gebhart/patrepeval huggingface dataset:
In Vitro Activity of Novel Rifamycins against Rifamycin-Resistant Staphylococcus aureus (2006)

We describe novel rifamycin derivatives (new chemical entities [NCEs]) that retain significant activity against a comprehensive collection of Staphylococcus aureus strains that are resistant to rifamycins. This collection of resistant strains contains 21 of the 26 known single-amino-acid alterations in RpoB, the target of rifamycins. Some NCEs also demonstrated a lower frequency of resistance development than rifampin and rifalazil in S. aureus as measured in a resistance emergence test. When assayed for activity against the strongest rifamycin-resistant mutants, several NCEs had MICs of 2 microg/ml, in contrast to MICs of rifampin and rifalazil, which were 512 microg/ml for the same strains. The properties of these NCEs therefore demonstrate a significant improvement over those of earlier rifamycins, which have been limited primarily to combination therapy due to resistance development, and suggest a potential use of these NCEs for monotherapy in several clinical indications.
Four decades of structure determination by mass spectrometry: From alkaloids to heparin (2002)

The early (1950's and 1960's) use of mass spectrometry in natural products chemistry and its evolution to the present significance in biochemistry is recounted. This methodology allowed the facile and speedy determination of the structure of a number of indole alkaloids, such as sarpagine, quebrachamine, and two groups isolated from the roots of Aspidosperma quebracho blanco. At the same time, the first strategy for the sequencing of small peptides by mass spectrometry was demonstrated. It slowly advanced, over a period of two decades, to an important alternative of the ubiquitous automated Edman degradation. Further advances in methodology and instrumentation established mass spectrometry as today's indispensable tool for the characterization of proteins in biochemistry and biology. A new concept of the ionization of highly acidic compounds as the protonated complexes with basic peptides, which allows the accurate determination of the molecular weights of the former, a highly sensitive method for the sequencing of heparin fragments and related sulfated glycosaminoglycans was developed more recently.
Undersampled radial MRI with multiple coils. Iterative image reconstruction using a total variation constraint (2007)

The reconstruction of artifact-free images from radially encoded MRI acquisitions poses a difficult task for undersampled data sets, that is for a much lower number of spokes in k-space than data samples per spoke. Here, we developed an iterative reconstruction method for undersampled radial MRI which (i) is based on a nonlinear optimization, (ii) allows for the incorporation of prior knowledge with use of penalty functions, and (iii) deals with data from multiple coils. The procedure arises as a two-step mechanism which first estimates the coil profiles and then renders a final image that complies with the actual observations. Prior knowledge is introduced by penalizing edges in coil profiles and by a total variation constraint for the final image. The latter condition leads to an effective suppression of undersampling (streaking) artifacts and further adds a certain degree of denoising. Apart from simulations, experimental results for a radial spin-echo MRI sequence are presented for phantoms and human brain in vivo at 2.9 T using 24, 48, and 96 spokes with 256 data samples. In comparison to conventional reconstructions (regridding) the proposed method yielded visually improved image quality in all cases.
A clinical prototype for active microwave imaging of the breast (2000)

Despite its recognized value in detecting and characterizing breast disease, X-ray mammography has important limitations that motivate the quest for alternatives to augment the diagnostic tools that are currently available to the radiologist. The rationale for pursuing electromagnetic methods is strong given the data in the literature, which show that the electromagnetic properties of breast malignancy are significantly different than normal in the high megahertz to low gigahertz spectral range, microwave illumination can effectively penetrate the breast at these frequencies, and the breast is a small readily accessible tissue volume, making it an ideal site for deploying advanced near-field imaging concepts that exploit model-based image reconstruction methodology. In this paper a clinical prototype of a microwave imaging system, which actively illuminates the breast with a 16-element transceiving monopole antenna array in the 300-1000 MHz range, is reported. Microwave exams have been delivered to five women through a water-coupled interface to the pendant breast with the participant positioned prone on an examination table. This configuration has been found to be a practical, comfortable approach to microwave breast imaging. Sessions lasted 10-15 min per breast and included full tomographic data acquisition at seven different array heights beginning at the chest wall and moving anteriorly toward the nipple for seven different frequencies at each array position. This clinical experience appears to be the first report of active near-field microwave imaging of the breast and is certainly the first attempt to exploit model-based image reconstructions from in vivo breast data in order to convert the measured microwave signals into spatial maps of electrical permittivity and conductivity. While clearly preliminary, the results are encouraging and have supplied some interesting findings. Specifically, it appears that the average relative permittivity of the breast as a whole correlates with radiologic breast density categorization and may be considerably higher than previously published values, which have been based on ex vivo tissue specimens.
Systematic Synthesis of Bisubstrate‐Type Inhibitors of N‐Acetylglucosaminyltransferases (2006)

Bisubstrate-type inhibitors for N-acetylglucosaminyltransferase (GnT)-V and -IX were designed and synthesized. These compounds carry both an acceptor trisaccaride and an UDP-GlcNAc component tethered by a linker of variable length. The acceptor trisaccharide unit was constructed using a combination of a polymer support and a resin capture-release strategy. Namely, starting with a beta-mannoside bound to low molecular weight monomethyl PEG (MPEG), successive glycosylations with donors having chloroacetyl group produced the trisaccharide, which was subjected to the capture-release purification using cysteine loaded resin. UDP-GlcNAc units carrying phosphate moieties were separately synthesized from the bromoacetamide-containing glucosamine derivative. Ligation between the acceptor thiol and each alkyl bromide on the donor unit readily proceeded, and produced the coupling product. The introduction of the UMP component gave target compounds. All of the synthesized compounds had significant activities to GnT-V and -IX. Their potencies were dependent upon the linkers length. GnT-IX was more sensitive to these inhibitors and optimum linker length was clearly different between these GnTs. The most potent inhibitor of GnT-V had Ki=18.3 microM, while that of GnT-IX had Ki = 4.7 microM.
Revisiting with a Relative-Density Calibration Approach the Determination of Growth Rates of Microorganisms by Use of Optical Density Data from Liquid Cultures (2010)

To solve the problems of measuring the growth rates of microorganisms from optical density (OD)-growth time plots, we used relative-density (RD) plots. The relationship of OD and RD was built from the diluted grown cultures. This method was satisfactorily applied to study the growth of Escherichia coli and the cyanobacterium Anabaena spiroides.
GTP-binding domain: three consensus sequence elements with distinct spacing. (1987)

A sequence comparison of nine functionally different GTP-binding protein families has yielded further information on the general characterization of the conservation and importance of amino acid sequences in the GTP-binding domain, including a consensus sequence composed of three consensus elements GXXXXGK, DXXG, and NKXD with consensus spacings of either 40-80 or approximately equal to 130-170 amino acid residues between the first and second elements and approximately 40-80 amino acid residues between the second and third sequence elements; the sequence NKXW in place of NKXD in the sequence element responsible for base specificity allows the use of ITP as well as GTP; dGTP can be used with essentially the same efficiency as GTP; signal transducing proteins and enzymes have been identified in the nine families; and family conservations allow the identification of the most probable consensus sequence element when more than one is present. Employing these features we have screened the protein sequence data base of the Protein Identification Resource and have identified only known GTP-binding proteins with the exception of protein 2C from foot-and-mouth disease virus as matching the consensus sequence. Based on this finding we predict that foot-and-mouth disease virus protein 2C binds GTP and, by analogy, that protein 2C from several related viruses (polio, rhino, encephalomyocarditis, and cowpea mosaic) will bind a nucleotide as part of its biologic activity.
Information theory, distance matrix, and molecular branching (1977)

Information theory was used in defining several measures of the topological properties of molecules, namely, information for adjacency, incidence, polynomial coefficients of the adjacency matrix, and for distances of molecular graphs. The latter was found to have a greater ability for discrimination between structural isomers than all known topological indices and to be a very appropriate measure of branching. All the quantities related to the distance matrix (two information measures, the Weiner number and the largest eigenvalue of the characteristic polynomial) were found to reflect in the same way the main features of molecular branching. On this basis, as well as on the basis of general expressions for information content and Wiener number derived for tree graphs, the essence of molecular branching was expressed in a number of rules. It was shown that these theoretical rules on branching are in agreement with the intuitive understanding of branching and are reflected in a large number of molecular properties.
DNA Detection Using Recombination Proteins (2006)

DNA amplification is essential to most nucleic acid testing strategies, but established techniques require sophisticated equipment or complex experimental procedures, and their uptake outside specialised laboratories has been limited. Our novel approach, recombinase polymerase amplification (RPA), couples isothermal recombinase-driven primer targeting of template material with strand-displacement DNA synthesis. It achieves exponential amplification with no need for pretreatment of sample DNA. Reactions are sensitive, specific, and rapid and operate at constant low temperature. We have also developed a probe-based detection system. Key aspects of the combined RPA amplification/detection process are illustrated by a test for the pathogen methicillin-resistant Staphylococcus aureus. The technology proves to be sensitive to fewer than ten copies of genomic DNA. Furthermore, products can be detected in a simple sandwich assay, thereby establishing an instrument-free DNA testing system. This unique combination of properties is a significant advance in the development of portable and widely accessible nucleic acid-based tests.
Atmospheric Pressure Chemical Vapor Deposition of Titanium Aluminum Nitride Films (1999)

The atmospheric pressure chemical vapor deposition of titanium aluminum nitride films was accomplished using a three-precursor system comprised of titanium tetrachloride, tert-butylamine, and trimethylaluminum at a substrate temperature of 600 °C. Smooth, specular, and highly adherent violet-black films were obtained. The aluminum content of the films varied with trimethylaluminum flow rate up to a maximum aluminum/titanium ratio of about 1:1. Higher aluminum flow rates afforded rough, poorly adherent coatings. Films having the compositions Ti0.83Al0.17N0.89, Ti0.69Al0.31N0.85, and Ti0.52Al0.48N1.38 were analyzed in detail. The films were characterized by X-ray powder diffraction, X-ray photoelectron spectroscopy, Rutherford backscattering spectrometry, scanning electron microscopy, atomic force microscopy, and resistivity measurements. The films were subjected to nanoindentation hardness testing and high-temperature oxidation studies. The Ti1-xAlxN films were found to be harder and more resistant to oxidation by ambient atmosphere than TiN films deposited from titanium tetrachloride and tert-butylamine at 600 °C. The dependence of the film properties on the aluminum content is discussed.
Synthesis of Pyridyl Disulfide-Functionalized Nanoparticles for Conjugating Thiol-Containing Small Molecules, Peptides, and Proteins (2010)

Previously we reported emulsion polymerization of propylene sulfide with Pluronic F127 as an emulsifier, yielding nanoparticles (NPs) in the 25 nm size range. Immunologically functional NPs were prepared by adding an antigen-Pluronic conjugate to the polymerization mixture ( Reddy , S. T. , et al. ( 2007 ) Nat. Biotechnol. 25, 1159 ). We sought a more flexible scheme for conjugation of antigens and other biomolecules to the NP surfaces that would allow for milder reaction conditions than achievable during the polymerization step. Here, we present the synthesis of such functionalizable NPs in the form of NPs that carry thiol-reactive groups, to which thiol-containing antigens (peptide or protein) or other biomolecules can be conjugated under mild conditions to yield immunofunctional NPs. The Pluronic-stabilized poly(propylene sulfide) (PPS) NPs with thiol-reactive pyridyl disulfide groups are prepared in two steps by (1) emulsion polymerization of propylene sulfide in the presence of a carboxylate-Pluronic and (2) reaction of the carboxylic acid groups on the NP surface with cysteamine pyridyl disulfide and a water-soluble carbodiimide reagent. We choose pyridyl disulfide groups to have a reduction-sensitive disulfide bond linking the antigen to the NP surface, allowing efficient release of antigen inside the cell in response to the reductive conditions within the endosome. The functionalizable NPs are characterized by proton NMR, dynamic light scattering (DLS), UV/vis spectroscopy, and transmission electron microscopy (TEM). Conjugation of small molecules and protein to the NP surface is presented.
[Typhus epidemiology in Switzerland 1980-1983. Slight or lack of effectiveness of the live vaccine Vivotif in tropical travel]. (1985)

214 cases of typhoid fever (TF) occurring in Switzerland between January 1980 and December 1984 were analyzed for travel history, vaccine status and nationality. A subgroup of Swiss tourists who acquired TF in India was compared to a sample of healthy Swiss tourists who travelled to India in 1983 to determine the factors predisposing to TF. Eighty cases of TF occurred in Swiss tourists to the Third World, of whom 26 had travelled in India. Among the latter, the length of stay was longer than in the control sample of 258 healthy tourists, and "trekking" (travelling off the usual tourist routes with backpacking) was more frequent. 20 of the 80 patients had been vaccinated with the live oral typhoid vaccine Vivotif (strain S. typhi Ty 21a, contained in gelatine capsules, to be taken with bicarbonate capsules), marketed in Switzerland in 1981-1984. Comparison of the vaccination rates in case and control groups indicated that the vaccine efficacy was not significantly different from 0% during the time of observation. This lack of efficacy may be related to inadequate dosage and to the lack of stability of the vaccine. Forty cases of TF occurred in Swiss who had travelled in European countries, of whom 8 had not travelled outside Switzerland. The remaining 94 cases occurred in non-Swiss travellers, a majority of whom were from Mediterranean countries. TF in Switzerland was associated with a history of travel in 96% of cases. The live oral typhoid vaccine Vivotif was ineffective between 1981 and 1983.(ABSTRACT TRUNCATED AT 250 WORDS)
Validation of Analytic Methods for Biomarkers Used in Drug Development (2008)

The role of biomarkers in drug discovery and development has gained precedence over the years. As biomarkers become integrated into drug development and clinical trials, quality assurance and, in particular, assay validation become essential with the need to establish standardized guidelines for analytic methods used in biomarker measurements. New biomarkers can revolutionize both the development and use of therapeutics but are contingent on the establishment of a concrete validation process that addresses technology integration and method validation as well as regulatory pathways for efficient biomarker development. This perspective focuses on the general principles of the biomarker validation process with an emphasis on assay validation and the collaborative efforts undertaken by various sectors to promote the standardization of this procedure for efficient biomarker development.
5-HT2A antagonists in psychiatric disorders. (2002)

Several lines of evidence support a role for serotoninergic (5-HT) system abnormalities in the pathogenesis and treatment of several psychiatric disorders. This review summarizes information about the association between the 5-HT2A receptor gene and its relevance to schizophrenia, tardive dyskinesia, major depression, suicidality, anorexia nervosa and obsessive-compulsive disorder. Evidence is presented that implies that selective 5-HT2A antagonists may be considered useful in investigating the role of 5-HT2A receptor function and in the treatment of psychosis, and possibly alcohol and cocaine dependence. Additionally, findings are reviewed on the importance of 5-HT2A receptor antagonism in contributing to the therapeutic effect of several clinically effective and potential atypical antipsychotics as well as several antidepressants. In conclusion, the ability of selective 5-HT2A receptor antagonists to interfere with the heightened state of dopamine activity without altering basal tone, suggests that these drugs possess antipsychotic activity and may provide the basis for new therapies for psychosis and drug dependence, in addition to contributing towards a more complete understanding of 5-HT2A receptor function.
Quantification of Multiple Gene Expression in Individual Cells (2004)

Quantitative gene expression analysis aims to define the gene expression patterns determining cell behavior. So far, these assessments can only be performed at the population level. Therefore, they determine the average gene expression within a population, overlooking possible cell-to-cell heterogeneity that could lead to different cell behaviors/cell fates. Understanding individual cell behavior requires multiple gene expression analyses of single cells, and may be fundamental for the understanding of all types of biological events and/or differentiation processes. We here describe a new reverse transcription-polymerase chain reaction (RT-PCR) approach allowing the simultaneous quantification of the expression of 20 genes in the same single cell. This method has broad application, in different species and any type of gene combination. RT efficiency is evaluated. Uniform and maximized amplification conditions for all genes are provided. Abundance relationships are maintained, allowing the precise quantification of the absolute number of mRNA molecules per cell, ranging from 2 to 1.28 x 10(9) for each individual gene. We evaluated the impact of this approach on functional genetic read-outs by studying an apparently homogeneous population (monoclonal T cells recovered 4 d after antigen stimulation), using either this method or conventional real-time RT-PCR. Single-cell studies revealed considerable cell-to-cell variation: All T cells did not express all individual genes. Gene coexpression patterns were very heterogeneous. mRNA copy numbers varied between different transcripts and in different cells. As a consequence, this single-cell assay introduces new and fundamental information regarding functional genomic read-outs. By comparison, we also show that conventional quantitative assays determining population averages supply insufficient information, and may even be highly misleading.
Acoustic diffraction of light in anisotropic media (1967)

The Bragg formalism which describes the diffraction of optical radiation by traveling acoustic waves is generalized to include diffraction in anisotropic media. When the diffracted and incident optical polarizations are different, the Bragg relations require important modification. The correctness of the suggested modifications is confirmed by experiments using optical diffraction from longitudinal and transverse acoustic waves in crystal quartz and in sapphire. A special case of diffraction from longitudinal waves in an anisotropic medium is discussed as a simple example of a collinear parametric interaction.
Rationale for Possible Targeting of Histone Deacetylase Signaling in Cancer Diseases with a Special Reference to Pancreatic Cancer (2010)

There is ongoing interest to identify signaling pathways and genes that play a key role in carcinogenesis and the development of resistance to antitumoral drugs. Given that histone deacetylases (HDACs) interact with various partners through complex molecular mechanims leading to the control of gene expression, they have captured the attention of a large number of researchers. As a family of transcriptional corepressors, they have emerged as important regulators of cell differentiation, cell cycle progression, and apoptosis. Several HDAC inhibitors (HDACis) have been shown to efficiently protect against the growth of tumor cells in vitro as well as in vivo . The pancreatic cancer which represents one of the most aggressive cancer still suffers from inefficient therapy. Recent data, although using in vitro tumor cell cultures and in vivo chimeric mouse model, have shown that some of the HDACi do express antipancreatic tumor activity. This provides hope that some of the HDACi could be potential efficient anti‐pancreatic cancer drugs. The purpose of this review is to analyze some of the current data of HDACi as possible targets of drug development and to provide some insight into the current problems with pancreatic cancer and points of interest for further study of HDACi as potential molecules for pancreatic cancer adjuvant therapy.