gebhart/patrepeval huggingface dataset:
The Use of Tranexamic Acid (AMCA) in lUDs as an Anti‐bleeding Agent (1976)

ABSTRACT Menstrual blood loss was evaluated in 200 women receiving a U‐coil intrauterine contraceptive device loaded with the antifibrinolytic, tranexamic acid (AMCA). The IUDs were inserted in patients at Ain Shams University, Cairo, Egypt, in May 1974; the women were followed up for 6 months. The AMCA‐loaded U‐coil has a core containing 38 mg of crystalline tranexamic acid loaded with a silastic tube 52 mm in length with an inside–outside diameter of 1.57–2.41 mm. The daily release rate of tranexamic acid was determined to be 4.3 μg with an initial high release of 29.0 μg. This group of women was compared to a similar group previously fitted with a copper loaded U‐coil. There were no pregnancies reported in either group, and expulsions were minimal. The 6‐month removal rates for the tranexamic acid U‐coil group was 1.1 per 100 acceptors. The corresponding figure for the copper comparison group was 9.9 per 100 acceptors. Reports of heavy menstrual bleeding were more prevalent at the one‐ and 3‐month follow‐ups for the copper U‐coil acceptors than for those using the AMCA loaded U‐coil. There were no apparent differences at the 6‐month follow‐up. The demonstrated capacity of tranexamic acid to reduce menstrual blood loss based on perceptual reports suggests that this agent can be valuable in increasing the acceptability and safety of intrauterine devices.
CAR's made it to the pancreas (2012)

Despite intensive treatment, pancreatic adenocarcinoma still has the worst prognosis among all malignancies. Using clinically relevant models, we demonstrated the therapeutic efficacy of adoptively transferred T cells engineered with a carcinoembryonic antigen (CEA)- and ERBB2-specific chimeric antigen receptor against pancreatic carcinoma. Targeting CD24, a putative cancer stem cell antigen expressed by a minority of carcinoma cells, was likewise effective.
DNA‐Templated Introduction of an Aldehyde Handle in Proteins (2016)

Many medical and biotechnological applications rely on protein labeling, but a key challenge is the production of homogeneous and site-specific conjugates. This can rarely be achieved by simple residue-specific random labeling, but generally requires genetic engineering. Using site-selective DNA-templated reductive amination, we created DNA-protein conjugates with control over labeling stoichiometry and without genetic engineering. A guiding DNA strand with a metal-binding functionality facilitates site-selectivity by directing the coupling of a second reactive DNA strand in the vicinity of a protein metal-binding site. We demonstrate DNA-templated reductive amination for His6 -tagged proteins and metal-binding proteins, including IgG1 antibodies. We also used a cleavable linker between the DNA and the protein to remove the DNA and introduce a single aldehyde on the protein. This functions as a handle for further modifications with desired labels. In addition to directing the aldehyde positioning, the DNA provides a straightforward route for purification between reaction steps.
A Critical Role for Eosinophils in Allergic Airways Remodeling (2004)

Features of chronic asthma include airway hyperresponsiveness, inflammatory infiltrates, and structural changes in the airways, termed remodeling. The contribution of eosinophils, cells associated with asthma and allergy, remains to be established. We show that in mice with a total ablation of the eosinophil lineage, increases in airway hyperresponsiveness and mucus secretion were similar to those observed in wild-type mice, but eosinophil-deficient mice were significantly protected from peribronchiolar collagen deposition and increases in airway smooth muscle. These data suggest that eosinophils contribute substantially to airway remodeling but are not obligatory for allergen-induced lung dysfunction, and support an important role for eosinophil-targeted therapies in chronic asthma.
A telemetry-instrumentation system for chronically implanted glucose and oxygen sensors (1988)

An implantable potentiostat-telemetry system for in vivo operation of glucose and oxygen sensors is described. The device conveys signals from implanted chemical-specific sensors to a remote receiver via radio telemetry. Reference signals encoded in the analog FM transmission allow the receiver to automatically compensate for variability between simultaneously operated transmitters. The implant has several programmable operating modes that provide different signal gain and power consumption. All-CMOS circuitry is used, allowing operation for up to three months on a single lithium cell. Design, fabrication, and operation of the device are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Mouse urinary peptides provide a molecular basis for genotype discrimination by nasal sensory neurons (2013)

Selected groups of peptides, including those that are presented by major histocompatibility complex (MHC) proteins, have been proposed to transmit information to the olfactory system of vertebrates via their ability to stimulate chemosensory neurons. However, the lack of knowledge about such peptides in natural sources accessible for nasal recognition has been a major barrier for this hypothesis. Here we analyse urinary peptides from selected mouse strains with respect to genotype-related individual differences. We discover many abundant peptides with single amino-acid variations corresponding to genomic differences. The polymorphism of major urinary proteins is reflected by variations in prominent urinary peptides. We also demonstrate an MHC-dependent peptide (SIINFEKL) occurring at very low concentrations in mouse urine. Chemoreceptive neurons in the vomeronasal organ detect and discriminate single amino-acid variation peptides as well as SIINFEKL. Hence, urinary peptides represent a real-time sampling of the expressed genome available for chemosensory assessment by other individuals.
DNA origami as biocompatible surface to match single-molecule and ensemble experiments (2012)

Single-molecule experiments on immobilized molecules allow unique insights into the dynamics of molecular machines and enzymes as well as their interactions. The immobilization, however, can invoke perturbation to the activity of biomolecules causing incongruities between single molecule and ensemble measurements. Here we introduce the recently developed DNA origami as a platform to transfer ensemble assays to the immobilized single molecule level without changing the nanoenvironment of the biomolecules. The idea is a stepwise transfer of common functional assays first to the surface of a DNA origami, which can be checked at the ensemble level, and then to the microscope glass slide for single-molecule inquiry using the DNA origami as a transfer platform. We studied the structural flexibility of a DNA Holliday junction and the TATA-binding protein (TBP)-induced bending of DNA both on freely diffusing molecules and attached to the origami structure by fluorescence resonance energy transfer. This resulted in highly congruent data sets demonstrating that the DNA origami does not influence the functionality of the biomolecule. Single-molecule data collected from surfaceimmobilized biomolecule-loaded DNA origami are in very good agreement with data from solution measurements supporting the fact that the DNA origami can be used as biocompatible surface in many fluorescence-based measurements.
Wnt‐3a regulates chondrocyte differentiation via c‐Jun/AP‐1 pathway (2005)

Our previous study indicated that interleukin (IL)-1beta induces expression of several Wnt proteins in chondrocytes and causes chondrocyte dedifferentiation via the c-Jun/activator protein-1 (AP-1) pathway. This study examined whether Wnt-3a causes chondrocyte dedifferentiation via the c-Jun/AP-1 pathway. Wnt-3a inhibited chondrogenesis of mesenchymal cells by stabilizing cell-cell adhesion in a manner independent of beta-catenin transcriptional activity. Wnt-3a also induced dedifferentiation of articular chondrocytes by stimulating the transcriptional activity of beta-catenin-T cell-factor/lymphoid-enhancer-factor (Tcf/Lef) complex. In chondrocytes, Wnt-3a caused the expression of c-Jun and its phosphorylation by c-Jun N-terminal kinase (JNK), resulting in activation of AP-1. AP-1 activation suppressed the expression of Sox-9, a major transcription factor regulating type II collagen expression. Collectively, our results suggest that Wnt-3a inhibits chondrogenesis by stabilizing cell-cell adhesion and that it causes dedifferentiation of chondrocytes by activating of beta-catenin-Tcf/Lef transcriptional complex and the c-Jun/AP-1 pathway.
Disruption of Virion Host Shutoff Activity Improves the Immunogenicity and Protective Capacity of a Replication-Incompetent Herpes Simplex Virus Type 1 Vaccine Strain (2000)

The virion host shutoff (vhs) protein encoded by herpes simplex virus type 1 (HSV-1) destabilizes both viral and host mRNAs. An HSV-1 strain with a mutation in vhs is attenuated in virulence and induces immune responses in mice that are protective against corneal infection with virulent HSV-1, but it has the capacity to establish latency. Similarly, a replication-incompetent HSV-1 strain with a mutation in ICP8 elicits an immune response protective against corneal challenge, but it may be limited in viral antigen production. We hypothesized therefore that inactivation of vhs in an ICP8(-) virus would yield a replication-incompetent mutant with enhanced immunogenicity and protective capacity. In this study, a vhs(-)/ICP8(-) HSV-1 mutant was engineered. BALB/c mice were immunized with incremental doses of the vhs(-)/ICP8(-) double mutant or vhs(-) or ICP8(-) single mutants, or the mice were mock immunized, and protective immunity against corneal challenge with virulent HSV-1 was assessed. Mice immunized with the vhs(-)/ICP8(-) mutant showed prechallenge serum immunoglobulin G titers comparable to those immunized with replication-competent vhs(-) virus and exceed those of mice immunized with the ICP8(-) single mutant. Following corneal challenge, the degrees of protection against ocular disease, weight loss, encephalitis, and establishment of latency were similar for vhs(-)/ICP8(-) and vhs(-) virus-vaccinated mice. Moreover, the double deleted vhs(-)/ICP8(-) virus protected mice better in all respects than the single deleted ICP8(-) mutant virus. The data indicate that inactivation of vhs in a replication-incompetent virus significantly enhances its protective efficacy while retaining its safety for potential human vaccination. Possible mechanisms of enhanced immunogenicity are discussed.
Immunochemical characterization of a polyclonal human antibody to factor IX (1977)

Inhibitors of clotting factors occuring in humans are often antibody molecules synthesized in response to exogeneous proteins used in replacement therapy. Extensive studies of inhibitors to factor VIII indicate such antibodies may be monoclonal or polyclonal in nature. To date, only one factor IX inhibitor has been subjected to detailed immunochemical analysis and it appears to be a monoclonal IgGA lambda antibody. We have discovered a second inhibitor of factor IX in a patient with severe hemophilia B and have subjected it to immunochemical analysis. Studies on this second inhibitor have been carried out before and after an anamnestic response. Column chromatography, preparative zone electrophoresis, and specific inhibitor neutralization assays using monospecific heterologous antisera to human immunoglobulin classes, subclasses, and light-chain types indicate that the antibody is of the IgG class and contains both kappa and lambda light chains and probably all four IgG subclasses. Thus, the inhibitor appears to be polyclonal by immunochemical and structural criteria. In addition, preparative isoelectric focusing of pre- and postanamnestic inhibitor samples indicates that recruitment of new clones of IgG antibody occurs as a result of anamnesis. It is conceivable that an antibody initially restricted in immunoglobulin subclass became polyclonal following an anamnestic response.
Sistema de calidad de los suministradores: influencia en los costes (1998)

La seleccion y calificacion de suministradores es uno de los eslabones basicos para la obtencion de la calidad, conjuntamente con la estrategia de mejora permanente, conocimiento del mercado y competencia, informacion y formacion de personas, y la cualificacion del grado de eficacia. Por ello, el Sistema de Calificacion de los Suministradores (SCS) se convertira en un sistema de gestion integral, en el que participaran activamente las areas administrativas, ejecutivas y de calidad, que proporcionara informacion en todo momento acerca de los suministradores, basado en una estructura documental y con el proposito de aportar al sistema de calidad de la empresa un valor anadido; a cumplir la normativa; y a potenciar la imagen de la empresa
Multizone Bifocal Contact Lens Design (1986)

A satisfactory bifocal contact lens has not yet reached the marketplace because of deficiencies in the present designs. The two-zone concentric design allows both the near and far images to be present simultaneously, however the image quality is not very good. Recently several new bifocal contact lenses with multiple zones have been suggested. This paper presents computer calculations of the image quality of several of these new designs. The zone-plate design, with an intermediate blaze angle, gives the best image quality of the lenses that were examined.
Refractive-index profiling of graded-index planar waveguides from effective indexes measured with different external refractive indexes (2000)

We extend the well-known inverse Wentzel-Kramer-Brillouin (WKB) method for refractive-index profiling of graded-index planar waveguides. We demonstrate, with numerical examples and experimental results, that the refractive-index profile of a graded-index planar waveguide can be calculated from effective indexes measured with different external refractive indexes. With this technique, single-mode and two-mode waveguides can be profiled easily to a good accuracy.
Molecular Dissection of the Human α2-Macroglobulin Subunit Reveals Domains with Antagonistic Activities in Cell Signaling (2008)

alpha(2)-Macroglobulin (alpha(2)M) is a plasma protease inhibitor, which reversibly binds growth factors and, in its activated form, binds to low density lipoprotein receptor-related protein (LRP-1), an endocytic receptor with cell signaling activity. Because distinct domains in alpha(2)M are responsible for its various functions, we hypothesized that the overall effects of alpha(2)M on cell physiology reflect the integrated activities of multiple domains, some of which may be antagonistic. To test this hypothesis, we expressed the growth factor carrier site and the LRP-1 recognition domain (RBD) as separate GST fusion proteins (FP3 and FP6, respectively). FP6 rapidly and robustly activated Akt and ERK/MAP kinase in Schwann cells and PC12 cells. This response was blocked by LRP-1 gene silencing or by co-incubation with the LRP-1 antagonist, receptor-associated protein. The activity of FP6 also was blocked by mutating Lys(1370) and Lys(1374), which precludes LRP-1 binding. FP3 blocked activation of Akt and ERK/MAP kinase in response to nerve growth factor-beta (NGF-beta) but not FP6. In PC12 cells, FP6 promoted neurite outgrowth and expression of growth-associated protein-43, whereas FP3 antagonized the same responses when NGF-beta was added. The ability of FP6 to trigger LRP-1-dependent cell signaling in PC12 cells was reproduced by the 18-kDa RBD, isolated from plasma-purified alpha(2)M by proteolysis and chromatography. We propose that the effects of intact alpha(2)M on cell physiology reflect the degree of penetration of activities associated with different domains, such as FP3 and FP6, which may be regulated asynchronously by conformational change and by other regulatory proteins in the cellular microenvironment.
Single, High-Dose Intraspinal Injection of Chondroitinase Reduces Glycosaminoglycans in Injured Spinal Cord and Promotes Corticospinal Axonal Regrowth after Hemisection but Not Contusion (2008)

Chondroitin sulfate proteoglycans (CSPGs) inhibit axonal growth, and treatment with chondroitinase ABC promotes axonal regeneration in some models of central nervous system (CNS) injury. The aims of this study were (1) to compare the spatiotemporal appearance of CSPG expression between spinal cord contusion and hemisection models, and (2) to evaluate chondroitinase treatment effects on axonal regrowth in the two injury models. After hemisection, CSPG-immunoreactivity (IR) in the injury site rose to peak levels at 18 days but then decreased dramatically by 49 days; in contrast, CSPG-IR remained high for at least 49 days after contusion. After hemisection, many anterogradely labeled corticospinal tract (CST) axons remained close to CSPG-rich lesion sites, but after contusion, most CST axons retracted by approximately 1 mm rostral from the rostral-most CSPG-rich cyst. Intraspinal injection of chondroitinase at 0, 1, 2, and 4 weeks following injury dramatically reduced CSPG-IR in both injury models within 4 days, and CSPG-IR remained low for at least 3 weeks. After the chondroitinase treatment, many axons grew around the lesion site in hemisected spinal cords but not in contused spinal cords. We propose that improved axonal growth in hemisected spinal cords is due to decreased inhibition resulting from degradation of CSPGs located adjacent to severed CST axons. However, in spinal cord contusions, retracted CST axons fail to grow across gliotic regions that surround CSPG-rich injury sites despite efficient degradation with chondroitinase, suggesting that other inhibitors of axonal growth persist in the gliotic regions.
Digital processing of ECG and PPG signals for study of arterial parameters for cardiovascular risk assessment (2015)

One of the biggest single cause of mortality in the world is cardiovascular disease (CVD) and hence it is recognized that an early detection of its onset is vital for effective preventive therapies. Aortic stiffness has been shown to be an independent predictor of CVD, but its measurement is complex and time consuming. An alternative much simpler way of doing it is by looking for arterial properties such as arterial stiffness. This paper presents methods of estimating arterial parameters from measured ECG and PPG signals. PPG signal can be acquired easily by measuring the transmission of infra-red light through the finger tip. Two methods of obtaining arterial parameters have been used, one using simultaneously acquired ECG and PPG signals and another using PPG signal only. Pulse wave velocity, which is an indicator of arterial stiffness, has been measured using pulse wave transmit time derived from simultaneously recorded ECG and PPG signals. Arterial parameters like stiffness index, augmentation index etc have been derived from the PPG signals. These parameters have been obtained for subjects in two age groups and it is observed that the parameters show clear changes for the two age groups thus demonstrating their efficacy in detecting changes in the arteries with age. Power spectral analysis has been performed to show how frequency spectra are different for the two age groups. This study demonstrates the usefulness of ECG and PPG analysis in investigating the changes in the arterial characteristics of the vascular system with age; it has potential applications in healthcare.
Direct Selective Functionalization of Nanometer-Separated Gold Electrodes with DNA Oligonucleotides (2003)

The ability to pattern a surface locally with different molecular monolayers in a well-controlled fashion and at nanoscale resolution has importance for molecular electronics and biotechnology applications, as well as for nanoengineering. Here, we report a new technique for selectively functionalizing closely spaced gold electrodes of separation below 50 nm with different thiolated oligonucleotides using a local, selective electrochemical desorption of a molecular protection layer followed by the subsequent adsorption of the oligonucleotides onto the exposed surface. This technique does not rely on the use of a local probe such as an atomic force microscope tip. We furthermore show that the surface-bound oligonucleotides retain their unique molecular recognition and self-assembly properties and so functionalize the electrode array.
Diabetic Retinopathy: A clinical overview (1992)

After an introductory summary, this review presents a description of the natural course of diabetic retinopathy, then briefly considers selected pathogenetic and epidemiological concepts, and concludes with a discussion of current treatment.
Calcium-dependent cell-cell adhesion molecules (cadherins): subclass specificities and possible involvement of actin bundles. (1987)

Cadherins are a family of cell-cell adhesion molecules and are divided into subclasses with distinct adhesive specificities and tissue distribution. Here we examined the distribution of cadherins at contact sites between cells expressing the same or different cadherin subclasses. Each cadherin was concentrated at the boundary between cells expressing an identical cadherin subclass, irrespective of the cell types connected. However, such localization decreased or disappeared at the boundary between cells containing different cadherin subclasses. We also found that the localization of cadherins precisely coincided with that of actin bundles; both were detected at the apical region of cell sheets. This co-localization was retained even after cells were either treated with cytochalasin D or extracted with the detergent NP40. These results suggest that each cadherin subclass preferentially interacts with its own molecular type at intercellular boundaries, and that cadherin molecules may be associated with actin-based cytoskeletal elements.
Quinazolineacetic acids and related analogs as aldose reductase inhibitors (1991)

A variety of 2,4-dioxoquinazolineacetic acids (10, 11) were synthesized as hybrids of the known aldose reductase inhibitors alrestatin (8), ICI-105,552 (9), and ICI-128,436 (2) and evaluated for their ability to inhibit partially purified bovine lens aldose reductase (in vitro) and their effectiveness to decrease galactitol accumulation in the 4-day galactosemic rat model (in vivo). In support to SAR studies, related analogues pyrimidinediones (12), dihydroquinazolones (13), and indazolidinones (14,15) were synthesized and tested in the in vitro and in vivo assays. All prepared compounds (10-15) have shown a high level of in vitro activity (IC50 approximately 10(-6) to 4 x 10(-8) M). However, only the 2,4-quinazolinedione analogues 10 and 11, with similar N-aralkyl substitution found in 2 and 9, have exhibited good oral potency. The remaining compounds were either inactive or had only a marginal in vivo activity. The structure-activity data support the presence of a secondary hydrophobic pocket in the vicinity of the primary lipophilic region of the enzyme.