gebhart/patrepeval huggingface dataset:
Mucosal Adjuvants (2005)

Vaccines delivered through mucosal surfaces are increasingly studied because of their properties to effectively induce mucosal immune responses, are cheap, easily administrable and suitable for mass vaccinations. The prospects of development of edible and intranasally administered (perhaps through nose drops or spray) vaccines are inciting a lot of interest and generating many studies. One major obstacle is to be able to induce systemic as well as mucosal responses to mucosal vaccines. Apart from immunizing with live viruses, this has proven to be a challenge and one way to overcome it is by using adjuvants. It is well established that toxins with little or no capacity to activate adenylate cyclase and thus lacking toxicity (CT or mutant Echerichia Coli labile toxin) improve performance of mucosal vaccines. Synthetic oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG) have synergistic action with other adjuvants, such as alum and CT when delivered mucosally. There are several other important candidates for use as mucosal adjuvants. The proinflammatory cytokines IL-1alpha, IL-12, and IL-18 can replace CT as a mucosal adjuvant for antibody induction and induce an increase of mucosal CTL's. IL-15 also has the potential to increase antigen-specific CTL activity when used as an adjuvant while IL-5 and IL-6 were shown to be able to markedly increase IgA reactivity to co-expressed heterologous antigen. Chemokines such as MCP-1 could also be used as potential adjuvant for mucosally administered DNA vaccines as it significantly increases mucosal IgA secretion and CTL responses.
Spectroscopic polarimetry with a channeled spectrum (1999)

We describe a novel method for the spectroscopic measurement of the state of polarization (SOP) of light. A pair of thick birefringent retarders is incorporated into the spectroscopic polarimeter, so the generated channeled spectrum is composed of three quasi-cosinusoidal components carrying the information about the SOP of the light that is being measured. Fourier inversion of the channeled spectrum provides significant parameters for determination of the spectrally resolved Stokes parameters of light. No mechanically movable components for polarization control or active devices for polarization modulation are used, and all the Stokes parameters can be determined at once from only the single spectrum. The effectiveness of this method is demonstrated by the generation of elliptically polarized light whose SOP varies with wave number.
Archaic to modern 2 (2006)

This is the second in a series of articles about converting archaic (66, 77) Fortran to modern (90, 95, 2003) Fortran. In the first, I discussed revision control (rcs), compilation control (make), and checking procedure interfaces and common blocks. The idea is to give an older, Fortran 77 (or earlier) code a check-up before trying to modify it. I also discussed automatic conversion of older Fixed Format source files to the modern Free Format. Free Format is easier to use, and can eliminate some problems present when using Fixed Format, mainly associated with searching for names. In this article, I'll discuss the Fortran kind mechanism for selecting types and the Fortran module for sharing data among procedures. Next, I'll try to tie the notions of agreement in type, kind, and rank, the use of procedure interfaces and common block consistency issues together with the use of modules.
Light paths in retinal vessel oximetry (2001)

The oxygen utilization and, therefore, the metabolic state, of a distinctive area of the retina may be calculated from the diameter of the supplying artery and vein, the haemoglobin oxygenation, and the velocity of the blood. The first two parameters can be determined by imaging spectrometry at the patients ocular fundus. However, the reflected light emerging from a vessel followed different pathways through the ocular fundus layers and the vessel embedded in the retina. The contribution of the single pathways to the vessel reflection profile is investigated by a Monte Carlo simulation. Considering retinal vessels with diameters of 25-200 microm we found the reflection from a thin vessel to be determined by the single and double transmission of light at 560 nm. The backscattering from the blood column determines the reflectance in the case of a thick vessel. However, both components are in the same order of magnitude. This has to be considered in the calculation of the oxygen saturation of blood in retinal vessels from their reflection spectra.
Neuronavigated rTMS in a patient with chronic tinnitus. Effects of 4 weeks treatment (2003)

Clinical, neurophysiological and neuroimaging data suggest that chronic tinnitus resembles neuropsychiatric syndromes characterised by focal brain activation. Low frequency repetitive transcranial magnetic stimulation (rTMS) has been proposed as an efficient method in treating brain hyperexcitability disorders. In one patient suffering from chronic tinnitus, [18F]deoxyglucose PET revealed increased metabolic activity in a circumscript area of the left primary auditory cortex (PAC). The effect of MRI and PET guided neuronavigated 1 Hz rTMS of this area was evaluated in a single-blind, sham-controlled, cross-over manner, followed by a 4-week open treatment. Following active stimulation there was a remarkable effect, enduring several weeks, on tinnitus sensation, which was paralleled by altered cortical excitability. These findings suggest that neuronavigated rTMS of increased PAC activity might offer a new option for treating auditory phantom perceptions like chronic tinnitus.
Isolation and functional characterization of the heavy and light chains of human tissue-type plasminogen activator. (1986)

Two-chain tissue-type plasminogen activator (t-PA), which consists of a heavy chain (Mr congruent to 38,000) and a light chain (Mr congruent to 31,000) connected by a disulfide bridge, was reduced with 2-mercaptoethanol and then air-reoxidized at a low protein concentration and carboxamidomethylated. The two chains were separated by means of zinc chelate-agarose, which was found to bind the light chain selectively. The light chain was fully active on the tripeptide substrate H-D-isoleucyl-L-prolyl-L-arginine p-nitroanilide (S-2288) and partially active on plasminogen. The plasminogen activator activity of the light chain was, in contrast to that of two-chain t-PA, not stimulated by fibrin or fibrinogen fragments. Fibrin-agarose chromatography of radiolabeled chains showed that only the heavy chain bound to fibrin. These results indicate that the active site-containing light chain in t-PA needs the heavy chain for fibrin stimulation of its plasminogen activator activity.
Human antibody responses to meningococcal outer membrane antigens after three doses of the Norwegian group B meningococcal vaccine (1995)

The antibody kinetics in sera from 27 adults after three doses of the Norwegian group B meningococcal outer membrane vesicle (OMV) vaccine was studied. The vaccinees received the third dose 4 to 5 years after the first two. Antibody responses against outer membrane proteins (OMPs) and lipopolysaccharides were studied by enzyme-linked immunosorbent assay and immunoblotting and with serum bactericidal assays (SBA) with three variants of the vaccine strain, 44/76. Six weeks after the second injection, the geometric mean (GM) of the levels of immunoglobulin G (IgG) against OMVs was about sevenfold higher than that of prevaccination levels, and 74% of the vaccinees developed a greater-than-twofold rise in SBA titer. After 6 months, the GM of IgG levels declined to about threefold higher, and after 4 to 5 years it declined to about twofold higher, than that before vaccination. The third dose induced a rapid increase in SBA titers in 96% of the vaccinees, and the GM of levels of IgG against OMVs rose to about 14-fold the prevaccination level. One year later, the IgG antibody levels had dropped to 4.6-fold the prevaccination level, but 88% of the vaccinees still showed bactericidal activity. The response after the two first doses was higher in individuals with prevaccination antibodies, but no such effect was found after three doses. The use of defined mutants in SBA and linear multiple regression analyses indicated that among the major OMPs, antibodies to the Opc and class 1 proteins made the most important single contributions to the bactericidal activity against the vaccine strain, but it also demonstrated the importance of antibodies against other antigens. After three doses, 68% of the vaccinees showed a significant SBA response against a strain lacking both the Opc and the class 1 proteins. Three doses converted almost all subjects to SBA responders and gave higher antibody levels and relatively less serosubtype-specific bactericidal activity than did two doses, probably indicating a broader cross-protection against heterologous strains.
Comparison of complete versus fragmented technetium-99m-labeled anti-CEA monoclonal antibodies for immunoscintigraphy in colorectal cancer. (1995)

Lesions known for their good vascularization, vascular permeability and antigen accessibility were detected earlier and with higher sensitivity with fragments than with complete MAbs due to faster background clearance despite lower absolute antibody uptake.
Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy (2018)

Current non-invasive approaches for detection of urothelial cancers are suboptimal. We developed a test to detect urothelial neoplasms using DNA recovered from cells shed into urine. UroSEEK incorporates massive parallel sequencing assays for mutations in 11 genes and copy number changes on 39 chromosome arms. In 570 patients at risk for bladder cancer (BC), UroSEEK was positive in 83% of those who developed BC. Combined with cytology, UroSEEK detected 95% of patients who developed BC. Of 56 patients with upper tract urothelial cancer, 75% tested positive by UroSEEK, including 79% of those with non-invasive tumors. UroSEEK detected genetic abnormalities in 68% of urines obtained from BC patients under surveillance who demonstrated clinical evidence of recurrence. The advantages of UroSEEK over cytology were evident in low-grade BCs; UroSEEK detected 67% of cases whereas cytology detected none. These results establish the foundation for a new non-invasive approach for detection of urothelial cancer.
Tactical Approaches to Interconverting GPCR Agonists and Antagonists (2015)

There are many reported examples of small structural modifications to GPCR-targeted ligands leading to major changes in their functional activity, converting agonists into antagonists or vice versa. These shifts in functional activity are often accompanied by negligible changes in binding affinity. The current perspective focuses on outlining and analyzing various approaches that have been used to interconvert GPCR agonists, partial agonists, and antagonists in order to achieve the intended functional activity at a GPCR of therapeutic interest. An improved understanding of specific structural modifications that are likely to alter the functional activity of a GPCR ligand may be of use to researchers designing GPCR-targeted drugs and/or probe compounds, specifically in cases where a particular ligand exhibits good potency but not the preferred functional activity at the GPCR of choice.
Inhibitors of the heat shock response: Biology and pharmacology (2007)

A number of human diseases can be linked to aberrations in protein folding which cause an imbalance in protein homeostasis. Molecular chaperones, including heat shock proteins, act to assist protein folding, stability and activity in the cell. Attention has begun to focus on modulating the expression and/or activity of this group of proteins for the treatment of a wide variety of human diseases. This review will describe the progress made to date in developing pharmacological modulators of the heat shock response, including both agents which affect the entire heat shock response and those that specifically target the HSP70 and HSP90 chaperone families.
New Lupane-type Triterpenoid Saponins from Leaves of Oplopanax horridus (Devil's Club) (2010)

Two new lupane type saponins, along with one known saponin were isolated from leaves of Oplopanax horridus (Devil's Club). The structures of the two new compounds were elucidated as 3alpha-hydroxy-lup-20(29)-ene-23, 28-dioic acid-3-O-beta-D-glucopyranoside (2) and 24-nor-3-oxo-lup-20(29)-en-28-oic acid-28-O-alpha-L-rhamnopyranosyl(1''' --> 4")-beta-D-glucopyranosyl(1" --> 6')-beta-D-glucopyranoside (3) on the basis of spectroscopic analysis and chemical evidence. The known compound was identified as 3alpha-hydroxy-lup-20(29)-ene-23, 28-dioic acid (1) by comparison of its spectral data with those reported. Compound 1 was isolated for the first time from the title plant.
Population reference intervals for minimal erythemal doses in monochromator phototesting (2009)

Results of the current investigation are broadly in agreement with values published 25 years ago by this centre. This validates the phototesting process based on the use of monochromators with attention to careful control of conditions during UV exposure and MED reading, supported by dosimetric calibration.
Force feedback for virtual reality based minimally invasive surgery simulator. (1996)

This paper presents ongoing research towards an endoscopic surgery simulation system. Our specific application of interest is laparoscopic surgery. The goal is to conceive an endoscopic surgical training tool which allows to realistically simulate the interactions between one or several surgical instruments and the gastrointestinal organs in a virtual reality based environment. An artificial patient is being developed into which endoscopic surgical instruments can be inserted to operate upon virtual organs displayed on a video monitor. In order to achieve a faithful and precise simulation, not only a realistic graphical representation of the organic tissue and its behavior is needed, but also the forces and moments on the surgical instruments encountered during an operation are required to be simulated. The laparoscopic surgery simulator must therefore provide force feedback through the endoscopic instruments manipulated by the surgeon. This paper details the mechanical design of the force feedback mechanisms and addresses some of the technical challenges of this project.
Maximum likelihood sequence estimators: a geometric view (1989)

Communication issues are described in terms of macro operations between the data and the observation spaces. The problem of recovering the data is related to the inversion of an operator (the channel mapping); for this reason results available in linear algebra and functional analysis are applicable. Traditional concepts in communications are identified with these operations. An approach to the maximum-likelihood sequence estimator based on a sufficient statistic derived from these concepts is proposed. Intersymbol interference is removed by linear equalization, and a Viterbi-like dynamic programming algorithm takes into account the correlated noise in the metric evaluation. The performance of suboptimal receivers obtained by means of metric simplification is analyzed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synthesis and properties of highly birefringent liquid crystalline materials: 2,5-bis(5-alkyl-2-butadinylthiophene-yl) styrene monomers (2009)

Abstract In order to obtain liquid crystals with high birefringence (Δn), a series of new liquid crystals monomers incorporating styrene, a 2,5-disubstituted thiophene ring and diacetylenes, which were highly conjugated along the molecular long axis, were synthesized. Their physical properties were evaluated. As expected, they exhibited high Δn values of 0.4–0.7 and a low melting point and were of potential use for polymer-dispersed liquid crystal displays (PDLCDs), cholesteric displays and laser beam steering applications. Keywords: high birefringenceliquid crystalsstyrene monomer Acknowledgement This research was supported by the National Natural Science Foundation of China (Grant nos: 20634010, 20874002, 20874003 and 20974002).
Efficient gene tagging in Arabidopsis thaliana using a gene trap approach (1997)

Large quantities of DNA sequence information about plant genes are rapidly accumulating in public databases, but to progress from DNA sequence to biological function a mutant allele for each of the genes ideally should be available. Here we describe a gene trap construct that allowed us to disrupt transcribed genes with a high efficiency in Arabidopsis thaliana. In the T-DNA vector used, the expression of a bacterial reporter gene coding for neomycin phosphotransferase II (nptII) depends on the in vivo generation of a translation fusion upon the T-DNA integration into the Arabidopsis genome. Analysis of 20 selected transgenic lines showed that 12 lines are T-DNA insertion mutants. The disrupted genes analyzed encoded ribosomal proteins (three lines), aspartate tRNA synthase, DNA ligase, basic-domain leucine zipper DNA binding protein, ATP-binding cassette transporter, and five proteins of unknown function. Four tagged genes were new for Arabidopsis. The results presented here suggest that gene trapping, using nptII as a reporter gene, can be as high as 80% and opens novel perspectives for systematic gene tagging in A. thaliana.
CDKN2 in HPV‐positive and HPV‐negative cervical‐carcinoma cell lines (1995)

Human cervical cancers frequently contain retinoblastoma protein (Rb) that is inactivated by binding with human papilloma virus (HPV) E7 protein or through mutation. The CDKN2 gene encodes p16INK4 which inhibits cdk4-cyclin D phosphorylation of Rb, preventing the G1-S transition. To determine whether abnormalities of CDKN2 occur in cervical-cancer cells, II cervical cell lines, including 8 HPV-positive cell lines, 2 HPV-negative cell lines containing mutant Rb, and one tumorigenic cell line derived from normal cervical cells following transfection with HPV-16 and v-H-ras (CX16-2HR), were analyzed. No cell line had a homozygous deletion of exon 1 or 2 of CDKN2, and only one cell line, CX16-2HR, had an altered DNA sequence, which represents a common polymorphism at codon 148. To exclude the possibility of other subtle inactivating mutations, immunoblot analysis of protein lysates was performed using a polyclonal anti-p16INK4 rabbit anti-serum. Abundant levels of normal-sized p16INK4 were observed in all cell samples. Thus, no alterations of CDKN2 were detected in these cervical cell lines. These results confirm that mutational inactivation of p16INK4 is a rare event in tumor samples with compromised Rb activity.
Preparation of 4-Hydroxy-2-trifluoromethylthiophene: A Novel Bioisostere of α,α,α-Trifluoro-m-cresol (2000)

A simple and convenient four-step synthesis of 4-hydroxy-2-trifluoromethylthiophene (1) a novel bioisostere of α,α,α-trifluoro-m-cresol is reported. The key step is the condensation between ethyl 3-methoxy-4,4,4-trifluorocrotonate and methyl thioglycolate to form methyl 3-hydroxy-5-trifluoromethylthiophene-2-carboxylate (6). Hydrolysis of the ester followed by decarboxylation furnishes 1. Multi-hundred gram quantities of 1 have been obtained utilizing the present procedure.
Axin Forms a Complex with MEKK1 and Activates c-Jun NH2-terminal Kinase/Stress-activated Protein Kinase through Domains Distinct from Wnt Signaling (1999)

Axin negatively regulates the Wnt pathway during axis formation and plays a central role in cell growth control and tumorigenesis. We found that Axin also serves as a scaffold protein for mitogen-activated protein kinase activation and further determined the structural requirement for this activation. Overexpression of Axin in 293T cells leads to differential activation of mitogen-activated protein kinases, with robust induction for c-Jun NH(2)-terminal kinase (JNK)/stress-activated protein kinase, moderate induction for p38, and negligible induction for extracellular signal-regulated kinase. Axin forms a complex with MEKK1 through a novel domain that we term MEKK1-interacting domain. MKK4 and MKK7, which act downstream of MEKK1, are also involved in Axin-mediated JNK activation. Domains essential in Wnt signaling, i. e. binding sites for adenomatous polyposis coli, glycogen synthase kinase-3beta, and beta-catenin, are not required for JNK activation, suggesting distinct domain utilization between the Wnt pathway and JNK signal transduction. Dimerization/oligomerization of Axin through its C terminus is required for JNK activation, although MEKK1 is capable of binding C terminus-deleted monomeric Axin. Furthermore, Axin without the MEKK1-interacting domain has a dominant-negative effect on JNK activation by wild-type Axin. Our results suggest that Axin, in addition to its function in the Wnt pathway, may play a dual role in cells through its activation of JNK/stress-activated protein kinase signaling cascade.
Glucose transport by human renal Na + / d -glucose cotransporters SGLT1 and SGLT2 (2010)

The human Na(+)/D-glucose cotransporter 2 (hSGLT2) is believed to be responsible for the bulk of glucose reabsorption in the kidney proximal convoluted tubule. Since blocking reabsorption increases urinary glucose excretion, hSGLT2 has become a novel drug target for Type 2 diabetes treatment. Glucose transport by hSGLT2 was studied at 37°C in human embryonic kidney 293T cells using whole cell patch-clamp electrophysiology. We compared hSGLT2 with hSGLT1, the transporter in the straight proximal tubule (S3 segment). hSGLT2 transports with surprisingly similar glucose affinity and lower concentrative power than hSGLT1: Na(+)/D-glucose cotransport by hSGLT2 was electrogenic with apparent glucose and Na(+) affinities of 5 and 25 mM, and a Na(+):glucose coupling ratio of 1; hSGLT1 affinities were 2 and 70 mM and coupling ratio of 2. Both proteins showed voltage-dependent steady-state transport; however, unlike hSGLT1, hSGLT2 did not exhibit detectable pre-steady-state currents in response to rapid jumps in membrane voltage. D-Galactose was transported by both proteins, but with very low affinity by hSGLT2 (≥100 vs. 6 mM). β-D-Glucopyranosides were either substrates or blockers. Phlorizin exhibited higher affinity with hSGLT2 (K(i) 11 vs. 140 nM) and a lower Off-rate (0.03 vs. 0.2 s⁻¹) compared with hSGLT1. These studies indicate that, in the early proximal tubule, hSGLT2 works at 50% capacity and becomes saturated only when glucose is ≥35 mM. Furthermore, results on hSGLT1 suggest it may play a significant role in the reabsorption of filtered glucose in the late proximal tubule. Our electrophysiological study provides groundwork for a molecular understanding of how hSGLT inhibitors affect renal glucose reabsorption.
Extracranial carotid arteries: evaluation with "black blood" MR angiography. (1990)

The authors evaluated the accuracy of "black blood" magnetic resonance (MR) angiography for depicting disease involving the extracranial carotid arteries. Two- and three-dimensional flow-compensated gradient-echo sequences were employed to create "bright blood" images. A thin-section spin-echo sequence with flow presaturation allowed the creation of black blood images. Projection angiograms were made from bright and black blood images with application of a maximum- or minimum-intensity projection algorithm, respectively. These methods were used in 13 healthy volunteers and 17 patients, and a prospective blinded comparison of MR angiography and conventional angiography was performed. Normal carotid arteries were well shown with both bright and black blood methods; in patients, both methods were sensitive for detecting carotid disease. However, bright blood angiography exaggerated the severity of carotid lesions in 13 of 33 arteries, mostly in severe disease; this problem was not encountered with black blood angiography. The authors conclude that bright blood angiography is a sensitive method for screening carotid disease; when a significant abnormality is found, black blood angiography should be performed for more precise delineation of the lesion.