gebhart/patrepeval huggingface dataset:
Thermodynamic basis of the enhanced specificity of structured DNA probes (1999)

Molecular beacons are DNA probes that form a stem-and-loop structure and possess an internally quenched fluorophore. When they bind to complementary nucleic acids, they undergo a conformational transition that switches on their fluorescence. These probes recognize their targets with higher specificity than probes that cannot form a hairpin stem, and they easily discriminate targets that differ from one another by only a single nucleotide. Our results show that molecular beacons can exist in three different states: bound to a target, free in the form of a hairpin structure, and free in the form of a random coil. Thermodynamic analysis of the transitions between these states reveals that enhanced specificity is a general feature of conformationally constrained probes.
Off-target effects by siRNA can induce toxic phenotype (2006)

Although recent microarray studies have provided evidence of RNA interference (RNAi)-mediated off-target gene modulation, little is known about whether these changes induce observable phenotypic outcomes. Here we show that a fraction of randomly selected small inhibitory RNAs (siRNAs) can induce changes in cell viability in a target-independent fashion. The observed toxicity requires an intact RNAi pathway and can be eliminated by the addition of chemical modifications that reduce off-target effects. Furthermore, an analysis of toxic and nontoxic duplexes identifies a strong correlation between the toxicity and the presence of a 4-base-pair motif (UGGC) in the RISC-entering strand of toxic siRNA. This article provides further evidence of siRNA-induced off-target effects generating a measurable phenotype and also provides an example of how such undesirable phenotypes can be mitigated by addition of chemical modifications to the siRNA.
Two different genes coding for fibronectin‐binding proteins from Streptococcus dysgalactiae (1993)

The binding of Streptococcus dysgalactiae to fibronectin involves fibronectin-binding protein(s) present on the bacterial surface. Previously, we reported the cloning of two different genes coding for cell-wall-associated fibronectin-binding proteins from S. dysgalactiae strain S2 [Lindgren, P.-E., Speziale, P., McGavin, M. J., Monstein, H.-J., Höök, M., Visai, L., Kostiainen, T., Bozzini, S. & Lindberg, M. (1992) J. Biol. Chem. 267, 1924-1931]. The two genes, fnbA and fnbB, have now been sequenced and the primary amino acid sequences of the two fibronectin-binding proteins, FnBA and FnBB, have been deduced. The two proteins have predicted molecular masses of 117 kDa and 122 kDa, respectively, and are organized in a similar way. The fibronectin-binding activities are localized in repeated motifs, 32-37 amino acids long, in the COOH-terminal regions of the proteins. The two fibronectin-binding proteins have heterologous amino acid sequences, except for the COOH-terminal ends which include the fibronectin-binding repeats. The fibronectin-binding regions of the genes have been fused to IgG-binding domains of protein A, utilizing the IgG-binding capacity of the resulting fusion proteins, to facilitate isolation of the fibronectin-binding domains.
Offloading security applications into the network (2014)

Users currently experience different levels of protection when accessing the Internet via their various personal devices and network connections, due to variable network security conditions and security applications available at each device. The SECURED project addresses these issues by designing an architecture to offload security applications from the end-user devices to a suitable trusted node in the network: the Network Edge Device (NED). Users populate a repository with their security applications and policy, which will then be fetched by the closest NED to protect the user's traffic when he connects to a network. This setting provides uniform protection, independent of the actual user device and network location (e.g. public WiFi hotspot or 3G mobile connection). In other words, a user-centric approach is fostered by this architecture, opposed to the current device- or network-based security schema, with cost and protection benefits and simultaneously enabling new business models for service and network providers.
Oral ketamine augmentation for chronic suicidality in treatment-resistant depression (2014)

griffith.edu.audecreased to 10 on the MADRS and 2 on the suicide item.She continued to receive monthly doses of oral ketamine and her mental state continued to improve with no suicide ideation between treatments.Pre-treatment blood tests included liver function tests and CBC with differential.Blood pressure and pulse rate were monitored before and 30 minutes after each dose.Neither patient experienced adverse events or significant changes in vital signs during the treatment.Although case reports require cautious consideration, these results are consistent with recent findings supporting the use of ketamine in treating severe depression.The possibility of using oral ketamine as a viable alternative to IV ketamine infusion is of special interest.1.
Triphosgene, a Crystalline Phosgene Substitute (1987)

Thermally stable, not very volatile, easy to transport and to store, accurately dosable —these are the advantages of bis(trichloromethyl) carbonate 1 as a substitute for phosgene. In addition, stoichiometric amounts of 1 suffice for chloroformylations, carbonylations, chlorinations, and dehydrations, which, moreover, proceed in good to very good yields. equation image
Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells (2014)

Valency requirements for B cell activation upon antigen encounter are poorly understood. OB1 transnuclear B cells express an IgG1 B cell receptor (BCR) specific for ovalbumin (OVA), the epitope of which can be mimicked using short synthetic peptides to allow antigen-specific engagement of the BCR. By altering length and valency of epitope-bearing synthetic peptides, we examined the properties of ligands required for optimal OB1 B cell activation. Monovalent engagement of the BCR with an epitope-bearing 17-mer synthetic peptide readily activated OB1 B cells. Dimers of the minimal peptide epitope oriented in an N to N configuration were more stimulatory than their C to C counterparts. Although shorter length correlated with less activation, a monomeric 8-mer peptide epitope behaved as a weak agonist that blocked responses to cell-bound peptide antigen, a blockade which could not be reversed by CD40 ligation. The 8-mer not only delivered a suboptimal signal, which blocked subsequent responses to OVA, anti-IgG, and anti-kappa, but also competed for binding with OVA. Our results show that fine-tuning of BCR-ligand recognition can lead to B cell nonresponsiveness, activation, or inhibition.
Migration of adaptive antennas into existing networks (2002)

This paper addresses migration of adaptive antennas into cellular networks with a conventional antenna technique. Two strategies can be distinguished: an operator can either install adaptive antennas in all cells in one step or gradually introduce adaptive antennas in a step-by-step manner. The latter method is preferred, since it results in lower introduction costs for the operator. The goal with this study has been to investigate whether the step-by-step migration is feasible. Simulations of a realistic heterogeneous network indicate that this approach is indeed possible.
Glycoprotein Complex Anchoring Dystrophin to Sarcolemma1 (1990)

We found six groups of proteins, A0-A5, besides dystrophin itself in a dystrophin preparation obtained by the reported method [Campbell, K.P. & Kahl, S.D.(1989) Nature 338, 259-262] with some modifications. Their molecular weights were 94, 62, 52, 43, 36, and 24 kDa, respectively. Their molar ratios to dystrophin were 0.14, 2.2, 0.88, 0.90, 1.7, and 0.34, respectively. Each of A1, A3, and A4 was split into several bands. But each group of bands except A3 seemed to behave like the same kind of protein. The doublet of A3 was subdivided into A3a and A3b in the decreasing order of molecular weight. All the A-proteins except A2 were cross-linked with dystrophin molecule by a cross-linker, bis(sulfosuccinimidyl)suberate, suggesting them to be dystrophin-associated proteins. When dystrophin preparation was treated with KI, which is known to break membrane cytoskeletal interactions, as described by Campbell and Kahl, A2, A3, and A4 were absorbed by wheat germ lectin (WGL) Sepharose, but the dystrophin molecule and A1 were not absorbed. On the other hand, A2 and A3b reacted with biotinyl WGL but A3a and A4 did not in blotting analysis. This apparent discrepancy can be explained if we postulate that A3a and/or A4 would associate with A2 and/or A3b. On the basis of these results including stoichiometric considerations, we are of the opinion that the complex of A2.A4 among various possible ones is the most important to anchor dystrophin to sarcolemma. In this A2.A4 complex, A4 but not A2 is directly associated with dystrophin.
Single-pulse coherent anti-Stokes Raman spectroscopy in the fingerprint spectral region (2003)

Quantum coherent control techniques are applied to achieve high spectral resolution nonlinear vibrational spectroscopy using a single ultrashort laser source. By controlling the spectral phase of ∼10 fs pulses, we are able to obtain detailed coherent anti-Stokes Raman (CARS) spectra in the important fingerprint spectral region, which reflects the structural chemical information. A full theoretical analysis and an experimental demonstration of two alternative schemes leading to spectral resolution two orders of magnitude better than the pulse bandwidth are presented. The first involves selective excitation of vibrational levels within the pulse bandwidth by periodic modulation of the spectral phase of the pulse. In the second scheme an effective narrow probing of the vibrational level has been achieved by phase shifting of a narrow spectral band. Single-pulse CARS offers an attractive alternative to conventional multibeam nonlinear vibrational spectroscopy techniques.
Endogenous interleukin‐10 suppresses allergen‐induced airway inflammation and nonspecific airway responsiveness (2000)

These results indicate that IL-10 plays an important and possibly direct role in the control of airway inflammation and responsiveness in an in vivo mouse model of allergy.
A Pilot Study to Evaluate the Effects of Perfusion-decellularized Porcine Hepatic-derived Wound Matrix on Difficult-to-heal Diabetic Foot Ulcers (2017)

These results suggest that PDPHD-WM may be an appropriate modality to treat difficult-to-heal DFUs, and a larger randomized placebo-controlled trial should be performed to investigate these findings. To the best of the authors' knowledge, this is the first collected data on using PDPHD-WM to treat DFUs.
Protocol issues for delayed Gd(DTPA)2--enhanced MRI (dGEMRIC) for clinical evaluation of articular cartilage (2001)

Biochemical and histologic data have validated the technique of delayed gadolinium-enhanced MRI, in which the T(1) values of cartilage after penetration of Gd(DTPA)2-allow assessment of the glycosaminoglycan (GAG) component of articular cartilage. This work describes the factors that have been found to be important for the practical implementation of the technique: 1) Exercise immediately after intravenous contrast administration was necessary for effective penetration of the contrast into the articular cartilage; 2) double-dose contrast was better than single-dose; 3) after contrast administration, a time window of 30-90 min for the hip, and 2-3 hr for all compartments of the knee proved to be appropriate for assessing articular cartilage; and 4) in some cases of hypointensities in the subchondral patellar bone, decreased penetration of the contrast agent into cartilage from bone was found. With the protocol described, ROIs on T(1) images were reproducible within 15% on two separate imaging sessions, and initial clinical studies demonstrated the possible applications of the technique. Magn Reson Med 45:36-41, 2001.
Reliability investigations for manufacturable high density PRAM (2005)

In this paper, PRAM (phase-change memory), exploiting new memory materials called chalcogenides, is introduced. The reliability issues for high-density commercial memory products such as disturbance immunity, endurance, and data retention are addressed and evaluated by using a 64 Mb PRAM with 0.12 /spl mu/m technology. Moreover, observed degradation modes and underlying physical mechanisms are investigated.
Nipah viral encephalitis or Japanese encephalitis? MR findings in a new zoonotic disease. (2000)

The brain MR findings in patients infected with the newly discovered Nipah paramyxovirus are different from those of patients with Japanese encephalitis. In a zoonotic epidemic, this striking difference in the appearance and distribution of lesions is useful in differentiating these diseases. Diffusion-weighted imaging was advantageous in increasing lesion conspicuity.
Highly specific off-target binding identified and eliminated during the humanization of an antibody against FGF receptor 4 (2011)

Off-target binding can significantly affect the pharmacokinetics (PK), tissue distribution, efficacy and toxicity of a therapeutic antibody. Herein we describe the development of a humanized anti- fibroblast growth factor receptor 4 (FGFR4) antibody as a potential therapeutic for hepatocellular carcinoma (HCC). A chimeric anti FGFR4 monoclonal antibody (chLD1) was previously shown to block ligand binding and to inhibit FGFR4 mediated signaling as well as tumor growth in vivo. A humanized version of chLD1, hLD1.vB, had similar binding affinity and in vitro blocking activity, but it exhibited rapid clearance, poor target tissue biodistribution and limited efficacy when compared to chLD1 in a HUH7 human HCC xenograft mouse model. These problems were traced to instability of the molecule in rodent serum. Size exclusion high performance liquid chromatography, immunoprecipitation and mass spectral sequencing identified a specific interaction between hLD1.vB and mouse complement component 3 (C3). A PK study in C3 knock-out mice further confirmed this specific interaction. Subsequently, an affinity-matured variant derived from hLD1.vB (hLD1.v22), specifically selected for its lack of binding to mouse C3 was demonstrated to have a PK profile and in vivo efficacy similar to that of chLD1 in mice. Although reports of non-specific off-target binding have been observed for other antibodies, this represents the first report identifying a specific off-target interaction that affected disposition and biological activity. Screens developed to identify general non-specific interactions are likely to miss the rare and highly specific cross-reactivity identified in this study, thus highlighting the importance of animal models as a proxy for avoiding unexpected clinical outcomes.
Pathways to relapse: the neurobiology of drug- and stress-induced relapse to drug-taking. (2000)

Relapse is a major characteristic of drug addiction, and remains the primary problem in treating drug abuse. Without an understanding of the factors that determine renewed drug-seeking, the urge to use drugs, and the persistent craving for them, it is unlikely that health care professionals can provide effective treatment. Using an animal model of relapse, the author and her team are studying factors that induce reinstatement of drug-taking behaviour after short and long periods of abstinence, and they are exploring the neurobiological basis of these effects. In their experiments, rats are trained to self-administer drugs intravenously by pressing 1 of 2 levers. During a subsequent period, the drug is no longer available, but the rats are free to try to obtain the drug (a period of "extinction training"). After extinction of responding, the investigators test for the ability of various events to reinitiate drug-seeking. On this background of renewed drug-seeking or relapse, the investigators search for pharmacological and neurochemical manipulations that might block or attenuate such behaviour. They have found that the 2 most effective events for reinstating responding after both short and long drug-free periods are re-exposure to the drug itself and exposure to a brief period of stress. The critical neurochemical pathways mediating drug-induced relapse are not identical to those mediating stress-induced relapse. Relapse induced by "priming" injections of heroin or cocaine involves activation of the mesolimbic dopaminergic pathways, whereas relapse induced by stress involves actions of corticotropin-releasing factor (CRF) in the brain, and of brain noradrenergic (NE) systems. In addition, evidence shows that CRF and NE may interact at the level of the bed nucleus of the stria terminalis in stress-induced relapse. By contrast, relapse induced by "priming" injections of drugs is relatively unaffected by manipulation of CRF and NE systems of the brain.
p21WAF1-derived peptides linked to an internalization peptide inhibit human cancer cell growth. (1997)

We tested the ability of synthetic peptides derived from p21(WAF1), fused to the internalization peptide sequence derived from Antennapedia, to inhibit the growth of cancer cells in two human ovarian cancer cell lines expressing wild-type p53 or not. Two fused peptides corresponding to p21(WAF1) regions 17-33 and 63-77 inhibited cell growth in both cell lines while the same peptides without the internalization sequence were inactive. The fused peptides prevented growth at concentrations which inhibited cyclin-dependent kinase 2 and cdc2 activity, thus demonstrating that the peptides act by mimicking the action of p21(WAF1) on kinases. This study illustrates the potential pharmacological use of small peptides fused with the Antennapedia internalization sequence in proliferative disorders. The approach may be extended to other diseases in which cell penetration of a peptide may be of therapeutic benefit. More stable drug-like molecules with better pharmacological properties could be designed based on the results obtained with peptides.
Association of Cyclooxygenase-1-Dependent and -Independent Platelet Function Assays With Adverse Clinical Outcomes in Aspirin-Treated Patients Presenting for Cardiac Catheterization (2009)

In this prospective study of 700 aspirin-treated patients presenting for angiographic evaluation of coronary artery disease, residual platelet COX-1 function measured by serum thromboxane B(2) and COX-1-independent platelet function measured by PFA-100 collagen-ADP CT, but not indirect COX-1-dependent assays (arachidonic acid-stimulated platelet markers, shortened PFA-100 collagen-epinephrine CT), correlate with subsequent major adverse cardiovascular events. This study suggests that multiple mechanisms, including but not confined to inadequate inhibition of COX-1, are responsible for poor clinical outcomes in aspirin-treated patients, and therefore the term aspirin resistance is inappropriate.
Bone morphogenetic protein receptors and activin receptors are highly expressed in ossified ligament tissues of patients with ossification of the posterior longitudinal ligament. (1997)

Ossification of the posterior longitudinal ligament (OPLL) is a pathological ossification in the spinal ligament, with formation of ectopic bone mainly through endochondral ossification. Bone morphogenetic proteins (BMPs) and activins are multifunctional proteins that belong to the transforming growth factor-beta superfamily and that have been implicated in the formation of new bone and cartilage. BMPs and activins signal via type I and type II receptors for BMPs (BMPRs) and activins (ActRs), respectively. OP-1/BMP-7 binds to BMPR-II and ActR-II and forms complexes with BMPR-IA and -IB and ActR-I. We studied the expression of BMPR-IA, -IB, and -II, ActR-I, ActR-II, and OP-1/BMP-7 by immunohistochemistry in ossified ligament tissues of patients with OPLL and control ligament tissues from patients with cervical disc herniation. The expression of BMPRs and ActRs was elevated in OPLL compared with controls. Expressions of BMPR-IA, -IB, and -II were observed not only in chondrocytes at the fibrocartilage tissue around the calcified zone but also in fibroblast-like spindle cells at the nonossified ligament. ActR-I and -II were found co-localized in the hypertrophic chondrocytes near the calcified zone and in the ossified tissue. OP-1/BMP-7 was expressed in chondrocytes near the calcified zone. In the control cases, the BMPRs and ActRs were only weakly expressed in the fibrocartilage tissue at the site of ligament attachments to bone and OP-1/BMP-7 was not detected. Enhanced expression of BMPRs at the nonossified ligament in OPLL patients suggests that these cells have a greater potential to differentiate into osteogenic cells than ligament cells from non-OPLL patients. The high expression of BMPRs and ActRs in the ectopic ossified ligament suggests that BMPs and activin may be tightly involved in the pathological ossification process of OPLL.
UNITE: a database providing web‐based methods for the molecular identification of ectomycorrhizal fungi (2005)

Identification of ectomycorrhizal (ECM) fungi is often achieved through comparisons of ribosomal DNA internal transcribed spacer (ITS) sequences with accessioned sequences deposited in public databases. A major problem encountered is that annotation of the sequences in these databases is not always complete or trustworthy. In order to overcome this deficiency, we report on UNITE, an open-access database. UNITE comprises well annotated fungal ITS sequences from well defined herbarium specimens that include full herbarium reference identification data, collector/source and ecological data. At present UNITE contains 758 ITS sequences from 455 species and 67 genera of ECM fungi. UNITE can be searched by taxon name, via sequence similarity using blastn, and via phylogenetic sequence identification using galaxie. Following implementation, galaxie performs a phylogenetic analysis of the query sequence after alignment either to pre-existing generic alignments, or to matches retrieved from a blast search on the UNITE data. It should be noted that the current version of UNITE is dedicated to the reliable identification of ECM fungi. The UNITE database is accessible through the URL http://unite.zbi.ee
Circulating levels of tumor necrosis factor soluble receptors in systemic lupus erythematosus are significantly higher than in other rheumatic diseases and correlate with disease activity. (1997)

To investigate the difference in acute phase protein responses between patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and spondyloarthropathies (SpA).Circulating levels of cytokines inducing the production of acute phase proteins such as interleukin (IL)-6, IL-1 beta, and tumor necrosis factor (TNF)-alpha, and of cytokine inhibitors such as TNF soluble receptors (TNF-sR55 and TNF-sR75) and IL-1 receptor antagonist (IL-1ra), were measured in 2 cohorts of patients. The first cohort included 52 patients with SLE and 22 with RA, and the second included 21 with SLE, 20 with RA, and 18 with SpA. An examination at the time of blood collection and the Systemic Lupus Activity Measure (SLAM) index were used to assess disease activity in patients with SLE. Serum levels of IL-6 were measured using a biological assay, and concentrations of IL-1 beta, TNF-alpha, TNF-sR55, TNF-sR75, and IL-1ra were assessed by immunoassays.Although C-reactive protein (CRP) levels were significantly lower in SLE than in RA or SpA, the concentrations of circulating IL-6 or TNF-alpha were higher in SLE. The most striking observation was that TNF-sR levels were significantly higher in SLE than in RA or SpA. The TNF-alpha: TNF-sR ratio was also significantly lower in SLE than in RA. TNF-sR55 and TNF-sR75 levels correlated with disease activity in SLE.The weak acute phase protein response in SLE may be explained by a decreased ratio between inducing cytokines and their inhibitors. In addition, TNF-sR may prove a useful biological marker for the followup of SLE, where acute phase protein response is generally low during disease exacerbations.