gebhart/patrepeval huggingface dataset:
The mass-mobility correlation redux: The conformational landscape of anhydrous biomolecules (2009)

Structural separations on the basis of gas-phase ion mobility-mass spectrometry are increasingly used for the analysis of complex biological samples. As a tool to elucidate biomolecular structure, ion mobility-mass spectrometry methods are unique in that direct molecular structural information is obtained for all resolved species, largely irrespective of the complexity of the sample. Computational approaches are used to interpret and discern structural details consistent with the empirical results. To a first approximation, correlations of mobility with mass allow for qualitative identification of the molecular class to which a particular species belongs. These correlations allow simultaneous characterization of different classes of biomolecules, which provides a means for combining omics measurements, such as lipidomics, proteomics, glycomics, and metabolomics, in the same analysis. Examination of the correlation of fine structure reveals that specific structural motifs, chemical functionality, chemical connectivity, and composition may also be determined, depending on the specific biomolecular class. Mapping the coarse and fine structure in ion mobility-mass spectrometry conformation space measurements provides an atlas for interpretation and discovery in complicated spectra.
Circulating Nucleic Acids in Blood of Healthy Male and Female Donors (2005)

The analysis of circulating nucleic acids (cirNAs) in blood provides helpful information for medical diagnostics (1). Thus, there has been intensive investigation of the factors influencing nucleic acid concentrations in plasma and serum, such as changes in DNA concentrations in serum and plasma during storage of blood samples (2) and the influence of blood processing on cell-free DNA quantification (3)(4)(5). Recent observations demonstrated that cirNAs are found not only free in blood plasma but also bound to the cell surface (6). Physiologic factors determining cirNA concentrations in blood remain to be elucidated. In the present study, we compared the concentration of cell-surface–bound and cell-free cirNAs in blood samples from 15 healthy men and 20 healthy women.

Venous blood (8 mL) was collected into 13-mL tubes (cat. no. 55.459; Sarstedt) containing 2 mL of sterile phosphate-buffered saline (PBS) containing 50 mmol/L EDTA. The samples were stored at 4 °C and treated within 4 h after blood collection. Plasma was collected after low-speed centrifugation …
Expression of polyoma virus middle-T antigen in Saccharomyces cerevisiae (1986)

The polyoma middle-T gene, lacking its intron, was inserted into a yeast expression plasmid containing the phosphoglycerate kinase promoter. Such plasmids transformed yeast at low frequency and these transformants expressed middle-T antigen at a level of approximately 0.1% cell protein. Furthermore, expression of this protein was frequently lost during growth in liquid culture and this loss of middle-T was accompanied by a twofold increase in the rate of growth. The spontaneous production of a truncated middle-T antigen, lacking the C terminus, was also observed; the expression of this protein did not inhibit the growth rate of the cells. Recovery and analysis of the expression plasmids encoding the truncated molecule showed that a single C X G base pair had been deleted from a run of nine consecutive C X G base pairs (Pyr nucleotide 1239--1247) within the middle-T coding region. This frame-shift mutation results in premature termination of the protein and loss of the strongly hydrophobic region of the molecule believed to be responsible for the membrane association of middle-T antigen.
Molecular characterization of proteins from porcine spirochetes (1986)

Sonicated preparations of Treponema hyodysenteriae and Treponema innocens were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis. Treponemal proteins were electrophoresed on a 10% polyacrylamide slab gel in a discontinuous Tris-glycine system and either stained with Coomassie blue dye or transferred electrophoretically at 20 mA for 16 h and 30 mA for 3 h to nitrocellulose paper. Staining of the gels revealed at least 42 distinct T. hyodysenteriae and T. innocens proteins, with molecular sizes ranging from greater than 100 to 14 kilodaltons (kDa). Each species contained 12 to 16 major protein bands; five of the proteins were common to both species. Fourteen major antigens were identified in T. hyodysenteriae isolate B204 by using serum specimens from pigs in the acute stage of swine dysentery. Twelve additional antigens were detected in isolate B204 when convalescent-phase serum specimens were reacted to the blot. A wide band at 16 kDa was identified with convalescent-phase serum specimens in T. hyodysenteriae but not in T. innocens. This 16-kDa antigen was also identified in T. hyodysenteriae with colonic secretions from convalescent pigs.
T4 RNA ligase catalyzes the synthesis of dinucleoside polyphosphates (1999)

T4 RNA ligase has been shown to synthesize nucleoside and dinucleoside 5'-polyphosphates by displacement of the AMP from the E-AMP complex with polyphosphates and nucleoside diphosphates and triphosphates. Displacement of the AMP by tripolyphosphate (P3) was concentration dependent, as measured by SDS/PAGE. When the enzyme was incubated in the presence of 0.02 mm [alpha-32P] ATP, synthesis of labeled Ap4A was observed: ATP was acting as both donor (Km, microm) and acceptor (Km, mm) of AMP from the enzyme. Whereas, as previously known, ATP or dATP (but not other nucleotides) were able to form the E-AMP complex, the specificity of a compound to be acceptor of AMP from the E-AMP complex was very broad, and with Km values between 1 and 2 mm. In the presence of a low concentration (0.02 mm) of [alpha-32P] ATP (enough to form the E-AMP complex, but only marginally enough to form Ap4A) and 4 mm of the indicated nucleotides or P3, the relative rate of synthesis of the following radioactive (di)nucleotides was observed: Ap4X (from XTP, 100); Ap4dG (from dGTP, 74); Ap4G (from GTP, 49); Ap4dC (from dCTP, 23); Ap4C (from CTP, 9); Ap3A (from ADP, 5); Ap4ddA, (from ddATP, 1); p4A (from P3, 200). The enzyme also synthesized efficiently Ap3A in the presence of 1 mm ATP and 2 mm ADP. The following T4 RNA ligase donors were inhibitors of the synthesis of Ap4G: pCp > pAp > pA2'p.
Nonuniform photobleaching of dyed polymers for optical waveguides (1993)

An experimental technique for calibrating the photobleaching process in a nonlinear optical material is presented. The technique depends on the existence of a sharp interface between the bleached and unbleached layers of the material which travels across the film but otherwise has a constant shape. The sharp interface of constant shape is a feature of a general model and is consistent with our experimental results. By determining the dependence of the velocity on the bleaching intensity, the order of the photobleaching kinetics is determined.
Functional Importance of the Human Coronary Collateral Circulation (1971)

Abstract To determine the effect of intercoronary collateral vessels on the clinical features of coronary-artery disease, 61 patients with collateral vessels were compared with 58 patients without arteriographically demonstrable collateral vessels. No significant differences existed between the two groups in level of physical activity, duration of angina, frequency of prior myocardial infarction or prevalence of electrocardiographic, hemodynamic and ventriculographic abnormalities. Myocardial ischemia was more prevalent in patients with than in those without collateral vessels as evidenced by a significantly greater frequency of abnormal post-exercise electrocardiograms and myocardial lactate production. The incidence of acute myocardial infarction during the follow-up period was nearly identical in the two groups. Death was less frequent in patients with than in those without collateral vessels, but this observation did not achieve statistical significance. Thus, although collateral vessels do not necess...
The topographical effect of electrospun nanofibrous scaffolds on the in vivo and in vitro foreign body reaction (2009)

Topographical cues play an important role in influencing cellular behavior and are considered as significant parameters to be controlled in tissue engineering applications. This work investigated the biocompatibility with regard to scaffold architecture and topographical effect of nanofibrous scaffolds on the in vivo and in vitro foreign body reaction. Random and aligned polycaprolactone (PCL) nanofibers were fabricated by electrospinning technique, with diameters of 313 +/- 5 nm and 506 +/- 24 nm, respectively. Primary monocytes isolated from five human donors were cultured on PCL nanofibers, PCL film, and RGD-coated glass in vitro and cell density and morphology was evaluated at time points of day 0 (2 h), day 3, day 7, and day 10. The in vivo study was carried out by implanting PCL nanofibers and film scaffolds subcutaneously in rats to test the biocompatibility and host response at time points of week 1, week 2, and week 4. The in vitro studies revealed that the initial monocyte adhesion on the aligned fiber scaffold was significantly less (p < 0.001) when compared to the random fiber scaffold. The in vivo study showed that the thicknesses of fibrous capsule on fibrous scaffolds were 7.55 +/- 0.54 microm for aligned fibers and 4.13 +/- 0.31 microm for random fibers, which were significantly thinner than that of film implants 37.7 +/- 0.25 microm (p < 0.001). Additionally, cell infiltration was observed in aligned fibrous scaffolds both in vitro and in vivo, while on random fibers and films, distinct fibrous capsule boundaries were found on the surfaces. These results indicate that aligned electrospun nanofibers may serve as a promising scaffold for tissue engineering by minimizing host response, enhancing tissue-scaffold integration, and eliciting a thinner fibrous capsule.
T cell receptor-mediated recognition of self-ligand induces signaling in immature thymocytes before negative selection. (1992)

Shaping of the T cell repertoire by selection during intrathymic maturation involves T cell receptor (TCR) recognition of major histocompatibility complex/self-antigen complexes. In this communication, we studied the ability of minor lymphocyte stimulating (Mls) determinants to act as self-tolerogens in the selection of the T cell repertoire. We demonstrate that unprimed T cells from normal as well as TCR transgenic mice form Mls-specific conjugates with antigen-presenting cells, and that this TCR-ligand interaction leads to elevation of intercellular Ca2+ ([Ca2+]i). Peripheral T cells from TCR transgenic mice expressing receptors specific for self-Mls antigen show no reactivities to Mlsa. However, a proportion of immature thymocytes from these mice show specific binding and strong [Ca2+]i elevation in response to self-antigen-presenting cells, although these thymocytes do not proliferate. This self-reactivity of thymocytes is inhibited by antibodies specific for TCR, CD4, CD8, class II molecules, lymphocyte function-associated antigen 1, and intercellular adhesion molecule 1. These results demonstrate for the first time that before thymic negative selection, immature T cells can specifically interact with cells bearing self-antigen, and suggest that the resulting TCR-dependent signal transduction events provide a basis for negative selection of self-reactive T cells.
A new method for the synthesis of smooth, round, hydrophilic protein microspheres using low concentrations of polymeric dispersing agents (1995)

A new method for the synthesis of protein microspheres of wide size range having good spherical geometry and hydrophilicity using very low concentrations of polymeric dispersing agents is reported. The method involves the use of around 1% solution of a biomedical grade aliphatic polyurethane in a mixture of a hexane and dichloromethane as the dispersion medium, as opposed to a 25–30% solution of polymeric dispersing agents employed by previous workers to effect steric stabilization of the protein solution droplets. The versatility of the method is demonstrated by the synthesis of albumin microspheres, as well as those of the amphiphilic protein casein, the latter being more difficult to prepare by surfactant stabilization techniques. Significant advantages of the method include the avoidance of surfactants which become adsorbed on the particles and influence tissue reactions and drug release, and the ease of removal of the polymeric stabilizer from the final product. The method may find application for the preparation of a wide range of protein and polysaccharide microspheres for medical use.
Sparse Bit-Allocations Based on Partial Ordering Schemes With Application to Speech and Audio Coding (2006)

The majority of speech and audio encoders today operate at rates of less than 1-2 bit/input-sample. Reducing the rates even further is a challenge in particular for coders using waveform-based coding paradigms. Specifically for transform-based coders it is often the case that transform coefficients are quantized at less than 1 bit/coefficient (on average) in many areas of the spectrum. Dealing with such cases is particularly challenging when some coefficients are assumed to be independent identically distributed random variables with little underlying predictable structure. This prompts a study on how to improve encoding in such situations beyond simply increasing the dimension of quantizers, an option that may not be practical or perceptually relevant in some coder designs. This paper looks at a general class of schemes motivated by observations on statistical variations at low dimensions. These schemes, termed partial ordering schemes, show advantages objectively (in mean square error) and perceptually by targeting randomly positioned peaks in the spectrum. At low rates, such schemes create sparse bit allocations that allow for further optimization using random noise fill. A listening test is presented demonstrating the advantages of such an approach
Abstract 3618: Target-specific photo-activatable immunotherapy (PIT) for cancer based on a monoclonal antibody-photosensitizer conjugate (2011)

Abstract Three modes of cancer therapy, surgery, radiation and chemotherapy, have been central to modern oncologic therapy. Molecular targeted cancer therapies have been introduced to target specific pathways, while minimizing side effects but have had limited success except in several notable cases. The concept of amplifying the effect of molecular targeting by applying physical energy to the bound conjugate is relatively new. In this study, we describe a hydrophilic photosensitizer based on a near infrared (NIR) phthalocyanine dye, IR700, which is covalently conjugated to one of several humanized monoclonal antibodies (MAb) targeting human epidermal growth factor receptor (EGFR) type 1 (HER1) and 2 (HER2). When exposed to light the conjugate induces highly selective cell death in vivo, a process termed “photo-activatable immunotherapy” (PIT). In vitro studies were conducted with Trastuzumab-IR700 bound to HER2-expressing NIH3T3 cells (3T3/HER2) and panitumumab-IR700 bound to HER1-expressing A431 cells which were then irradiated with non harmful NIR light. EGFR-negative Balb3T3 cells were used as controls. In vivo studies were conducted with 3T3/HER2 and A431 xenograft tumors 1 day after intravenous administration of MAb-IR700 followed by non harmful, transcutaneous NIR light. MAb-IR700 demonstrated specific binding to target receptors on the cell membrane, which was followed by gradual internalization into endolysosomal compartments. MAb-IR700 bound target-specific cell death could be induced within 5 minutes of exposure to NIR light and resulted in cellular swelling, bleb formation, and rupture of vesicles indicating necrotic cell death. No phototoxicity was observed in co-cultured receptor-negative Balb3T3 cells after incubation with MAb-IR700, even when MAb-IR700 was not removed from the medium during light exposure. EGFR target-specific accumulation of MAb-IR700 was observed in the mouse xenograft tumors on NIR fluorescence images. Greater than 90% tumor shrinkage within 3 days of the NIR irradiation, was measured, with no apparent side effects, but was only observed in EGFR-expressing tumors. Furthermore, IR700 fluorescence produced by the MAb conjugate permitted guidance of light delivery and allowed for monitoring after therapy. The MAb-IR700 PIT was most effective, when conjugates were bound to the cell membrane, but showed no phototoxicity, when unbound, suggesting a novel mechanism for PIT compared with conventional photodynamic therapies. Target selective PIT based on MAb-IR700 conjugate membrane binding enables selective treatment of cancer with no apparent side effect to normal cells or surrounding tissue. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3618. doi:10.1158/1538-7445.AM2011-3618
Partial Improvement of Crystal Quality for Microgravity-Grown Apocrustacyanin C1 (1997)

The protein apocrustacyanin C(1) has been crystallized by vapour diffusion in both microgravity (the NASA space shuttle USML-2 mission) and on the ground. Rocking width measurements were made on the crystals at the ESRF Swiss-Norwegian beamline using a high-resolution psi-circle diffractometer from the University of Karlsruhe. Crystal perfection was then evaluated, from comparison of the reflection rocking curves from a total of five crystals (three grown in microgravity and two earth controls), and by plotting mosaicity versus reflection signal/noise. Comparison was then made with previous measurements of almost 'perfect' lysozyme crystals grown aboard IML-2 and Spacehab-I and reported by Snell et al. [Snell, Weisgerber, Helliwell, Weckert, Hölzer & Schroer (1995). Acta Cryst. D51, 1099-1102]. Overall, the best diffraction-quality apocrustacyanin C(1) crystal was microgravity grown, but one earth-grown crystal was as good as one of the other microgravity-grown crystals. The remaining two crystals (one from microgravity and one from earth) were poorer than the other three and of fairly equal quality. Crystal movement during growth in microgravity, resulting from the use of vapour-diffusion geometry, may be the cause of not realising the 'theoretical' limit of perfect protein crystal quality.
Single-shot ultrafast imaging using parallax-free alignment with a tilted lenslet array (2014)

We demonstrate single-shot, two-dimensional imaging of ultrafast phenomena using a streak camera and a tilted lenslet array. We derive conditions for parallax-free imaging and experimentally verify the geometry by observing scattering of femtosecond pulses.
Characterization of a Mycobacterium tuberculosis Peptide That Is Recognized by Human CD4+ and CD8+ T Cells in the Context of Multiple HLA Alleles (2004)

The secreted Mycobacterium tuberculosis 10-kDa culture filtrate protein (CFP)10 is a potent T cell Ag that is recognized by a high percentage of persons infected with M. tuberculosis. We determined the molecular basis for this widespread recognition by identifying and characterizing a 15-mer peptide, CFP10(71-85), that elicited IFN-gamma production and CTL activity by both CD4(+) and CD8(+) T cells from persons expressing multiple MHC class II and class I molecules, respectively. CFP10(71-85) contained at least two epitopes, one of 10 aa (peptide T1) and another of 9 aa (peptide T6). T1 was recognized by CD4(+) cells in the context of DRB1*04, DR5*0101, and DQB1*03, and by CD8(+) cells of A2(+) donors. T6 elicited responses by CD4(+) cells in the context of DRB1*04 and DQB1*03, and by CD8(+) cells of B35(+) donors. Deleting a single amino acid from the amino or carboxy terminus of either peptide markedly reduced IFN-gamma production, suggesting that they are minimal epitopes for both CD4(+) and CD8(+) cells. As far as we are aware, these are the shortest microbial peptides that have been found to elicit responses by both T cell subpopulations. The capacity of CFP10(71-85) to stimulate IFN-gamma production and CTL activity by CD4(+) and CD8(+) cells from persons expressing a spectrum of MHC molecules suggests that this peptide is an excellent candidate for inclusion in a subunit antituberculosis vaccine.
Imaging vascular endothelial activation: an approach using radiolabeled monoclonal antibodies against the endothelial cell adhesion molecule E-selectin. (1994)

Radiolabeled anti-E-selectin Mab can be used to image localized inflammatory tissues. This approach may be useful for investigating activated endothelium in human disease.
1H,13C and 15N backbone assignments of cyclophilin when bound to cyclosporin A (CsA) and preliminary structural characterization of the CsA binding site (1991)

The backbone 1H, 13C and 15N chemical shifts of cyclophilin (CyP) when bound to cyclosporin A (CsA) have been assigned from heteronuclear two- and three-dimensional NMR experiments involving selectively 15N- and uniformly 15N- and 15N,13C-labeled cyclophilin. From an analysis of the 1H and 15N chemical shifts of CyP that change upon binding to CsA and from CyP/CsA NOEs, we have determined the regions of cyclophilin involved in binding to CsA.
Direct Injection of Functional Single-Domain Antibodies from E. coli into Human Cells (2010)

Intracellular proteins have a great potential as targets for therapeutic antibodies (Abs) but the plasma membrane prevents access to these antigens. Ab fragments and IgGs are selected and engineered in E. coli and this microorganism may be also an ideal vector for their intracellular delivery. In this work we demonstrate that single-domain Ab (sdAbs) can be engineered to be injected into human cells by E. coli bacteria carrying molecular syringes assembled by a type III protein secretion system (T3SS). The injected sdAbs accumulate in the cytoplasm of HeLa cells at levels ca. 10⁵-10⁶ molecules per cell and their functionality is shown by the isolation of sdAb-antigen complexes. Injection of sdAbs does not require bacterial invasion or the transfer of genetic material. These results are proof-of-principle for the capacity of E. coli bacteria to directly deliver intracellular sdAbs (intrabodies) into human cells for analytical and therapeutic purposes.
Autoantibodies typical of non-organ-specific autoimmune diseases in HIV-seropositive patients (1992)

Although the aetiology of AIDS is known, in general the aetiology of multisystemic autoimmune diseases remains to be determined, and the sequence of events taking place remains obscure in both cases. It is possible that the large spectrum of antibodies found in HIV-infected patients reflects a specific stimulation of B-cells by nuclear antigens released by apoptosis during an early stage of disease.