gebhart/patrepeval huggingface dataset:
NHE-RF1 protein rescues ΔF508-CFTR function (2007)

In cystic fibrosis (CF), the DeltaF508-CFTR anterograde trafficking from the endoplasmic reticulum to the plasma membrane is inefficient. New strategies for increasing the delivery of DeltaF508-CFTR to the apical membranes are thus pathophysiologically relevant targets to study for CF treatment. Recent studies have demonstrated that PDZ-containing proteins play an essential role in determining polarized plasma membrane expression of ionic transporters. In the present study we have hypothesized that the PDZ-containing protein NHE-RF1, which binds to the carboxy terminus of CFTR, rescues DeltaF508-CFTR expression in the apical membrane of epithelial cells. The plasmids encoding DeltaF508-CFTR and NHE-RF1 were intranuclearly injected in A549 or Madin-Darby canine kidney (MDCK) cells, and DeltaF508-CFTR channel activity was functionally assayed using SPQ fluorescent probe. Cells injected with DeltaF508-CFTR alone presented a low chloride channel activity, whereas its coexpression with NHE-RF1 significantly increased both the basal and forskolin-activated chloride conductances. This last effect was lost with DeltaF508-CFTR deleted of its 13 last amino acids or by injection of a specific NHE-RF1 antisense oligonucleotide, but not by NHE-RF1 sense oligonucleotide. Immunocytochemical analysis performed in MDCK cells transiently transfected with DeltaF508-CFTR further revealed that NHE-RF1 specifically determined the apical plasma membrane expression of DeltaF508-CFTR but not that of a trafficking defective mutant potassium channel (KCNQ1). These data demonstrate that the modulation of the expression level of CFTR protein partners, like NHE-RF1, can rescue DeltaF508-CFTR activity.
Identification of L-selectin Binding Heparan Sulfates Attached to Collagen Type XVIII (2005)

L-selectin is a C-type lectin expressed on leukocytes that is involved in both lymphocyte homing to the lymph node and leukocyte extravasation during inflammation. Known L-selectin ligands include sulfated Lewis-type carbohydrates, glycolipids, and proteoglycans. Previously, we have shown that in situ detection of different types of L-selectin ligands is highly dependent on the tissue fixation protocol used. Here we use this knowledge to specifically examine the expression of L-selectin binding proteoglycans in normal mouse tissues. We show that L-selectin binding chondroitin/dermatan sulfate proteoglycans are present in cartilage, whereas L-selectin binding heparan sulfate proteoglycans are present in spleen and kidney. Furthermore, we show that L-selectin only binds a subset of renal heparan sulfates, attached to a collagen type XVIII protein backbone and predominantly present in medullary tubular and vascular basement membranes. As L-selectin does not bind other renal heparan sulfate proteoglycans such as perlecan, agrin, and syndecan-4, and not all collagen type XVIII expressed in the kidney binds L-selectin, this indicates that there is a specific L-selectin binding domain on heparan sulfate glycosaminoglycan chains. Using an in vitro L-selectin binding assay, we studied the contribution of N-sulfation, O-sulfation, C5-epimerization, unsubstituted glucosamine residues, and chain length in L-selectin binding to heparan sulfate/heparin glycosaminoglycan chains. Based on our results and the accepted model of heparan sulfate domain organization, we propose a model for the interaction of L-selectin with heparan sulfate glycosaminoglycan chains. Interestingly, this opens the possibility of active regulation of L-selectin binding to heparan sulfate proteoglycans, e.g. under inflammatory conditions.
Ex Vivo Expansion of Transplantable Human Hematopoietic Stem Cells: Where Do We Stand in the Year 2000? (2000)

Ex vivo expansion of hematopoietic precursors, progenitors and stem cells represents the modern era of cellular therapeutics in the 21st century. For the last 10 years, increasing means for identifying and purifying hematopoietic stem cells and cytokines have facilitated and improved the development of ex vivo stem cell expansion technology. However, technology has not yet reached a stage where ex vivo-expanded hematopoietic progenitors and stem cells can be used routinely for replacement therapy. Lessons learned over the past 10 years from investigations focused at developing optimal ex vivo stem cell expansion systems have continued to a much greater understanding of stem cell biology. This knowledge has led to novel attempts at ex vivo expansion of hematopoietic precursors, progenitors, and stem cells, and should facilitate development of a new generation of cellular therapeutics. This review addresses recent progress toward development of clinically useful protocols for stem cell expansion. In addition, we discuss the results of a limited number of clinical trials that address the efficacy of such procedures. Three major areas of ex vivo stem cell expansion that impact clinical feasibility are discussed, including: (1) selection of an optimal stem cell population for expansion, (2) definition of the desired characteristics of the expanded stem cell population to be used for engraftment, and (3) development of new reagents and procedures for expansion and infusion of hematopoietic progenitors and stem cells.
Head to the hinterlands with your practice? (1978)

An old woman sits on a bench, holding a purse labeled "G.O.P.," with Benjamin Harrison on the left and William McKinley on the right, vying for her attentions. Caption: Old Party (coyly)--Oh! you presidential aspirants are such flirts!
Substituent Effect on the Oxidation of Phenols and Aromatic Amines by Horseradish Peroxidase Compound I (1976)

A stopped-flow kinetic study shows that the reduction rate of horseradish peroxidase compound I by phenols and aromatic amines is greatly dependent upon the substituent effect on the benzene ring. Morever it has been possible to relate the reduction rate constants of monosubstituted substrates by a linear free-energy relationship (Hammett equation). The correlation of log (rate constants) with sigma values (Hammett equation) and the absence of correlation with sigma+ values (Okamoto-Brown equation) can be explained by a mechanism of aromatic substrate oxidations, in which the substrate gives an electron to the enzyme compound I and simultaneously loses a proton. The analogy which has been made with oxidation potentials of phenols or anilines strengthens the view that the reaction is only dependent on the relative ease of oxidation of the substrate. The rate constant obtained for p-aminophenol indicates that a value of 2.3 X 10(8) M-1 S-1 probably approaches the diffusion-controlled limit for a bimolecular reaction involving compound I and an aromatic substrate.
ISOLATION OF RAT PANCREATIC ISLETS BY DUCTAL INJECTION OF COLLAGENASE1 (1986)

SUTTON, ROBERT; PETERS, MAUREEN; MCSHANE, PHILIP; GRAY, DEREK W. R.; MORRIS, PETER J. Author Information
Nearest Neighbor Search in General Metric Spaces Using a Tree Data Structure with a Simple Heuristic (2003)

We present a new algorithm for nearest neighbor search in general metric spaces. The algorithm organizes the database into recursively partitioned Voronoi regions and represents these partitions in a tree. The separations between the Voronoi regions as well as the radius of each region are used with triangular inequality to derive the minimum possible distance between any point in a region and the query and to discard the region from further search if a smaller distance has already been found. The algorithm also orders the search sequence of the tree branches using the estimate of the minimum possible distance. This simple heuristic proves to considerably enhance the pruning of the search tree. The efficiency of the algorithm is demonstrated on several artificial data sets and real problems in computational chemistry.
The initial steps of ovarian cancer cell metastasis are mediated by MMP-2 cleavage of vitronectin and fibronectin (2008)

Most patients (80%) with ovarian cancer (OvCa) present with metastatic disease. Attachment of OvCa cells to peritoneum and omentum represents the first rate-limiting step for metastatic spread. Therefore, identifying factors regulating cell attachment in the abdominal cavity is critical to the development of therapeutic agents. We show here that MMP-2 expression was upregulated in OvCa cells upon attachment to their microenvironment. Downregulation of MMP-2 mRNA or pharmacological inhibition of MMP-2 proteolytic function, in both human OvCa primary cells and cell lines, reduced attachment of OvCa cells to a 3D organotypic model of metastatic OvCa, full human omentum or peritoneum, and in vivo to mouse peritoneum and omentum. Absence of MMP-2 in the host did not alter OvCa adhesion, as determined utilizing mice harboring homozygous null mutations in either the Mmp2 or Mmp9 genes. Conversely, adhesion induced upregulation of MMP-2 mRNA in OvCa cells. MMP-2 inhibition in OvCa cells through pharmacological or antibody treatment prior to i.p. dissemination in nude mice significantly decreased tumor growth and metastasis and extended survival. MMP-2 enhanced peritoneal adhesion of OvCa cells through cleavage of ECM proteins fibronectin (FN) and vitronectin (Vn) into small fragments and increased binding of OvCa cells to these FN and Vn fragments and their receptors, alpha5beta1 and alphaVbeta3 integrin. These findings indicate that MMP-2 expressed by metastatic OvCa cells functionally regulates their attachment to peritoneal surfaces.
Central pain: an overview. (2002)

Central pain is a particular form of neuropathic pain. Due to lesions in the spinothalamocortical pathways, ectopic neuronal discharges can occur into different neurons of the spinal cord and brain. Functional MRI, and positron emission tomography might be able to visualize ongoing pain activity which is, sometimes the consequence of spinothalamocortical lesions. Sometimes the patient experiences a burning ice-like sensation. This is more frequent in spinal cord lesions than in brain injuries. Some adrenergic, gabergic neurotransmitters, glycine, prostanoids and glutamate may play a role in pain transmission. These transmitters can induce changes in the neuronal membrane potential. Consequently, amitriptyline as an adrenergic reuptake inhibitor and the sodium channel blockers are the drugs of first-choice. A test procedure with placebo, opioids, lignocaine, propofol and ketamine might give some insight into advanced drug treatment. If oral or transdermal drug delivery is not indicated or ineffective, the intrathecal administration route can be attempted with baclofen, clonidine, opioids and midazolam. Invasive electrostimulation is the last treatment option. Thalamic stimulation can be tried in spinal cord injuries, and sensory motor cortex stimulation is sometimes the last resort for brain lesions associated with pain.
Phosphorus-31 nuclear magnetic resonance study of alkaline phosphatase: the role of inorganic phosphate in limiting the enzyme turnover rate at alkaline pH (1976)

<P>Abstract copyright UK Data Service and data collection copyright owner.</P>
Determination of 24,25‐dihydroxyvitamin D3 in human plasma using liquid chromatography‐mass spectrometry after derivatization with a Cookson‐type reagent (2001)

A practical LC-MS method for determination of (24R)-24,25-dihydroxyvitamin D(3) [24,25(OH)(2)D(3)] in human plasma has been developed using derivatization with a Cookson-type reagent, 4-[4-(6-methoxy-2-benzoxazolyl)phenyl]-1,2,4-triazoline-3,5-dione (MBOTAD). The derivatization with MBOTAD significantly improved the ionization efficiency of the analyte with a detection limit of 18 fmol [equivalent to 7.5 pg of 24,25(OH)(2)D(3)] per injection. The method employed protein precipitation with acetonitrile, purification with OASIS HLB cartridge and silica gel column, derivatization with MBOTAD and atmospheric pressure chemical ionization MS detection. The mass spectrometer was operated in the positive-ion mode of mass chromatography and [26,26,26,27,27,27-(2)H(6)]-24,25(OH)(2)D(3) was used as an internal standard. The intra- and inter-assay coefficients of variation were below 3.4 and 2.5%, respectively, and the analytical recovery of 24,25(OH)(2)D(3) was quantitative. Assay linearity was obtained in the range of 0.05-1.2 ng per tube and the limit of quantitation was 0.23 ng/mL for a 0.3 mL plasma aliquot. The developed method was applied to plasma samples obtained from volunteers and gave satisfactory results.
Pathological and biochemical studies of fetal Krabbe disease (1994)

Morphological and biochemical analysis of tissue from a 21-week-old fetus with Krabbe disease was performed. Galactosylceramidase activity was virtually absent in cultured amniotic cells obtained during the pregnancy of this fetus. The prenatal diagnosis was confirmed by enzymatic analysis of fetal cultured skin fibroblasts and by enzyme analysis of fetal brain, kidney and liver. The galactocerebroside content of brain and spinal cord of the affected fetus was essentially identical to that observed in an age-matched control fetus. Accumulation of galactosylsphingosine was found in all tissues examined from the fetus with Krabbe disease. The highest galactosylsphingosine level was detected in spinal cord of the affected fetus: it was 40 times the concentration observed in controls. The occurrence of inclusion bodies were limited to spinal cord of the fetus with Krabbe disease. These data verify that the pathological and biochemical findings of Krabbe disease are present during the second trimester of pregnancy.
Suppression of Leakage Current in Solid-Phase Crystallization Silicon Thin-Film Transistors Employing Off-State-Bias Annealing (2009)

We have fabricated p-channel metal oxide semiconductor (PMOS) solid-phase crystallization silicon (SPC-Si) thin-film transistors (TFTs) employing an alternating magnetic field on a glass substrate, which exhibit better current uniformity than excimer-laser annealed low-temperature polycrystalline silicon (ELA LTPS) TFTs, and superior stability to hydrogenated amorphous silicon (a-Si:H) TFTs. The leakage current of the SPC-Si TFT was larger than that of an a-Si:H TFT and an ELA poly-Si TFT owing to its many grain boundaries. The leakage current of the SPC-Si TFT was successfully suppressed through off-state-bias annealing. Off-state-bias annealing forced electron carriers to be trapped in the gate insulator, thus reducing the gate–drain field and suppressing the leakage current of the SPC-Si TFT. Our experimental result showed that the trapped electron charges in the gate insulator did not escape under thermal annealing or AC-bias stress. The off-state-bias annealed PMOS SPC-Si TFT could be a suitable pixel element for high-quality display applications employing an alternating magnetic field.
The Foam Nose—A New Disposable Heat and Moisture Exchanger: A Comparison With Other Similar Devices (1979)

The Foam Nose (Kemi-Intressen AB), a heat- and moisture exchanger (HME), was compared with two other commercially available HME's with respect to its heat and moisture exchanging capacity. During steady state, 77% of the expired humidity is restored to the airways with the Foam Nose, 63% with HME Portex and 63% with HME Dameca.
DBMSs on a Modern Processor: Where Does Time Go? (1999)

Recent high-performance processors employ sophisticated techniques to overlap and simultaneously execute multiple computation and memory operations. Intuitively, these techniques should help database applications, which are becoming increasingly compute and memory bound. Unfortunately, recent studies report that they do not improve database system performance to the same extent as scientific workloads. Recent work on database systems focusing on minimizing memory latencies, such as cache-conscious algorithms for sorting and data placement, is one step toward addressing this problem. However, to best design high performance DBMSs, we must carefully evaluate and understand the processor and memory behavior of commercial DBMSs on today’s hardware platforms. In this paper we answer the question &amp;amp;quot;Where does time go when a database system executes on a modern computer platform? &amp;amp;quot; We examine four commercial DBMSs running on an Intel Xeon and NT 4.0. We introduce a framework for analyzing query execution time on a DBMS running on a server with a modern processor and memory architecture. To focus on processor and memory interactions and exclude effects from the I/O subsystem, we use a memory resident database. Using simple queues, we find that database developers should (a) optimize data placement for the second level of data cache, and not the first, (b) optimize instruction placement to reduce first-level instruction cache stalls, but (c) not expect the overall execution time to decrease significantly without addressing stalls related to subtle implementation issues (e.g., branch prediction). 1
A learning method for use in intelligent computer relays for high impedance faults (1991)

An attempt is made to find an intelligent detection system. This intelligent system has two specific properties. First, it is capable of taking advantage of multiple detection parameters or variables. Second, it provides adaptability using inductive reasoning, incorporated with some critic modules in a detection system. Inductive reasoning which will minimize entropy was used to acquire the knowledge of fault class and nonfault class. This knowledge was used to make the intelligent system adaptive to surrounding environments. A learning detection system was implemented with inductive reasoning and an event detector. An example execution is shown with a decision rule which was derived using training sample data consisting of high impedance faults, switching events, and normal status. A complicated set of test data is used to test the performance of the learning detection system. It is found that, even when it met very complicated situations, the learning detection system made smart decisions and evolved to a new situation with a newly derived decision rule.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Hereditary and Acquired Risk Factors for Childhood Stroke (1994)

Forty-four patients aged from one month to 16 years suffering from arterial stroke were carefully studied for any hereditary and acquired risk factors for stroke. No physiologic anticoagulant deficiency or antiphospholipid syndrome was found. Two patients had mitochondrial disease (MELAS). Six patients had migraineous stroke. Migraine and thrombotic disease in the families of the patients were not more prevalent than in the families of the controls. Preceding infections occurred in 34% of the patients, that is, significantly more common than in the age-matched controls. Two children had borreliosis. Repeat strokes occurred particularly in patients with migraine (n = 4) and MELAS (n = 2). The hereditary factors studied here seem to play only a minor role in pediatric patients. Repeated strokes have a varied etiology and are difficult to prevent. Important triggers of strokes are infections.
Quantification of maternal microchimerism by HLA‐specific real‐time polymerase chain reaction: Studies of healthy women and women with scleroderma (2004)

MMc is not uncommon in the peripheral blood of healthy adults, is increased in frequency in patients with SSc, and may be present in bone marrow and disease-affected tissues although absent in the peripheral blood.
Directed Electrophilic Cyclizations:  Efficient Methodology for the Synthesis of Fused Polycyclic Aromatics (1997)

A versatile method for the synthesis of complex, fused polycyclic aromatic systems in high chemical yield is described. Construction is achieved using a general two-step synthetic sequence. Pd-catalyzed Suzuki and Negishi type cross-coupling chemistries allow for the preparation of nonfused skeletal ring systems in yields consistently >80%. The critical ring-forming step, which generally proceeds in very high to quantitative yield, utilizes 4-alkoxyphenylethynyl groups and is induced by strong electrophiles such as trifluoroacetic acid and iodonium tetrafluoroborate. The reaction in essence produces phenanthrene moieties which are integrated into extended polycyclic aromatic structures. Fused polycyclic benzenoids as well as benzenoid/thiophene systems may be prepared utilizing this methodology. The scope of the described cross-coupling/cyclization chemistry including mechanistic insights and problematic side reactions are described.
Biomimetic High Density Lipoprotein Nanoparticles For Nucleic Acid Delivery (2011)

We report a gold nanoparticle-templated high density lipoprotein (HDL AuNP) platform for gene therapy that combines lipid-based nucleic acid transfection strategies with HDL biomimicry. For proof-of-concept, HDL AuNPs are shown to adsorb antisense cholesterylated DNA. The conjugates are internalized by human cells, can be tracked within cells using transmission electron microscopy, and regulate target gene expression. Overall, the ability to directly image the AuNP core within cells, the chemical tailorability of the HDL AuNP platform, and the potential for cell-specific targeting afforded by HDL biomimicry make this platform appealing for nucleic acid delivery.
Specific concentration of polynucleotide immune complexes in the cryoprecipitates of patients with systemic lupus erythematosus. (1975)

Although the association of cryoglobulinemia with hypocomplementemia and tissue injury in systemic lupus erythematosus is well recognized, composition of cryoprecipitates in terms of circulating antigens and antibodies in this disease is less clear. To clarify this question, cryoprecipitates from patients with SLE were examined with sensitive assay techniques for certain antipolynucleotide antibodies and DNA antigen. DNA antibodies were highly enriched relative to serum levels in the majority of cryoprecipitates. DNA antigen was also demonstrable. Antibody to ribonucleoprotein, although less frequently present, was similarly enriched in certain cryoprecipitates. In contrast, anti-double strand RNA, which was commonly detectable in relatively high titer in serum, was only minimally concentrated in a minority of cryoprecipitates. Absorption experiments using red blood cells heavily coated with polynucleotide antigen indicated that a major proportion of the IgG in certain cryoprecipitates was specific antibody. The data strongly suggest that the cryoprecipitates in systemic lupus erythematosus represent circulating immune complexes that are soluble at 37 degrees C and come out of solution in the cold. The marked concentration of immune complexes in the cryoglobulin offers a simple and direct method for determination of the nature of the complexes. The accumulated evidence obtained in the present study indicates that these complexes closely reflect, in their composition, the circulating immune complexes which are most significant pathogenetically in renal tissue injury.