gebhart/patrepeval huggingface dataset:
Low-Molecular Weight Inhibitors of Galectins (2012)

The galectins are known to be able to recognize and cross-link ß-D-galactopyranoside-containing glycoconjugates as a result of presenting multiple binding sites. This review summarizes efforts in our group for the last ten years towards low-molecular weight chemically modified carbohydrate derivatives. In addition to providing an avenue for improved affinity and galectin-selectivity, we have focused on the chemical synthesis of low-molecular weight inhibitors, since synthetic derivatives offer opportunities to design more “drug-like” in order to circumvent drawbacks typically associated with natural oligosaccharides and fragments, such as low affinity (high µM to mM for galectins), limited chemical and metabolic stability, and high polarity leading to low bioavailability and rapid clearance. The examples described in the review provide evidence that it is possible to improve both affinity and selectivity of low-molecular weight compounds for galectins by chemically modifying galactose (and other monosaccharides) with non-carbohydrate structural elements targeting ligand sub-sites flanking the core galactose-binding sub-site C. Indeed, inhibitors have been made that possess both low-nM affinities for galectins and that show potent in vivo efficacy. Hence, promising low-molecular weight galectin-targeting lead structures have been identified, although it remains to investigate and optimize ADME and toxicology aspects of these compounds in order to fully reach the status of identifying clinical candidates.
Immunohistochemical and subcellular localization of parkin protein: Absence of protein in autosomal recessive juvenile parkinsonism patients (1999)

Autosomal recessive juvenile parkinsonism (AR-JP) is a distinct clinical entity characterized by a selective degeneration of nigral neurons. Recently, the parkin gene responsible for AR-JP has been identified. Now, we report the subcellular localization of Parkin protein in patients with AR-JP or Parkinson's disease (PD) and in controls by immunoblotting and immunohistochemistry using antibodies raised against the Parkin molecule. Parkin protein was absent in all regions of the brains of patients with AR-JP. Parkin protein was not decreased in the brains of sporadic PD patients. Immunoreactivity was detected in a few Lewy bodies. Parkin protein was located in both the Golgi complex and cytosol.
Dok‐7 myasthenia: Phenotypic and molecular genetic studies in 16 patients (2008)

First, the clinical features of Dok-7 myasthenia are highly variable. Second, some mutations are complex and identifiable only in cloned complementary DNA. Third, Dok-7 is essential for maintaining not only the size but also the structural integrity of the EP. Fourth, the profound structural alterations at the EPs likely contribute importantly to the reduced safety margin of neuromuscular transmission.
Is asthma prevention possible with dietary manipulation? (2002)

What we know: Primary prevention of asthma should be possible because the recent increase in asthma is due to environmental factors. The major modifiable dietary environmental risk factors for childhood asthma are lack of breastfeeding and low intake of omega-3 fatty acids. Randomised controlled trials (RCTs) have shown that interventions using probiotics, hydrolysed milk formulas, and combined dietary manipulation plus airborne allergen avoidance reduce asthma and/or atopy in newborns. Observational studies have shown a 30%-50% reduction in childhood asthma with exclusive breastfeeding for three months, and similar reductions in children who eat fish regularly (ie, have a high intake of omega-3 fatty acids). What we need to know: Will further RCTs using intervention with probiotics reveal identifiable subgroups of children who respond and children who do not respond? Will supplementation of the diet with omega-3 oil reduce the rate of significant clinical atopic disease, particularly asthma? If so, for how long will supplements need to be given? Will effective primary prevention require multiple intervention strategies? If so, how feasible are these as public health interventions? What are the benefits and harms of allergen-avoidance diets in high-risk women who are breastfeeding? Can protein hydrolysate formulas reduce rates of atopy and/or asthma?
Magnetic Nanoparticle Sensors (2009)

Many types of biosensors employ magnetic nanoparticles (diameter = 5-300 nm) or magnetic particles (diameter = 300-5,000 nm) which have been surface functionalized to recognize specific molecular targets. Here we cover three types of biosensors that employ different biosensing principles, magnetic materials, and instrumentation. The first type consists of magnetic relaxation switch assay-sensors, which are based on the effects magnetic particles exert on water proton relaxation rates. The second type consists of magnetic particle relaxation sensors, which determine the relaxation of the magnetic moment within the magnetic particle. The third type is magnetoresistive sensors, which detect the presence of magnetic particles on the surface of electronic devices that are sensitive to changes in magnetic fields on their surface. Recent improvements in the design of magnetic nanoparticles (and magnetic particles), together with improvements in instrumentation, suggest that magnetic material-based biosensors may become widely used in the future.
Common and different antigenic properties of the rabies virus glycoprotein of strains SAD-Vnukovo and Pitman-Moore. (1992)

Two fixed rabies virus strains, SAD-Vnukovo and Pitman-Moore (PM) were used as combined immunogens for the generation of hybridomas secreting specific monoclonal antibodies (MoAbs). The obtained hybridomas were primarily screened by an ELISA for production of MoAbs to antigen of SAD-Vnukovo strain. Six positive clones were established. A panel of MoAbs has been characterized according to reactivity in immunofluorescence, immunoblot, ELISA and neutralization tests. All MoAbs were positive in immunofluorescence when cells infected with the SAD-Vnukovo strain were used. By immunoblot, four MoAbs showed specificity for the viral glycoprotein of both SAD-Vnukovo and PM rabies strains. This pattern of reactivity indicated the existence of shared conformation-independent epitopes located on the related antigens. However, in ELISA, the tested MoAbs did not recognize viral glycoproteins of the PM strain. This indicates, that the different strain-specific conformations of the native glycoprotein determine the accessibility of the common linear determinants for respective antibodies. Only one antibody, with conformation-dependent glycoprotein specificity, was capable to neutralize the CVS strain of rabies virus.
Loop-Mediated Isothermal Amplification Technology: Towards Point of Care Diagnostics (2012)

The invention of the loop-mediated isothermal amplification (LAMP) method a decade ago has given new impetus towards development of point of care diagnostic tests based on amplification of pathogen DNA, a technology that has been the precinct of well-developed laboratories. The LAMP technology amplifies DNA with high sensitivity relying on an enzyme with strand displacement activity under isothermal conditions. Additionally, the technology uses four to six specially designed primers recognising six to eight regions of the target DNA sequence, hence a high specificity. The auto-cycling reactions lead to accumulation of a large amount of the target DNA and other reaction by-products, such as magnesium pyrophosphate, that allow rapid detection using varied formats [1], [2]. Over the last 10 years, LAMP has been used widely in the laboratory setting to detect pathogens of medical and veterinary importance, plant parasitic diseases, genetically modified products, and tumour and embryo sex identification, among other uses [3]. However, its application under field conditions has been limited, partly due to the infancy of the technologies associated with LAMP, such as field-based template preparation methods and product detection formats. In this Viewpoint, the author highlights the essential technologies that require development before the LAMP platform can be progressed into a realistic point of care format for resource-poor endemic areas.
Analysis of dose intensity for adjuvant chemotherapy trials in stage II breast cancer. (1986)

We have analyzed the relationship between dose intensity of cyclophosphamide, methotrexate, and fluorouracil (CMF)-containing adjuvant chemotherapy of stage II breast cancer and 3-year relapse-free survival. Studies using only one or two drugs of CMF or melphalan instead of cyclophosphamide were included in the analysis by using simple techniques developed for this purpose. There was a clear-cut relationship between relapse-free survival and dose intensity in trials containing all four prognostic groups: less than 50 years, one to three and more than three positive nodes; and greater than or equal to 50 years, one to three and more than three positive nodes (P less than 10(-5)). Relapse-free survival also correlated with dose intensity for each of the four prognostic groups analyzed separately (P less than .005). Dose intensity was an independently significant correlate of relapse-free survival in multivariate analysis (P less than 10(-5)). This is a retrospective study, and the hypothesis that dose intensity contributes to outcome independently of other variables should be tested prospectively. Methods of increasing dose intensity also require testing in randomized trials before they can be applied to routine clinical practice.
Precision tracking of driving wave forms for inertial reaction devices (2005)

Inertial reaction devices (also referred to as impact drive, or slip-stick devices) enable nano/micro resolution positioning over macroscopic ranges. Such positioning devices are characterized by the displacement of a mass by utilizing stick-slip phenomena between the mass and the device’s actuators. The displacement of the actuator (i.e., the driving wave form) is chosen such that the mass sticks to the actuator and is displaced with the actuator during the first tracking phase, and the mass slips with respect to the actuator during the second retrace phase during which the actuator’s position is reset. However, as the driving wave form’s frequency is increased to operate an inertial-reaction device at high speed, induced mechanical vibrations prevent accurate actuator positioning and thereby, limit the maximum achievable operating speed. In this article, the actuator dynamics is modeled and iteratively inverted to find the input that compensates for the induced mechanical vibrations. This inversion-based input allows the actuator to track high-frequency driving wave forms without exciting mechanical vibrations, and thereby, allows the inertial reaction device to operate at higher operating speeds. The method is applied to a rotational inertial-reaction device, and experimental results show that the use of the inversion-based iterative approach enables tracking of the desired wave form at an order-of-magnitude higher frequency.
Improved multiplex-PCR method for the simultaneous detection of food bacteria producing biogenic amines (2005)

This study describes a simple and rapid multiplex-PCR method to determine the ability to produce histamine, tyramine and putrescine by bacteria. The assay is an improved method based on an assay designed for lactic acid bacteria. This improved method includes a pair of primers based on sequences from histidine decarboxylases from Gram-negative bacteria. Under the optimised conditions, the assay yielded a 367-bp DNA fragment from histidine decarboxylases of Gram-positive bacteria, 534-bp fragment from histidine decarboxylases of Gram-negative bacteria, 924-bp from bacterial tyrosine decarboxylases, and 1446-bp fragment from bacterial ornithine decarboxylases. The method was successfully applied to several biogenic amine-producing bacterial strains, even when DNAs of several target organisms were included in the same reaction. This simple method could be easily incorporated in food control laboratories to detect potentially biogenic amine-producing bacteria in foods.
p53: A Potential Target Antigen for Immunotherapy of Cancer (2000)

Approximately 50% of all human malignancies exhibit mutation and aberrant expression of p53, making this protein an interesting candidate target for immunotherapy of cancer. Mutations in p53 are highly diverse. Therefore, targeting of determinants within the wild-type p53 sequence appears most practical. Despite the fact that p53 is ubiquitously expressed, adoptive immunotherapy of tumor-bearing mice with p53-specific cytotoxic T lymphocytes (CTL) results in eradication of p53-overexpressing tumors in the absence of immunopathological damage to normal tissues. These CTL also eliminate tumors that do not show greatly enhanced expression of p53, indicating that the sensitivity of these tumors for p53-specific CTL is determined by the efficiency by which p53-derived peptides are processed into class I MHC, rather than by the steady state levels of p53. Of note, although p53-specific CTL can readily be isolated from p53-/- mice, tolerance for this self antigen may prevent induction of similarly effective CTL in p53+/+ subjects. The T helper (Th) branch of the p53-specific immune response does not seem to be profoundly affected by tolerance. In addition, more and more evidence is obtained for the pivotal role of tumor-specific Th cells in the induction and effector phases of the antitumor response, also against tumors that lack class II MHC expression. The efficacy of Th cells, specific for a recently identified class II MHC-restricted p53 peptide, against p53-overexpressing tumors is currently being investigated. In addition, natural and induced Th responses are analyzed both in a murine tumor model and in a phase I clinical trial involving p53-specific vaccination of colon cancer patients.
Underlying Causes and Long-Term Survival in Patients with Initially Unexplained Cardiomyopathy (2000)

Background Previous studies of the prognosis of patients with heart failure due to cardiomyopathy categorized patients according to whether they had ischemic or nonischemic disease. The prognostic value of identifying more specific underlying causes of cardiomyopathy is unknown.
In vivo targeting of an anti-tumor antibody coupled to antigenic MHC class I complexes induces specific growth inhibition and regression of established syngeneic tumor grafts. (2003)

The concept of antibody-mediated targeting of antigenic MHC/peptide complexes on tumor cells in order to sensitize them to T-lymphocyte cytotoxicity represents an attractive new immunotherapy strategy. In vitro experiments have shown that an antibody chemically conjugated or fused to monomeric MHC/peptide can be oligomerized on the surface of tumor cells, rendering them susceptible to efficient lysis by MHC-peptide restricted specific T-cell clones. However, this strategy has not yet been tested entirely in vivo in immunocompetent animals. To this aim, we took advantage of OT-1 mice which have a transgenic T-cell receptor specific for the ovalbumin (ova) immunodominant peptide (257-264) expressed in the context of the MHC class I H-2K(b). We prepared and characterized conjugates between the Fab' fragment from a high-affinity monoclonal antibody to carcinoembryonic antigen (CEA) and the H-2K(b) /ova peptide complex. First, we showed in OT-1 mice that the grafting and growth of a syngeneic colon carcinoma line transfected with CEA could be specifically inhibited by systemic injections of the conjugate. Next, using CEA transgenic C57BL/6 mice adoptively transferred with OT-1 spleen cells and immunized with ovalbumin, we demonstrated that systemic injections of the anti-CEA-H-2K(b) /ova conjugate could induce specific growth inhibition and regression of well-established, palpable subcutaneous grafts from the syngeneic CEA-transfected colon carcinoma line. These results, obtained in a well-characterized syngeneic carcinoma model, demonstrate that the antibody-MHC/peptide strategy can function in vivo. Further preclinical experimental studies, using an anti-viral T-cell response, will be performed before this new form of immunotherapy can be considered for clinical use.
Modulation of Caspase Activity Regulates Skeletal Muscle Regeneration and Function in Response to Vasopressin and Tumor Necrosis Factor (2009)

Muscle homeostasis involves de novo myogenesis, as observed in conditions of acute or chronic muscle damage. Tumor Necrosis Factor (TNF) triggers skeletal muscle wasting in several pathological conditions and inhibits muscle regeneration. We show that intramuscular treatment with the myogenic factor Arg(8)-vasopressin (AVP) enhanced skeletal muscle regeneration and rescued the inhibitory effects of TNF on muscle regeneration. The functional analysis of regenerating muscle performance following TNF or AVP treatments revealed that these factors exerted opposite effects on muscle function. Principal component analysis showed that TNF and AVP mainly affect muscle tetanic force and fatigue. Importantly, AVP counteracted the effects of TNF on muscle function when delivered in combination with the latter. Muscle regeneration is, at least in part, regulated by caspase activation, and AVP abrogated TNF-dependent caspase activation. The contrasting effects of AVP and TNF in vivo are recapitulated in myogenic cell cultures, which express both PW1, a caspase activator, and Hsp70, a caspase inhibitor. We identified PW1 as a potential Hsp70 partner by screening for proteins interacting with PW1. Hsp70 and PW1 co-immunoprecipitated and co-localized in muscle cells. In vivo Hsp70 protein level was upregulated by AVP, and Hsp70 overexpression counteracted the TNF block of muscle regeneration. Our results show that AVP counteracts the effects of TNF through cross-talk at the Hsp70 level. Therefore, muscle regeneration, both in the absence and in the presence of cytokines may be enhanced by increasing Hsp70 expression.
Neurodegeneration and hereditary dementias: 40 years of learning (2006)

The invitation to participate in the commemorative issue celebrating the 100 th anniversary of Dr. Alois Alzheimer's report on the disease that would later bear his name has evoked memories of my early experiences in the study of dementia, my teachers, my role-models, my aspirations and my accomplishments. Early in my career, I was fascinated with the study of hereditary neurological disorders. The observation of families in which dementia was inherited in an autosomal dominant pattern excited my scientific curiosity. Three very different phenotypes in patients from three separate families have been the basis for novel scientific discovery, which has taken place over the past 30 years. This could not have taken place without the help of many generous patients and their families as well as wonderful colleagues for whom I am deeply grateful. Some of the original observations in these families have led to the discovery of genetic mutations in three genes that are among the most commonly affected in hereditary dementia. The work on these families has enriched the scientific community and our knowledge of dementing illnesses.
Modeling Enlargement Attacks Against UWB Distance Bounding Protocols (2016)

Distance bounding protocols make it possible to determine a trusted upper bound on the distance between two devices. Their key property is to resist reduction attacks, i.e., attacks aimed at reducing the distance measured by the protocol. Recently, researchers have also focused on enlargement attacks, aimed at enlarging the measured distance. Providing security against such attacks is important for secure positioning techniques. The contribution of this paper is to provide a probabilistic model for the success of an enlargement attack against a distance bounding protocol realized with the IEEE 802.15.4a ultra-wideband standard. The model captures several variables, such as the propagation environment, the signal-to-noise ratio, and the time-of-arrival estimation algorithm. We focus on non-coherent receivers, which can be used in low-cost low-power applications. We validate our model by comparison with physical-layer simulations and goodness-of-fit tests. The results show that our probabilistic model is sufficiently realistic to replace physical-layer simulations. Our model can be used to evaluate the security of the ranging/positioning solutions that can be subject to enlargement attacks. We expect that it will significantly facilitate future research on secure ranging and secure positioning.
Fluctuations and critical phenomena of a filled elastomer under deformation (2006)

Fluctuations and critical phenomena have drawn much attention for many years. But, no report anticipates that an elastomer containing fillers under gentle deformations will show similar effects. In this letter, we discover for the first time that a filled rubber system under about 2% strain may display feature fluctuations that could be associated with a transition of the filler from an elastic solid state to a dispersed fluid state and that is reminiscent of critical phenomena. In addition, we show that the fluctuation of macroscopic parameters can be related to the microscopic fluctuation of filler structures in the rubber compound and in principle it can act as a probe of what is happening physically at the microscopic scale.
Thrombolytics and Myocardial Infarction (2010)

Coronary artery disease is the single leading cause of death in the United States. Occlusion of the coronary artery was identified to be the cause of myocardial infarction almost a century ago. Following a series of investigations, streptokinase was discovered and demonstrated to be beneficial for the treatment of patients with acute myocardial infarction in terms of reducing short- and long-term mortality. Newer agents including tissue plasminogen activators such as alteplase, reteplase, tenecteplase were developed subsequently. In the present era, thrombolytic therapy and primary percutaneous coronary intervention has revolutionized the way patients with acute myocardial infarction are managed resulting in significant reduction in cardiovascular death. This article provides an overview of the various thrombolytic agents utilized in the management of patients with acute myocardial infarction.
A Novel Method for Transfection and Expression of Reconstituted DNA-Protein Complexes in Eukaryotic Cells (1987)

Transfection of foreign DNA into eukaryotic cells has become an important tool in molecular biology. Based on the results of previous studies of the core structure of human adenoviruses, we have developed a novel transfection method. The procedure involves the in vitro reconstitution of foreign DNA-of viral or other origins-with the major core protein VII of adenovirus type 2 (Ad2) or protamine from salmon sperm. Both proteins are rich in basic amino acids and appear to share structural features. The DNA-protein complexes are added directly to the medium of eukaryotic cells. The in vitro formation of specific DNA-protein complexes can be assessed by gel electrophoretic analyses. Bovine serum albumin does not enter into specific complexes with DNA. Transfection of DNA-protein VII or DNA-protamine complexes results in their rapid transport into the cell nuclei. About 2-4 hr after transfection, up to 40% of the DNA added to cell cultures in complexes can be found in the nucleus, as compared with less than 10% of the DNA when other transfection methods are applied or when naked DNA is added to cell cultures. DNAs transfected by the new method into mammalian or insect cells retain their characteristic restriction patterns at least 48 hr after transfection and are expressed efficiently. Supercoiled circular plasmid DNAs are converted to open circular or linear DNA. Expression has been measured both for transiently expressed genes (chloramphenicol acetyltransferase gene, Ad2 DNA in human HeLa cells) and for genes that have been integrated into the host genome and are expressed permanently, such as the gene for neomycin phosphotransferase in hamster BHK21 cells.(ABSTRACT TRUNCATED AT 250 WORDS)