gebhart/patrepeval huggingface dataset:
C-Reactive Protein Frequently Colocalizes With the Terminal Complement Complex in the Intima of Early Atherosclerotic Lesions of Human Coronary Arteries (1998)

There is increasing evidence that complement activation may play a role in atherogenesis. Complement proteins have been demonstrated to be present in early atherosclerotic lesions of animals and humans, and cholesterol-induced atherosclerotic lesion formation is reduced in complement-deficient animals. Potential complement activators in atherosclerotic lesions are now a subject matter of debate. C-reactive protein (CRP) is an acute-phase protein that is involved in inflammatory processes in numerous ways. It binds to lipoproteins and activates the complement system via the classic pathway. In this study we have investigated early atherosclerotic lesions of human coronary arteries by means of immunohistochemical staining. We demonstrate here that CRP deposits in the arterial wall in early atherosclerotic lesions with 2 predominant manifestations. First, there is a diffuse rather than a focal deposition in the deep fibroelastic layer and in the fibromuscular layer of the intima adjacent to the media. In this location, CRP frequently colocalizes with the terminal complement complex. Second, the majority of foam cells below the endothelium show positive staining for CRP. In this location, no colocalization with the terminal complement proteins can be observed. Our data suggest that CRP may promote atherosclerotic lesion formation by activating the complement system and being involved in foam cell formation.
Quiet calls (2001)

Quiet Calls is a technology allowing mobile telephone users to respond to telephone conversations without talking aloud. QC-Hold, a Quiet Calls prototype, combines three buttons for responding to calls with a PDA/mobile phone unit to silently send pre-recorded audio directly into the phone. This permits a mixed-mode communication where callers in public settings use a quiet means of communication, and other callers experience a voice telephone call. An evaluation of QC-Hold shows that it is easily used and suggests ways in which Quiet Calls offers a new form of communication, extending the choices offered by synchronous phone calling and asynchronous voicemail.
Multiple sites of V lambda diversification in cattle. (1998)

Ig repertoire diversification in cattle was studied in the ileal Peyer's patch (IPP) follicles of young calves and in the spleens of late first-trimester bovine fetuses. To investigate follicular diversification, individual IPP follicles were isolated by microdissection; VA diversity was examined by RT-PCR and subsequent cloning and sequencing. When 52 intrafollicular sequences from a 4-wk-old calf were determined and compared, two major groups, one of 23 members and the other of 25, could be delineated. An examination of these groups revealed clear genealogic relationships that implicated in situ diversification of V lambda sequences within the confines of an IPP follicle. V lambda expression was also examined in early (95 and 110 gestational day) fetal bovine spleens. Although earlier studies in cattle and sheep implicated the IPP as a likely site of Ab diversification, a close investigation of V lambda sequences in late first-trimester fetal calves revealed that diversity appears in the early fetal spleen before the establishment of a diverse repertoire in the ileum. When the sequences for the fetal spleen were compared with an existing pool of germline sequences, we found evidence of possible gene conversion events and possible untemplated point mutations occurring in sequences recovered from fetal spleens. We conclude that IPP is not the sole site of VA diversification in cattle. Also, as suggested for rabbits, cattle may use both gene conversion and untemplated somatic point mutation to diversify their primary VA repertoire.
MICROFLORA OF COCOA BEANS BEFORE AND AFTER ROASTING AT 150 C1 (1971)

Cocoa beans representative of different fermentation practices, flavor types, and geographic origins were collected and analyzed microbiologically before and after roasting under laboratory conditions which simulated commercial practices. The detectable number of microorganisms per gram of bean before roasting ranged from 3 × 105 to 4.7 × 107. After roasting the beans for 40 min at 150 C the counts ranged from 103 to 1.6 × 105 per gram. The genus Bacillus accounted for 91% of the 277 isolates. Only bacilli were found in roasted beans and Bacillus stearothermophilus and Bacillus coagulans were the predominant species. Microorganisms identified in unroasted beans were nineteen species of Bacillus, two of Streptococcus, two of Micrococcus, two of Escherichia, and single species of Aerobacter, Flavobacterium, and Microbacterium.
Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells (2014)

Breast cancer patients often develop metastatic disease years after resection of the primary tumor. The patients are asymptomatic because the disseminated cells appear to become dormant and are undetectable. Because the proliferation of these cells is slowed, dormant cells are often unresponsive to traditional chemotherapies that exploit the rapid cell cycling of most cancer cells. We generated a bone marrow-metastatic human breast cancer cell line (BM2) by tracking and isolating fluorescent-labeled MDA-MB-231 cells that disseminated to the bone marrow in mice. Coculturing BM2 cells with bone marrow mesenchymal stem cells (BM-MSCs) isolated from human donors revealed that BM-MSCs suppressed the proliferation of BM2 cells, decreased the abundance of stem cell-like surface markers, inhibited their invasion through Matrigel Transwells, and decreased their sensitivity to docetaxel, a common chemotherapy agent. Acquisition of these dormant phenotypes in BM2 cells was also observed by culturing the cells in BM-MSC-conditioned medium or with exosomes isolated from BM-MSC cultures, which were taken up by BM2 cells. Among various microRNAs (miRNAs) increased in BM-MSC-derived exosomes compared with those from adult fibroblasts, overexpression of miR-23b in BM2 cells induced dormant phenotypes through the suppression of a target gene, MARCKS, which encodes a protein that promotes cell cycling and motility. Metastatic breast cancer cells in patient bone marrow had increased miR-23b and decreased MARCKS expression. Together, these findings suggest that exosomal transfer of miRNAs from the bone marrow may promote breast cancer cell dormancy in a metastatic niche.
The Scattering of Light and the Radial Distribution Function of High Polymer Solutions (1948)

A radial distribution function of polymer segments in a solution of a high polymer may be defined as a quantity proportional to the density of segments at a given distance from some given segment. An approximate expression is derived for this function for dilute solutions of chain molecules of moderate degrees of polymerization. By Fourier inversion a simple expression for the intensity of light scattering, as a function of angle and concentration, may be obtained.
In Situ MALDI-TOF MS Regional Analysis of Neutral Phospholipids in Lens Tissue (2004)

Phospholipids (PLs) are important sources of lipid second messengers that participate in cell signaling pathways. Consequently, their analysis in biological tissues has received increased attention. Current approaches for PL analysis include an extraction step and subsequent identification of the main PL classes by either 31P NMR spectroscopy or chromatographic separation followed by mass spectrometric detection. Previous in vitro studies revealed regional changes in the PL composition of mammalian lenses at different growth stages. In this report, we demonstrate the feasibility of direct in situ analysis of two relevant PL classes, phosphatidylcholines (PCs) and sphingomyelins (SMs), in slices of fresh or fixed (2.5% formaldehyde) mammalian lenses. The chosen matrix was p-nitroaniline, as it generated superior sensitivity when compared to 2,5-dihydroxybenzoic acid, the compound most commonly used for in vitro analysis of PLs by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Regional differences in the relative amounts of PCs and SMs were in agreement with trends demonstrated by previous in vitro studies. Fresh and fixed tissue of the same lens gave comparable relative levels of PCs and SMs. In situ analysis of PLs by MALDI-TOF MS offers a rapid and sensitive tool for the mapping of PLs in biological tissues.
Vibrationally induced inversion of photoelectron forward-backward asymmetry in chiral molecule photoionization by circularly polarized light (2013)

Electron-nuclei coupling accompanying excitation and relaxation processes is a fascinating phenomenon in molecular dynamics. A striking and unexpected example of such coupling is presented here in the context of photoelectron circular dichroism measurements on randomly oriented, chiral methyloxirane molecules, unaffected by any continuum resonance. Here, we report that the forward-backward asymmetry in the electron angular distribution, with respect to the photon axis, which is associated with photoelectron circular dichroism can surprisingly reverse direction according to the ion vibrational mode excited. This vibrational dependence represents a clear breakdown of the usual Franck-Condon assumption, ascribed to the enhanced sensitivity of photoelectron circular dichroism (compared with other observables like cross-sections or the conventional anisotropy parameter-β) to the scattering phase off the chiral molecular potential, inducing a dependence on the nuclear geometry sampled in the photoionization process. Important consequences for the interpretation of such dichroism measurements within analytical contexts are discussed.
Post-transcriptional gene-silencing: RNAs on the attack or on the defense? (2000)

Post-transcriptional gene-silencing (PTGS) was first discovered in plants and results from the sequence-specific degradation of RNA. Degradation can be activated by introducing transgenes, RNA viruses or DNA sequences that are homologous to expressed genes. A similar RNA degradation mechanism which is inducible by double-stranded RNA (dsRNAs), has been discovered recently in vertebrates, invertebrates and protozoa. dsRNAs may also be potent activators of PTGS in plants. PTGS is not cell autonomous, suggesting the synthesis of sequence-specific silencing signals which are not only moving through the plant but are also amplified and an RNA-directed RNA Polymerase which has recently been cloned from various plant species is a candidate enzyme for amplifying silencing signals. The natural role of PTGS seems to be as a defence against plant viruses, so what first appeared to be RNAs on the attack may now be considered RNAs on the defense. BioEssays 22:520-531, 2000.
GSK3 takes centre stage more than 20 years after its discovery (2001)

Identified originally as a regulator of glycogen metabolism, glycogen synthase kinase-3 (GSK3) is now a well-established component of the Wnt signalling pathway, which is essential for setting up the entire body pattern during embryonic development. It may also play important roles in protein synthesis, cell proliferation, cell differentiation, microtubule dynamics and cell motility by phosphorylating initiation factors, components of the cell-division cycle, transcription factors and proteins involved in microtubule function and cell adhesion. Generation of the mouse knockout of GSK3β, as well as studies in neurons, also suggest an important role in apoptosis. The substrate specificity of GSK3 is unusual in that efficient phosphorylation of many of its substrates requires the presence of another phosphorylated residue optimally located four amino acids C-terminal to the site of GSK3 phosphorylation. Recent experiments, including the elucidation of its three-dimensional structure, have enhanced our understanding of the molecular basis for the unique substrate specificity of GSK3. Insulin and growth factors inhibit GSK3 by triggering its phosphorylation, turning the N-terminus into a pseudosubstrate inhibitor that competes for binding with the ‘priming phosphate’ of substrates. In contrast, Wnt proteins inhibit GSK3 in a completely different way, by disrupting a multiprotein complex comprising GSK3 and its substrates in the Wnt signalling pathway, which do not appear to require a ‘priming phosphate’. These latest findings have generated an enormous amount of interest in the development of drugs that inhibit GSK3 and which may have therapeutic potential for the treatment of diabetes, stroke and Alzheimer's disease.
Treatment of Motor Fluctuations in Parkinsonʼs Disease with an Oral Sustained-Release Preparation of L-Dopa (1986)

Ten patients with idiopathic Parkinson's disease and severe motor-fluctuations participated in an open inpatient trial comparing the efficacy of standard L-Dopa/benserazide (Madopar) treatment with that of an oral sustained-release preparation (Madopar HBS) combined with the standard drug. Clinical assessments of the patients' parkinsonian disabilities were performed daily by one of the investigators and subjects kept self-scoring "on-off" diaries throughout the trial. Plasma concentrations of L-Dopa were followed during both types of therapy in five cases using standard high performance liquid chromatography technique. Sustained-release L-Dopa treatment led to a reduction in end-of-dose deterioration and on-off swings in six patients and doses needed averaged 1.6-fold of previous standard L-Dopa. Drug-induced dyskinesias decreased in one case with sustained-release therapy, remained unchanged in three, and increased in six cases when compared with conventional L-Dopa. Plasma levels of L-Dopa were more stable with the sustained-release preparation in four of five patients. During subsequent outpatient follow-ups of up to 4 months, three of the six responders in this study continued to obtain benefit from the trial drug. It is concluded that oral sustained-release L-Dopa treatment can reduce response-fluctuations in patients with Parkinson's disease.
Activation of Cancer Cell Migration and Invasion by Ectopic Synthesis of Coagulation Factor VII (2006)

Blood coagulation factor VII (fVII) is physiologically synthesized in the liver and released into the blood. Binding of fVII to tissue factor (TF) at sites of vascular injury triggers coagulation and hemostasis. TF/fVIIa complex formation on the surface of cancer cells plays important roles in cancer biology. Although fVII is synthesized by hepatocellular carcinoma, it remained unclear how TF/fVIIa complex formation and promigratory signaling can occur for most other cancers in extravascular locations. Here, we show by reverse transcription-PCR analysis that nonhepatic cancer cell lines constitutively express fVII mRNA and that endogenously synthesized fVIIa triggers coagulation activation on these cells. fVIIa expression in cancer cells is inducible under hypoxic conditions and hypoxia-inducible factor-2 alpha bound the promoter region of the FVII gene in chromatin immunoprecipitation analyses. Constitutive fVII expression in an ovarian cancer cell line enhanced both migration and invasion. Enhanced motility was blocked by anti-TF antibodies, factor Xa inhibition, and anti-protease-activated receptor-1 antibody treatment, confirming that TF/fVIIa stimulated migration by triggering cell signaling. This study shows that ectopic synthesis of fVII by cancer cells is sufficient to support proinvasive factor Xa-mediated protease-activated receptor-1 signaling and that this pathway is inducible under hypoxia.
Rabbit monoclonal antibodies: generating a fusion partner to produce rabbit-rabbit hybridomas. (1995)

During the last 15 years several laboratories have attempted to generate rabbit monoclonal antibodies, mainly because rabbits recognize antigens and epitopes that are not immunogenic in mice or rats, two species from which monoclonal antibodies are usually generated. Monoclonal antibodies from rabbits could not be generated, however, because a plasmacytoma fusion partner was not available. To obtain a rabbit plasmacytoma cell line that could be used as a fusion partner we generated transgenic rabbits carrying two transgenes, c-myc and v-abl. These rabbits developed plasmacytomas, and we obtained several plasmacytoma cell lines from which we isolated hypoxanthine/aminopterin/thymidine-sensitive clones. One of these clones, when fused with spleen cells of immunized rabbits, produced stable hybridomas that secreted antibodies specific for the immunogen. The hybridomas can be cloned and propagated in nude mice, and they can be frozen without change in their ability to secrete specific monoclonal antibodies. These rabbit-rabbit hybridomas will be useful not only for production of monoclonal antibodies but also for studies of immunoglobulin gene rearrangements and isotype switching.
Large suspended inductors on silicon and their use in a 2- mu m CMOS RF amplifier (1993)

Large spiral inductors encased in oxide over silicon are shown to operate beyond the UHF band when the capacitance and loss resistance are greatly reduced by selective removal of the underlying substrate. Using a 100-nH inductor whose self-resonance lies at 3 GHz, a balanced tuned amplifier with a gain of 14 dB centered at 770 MHz has been implemented in a standard digital 2- mu m CMOS IC process. The core amplifier noise figure is 6 dB, and the power dissipation is 7 mW for a 3-V supply.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Structural Differences among Hemagglutinins of Influenza A Virus Subtypes Are Reflected in Their Antigenic Architecture: Analysis of H9 Escape Mutants (2003)

We used a panel of monoclonal antibodies to H9 hemagglutinin to select 18 escape mutants of mouse-adapted influenza A/Swine/Hong Kong/9/98 (H9N2) virus. Cross-reactions of the mutants with the antibodies and the sequencing of hemagglutinin genes revealed two minimally overlapping epitopes. We mapped the amino acid changes to two areas of the recently reported three-dimensional structure of A/Swine/Hong Kong/9/98 hemagglutinin. The grouping of the antigenically relevant amino acid positions in H9 hemagglutinin differs from the pattern observed in H3 and H5 hemagglutinins. Several positions in site B of H3 hemagglutinin are distributed in two sites of H9 hemagglutinin. Unlike any subtype analyzed so far, H9 hemagglutinin does not contain an antigenic site corresponding to site A in H3 hemagglutinin. Positions 145 and 193 (H3 numbering), which in H3 hemagglutinin belong to sites A and B, respectively, are within one site in H9 hemagglutinin. This finding is consistent with the peculiarity of the three-dimensional structure of the H9 molecule, that is, the absence from H9 hemagglutinin of the lateral loop that forms site A in H3 and the equivalent site in H5 hemagglutinins. The escape mutants analyzed displayed phenotypic variations, including decreased virulence for mice and changes in affinity for sialyl substrates. Our results demonstrate a correlation between intersubtype differences in three-dimensional structure and variations among subtypes in the distribution of antigenic areas. Our findings also suggest that covariation and pleiotropic effects of antibody-selected mutations may be important in the evolution of H9 influenza virus, a possible causative agent of a future pandemic.
Deletion of Central α-Helices in Human Apolipoprotein A-I:  Effect on Phospholipid Association (1997)

In order to better understand the structure-function properties of apolipoprotein (apo) A-I, we have constructed and expressed three apoA-I mutants using a system previously described for the expression of human apolipoprotein A-I (Rec.-apoA-I). These mutants (corresponding to deletion of apoA-I residues 100-143, 122-165, 144-186) have been studied for their ability to form reconstituted apoA-I-containing lipoproteins (LpA-I) with POPC and DMPC, and for their structural and physical properties. Rec.- and native apoA-I can form homogeneous discoidal Lp2A-I over a wide range of POPC/apoA-I ratios [(20-130)/1] and exhibit sizes ranging from 9.5 to 10.5 nm. When recombined with varying POPC content [(20-130)/1, POPC/A-I)], the three mutants produce homogeneous discoidal Lp2A-I that contain a low POPC/A-I molar ratio [(20-40)/l for all mutants] and exhibit a nearly constant size [7.5-7.6 nm for delta (100-143) and 7.9-8.0 nm for the other two mutants]. Kinetics of association of these proteins with DMPC are similar for delta (100-143) and Rec.-apoA-I (t 1/2 of 4.0 and 4.4 min, respectively) but appear significantly reduced for delta (122-165) and delta (144-186) (t 1/2 of 7.5 and 6.9 min, respectively). While in the lipid-free form, all proteins have a similar thermodynamic stability with a very comparable free energy of unfolding (delta GD degree) for the alpha-helical structure, as determined by isothermal denaturation studies. delta-(100-143) has a significantly lower alpha-helical content (33%) as compared to the other proteins [40, 41, and 45% for Rec.-apoA-I. delta (122-165), and delta (144-186), respectively]. When associated to POPC, delta (122-165) and delta (144-186) have a higher alpha-helicity (63 and 63%) and an enhanced stability (2.5 and 2.3 kcal/mol, respectively) as compared to delta (100-143) (49% and 1.8 kcal/mol) and Rec.-apoA-I (52% and 1.9 kcal/mol). These results suggest that the amphipathic alpha-helices within residues 100-186 are directly involved in interactions with phospholipids. The helical region 100-121 appears to be more important to the stabilization of the lipid-apoprotein complex formed whereas helices within residues 122-186 appear to be critical to the initial rates of association of the apoprotein with DMPC. These data suggest that an important role of the central domain 100-186 may be to maintain the plasticity of apoA-I and its ability to form different classes of HDL particles. Therefore, it is likely that this region may also play an important role in the functional properties of this apoprotein.
Production of self-assembling biomaterials for tissue engineering (2009)

Self-assembling peptide-based biomaterials are being developed for use as 3D tissue engineering scaffolds and for therapeutic drug-release applications. Chemical synthesis provides custom-made peptides in small quantities, but production approaches based upon transgenic organisms might be more cost-effective for large-scale peptide production. Long lead times for developing appropriate animal clones or plant lines and potential negative public opinion are obstacles to these routes. Microbes, particularly safe organisms used in the food industry, offer a more rapid route to the large-scale production of recombinant self-assembling biomaterials. In this review, recent advances and challenges in the recombinant production of collagen, elastin and de novo designed self-assembling peptides are discussed.