gebhart/patrepeval huggingface dataset:
Familial ligand-defective apolipoprotein B. Identification of a new mutation that decreases LDL receptor binding affinity. (1995)

Detection of new ligand-defective mutations of apolipopro- tein B (apoB) will enable identification of sequences in- volved in binding to the LDL receptor. Genomic DNA from patients attending a lipid clinic was screened by singlestrand conformation polymorphism analysis for novel muta- tions in the putative LDL receptor-binding domain of apoB-100. A 46-yr-old woman of Celtic and Native Ameri- can ancestry with primary hypercholesterolemia (total cho- lesterol [TC] 343 mg/dl; LDL cholesterol [LDL-C] 241 mg/ dl) and pronounced peripheral vascular disease was found to be heterozygous for a novel Arg3531-Cys mutation, caused by a C-T transition at nucleotide 10800. One unrelated 59yr-old man of Italian ancestry was found with the same mutation after screening 1,560 individuals. He had coronary heart disease, a TC of 310 mg/dl, and an LDL-C of 212 mg/ dl. A total of eight individuals were found with the defect in the families of the two patients. They had an age-and sex-adjusted TC of 24014 mg/dl and LDL-C of 169+10 mg/dl. This compares with eight unaffected family members with age-and sex-adjusted TC of 18512 mg/dl and LDL- C of 124+12 mg/dl. In a dual-label fibroblast binding assay, LDL from the eight subjects with the mutation had an affin- ity for the LDL receptor that was 63% that of control LDL. LDL from eight unaffected family members had an affinity of 91%. By way of comparison, LDL from six patients het- erozygous for the Arg3500-Gln mutation had an affinity of 36%. The percentage mass ratio of the defective Cys3531 LDL to normal LDL was 59:41, as determined using the mAb MB19 and dynamic laser light scattering. Thus, the defec- tive LDL had accumulated in the plasma of these patients. Using this mass ratio, it was calculated that the defective Cys353, LDL particles bound with 27% of normal affinity.
The Designer Cytokine Hyper-Interleukin-6 Is a Potent Activator of STAT3-dependent Gene Transcription in Vivoand in Vitro (1999)

Interleukin-6 (IL-6) triggers pivotal pathways in vivo. The designer protein hyper-IL-6 (H-IL-6) fuses the soluble IL-6 receptor (sIL-6R) through an intermediate linker with IL-6. The intracellular pathways that are triggered by H-IL-6 are not defined yet. Therefore, we studied the molecular mechanisms leading to H-IL-6-dependent gene activation. H-IL-6 stimulates haptoglobin mRNA expression in HepG2 cells, which is transcriptionally mediated as assessed by run-off experiments. The increase in haptoglobin gene transcription correlates with higher nuclear translocation of tyrosine-phosphorylated STAT3 and its DNA binding. As H-IL-6 stimulates STAT3-dependent gene transcription, we compared the molecular mechanism between IL-6 and H-IL-6. Transfection experiments were performed with a STAT3-dependent luciferase construct. The same amount of H-IL-6 stimulated luciferase activity faster, stronger, and for a longer period of time. Dose response experiments showed that a 10-fold lower dose of H-IL-6 stimulated STAT3-dependent gene transcription comparable with the higher amount of IL-6. Cotransfection with the gp80 and/or gp130 receptor revealed that the effect of H-IL-6 on STAT3-dependent gene transcription is restricted to the gp80/gp130 receptor ratio. High amounts of gp130 increased and high amounts of gp80 decreased the effect on H-IL-6-dependent gene transcription. To investigate the in vivo effect of H-IL-6 on gene transcription in the liver, H-IL-6 and IL-6 were injected into C3H mice. H-IL-6 was at least 10-fold more effective in stimulating the DNA binding and nuclear translocation of STAT3, which enhances haptoglobin mRNA and protein expression. Thus H-IL-6 stimulates STAT3-dependent gene transcription in liver cells in vitro and in vivo at least 10-fold more effectively than IL-6. Our results provide evidence that H-IL-6 is a promising designer protein for therapeutic intervention during different pathophysiological conditions also in humans.
Solution Structure of the Antitumor Candidate Trunkamide A by 2D NMR and Restrained Simulated Annealing Methods (2002)

Trunkamide A (1) is a cyclic heptapeptide extracted from the ascidian Lissoclinum sp. and has shown very promising cytotoxic activity. This compound incorporates several of the motifs commonly observed in the Patellin family, including dimethylallyl (Dma) Thr and Ser side chains and a thiazoline heterocycle. Given that little is known about the structures adopted by the cyclopeptides of the Patellin family, and with the aim of establishing structure-activity relationships, we have carried out the conformational analysis of trunkamide A by a combination of 2D NMR experiments and simulated annealing calculations. Our results show that the conformation of 1 is very rigid and is dominated by the volume of the dimethylallyl side chains and two trans-annular hydrogen bonds. We have also studied the conformation of 2, the l-Phe diastereoisomer of 1, the analysis of which provides a possible rationale for its epimerization to 1, a process that is observed in solution. Finally, we show how a thorough NMR characterization can be used, in combination with simulated annealing methods, to confirm the configuration of a stereogenic center in the backbone of a rigid cyclic peptide such as trunkamide A (1).
Ion-Beam-Etched Profile Control of MTJ Cells for Improving the Switching Characteristics of High-Density MRAM (2006)

The effect of the reduction of the sidewall redeposition layer of magnetic materials is investigated for submicron-patterned magnetic random access memory (MRAM) cells. The sidewall redeposition layer is made at the first etch step of a magnetic tunnel junction (MTJ) with ion beam etching (IBE) in the case that the sidewall angle of a hard mask is steep. By controlling the etched profile at the time of the first IBE step, formation of the redeposition layer is prevented. Functional test results of 1-Kb MRAM arrays show that the sidewall redeposition layer enlarges fluctuation of switching current, and reduces the write operation region. The effect of the sidewall redeposition on the switching characteristics of MRAM arrays is explained qualitatively by micromagnetic simulation solving the Landau-Lifshitz-Gilbert (LLG) equation
Fiber-top refractometer (2009)

We present a fiber-top device designed to measure variations of the refractive index of a liquid in which it is immersed. The sensitivity achieved with this first prototype is on the order of one part over 105 in a 30 kHz bandwidth. With a proper design, the device performs well also when immersed in liquids with refractive index equal to the refractive index of the core of the fiber.
Induction of Inducible Nitric Oxide Synthase-NO· by Lipoarabinomannan ofMycobacterium tuberculosisIs Mediated by MEK1-ERK, MKK7-JNK, and NF-κB Signaling Pathways (2001)

Nitric oxide (NO*) expression by inducible nitric oxide synthase (iNOS) is an important host defense mechanism against Mycobacterium tuberculosis in mononuclear phagocytes. The objective of this investigation was to examine the role of mitogen-activated protein (MAP) kinase (MAPK) and nuclear factor kappaB (NF-kappaB) signaling pathways in the regulation of iNOS and NO* by a mycobacterial cell wall lipoglycan known as mannose-capped lipoarabinomannan (ManLAM). Specific pharmacologic inhibition of the extracellular-signal-regulated kinase (ERK) or NF-kappaB pathway revealed that both these signaling cascades were required in gamma interferon (IFN-gamma)-ManLAM-induced iNOS protein and NO2- expression in mouse macrophages. Transient cotransfection of dominant-negative protein mutants of the c-Jun NH2-terminal kinase (JNK) pathway revealed that the MAP kinase kinase 7 (MKK7)-JNK cascade also mediated IFN-gamma-ManLAM induction of iNOS promoter activity whereas MKK4 did not. Overexpression of null mutant IkappaBalpha, a potent inhibitor of NF-kappaB activation, confirmed that the IkappaBalpha kinase (IKK)-NF-kappaB signaling pathway enhanced IFN-gamma-ManLAM-induced iNOS promoter activity. By contrast, activated p38mapk inhibited iNOS induction. These results indicate that combined IFN-gamma and ManLAM stimulation induced iNOS and NO. expression and that MEK1-ERK, MKK7-JNK, IKK-NF-kappaB, and p38mapk signaling pathways play important regulatory roles.
Origin and True Nature of the Starter Unit for the Rapamycin Polyketide Synthase (2001)

Competition feeding experiments performed in vivo have identified 1 as the true starter unit for the rapamycin polyketide synthase, and indicate its potential application for generating novel analogues of this clinically important immunosuppresant molecule.
Protein Processing and Inflammatory Signaling in Cystic Fibrosis: Challenges and Therapeutic Strategies (2010)

Cystic Fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) that regulates epithelial surface fluid secretion in respiratory and gastrointestinal tracts. The deletion of phenylalanine at position 508 (DeltaF508) in CFTR is the most common mutation that results in a temperature sensitive folding defect, retention of the protein in the endoplasmic reticulum (ER), and subsequent degradation by the proteasome. ER associated degradation (ERAD) is a major quality control pathway of the cell. The majority (99%) of the protein folding, DeltaF508-, mutant of CFTR is known to be degraded by this pathway to cause CF. Recent studies have revealed that inhibition of DeltaF508-CFTR ubiquitination and proteasomal degradation can increase its cell surface expression and may provide an approach to treat CF. The finely tuned balance of ER membrane interactions determine the cytosolic fate of newly synthesized CFTR. These ER membrane interactions induce ubiquitination and proteasomal targeting of DeltaF508- over wild type- CFTR. We discuss here challenges and therapeutic strategies targeting protein processing of DeltaF508-CFTR with the goal of rescuing functional DeltaF508-CFTR to the cell surface. It is evident from recent studies that CFTR plays a critical role in inflammatory response in addition to its well-described ion transport function. Previous studies in CF have focused only on improving chloride efflux as a marker for promising treatment. We propose that methods quantifying the therapeutic efficacy and recovery from CF should not include only changes in chloride efflux, but also recovery of the chronic inflammatory signaling, as evidenced by positive changes in inflammatory markers (in vitro and ex vivo), lung function (pulmonary function tests, PFT), and chronic lung disease (state of the art molecular imaging, in vivo). This will provide novel therapeutics with greater opportunities of potentially attenuating the progression of the chronic CF lung disease.
Speech-Driven Expressive Talking Lips with Conditional Sequential Generative Adversarial Networks (2019)

Articulation, emotion, and personality play strong roles in the orofacial movements. To improve the naturalness and expressiveness of <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">virtual agents</i> (VAs), it is important that we carefully model the complex interplay between these factors. This paper proposes a conditional generative adversarial network, called <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">conditional sequential GAN</i> (CSG), which learns the relationship between emotion, lexical content and lip movements in a principled manner. This model uses a set of spectral and emotional speech features directly extracted from the speech signal as conditioning inputs, generating realistic movements. A key feature of the approach is that it is a speech-driven framework that does not require transcripts. Our experiments show the superiority of this model over three state-of-the-art baselines in terms of objective and subjective evaluations. When the target emotion is known, we propose to create emotionally dependent models by either adapting the base model with the target emotional data (CSG-Emo-Adapted), or adding emotional conditions as the input of the model (CSG-Emo-Aware). Objective evaluations of these models show improvements for the CSG-Emo-Adapted compared with the CSG model, as the trajectory sequences are closer to the original sequences. Subjective evaluations show significantly better results for this model compared with the CSG model when the target emotion is happiness.
A prospective, randomized study of three surgical techniques for treatment of acute ruptures of the anterior cruciate ligament (1990)

Treatment of ACL tears is controversial. Recent reports on nonoperative treatment have shown poor results. Results after primary repair have deteriorated with time, leading to augmentation procedures that seem to have improved the results. However, there have been few prospective, randomized studies in this field. Our goal was to compare primary repair with a bone-patellar tendon-bone augmentation method and with a new method using the Kennedy Ligament Augmentation Device. One hundred fifty patients aged 16 to 50, all of whom had acute ACL tears, were randomized with the closed envelope method to one of three groups treated with open surgical methods. Fifty patients were treated with primary repair, 50 patients with patellar tendon augmentation, and 50 patients were augmented with the Kennedy Ligament Augmentation Device. All patients were operated on within 10 days of injury. The rehabilitation protocol was identical, consisting of a long leg cast for 2 weeks, followed by a brace with no weight-bearing and limited motion for 6 weeks. The patients were followed prospectively by one surgeon (LE) using the Lysholm functional score, Tegner activity level score, clinical evaluation and KT-1000 arthrometer at 6 months, 1, and 2 years. Three patients were lost to followup. There was no age or activity level difference between the groups. Sport activities led to 85% of the injuries, with skiing, soccer, and European handball representing 80% of injuries. All three groups reduced their activity level the 1st year. The repair group remained at the same level after 2 years.(ABSTRACT TRUNCATED AT 250 WORDS)
Unmasking of anti-ribosomal P autoantibodies in healthy individuals (1995)

Autoantibodies to the ribosomal P proteins (anti-P) are found almost exclusively in a subset of patients with systemic lupus erythematosus. To determine if anti-P autoantibodies are present in healthy individuals but in a masked state, sera from healthy adults were applied to affinity columns coated with ribosomes, and the affinity-purified fractions were analyzed for anti-P Abs by ELISA and immunoblot. Anti-P Abs were detectable in serum only after affinity chromatography, were predominantly of the IgG isotype, stained HEp-2 cells in the characteristic anti-P pattern, and demonstrated specificity for all three ribosomal P phosphoproteins. Using batch affinity chromatography, we identified anti-P autoantibodies in the affinity-purified serum fractions of 54 of 55 healthy individuals. Anti-P Abs from healthy adults generally bound less ribosomal P Ag per mg/ml IgG than anti-P from patients. Inhibition studies revealed that autologous serum contained an IgG inhibitor of anti-P Ab. We conclude that masked anti-P autoantibodies are present in the healthy population and hypothesize that detection of these autoantibodies in systemic lupus erythematosus represents disruption of these regulatory networks.
Multiple Transcription Factor Profiling by Enzyme-Linked Immunoassay (2002)

Transcription factor-DNA interactions have been widely studied in the regulation of gene expression. We have established an enzyme-linked immunoassay platform to quantify specific transcriptionfactor-DNA interactions. In our assay, dsDNA immobilized on a 96-well plate captures the transcriptionfactor from the nuclear extract of mammalian cells. The DNA-bound transcription factor is detected and quantified by enzyme-linked immunoassay using a transcription factor-specific antibody. We have profiled multiple transcription factors involved in inflammation including NFkappaB p50, NFkappaB p65, c-Rel, c-Fos, CREB-1, and ATF-2. When compared with the traditional electrophoretic mobility shift assay, the enzyme-linked immunoassay shows a 10-fold higher sensitivity, eliminates the use of radioactivity, allows for a high-throughput format, and is faster.
A Unified Algorithm for Boolean Shape Operations (1984)

A Boolean shape operation algorithm which is based on triangulation of potentially intersecting faces is proposed. The essential part of the algorithm is a method for mutual processing of intersecting triangular pairs. This triangulation method is very effective in simplifying the algorithm and in reducing the system size. The method is suitable for hardware implementation because the simple routines for processing the intersecting pairs appear frequently in the algorithm. In determining points on an intersecting line loop, previous computational results can be utilized to calculate the next point, helping to speed up the algorithm.
Cleavage behavior of calicheamicin gamma 1 and calicheamicin T. (1992)

Calicheamicin gamma 1 is a potent antitumor antibiotic that cleaves DNA with a high degree of specificity; there is much interest in the recognition process. We have investigated the DNA-cleaving properties of calicheamicin T, a truncated derivative of calicheamicin. We show that calicheamicin T cleaves DNA in a double-stranded fashion, indicating that the first two sugars are sufficient to facilitate binding of the aglycone in the minor groove. However, calicheamicin T cleaves DNA nonselectivity. This result suggests that cyclization kinetics do not determine the cleavage specificity of the intact drug. Instead, cleavage specificity probably reflects binding specificity. Because of the recognition sites reported in the original cleavage paper, calicheamicin has been assumed to recognize oligopyrimidine DNA sequences containing G-C base pairs. We show here that calicheamicin also cuts efficiently at A.T tracts, sometimes in preference to G.C-rich homopyrimidine tracts. Crystallographic data and experiments with chemical probes indicate that DNA sequences including G.C base pairs have significantly different local conformations from DNA sequences containing several (four or more) sequential A.T base pairs. This difference makes it unlikely that calicheamicin simply senses inherent groove conformation and suggests that there is some degree of "induced fit." The ability to recognize both A.T- and G.C-rich oligopyrimidine sequences with a high degree of specificity makes calicheamicin an unusual minor-groove binder.
Single Administration of p2TA (AB103), a CD28 Antagonist Peptide, Prevents Inflammatory and Thrombotic Reactions and Protects against Gastrointestinal Injury in Total-Body Irradiated Mice (2014)

The goal of this study was to elucidate the action of the CD28 mimetic peptide p2TA (AB103) that attenuates an excessive inflammatory response in mitigating radiation-induced inflammatory injuries. BALB/c and A/J mice were divided into four groups: Control (C), Peptide (P; 5 mg/kg of p2TA peptide), Radiation (R; total body irradiation with 8 Gy γ-rays), and Radiation + Peptide (RP; irradiation followed by p2TA peptide 24 h later). Gastrointestinal tissue damage was evaluated by analysis of jejunum histopathology and immunohistochemistry for cell proliferation (Cyclin D1) and inflammation (COX-2) markers, as well as the presence of macrophages (F4/80). Pro-inflammatory cytokines IL-6 and KC as well as fibrinogen were quantified in plasma samples obtained from the same mice. Our results demonstrated that administration of p2TA peptide significantly reduced the irradiation-induced increase of IL-6 and fibrinogen in plasma 7 days after exposure. Seven days after total body irradiation with 8 Gy of gamma rays numbers of intestinal crypt cells were reduced and villi were shorter in irradiated animals compared to the controls. The p2TA peptide delivery 24 h after irradiation led to improved morphology of villi and crypts, increased Cyclin D1 expression, decreased COX-2 staining and decreased numbers of macrophages in small intestine of irradiated mice. Our study suggests that attenuation of CD28 signaling is a promising therapeutic approach for mitigation of radiation-induced tissue injury.
드론을 이용한 실시간 지하시설물도 작성 (2017)

본 연구는 1998년부터 2010년까지 84개 시군에 대한 지하시설물 전산화가 완료되고 2011년부터 신규로 배관공사가 이루어지거나 기존관로 유지보수 갱신 배관공사에 대하여 2010년 개정된 국토지리정보원 고시 공공측량작업규정 제134호의 지하시설물도 작성시기에서 정확도 확보를 위하여 되메우기 전 노출관로에 대한 위치 및 심도측량으로 지하시설물도를 작성하게 되어있다. 실시간으로 작성하게 되어 있는 지하시설물도의 작성기법에 대하여 기존 방식과 대비 더욱 효율적이면서 부가가치가 높은 방식으로써 예산절감효과를 도출하여 현업에 적용 할 수 있는 응용기술을 모색하는데 그 목적이 있다. 최적화 된 드론영상자료를 기본으로 지상기준점 배치가 최대한 균등하게 분포되도록 이미지 프로세싱을 수행하여 오차범위에서 벗어난 지상기준점을 소거하고 재프로세싱 하여 양질의 성과를 도출함으로써 드론방식의 지하시설물도를 작성, 허용오차 범위 내에서 수용되는 검증결과를 수립하고, 프로세싱방법의 표준화가 될 수 있는 새로운 작업방법을 제시하고자 한다.
An ultra-compliant, scalable neural probe with molded biodissolvable delivery vehicle (2012)

This paper describes an ultra-compliant parylene-platinum neural probe embedded in a biodissolvable delivery vehicle. High probe compliance is achieved using thin wires (width of 10.0 μm and thickness of 2.7 μm) and by meandering the probe. The insertion of the ultra-compliant probe is achieved by encasing it in a dissolvable delivery vehicle made from molded carboxy-methylcellulose. In vivo implantations of delivery vehicles with 1.5 mm long shanks, widths of 100 μm and 300 μm and a targeted thickness of 135 μm have been done through the dura in the cortex of Sprague-Dawley rats at a speed of 80 mm-s <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> . The delivery vehicle becomes a gel over a period of less than three minutes, after which the handling portions of the delivery vehicle are removed leaving the shanks embedded in the brain.
Lichtabsorption von Farbstoff-Molekülpaaren in Sandwichsystemen aus monomolekularen Schichten (1969)

Abstract The absorption spectra of cyanine-like dye molecules in monolayer assemblies are investigated. Pairs between two different dye molecules were obtained by superposing monolayers containing the first and second dye respectively. The spectra of these aggregates are compared with the spectra of the corresponding monomers. The spectral shifts are calculated theoretically using a perturbation approach based on the timedependent Schrödinger equation. The electronic interaction integrals are calculated from wave functions given by the onedimensional electron gas theory making allowance for the polarization of the π-electrons and the solvent. A quantitative agreement between predicted and observed shifts and intensity changes is found. It is concluded from our experiments that during the coating process of the second dye layer the dye molecules in this layer are able to diffuse within the layer to form pairs with the dye molecules fixed in the first layer.
A Carrot Leucine-Rich-Repeat Protein That Inhibits Ice Recrystallization (1998)

Many organisms adapted to live at subzero temperatures express antifreeze proteins that improve their tolerance to freezing. Although structurally diverse, all antifreeze proteins interact with ice surfaces, depress the freezing temperature of aqueous solutions, and inhibit ice crystal growth. A protein purified from carrot shares these functional features with antifreeze proteins of fish. Expression of the carrot complementary DNA in tobacco resulted in the accumulation of antifreeze activity in the apoplast of plants grown at greenhouse temperatures. The sequence of carrot antifreeze protein is similar to that of polygalacturonase inhibitor proteins and contains leucine-rich repeats.