gebhart/patrepeval huggingface dataset:
Evaluation of Rearfoot Asymmetries in Running with Worn and New Running Shoes (1988)

The purpose of this study was to identify the kinematic characteristics of bilateral rearfoot asymmetry during heel–toe running under two experimental conditions: worn (broken-in) running shoes and new (standardized) running shoes. High-speed cinematography (150 fps) was used to film the lower limbs of four male runners in the frontal plane while running on a treadmill at their training pace. Six successive footfalls were analyzed for each subject and selected kinematical variables of the rearfoot function were calculated. Significant asymmetries were found in lower leg angle and Achilles tendon angle at touchdown and at maximum pronation. Total pronation and rearfoot angle were almost symmetric. The angular displacement graphs for the shank and foot revealed a distinct overall asymmetry between the lower limbs in both conditions. The mean values of the kinematical asymmetries were appreciably higher in the new shoe condition. It is proposed that the degree of these asymmetries is subject to changes due to injury, personal running style, and stability of the running shoe. Trends of bilateral dominance specific to rearfoot control in running were identified.
Requirement of Salicylic Acid for the Induction of Systemic Acquired Resistance (1993)

It has been proposed that salicylic acid acts as an endogenous signal responsible for inducing systemic acquired resistance in plants. The contribution of salicylic acid to systemic acquired resistance was investigated in transgenic tobacco plants harboring a bacterial gene encoding salicylate hydroxylase, which converts salicylic acid to catechol. Transgenic plants that express salicylate hydroxylase accumulated little or no salicylic acid and were defective in their ability to induce acquired resistance against tobacco mosaic virus. Thus, salicylic acid is essential for the development of systemic acquired resistance in tobacco.
Efficient Planar Single-Mode Fiber-to-Chip Coupler based on Two-Stage Adiabatic Evolution (2010)

A novel planar two-stage adiabatic single-mode fiber-to-chip coupler design is presented. The combination of rib and inverse tapers allows to make it 2–2.5 times shorter than state-of-the art inverse taper-based couplers with similar conversion efficiency.
Designed protein mimics of the Ebola virus glycoprotein GP2 α‐helical bundle: Stability and pH effects (2011)

Ebola virus (EboV) belongs to the Filoviridae family of viruses that causes severe and fatal hemhorragic fever. Infection by EboV involves fusion between the virus and host cell membranes mediated by the envelope glycoprotein GP2 of the virus. Similar to the envelope glycoproteins of other viruses, the central feature of the GP2 ectodomain postfusion structure is a six-helix bundle formed by the protein's N- and C-heptad repeat regions (NHR and CHR, respectively). Folding of this six-helix bundle provides the energetic driving force for membrane fusion; in other viruses, designed agents that disrupt formation of the six-helix bundle act as potent fusion inhibitors. To interrogate determinants of EboV GP2-mediated membrane fusion, we designed model proteins that consist of the NHR and CHR segments linked by short protein linkers. Circular dichroism and gel filtration studies indicate that these proteins adopt stable α-helical folds consistent with design. Thermal denaturation indicated that the GP2 six-helix bundle is highly stable at pH 5.3 (melting temperature, T(m) , of 86.8 ± 2.0°C and van't Hoff enthalpy, ΔH(vH) , of -28.2 ± 1.0 kcal/mol) and comparable in stability to other viral membrane fusion six-helix bundles. We found that the stability of our designed α-helical bundle proteins was dependent on buffering conditions with increasing stability at lower pH. Small pH differences (5.3-6.1) had dramatic effects (ΔT(m) = 37°C) suggesting a mechanism for conformational control that is dependent on environmental pH. These results suggest a role for low pH in stabilizing six-helix bundle formation during the process of GP2-mediated viral membrane fusion.
Use of Hybridization Probes in a Real-Time PCR Assay on the LightCycler<sup>®</sup> for the Detection of Methicillin-Resistant <i>Staphylococcus aureus</i> (2006)

The rapid and accurate identification of methicillin-resistant Staphylococcus aureus (MRSA) is of great importance for the affected patient, the involved ward, and the microbiological laboratory. Resistance to methicillin is encoded by the mecA gene in S. aureus. Because routine laboratory diagnostics may be time consuming and because species differentiation encounters a variety of difficulties, molecular techniques detecting both the mecA and a S. aureus-specific gene are used for rapid and accurate detection and identification of MRSA. Various protocols, including the manual extraction of DNA have been established. In this chapter, the identification of MRSA based on simultaneous detection of the mecA gene and the S. aureus-specific Sa442 DNA fragment using automated DNA extraction and real-time polymerase chain reaction is described. This method is an attractive alternative to labor-intensive manual protocols and can easily be incorporated into the diagnostic microbiology laboratory workflow, with the ability to obtain results within 4 h.
Isozyme-nonselective N-Substituted Bipiperidylcarboxamide Acetyl-CoA Carboxylase Inhibitors Reduce Tissue Malonyl-CoA Concentrations, Inhibit Fatty Acid Synthesis, and Increase Fatty Acid Oxidation in Cultured Cells and in Experimental Animals (2003)

Inhibition of acetyl-CoA carboxylase (ACC), with its resultant inhibition of fatty acid synthesis and stimulation of fatty acid oxidation, has the potential to favorably affect the multitude of cardiovascular risk factors associated with the metabolic syndrome. To achieve maximal effectiveness, an ACC inhibitor should inhibit both the lipogenic tissue isozyme (ACC1) and the oxidative tissue isozyme (ACC2). Herein, we describe the biochemical and acute physiological properties of CP-610431, an isozyme-nonselective ACC inhibitor identified through high throughput inhibition screening, and CP-640186, an analog with improved metabolic stability. CP-610431 inhibited ACC1 and ACC2 with IC50s of approximately 50 nm. Inhibition was reversible, uncompetitive with respect to ATP, and non-competitive with respect to bicarbonate, acetyl-CoA, and citrate, indicating interaction with the enzymatic carboxyl transfer reaction. CP-610431 also inhibited fatty acid synthesis, triglyceride (TG) synthesis, TG secretion, and apolipoprotein B secretion in HepG2 cells (ACC1) with EC50s of 1.6, 1.8, 3.0, and 5.7 microm, without affecting either cholesterol synthesis or apolipoprotein CIII secretion. CP-640186, also inhibited both isozymes with IC50sof approximately 55 nm but was 2-3 times more potent than CP-610431 in inhibiting HepG2 cell fatty acid and TG synthesis. CP-640186 also stimulated fatty acid oxidation in C2C12 cells (ACC2) and in rat epitrochlearis muscle strips with EC50s of 57 nm and 1.3 microm. In rats, CP-640186 lowered hepatic, soleus muscle, quadriceps muscle, and cardiac muscle malonyl-CoA with ED50s of 55, 6, 15, and 8 mg/kg. Consequently, CP-640186 inhibited fatty acid synthesis in rats, CD1 mice, and ob/ob mice with ED50s of 13, 11, and 4 mg/kg, and stimulated rat whole body fatty acid oxidation with an ED50 of approximately 30 mg/kg. Taken together, These observations indicate that isozyme-nonselective ACC inhibition has the potential to favorably affect risk factors associated with the metabolic syndrome.
Thrombolytic profiles of clot-targeted plasminogen activators. Parameters determining potency and initial and maximal rates. (1993)

The thrombolytic potency of the rscu-PA/antifibrin conjugates is determined by their clearance, as well as by rate and extent of initial binding to clots and by changes in binding during clot lysis. Clot targeting of rscu-PA with fibrin-specific antibodies increases its thrombolytic potency but does not alter the maximal rate or the minimal lag phase of clot lysis. These parameters appear to be independent of the nature of the plasminogen activator and of targeting.
Tissue-Specific Transformation by Oncogenic Mutants of Epidermal Growth Factor Receptor (1994)

Mutations in the receptor for the epidermal growth factor provide valuable insight into mechanisms of growth control. Oncogenic mutants of this receptor tyrosine kinase cause erythroid leukemia, fibrosarcoma, angiosarcoma, glioblastoma, and melanoma. Mutations in the avian protooncogene occur by retroviral mechanisms. Deletion of the ligand-binding domain results in erythroblastosis, while additional mutations in cytoplasmic structures broaden the disease potential to other cell types. A carboxyl-terminal structure of erbB oncogenes modulates growth responses in a complex, cell-specific manner; this tissue-specificity region appears to promote growth in erythroblasts and to produce trans-dominant inhibition in fibroblasts. Human glioblastoma multiforme frequently contains receptor mutations that are reminiscent of avian oncogenes. In hereditary melanoma of Xiphophorus, aberrant regulation of transcription by a recombinant promoter determines tissue-specific tumorigenesis. The diversity of oncogenic mutations raises important questions concerning the roles of several receptor structures. The extracellular domain inhibits the receptor when unoccupied by ligand, for example, through a mechanism that is unknown. The auto-phosphorylation sites are dispensable for transformation, so their function in neoplastic growth is unclear. The carboxyl-terminal region promotes or blocks transformation in different tissues, suggesting complex regulation by unknown cellular factors. These issues are critical to understanding of the mechanisms of receptor activation and tissue tropism for this family of oncogenes.
Structural Characterization of a Low Density Lipoprotein Receptor-active Apolipoprotein E Peptide, ApoE3-(126–183) (2000)

Apolipoprotein E (apoE) plays a critical role in lipoprotein particle clearance from blood plasma through its interaction with the low density lipoprotein (LDL) receptor and other related receptors. Here, we studied a 58-residue peptide encompassing the receptor binding region of apoE. ApoE3-(126-183) was generated by cyanogen bromide cleavage of recombinant apoE3-(1-183), purified by reversed-phase high pressure liquid chromatography, and characterized by mass spectrometry. Far UV CD spectroscopy of the peptide showed that it is unstructured in aqueous solution. The addition of trifluoroethanol or dodecylphosphocholine induces the peptide to adopt an alpha-helical conformation. ApoE3-(126-183) efficiently transforms dimyristoylphosphatidylglycerol (DMPG) vesicles into peptide-lipid complexes. Analysis of apoE3-(126-183). DMPG complexes by electron microscopy revealed disc-shaped particles with an average diameter of 13 +/- 3 nm. Flotation equilibrium analysis yielded a particle molecular mass of 252 kDa. Far UV CD analysis of apoE3-(126-183).DMPG discs provided evidence that the peptide adopts a helical conformation. Competition binding experiments with (125)I-labeled low density lipoprotein (LDL) were conducted to assess the ability of apoE3-(126-183).DMPG complexes to bind to the LDL receptor. Both N-terminal apoE and the peptide, when complexed with DMPG, competed with (125)I-LDL for binding sites on the surface of cultured human skin fibroblasts. Under the conditions employed, apoE3-(126-183).DMPG complexes were similar to apoE3-(1-183).DMPG discs in their ability to bind to the receptor, demonstrating that the peptide represents a good model to study the interaction between apoE and the LDL receptor. Preliminary NMR results indicated that a high resolution structure of the apoE3-(126-183) peptide is obtainable.
Evaluation of a potential epigenetic biomarker by quantitative methyl‐single nucleotide polymorphism analysis (2002)

Tumorigenesis is characterized by alterations of methylation profiles including loss and gain of 5-methylcytosine. Recently, we identified a single CpG, which seemed to be consistently hypomethylated in pilocytic astrocytomas but not in other gliomas. To evaluate its applicability as a biomarker, we examined its methylation status in a large panel of gliomas (n = 97). Methylation-dependent DNA sequence variation may be considered a kind of single nucleotide polymorphism (methylSNP). MethylSNPs can be easily converted into common SNPs of the C/T type by sodium bisulfite treatment of the DNA and afterwards subjected to conventional SNP typing. We adapted SnaPshot trade mark and Pyrosequencing trade mark to determine the methylation of our test CpG in a quantitative manner. The adapted methods, called SNaPmeth and PyroMeth, respectively, gave nearly identical results, however data obtained with PyroMeth showed less scattering. Furthermore, the integrated software for allele frequency determination from Pyrosequencing could be used directly for data analysis while SnaPmeth data had to be exported and processed manually. Although data did not confirm our previous result of a preferential hypomethylation of the tested CpG in pilocytic astrocytomas, we consider quantitative methylSNP analysis by SNaPmeth or PyroMeth a favorable alternative to existing high-throughput methylation assays. It combines single CpG analysis with accurate quantitation and is amenable to high throughput.
The Role of Sphingosine 1‐Phosphate Receptors in the Trafficking of Hematopoietic Progenitor Cells (2005)

Sphingosine 1-phosphate (S1P) is an ubiquitously present extracellular lipid mediator that is released by several cell types, particularly by activated platelets. The effects of S1P are mediated by a specific family of G protein-coupled sphingosine 1-phosphate receptors (S1P1-S1P5). We demonstrate that S1P acts on hematopoietic progenitor cells as a chemotactic factor, attracting peripheral blood CD34(+) cells in vitro. Furthermore, constant activation of S1P receptors augments CXCR4-mediated signal transduction induced by stromal cell-derived factor 1 (SDF-1). These effects are most likely mediated by the S1P1 receptor consistently expressed in both primitive and committed CD34(+) hematopoietic progenitor cells (HPCs). In vivo, sustained activation of S1P1 by a receptor agonist during the homing process resulted in increased engraftment. Given the fact that activated platelets represent a major source of extracellular S1P, SDF-1-mediated stem cell homing may occur at sites of tissue injury in addition to the bone marrow. This could explain the previously observed contribution of primary hematopoietic stem cells to tissue repair in myocardial infarction and other diseases.
Two neutralizing monoclonal antibodies against human granulocyte-macrophage colony-stimulating factor recognize the receptor binding domain of the molecule. (1990)

Using a series of mutant and chimeric human-mouse granulocyte-macrophage-CSF molecules the binding epitopes of two neutralizing mAb antibodies to human GM-CSF have been mapped. Both intact antibody and Fab fragments neutralize the biologic activity of human GM-CSF. The epitope of one of the antibodies contains residues widely separated in the primary structure of the growth factor that suggests that these two regions are adjacent in the tertiary structure of the molecule. In addition, evidence is presented that both mAb neutralize the activity of this cytokine by blocking the receptor binding domain of human GM-CSF.
Sporadic pediatric papillary thyroid carcinoma harboring the ETV6/NTRK3 fusion oncogene in a 7-year-old Japanese girl: a case report and review of literature (2018)

Genetic evaluation showed ETV6/NTRK3 fusion but no BRAF mutations or RET/PTC rearrangements. RET/PTC rearrangement and BRAF mutations often contribute to the pathogenesis of PTC; however, rearrangements of NTRK genes are relatively rare in pediatric PTC. Although NTRK rearrangement has been shown to often present unique pathological types and infiltrative architectures in the western population, such findings were not observed in this patient. Thus, the present case of classic PTC with ETV6/NTRK3 rearrangement highlights the disparate collection of clinic-pathological features compared to the trend in the western population. We therefore emphasize the need to further accumulate clinical as well as genetic data in pediatric PTCs.
Cytokine signaling in the brain: Putting a SOCS in it? (2002)

A new family of cytokine-inducible proteins, termed "suppressors of cytokine signaling" (SOCS), was discovered recently; these proteins function as negative regulators of signaling pathways involved in the cellular actions of many cytokines, growth factors, and hormones. Gene manipulation studies in mice point to the central importance of individual SOCS proteins in maintaining homeostasis by limiting cellular responses to specific cytokines or growth factors in a variety of different physiological systems. Cytokines modulate a wide variety of biological responses in the CNS, so members of the SOCS family might play crucial roles in regulating intracellular signaling by these effectors in both normal and disease states. Although to date studies of the neurobiology of the SOCS family have been limited, we know that many SOCS genes are constitutively expressed in the developing and adult brain, whereas the expression of others, particularly the SOCS1 and SOCS3 genes, can be highly regulated. Furthermore, roles for the SOCS are now evident in the modulation of neuroimmunoendocrine functions affected by a variety of cytokines, including leptin and members of the growth hormone and the interleukin-6/gp130 superfamilies. Overall, these findings point to the SOCS as likely crucial negative modulators in the temporal and spatial regulation and intensity of cytokine signaling and therefore actions in the CNS.
Inter-pulse interval between rectangular voltage pulses affects electroporation threshold of artificial lipid bilayers (2002)

This paper describes experiments that determine how the inter-pulse interval between rectangular pulses in a train of pulses alters the threshold of electroporation of 1-pamitoyl 2-oleoyl phosphatidycholine bilayer lipid membranes. The bilayers were exposed to a train of sixteen 100-micros duration pulses. Threshold voltage and the sequence number of the pulse in the train, where onset of the electroporation occurred, were recorded for six inter-pulse intervals (infinity, 1000 micros, 100 micros, 10 micros, 1 micros, 0 micros). The threshold voltage of the pulse train decreased linearly with the logarithm of the inter-pulse interval. When the inter-pulse interval was 1 microm, electroporation threshold dropped to that of a single pulse with duration 1600 micros (equal to the sum of all pulse durations in the train). In this case, the occurrence of bilayer rupture was almost equally frequent for all pulses in the train. When the inter-pulse interval between the pulses exceeded 1 micros, the influence of the previous pulse on the response to the following pulse declined. It became more likely that the bilayer ruptured during the first half of the train. These experimental observations suggest that a train of pulses applied with short inter-pulse interval (less than 1 ms) can lower the electroporation threshold of bilayer lipid membranes.
Nucleophilic Catalysis of Carbohydrate Oxime Formation by Anilines (2010)

Chemoselective formation of glycoconjugates from unprotected glycans is needed to further develop chemical biology involving glycans. Carbohydrate oxime formation is often slow, and organocatalysis by anilines would be highly promising. Here, we present that carbohydrate oxime formation can be catalyzed with up to 20-fold increases in overall reaction rate at 100 mM aniline. Application of this methodology provided access to complex glycoconjugates.
Human Papillomavirus Type 16-Positive Cervical Cancer Is Associated with Impaired CD4+ T-Cell Immunity against Early Antigens E2 and E6 (2004)

Cervical cancer is the possible outcome of genital infection with high-risk human papillomavirus (HPV) and is preceded by a phase of persistent HPV infection during which the host immune system fails to eliminate the virus. Fortunately, the majority of genital HPV infections are cleared before the development of (pre)malignant lesions. Analysis of CD4+ T-helper (Th) immunity against the E2, E6, and E7 antigens of HPV16 in healthy women revealed strong proliferative E2- and E6-specific responses associated with prominent IFN-gamma and interleukin 5 secretion. This indicates that the naturally arising virus-induced immune response displays a mixed Th1/Th2 cytokine profile. Of all HPV16+ cervical cancer patients, approximately half failed to mount a detectable immune response against the HPV16-derived peptides. The other half of the patients showed impaired HPV16-specific proliferative responses, which generally lacked both IFN-gamma and interleukin 5. This indicates that the HPV16-specific CD4+ T-cell response in cervical cancer patients is either absent or severely impaired, despite a relatively good immune status of the patients, as indicated by intact responses against recall antigens. It is highly conceivable that proper CD4+ T-cell help is important for launching an effective immune attack against HPV because infection of cervical epithelia by this virus is, at least initially, not accompanied by gross disturbance of this tissue and/or strong proinflammatory stimuli. Therefore, our observations concerning the lack of functional HPV16-specific CD4+ T-cell immunity in patients with cervical cancer offer a possible explanation for the development of this disease.
Structure of the intramolecular human telomeric G-quadruplex in potassium solution: a novel adenine triple formation (2007)

We report the NMR solution structure of the intramolecular G-quadruplex formed in human telomeric DNA in K(+). The hybrid-type telomeric G-quadruplex consists of three G-tetrads linked with mixed parallel-antiparallel G-strands, with the bottom two G-tetrads having the same G-arrangement (anti:anti:syn:anti) and the top G-tetrad having the reversed G-arrangement (syn:syn:anti:syn). The three TTA loop segments adopt different conformations, with the first TTA assuming a double-chain-reversal loop conformation, and the second and third TTA assuming lateral loop conformations. The NMR structure is very well defined, including the three TTA loops and the two flanking sequences at 5'- and 3'-ends. Our study indicates that the three loop regions interact with the core G-tetrads in a specific way that defines and stabilizes the unique human telomeric G-quadruplex structure in K(+). Significantly, a novel adenine triple platform is formed with three naturally occurring adenine residues, A21, A3 and A9, capping the top tetrad of the hybrid-type telomeric G-quadruplex. This adenine triple is likely to play an important role in the formation of a stable human telomeric G-quadruplex structure in K(+). The unique human telomeric G-quadruplex structure formed in K(+) suggests that it can be specifically targeted for anticancer drug design.