhibition of leucocyte elastase by these oligosaccharides can be classified as tight-binding hyperbolic non-competitive. Ki values ranged from 40 nM to 100 microM and were found to be inversely correlated with the chain length of the oligosaccharides. Desulphated compounds lacked inhibitory potential towards leucocyte elastase. Over-O-sulphated di- and tetra-saccharides are more potent inhibitors than their over-N-sulphated counterparts. It is proposed that the therapeutic use of heparin and its derivatives could be extended to disease states such as emphysema and rheumatoid arthritis, where the role of leucocyte elastase has been clearly established.
Autophagic dysfunction in mucolipidosis type IV patients (2008)

Mutations in Mucolipin 1 (MCOLN1) have been linked to mucolipidosis type IV (MLIV), a lysosomal storage disease characterized by several neurological and ophthalmological abnormalities. It has been proposed that MCOLN1 might regulate transport of membrane components in the late endosomal-lysosomal pathway; however, the mechanisms by which defects of MCOLN1 function result in mental and psychomotor retardation remain largely unknown. In this study, we show constitutive activation of autophagy in fibroblasts obtained from MLIV patients. Accumulation of autophagosomes in MLIV cells was due to the increased de novo autophagosome formation and to delayed fusion of autophagosomes with late endosomes/lysosomes. Impairment of the autophagic pathway led to increased levels and aggregation of p62, suggesting that abnormal accumulation of ubiquitin proteins may contribute to the neurodegeneration observed in MLIV patients. In addition, we found that delivery of platelet-derived growth factor receptor to lysosomes is delayed in MCOLN1-deficient cells, suggesting that MCOLN1 is necessary for efficient fusion of both autophagosomes and late endosomes with lysosomes. Our data are in agreement with recent evidence showing that autophagic defects may be a common characteristic of many neurodegenerative disorders.
Pegylated Alpha Interferon Is an Effective Treatment for Virulent Venezuelan Equine Encephalitis Virus and Has Profound Effects on the Host Immune Response to Infection (2000)

Venezuelan equine encephalitis virus (VEEV) is a highly infectious alphavirus endemic in parts of Central and South America. The disease is transmitted by mosquitoes, and the natural reservoir is the small rodent population, with epidemics occurring in horses and occasionally humans. Following infection, VEEV replicates in lymphoid tissues prior to invasion of the central nervous system. Treatment of VEEV-infected BALB/c mice with polyethylene glycol-conjugated alpha interferon (PEG IFN-alpha) results in a greatly enhanced survival from either a subcutaneous or an aerosol infection. Virus is undetectable within PEG IFN-alpha-treated individuals by day 30 postinfection (p.i.). Treatment results in a number of changes to the immune response characteristics normally associated with VEEV infection. Increased macrophage activation occurs in PEG IFN-alpha-treated BALB/c mice infected with VEEV. The rapid activation of splenic CD4, CD8, and B cells by day 2 p.i. normally associated with VEEV infection is absent in PEG IFN-alpha-treated mice. The high tumor necrosis factor alpha production by macrophages from untreated mice is greatly diminished in PEG IFN-alpha-treated mice. These results suggest key immunological mechanisms targeted by this lethal alphavirus that can be modulated by prolonged exposure to IFN-alpha.
B cell clones that sustain long-term plasmablast growth in T-independent extrafollicular antibody responses (2006)

Some antigens induce Ab responses without T lymphocyte help. Among these, many polysaccharide-based antigens cause marginal zone B cells to proliferate and differentiate into plasma cells. B1 cells also respond to some of these antigens. In this article, we report that antigen-specific B1b cells, in response to the T-independent antigen (4-hydroxy-3-nitrophenyl)-acetyl (NP)-Ficoll, develop into clones that sustain Ab production for months with continued production of plasma cells and the accumulation of antigen-specific B cells in follicles. The persistence of this T-independent plasmablast response contrasts with the short-term plasmablast growth associated with T-dependent extrafollicular responses. The nature of the cells responding to NP-Ficoll was probed by using chimeras that have B1 cells but lack primary B lymphopoietic capacity and have very few B2 cells or T cells. The chimeras were constructed by transferring 10(5) IgM(+) IgD(-) peritoneal exudate cells into mice unable to produce their own T and B cells because of deficiency in recombinase-activating gene 1 (RAG-1). The chimeras mounted sustained IgM and IgG3 anti-NP Ab responses to NP-Ficoll. This finding was associated with continued NP-specific extrafollicular plasmablast growth and the accumulation of NP-specific B cells in follicles. B cells were not found in the marginal zones of chimeras, and they also lacked recirculating IgD(+) cells and CD3(+) cells. The absence of B2 and T cells confirms that hemopoietic cell chimerism leading to primary lymphopoiesis had not been established.
Topography of Cross-sectional and Longitudinal Glucose Metabolic Deficits in Alzheimer's Disease (1992)

Positron emission tomographic studies of cerebral glucose metabolism have shown high diagnostic specificity in distinguishing among the degenerative dementias and differentiating between Alzheimer's disease (AD) and normal aging. The current investigation was undertaken to characterize the regional glucose metabolic deficits in AD, using cross-sectional and longitudinal study designs. All subjects met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD (n = 45) or were normal (n = 20), and the AD subjects were subdivided into incipient and mild AD and moderate plus moderately severe subgroups based on the Global Deterioration Scale. The subjects underwent a non-contrast computed tomographic scan and a positron emission tomographic (PETT VI) scan. The AD subjects (n = 14) and normal control subjects (n = 15) received evaluations 2 to 3 years after baseline study. The brain regions that show glucose metabolic deficits cross-sectionally (temporal and parietal association areas, with lesser degrees of deficit in subcortical gray matter structures), over the stages of AD, also show further deficits longitudinally within the same AD subjects. The reduction in glucose metabolism is greater than would be expected from the degree of brain atrophy. The glucose metabolic deficits are discussed in the context of neuropathologic findings and neurotransmitter deficits in AD.
Fast Edge Detection Using Structured Forests (2014)

Edge detection is a critical component of many vision systems, including object detectors and image segmentation algorithms. Patches of edges exhibit well-known forms of local structure, such as straight lines or T-junctions. In this paper we take advantage of the structure present in local image patches to learn both an accurate and computationally efficient edge detector. We formulate the problem of predicting local edge masks in a structured learning framework applied to random decision forests. Our novel approach to learning decision trees robustly maps the structured labels to a discrete space on which standard information gain measures may be evaluated. The result is an approach that obtains realtime performance that is orders of magnitude faster than many competing state-of-the-art approaches, while also achieving state-of-the-art edge detection results on the BSDS500 Segmentation dataset and NYU Depth dataset. Finally, we show the potential of our approach as a general purpose edge detector by showing our learned edge models generalize well across datasets.
Canine X‐linked muscular dystrophy as an animal model of Duchenne muscular dystrophy: A review (1992)

Canine X-linked muscular dystrophy is a spontaneously occurring, progressive, degenerative myopathy of dogs that is clinically and pathologically similar to Duchenne muscular dystrophy in man. The molecular basis for the disease has been shown to be a lack of dystrophin, the protein product of the Duchenne muscular dystrophy gene. Breeding colonies of dystrophic dogs have been established. This report reviews the findings of genetic, clinical, pathologic, molecular biologic, and immunocytochemical studies of the canine model, and compares the features of the canine disease to those of Duchenne dystrophy in man.
Serum alpha-fetoprotein in patients with neoplasms of the gastrointestinal tract. (1975)

Serum alpha-fetoprotein levels were measured by a sensitive double-antibody radioimmunoassay in 580 patients with a variety of malignant and nonmalignant gastrointestinal diseases to determine the incidence of levels elevated above 40 ng/ml. Over 200 normal control subjects have all had levels below 40 ng/ml. Fifteen % of 95 patients with gastric carcinoma, 3 percent of 191 patients with colorectal carcinoma, 24 percent of 45 patients with pancreatic carcinoma, 25 percent of 8 patients with biliary tract carcinoma, and 70 percent of 73 patients with hepatocellular carcinoma had elevated serum alpha-fetoprotein. None of 14 patients with esophageal or small bowel carcinoma had elevated levels. In contrast, 1 percent of 154 patients with nonmalignant, nonhepatic gastrointestinal disease had elevations of serum alpha-fetoprotein. Alpha-Fetoprotein appears to be a potential marker for tumor activity in some patients with certain gastrointestinal cancers.
Rapid DNA sequencing by horizontal ultrathin gel electrophoresis (1991)

A horizontal polyacrylamide gel electrophoresis apparatus has been developed that decreases the time required to separate the DNA fragments produced in enzymatic sequencing reactions. The configuration of this apparatus and the use of circulating coolant directly under the glass plates result in heat exchange that is approximately nine times more efficient than passive thermal transfer methods commonly used. Bubble-free gels as thin as 25 microns can be routinely cast on this device. The application to these ultrathin gels of electric fields up to 250 volts/cm permits the rapid separation of multiple DNA sequencing reactions in parallel. When used in conjunction with 32P-based autoradiography, the DNA bands appear substantially sharper than those obtained in conventional electrophoresis. This increased sharpness permits shorter autoradiographic exposure times and longer sequence reads.
Antitumor activity of a monoclonal antibody against CD47 in xenograft models of human leukemia (2007)

The ligation of CD47 induces the apoptosis of leukemic cells in a caspase-independent manner. We generated a monoclonal antibody against CD47 (mAb-MABL) that possibly induced apoptosis from the ligation of CD47 in CCRF-CEM and JOK-1 cells in vitro. To confirm whether the ligation of CD47 caused cell death in vivo, we examined the antitumor activity of F(ab')2 of mAb-MABL in two xenograft models: The acute lymphoblastic leukemia (CCRF-CEM) and the B-cell chronic lymphocytic leukemia (JOK-1) cell line. Furthermore, in order to clarify the apoptotic activity selective for the tumor cells, we examined F(ab')2 of mAb-MABL apoptotic effects on CD34+ hematopoietic progenitor/stem and human endothelial cells. Male SCID mice were intravenously injected with CCRF-CEM (5 x 10(6) cells/mouse) or JOK-1 cells (5 x 10(6) cells/mouse) and intraperitoneally with JOK-1 cells (2 x 10(7) cells/mice). After the implantation of the cells, the mice were intravenously administered the vehicle or the F(ab')2 fragment of mAb-MABL at several doses and the length of survival was measured. F(ab')2 of mAb-MABL markedly prolonged the survival of mice transplanted with CCRF-CEM and JOK-1. Significantly, 40% of the mice intraperitoneally injected with JOK-1 cells became tumor-free when administered F(ab')2 of mAb-MABL, whereas even a high dose of fludarabine only slightly prolonged the median survival time. On the contrary, F(ab')2 of mAb-MABL showed no apoptotic effect on CD34+ hematopoietic progenitor/stem or human endothelial cells. Thus, monoclonal antibodies that cause cell death from the ligation of CD47 could be novel therapeutic agents for incurable leukemia after further optimization such as humanization or making single chain diabodies.
Multicolor Discrete Frequency Infrared Spectroscopic Imaging (2019)

Advancement of discrete frequency infrared (DFIR) spectroscopic microscopes in image quality and data throughput are critical to their use for analytical measurements. Here, we report the development and characterization of a point scanning instrument with minimal aberrations and capable of diffraction-limited performance across all fingerprint region wavelengths over arbitrarily large samples. The performance of this system is compared to commercial state of the art Fourier transform infrared (FT-IR) imaging systems. We show that for large samples or smaller set of discrete frequencies, point scanning far exceeds (∼10-100 fold) comparable data acquired with FT-IR instruments. Further we show improvements in image quality using refractive lenses that show significantly improved contrast across the spatial frequency bandwidth. Finally, we introduce the ability to image two tunable frequencies simultaneously using a single detector by means of demodulation to further speed up data acquisition and reduce the impact of scattering. Together, the advancements provide significantly better spectral quality and spatial fidelity than current state of the art imaging systems while promising to make spectral scanning even faster.
Immunity against a therapeutic xenoprotein/Fc construct delivered by gene transfer is reduced through binding to the inhibitory receptor FcγRIIb (2011)

The present study shows that inhibitory FcγRIIb receptors interacting with the wild-type IgG1-Fc reduce immunity against Ex4/Fc, suggesting an approach for reducing the immunogenicity of therapeutic proteins in the context of gene therapy.
Bile Acid Reduces the Secretion of Very Low Density Lipoprotein by Repressing Microsomal Triglyceride Transfer Protein Gene Expression Mediated by Hepatocyte Nuclear Factor-4 (2004)

Microsomal triglyceride transfer protein (MTP) is involved in the transfer of triglycerides, cholesterol esters, and phospholipids to newly synthesized apolipoprotein (apo) B. It is therefore essential for lipoprotein synthesis and secretion in the liver and the small intestine. Although several recent experiments have revealed the transcriptional regulation of the MTP gene, little has been revealed to date about hepatocyte nuclear factor-4 (HNF-4)-dependent regulation. We here report that the human MTP gene promoter contains a pair of functional responsive elements for HNF-4 and HNF-1, the latter of which is another target gene of HNF-4. Chromatin immunoprecipitation assays provide evidence that endogenous HNF-4 and HNF-1 can bind these elements in chromatin. In Hep G2 cells overexpression of either a dominant negative form of HNF-4 or small interfering RNAs (siRNAs) against HNF-4 dramatically reduces the activities of both the wild type and the HNF-4 site mutant MTP promoter. This suggests that HNF-4 regulates MTP gene expression either directly or indirectly through elevated HNF-1 levels. When Hep G2 cells were cultured with chenodeoxycholic acid (CDCA), a ligand for the farnesoid X receptor (FXR), mRNA levels for MTP and apo B were reduced because of increased expression of the factor small heterodimer partner (SHP), which factor suppresses HNF-4 activities. Chenodeoxycholic acid, but not a synthetic FXR ligand, attenuated expression of HNF-4, bringing about a further suppression of MTP gene expression. Over time the intracellular MTP protein levels and apo B secretion in the culture medium significantly declined. These results indicate that two nuclear receptors, HNF-4 and FXR, are closely involved in MTP gene expression, and the results provide evidence for a novel interaction between bile acids and lipoprotein metabolism.
The Cellular Functions of the Yeast Lipin Homolog Pah1p Are Dependent on Its Phosphatidate Phosphatase Activity (2007)

The Saccharomyces cerevisiae PAH1-encoded Mg2+-dependent phosphatidate phosphatase (PAP1, 3-sn-phosphatidate phosphohydrolase, EC 3.1.3.4) catalyzes the dephosphorylation of phosphatidate to yield diacylglycerol and Pi. This enzyme plays a major role in the synthesis of triacylglycerols and phospholipids in S. cerevisiae. PAP1 contains the DXDX(T/V) catalytic motif (DIDGT at residues 398-402) that is shared by the mammalian fat-regulating protein lipin 1 and the superfamily of haloacid dehalogenase-like proteins. The yeast enzyme also contains a conserved glycine residue (Gly80) that is essential for the fat-regulating function of lipin 1 in a mouse model. In this study, we examined the roles of the putative catalytic motif and the conserved glycine for PAP1 activity by a mutational analysis. The PAP1 activities of the D398E and D400E mutant enzymes were reduced by >99.9%, and the activity of the G80R mutant enzyme was reduced by 98%. The mutant PAH1 alleles whose products lacked PAP1 activity were nonfunctional in vivo and failed to complement the pah1Delta mutant phenotypes of temperature sensitivity, respiratory deficiency, nuclear/endoplasmic reticulum membrane expansion, derepression of INO1 expression, and alterations in lipid composition. These results demonstrated that the PAP1 activity of the PAH1 gene product is essential for its roles in lipid metabolism and cell physiology.
Autosomal recessive retinitis pigmentosa and cone-rod dystrophy caused by splice site mutations in the Stargardt's disease gene ABCR (1998)

Ophthalmological and molecular genetic studies were performed in a consanguineous family with individuals showing either retinitis pigmentosa (RP) or cone-rod dystrophy (CRD). Assuming pseudodominant (recessive) inheritance of allelic defects, linkage analysis positioned the causal gene at 1p21-p13 (lod score 4.22), a genomic segment known to harbor the ABCR gene involved in Stargardt's disease (STGD) and age-related macular degeneration (AMD). We completed the exon-intron structure of the ABCR gene and detected a severe homozygous 5[prime] splice site mutation, IVS30+1G->T, in the four RP patients. The five CRD patients in this family are compound heterozygotes for the IVS30+1G->T mutation and a 5[prime] splice site mutation in intron 40 (IVS40+5G->A). Both splice site mutations were found heterozygously in two unrelated STGD patients, but not in 100 control individuals. In these patients the second mutation was either a missense mutation or unknown. Since thus far no STGD patients have been reported to carry two ABCR null alleles and taking into account that the RP phenotype is more severe than the STGD phenotype, we hypothesize that the intron 30 splice site mutation represents a true null allele. Since the intron 30 mutation is found heterozygously in the CRD patients, the IVS40+5G->A mutation probably renders the exon 40 5[prime] splice site partially functional. These results show that mutations in the ABCR gene not only result in STGD and AMD, but can also cause autosomal recessive RP and CRD. Since the heterozygote frequency for ABCR mutations is estimated at 0.02, mutations in ABCR might be an important cause of autosomal recessive and sporadic forms of RP and CRD.