gebhart/patrepeval huggingface dataset:
Identification of mesenchymal stem cells in aorta-gonad-mesonephros and yolk sac of human embryos (2007)

Mesenchymal stem cells (MSCs) are multipotent stem cells that can generate various microenvironment components in bone marrow, ensuring a precise control over self-renewal and multilineage differentiation of hematopoietic stem cells. Nevertheless, their spatiotemporal correlation with embryonic hematopoiesis remains rudimentary, particularly in relation to the human being. Here, we reported that human aorta-gonad-mesonephros (AGM) resided with bona fide MSCs. They were highly proliferative as fibroblastoid population bearing uniform surface markers (CD45(-), CD34(-), CD105(+), CD73(+), CD29(+), and CD44(+)), expressed pluripotential molecules Oct-4 and Nanog, and clonally demonstrated trilineage differentiation capacity (osteocytes, chondrocytes, and adipocytes). The frequency and absolute number of MSCs in aorta plus surrounding mesenchyme (E26-E27) were 0.3% and 164, respectively. Moreover, they were functionally equivalent to MSCs from adult bone marrow, that is, supporting long-term hematopoiesis and suppressing T-lymphocyte proliferation in vitro. In comparison, the matching yolk sac contained bipotent mesenchymal precursors that propagated more slowly and failed to generate chondrocytes in vitro. Together with previous knowledge, we propose that a proportion of MSCs initially develop in human AGM prior to their emergence in embryonic circulation and fetal liver.
Mitogen-activated protein kinases enhance long-range activation by the β-globin locus control region (1998)

The human beta-globin locus control region (LCR), which consists of four erythroid-specific DNase I hypersensitive sites (HS1-HS4), functions over a long distance to control the transcription, chromatin structure, and replication of the beta-globin genes. We have used stable transfection assays to show that activation of the mitogen-activated protein (MAP) kinase pathway by low concentrations of the phorbol ester phorbol 12-tetradecanoate 13-acetate (TPA) induces enhancer activity of the LCR subregion HS2, but not HS3. Although HS2 enhancer activity is diminished with increasing distance from the promoter, the relative level of induction by TPA is independent of HS2-promoter distance. Mutation of cis-elements within HS2 reveals that the tandem-binding sites for the hematopoietic-specific transcription factor NF-E2 are required for induction by TPA, and induction is conferred by expressing NF-E2 in an NF-E2-null cell line. These results show that MAP kinases target factors functioning through the NF-E2 sites to enhance long-range transactivation by the LCR.
Mast Cells in Autoantibody Responses and Arthritis (2005)

A pathogenic role for autoantibodies, immune complexes and mast cells has long been hypothesized in rheumatoid arthritis (RA). Recent studies demonstrating novel RA-associated autoantibodies and the efficacy of B cell-directed therapy have led to a renewed interest in the role of humoral immunity in RA. Mouse models of arthritis have provided further support for a direct pathogenic role of autoantibodies in the development of synovial inflammation. Interestingly, in antibody-mediated K/BxN serum transfer arthritis, mast cells have now been identified as a critical cellular mediator of autoantibody-driven joint inflammation. Here, we focus on the role of autoantibodies and mast cells in murine and human inflammatory arthritis.
Molecular Modelling Studies on the Binding of Some Protides to the Putative Human Phosphoramidase Hint1 (2007)

The aim of the present work is to investigate through molecular modelling the possible role of the human enzyme Hint1 in the final P-N bond cleavage of phosphoramidate ProTides, which would lead to the intracellular delivery of unmasked nucleoside analogue monophosphates. Herein, we report our preliminary analysis based on docking studies of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdU) related aminoacyl phosphates with Hint1 and the effect of the amino acid moiety on the enzyme-substrate binding affinity.
π-Stacking Interactions (1998)

A representative set of high resolution x-ray crystal structures of nonhomologous proteins have been examined to determine the preferred positions and orientations of noncovalent interactions between the aromatic side chains of the amino acids phenylalanine, tyrosine, histidine, and tryptophan. To study the primary interactions between aromatic amino acids, care has been taken to examine only isolated pairs (dimers) of amino acids because trimers and higher order clusters of aromatic amino acids behave differently than their dimer counterparts. We find that pairs (dimers) of aromatic side chain amino acids preferentially align their respective aromatic rings in an off-centered parallel orientation. Further, we find that this parallel-displaced structure is 0.5-0.75 kcal/mol more stable than a T-shaped structure for phenylalanine interactions and 1 kcal/mol more stable than a T-shaped structure for the full set of aromatic side chain amino acids. This experimentally determined structure and energy difference is consistent with ab initio and molecular mechanics calculations of benzene dimer, however, the results are not in agreement with previously published analyses of aromatic amino acids in proteins. The preferred orientation is referred to as parallel displaced pi-stacking.
Application of Nucleic Acid Amplification in Clinical Microbiology (2003)

Since the discovery of the doublehelix structure of DNA (1), no single event has had the same impact on the field of molecular biology as the rediscovery by Kary Mullis in the early 1980s of the polymerase chain reaction (PCR) (2-4), which was first published in principle by Keld Kleppe in 1971 (5). This elegant technology with its apparent simple theory has revolutionized almost every aspect of classical molecular biology, and is at the present moment beginning to make a major impact upon many medical—especially diagnostic-specialities. The field of clinical microbiology has been among the first to embrace the polymerase chain reaction technology, and the expectations of the future impact of this technology are high. First and foremost, the diagnostic possibilities of this technology are stunning, but in this era of emerging implementation, it is crucial to focus not only on the possibilities, but also on the pitfalls of the technology. Failure to do so will increase the cost of implementation manifold, and will risk to disrepute the technology in the eyes of the clinicians.
Typical Dynamic Moduli for North Carolina Asphalt Concrete Mixes (2005)

This report presents results from an experimental study on the dynamic modulus testing of hot mix asphalts (HMAs) in uniaxial compression and indirect tension (IDT) modes. The study includes 42 mixtures that are commonly used in North Carolina and have varying aggregate sources, aggregate gradations, asphalt sources, asphalt grades, and asphalt contents. The procedures outlined in the AASHTO TP 62-03 Standard Method of Test for Determining Dynamic Modulus of Hot-Mix Asphalt Concrete Mixtures have been modified in this study by reducing the number of test temperatures from five to four and by increasing the number of loading frequencies. This modified four-temperature protocol resulted in a reduction of the testing time. The dynamic modulus database developed from the axial compression testing was used to evaluate the prediction accuracy of the two dynamic modulus predictive models that are currently available, i.e., the Witczak and Hirsch models. A case study was conducted to determine the effects of predictive errors on the fatigue cracking and rutting performance of HMA pavements. The database was also used to investigate the effects of different mixture variables on the dynamic modulus. It was found that the binder variables (i.e., the source, performance grade, and content) have a much more significant effect on the dynamic modulus than the aggregate variables (i.e., source and gradation). An analytical solution to determine the dynamic modulus, phase angle, and Poisson's ratio using the IDT test was developed using the theory of linear viscoelasticity. The resulting IDT dynamic modulus was found to be statistically the same as the dynamic modulus determined from the axial compression testing about 80% of the time. It was found that the amount of variability between replicates increases as the nominal maximum aggregate size (NMAS) increases. The digital image correlation (DIC) method, a noncontact, full-field displacement measurement technique, was employed to investigate the relationship between the displacement gauge length in the IDT test and the NMAS.
Using 915 nm Laser Excited Tm3+/Er3+/Ho3+-Doped NaYbF4 Upconversion Nanoparticles for in Vitro and Deeper in Vivo Bioimaging without Overheating Irradiation (2011)

Successful further development of superhigh-constrast upconversion (UC) bioimaging requires addressing the existing paradox: 980 nm laser light is used to excite upconversion nanoparticles (UCNPs), while 980 nm light has strong optical absorption of water and biological specimens. The overheating caused by 980 nm excitation laser light in UC bioimaging is computationally and experimentally investigated for the first time. A new promising excitation approach for better near-infrared to near-infrared (NIR-to-NIR) UC photoluminescence in vitro or in vivo imaging is proposed employing a cost-effective 915 nm laser. This novel laser excitation method provides drastically less heating of the biological specimen and larger imaging depth in the animals or tissues due to quite low water absorption. Experimentally obtained thermal-graphic maps of the mouse in response to the laser heating are investigated to demonstrate the less heating advantage of the 915 nm laser. Our tissue phantom experiments and simulations verified that the 915 nm laser is superior to the 980 nm laser for deep tissue imaging. A novel and facile strategy for surface functionalization is utilized to render UCNPs hydrophilic, stable, and cell targeting. These as-prepared UCNPs were characterized by TEM, emission spectroscopy, XRD, FTIR, and zeta potential. Specifically targeting UCNPs excited with a 915 nm laser have shown very high contrast UC bioimaging. Highly stable DSPE-mPEG-5000-encapsulated UCNPs were injected into mice to perform in vivo imaging. Imaging and spectroscopy analysis of UC photoluminescence demonstrated that a 915 nm laser can serve as a new promising excitation light for UC animal imaging.
Estimation of Respiratory Rates Using the Built-in Microphone of a Smartphone or Headset (2015)

This paper proposes accurate respiratory rate estimation using nasal breath sound recordings from a smartphone. Specifically, the proposed method detects nasal airflow using a built-in smartphone microphone or a headset microphone placed underneath the nose. In addition, we also examined if tracheal breath sounds recorded by the built-in microphone of a smartphone placed on the paralaryngeal space can also be used to estimate different respiratory rates ranging from as low as 6 breaths/min to as high as 90 breaths/min. The true breathing rates were measured using inductance plethysmography bands placed around the chest and the abdomen of the subject. Inspiration and expiration were detected by averaging the power of nasal breath sounds. We investigated the suitability of using the smartphone-acquired breath sounds for respiratory rate estimation using two different spectral analyses of the sound envelope signals: The Welch periodogram and the autoregressive spectrum. To evaluate the performance of the proposed methods, data were collected from ten healthy subjects. For the breathing range studied (6-90 breaths/min), experimental results showed that our approach achieves an excellent performance accuracy for the nasal sound as the median errors were less than 1% for all breathing ranges. The tracheal sound, however, resulted in poor estimates of the respiratory rates using either spectral method. For both nasal and tracheal sounds, significant estimation outliers resulted for high breathing rates when subjects had nasal congestion, which often resulted in the doubling of the respiratory rates. Finally, we show that respiratory rates from the nasal sound can be accurately estimated even if a smartphone's microphone is as far as 30 cm away from the nose.
An Implantable Telemetry Platform System for In Vivo Monitoring of Physiological Parameters (2004)

This paper describes a microcontroller-based multichannel telemetry system, suitable for in vivo monitoring of physiological parameters. The device can digitalize and transmit up to three analog signals coming from different sensors. The telemetry transmission is obtained by using a carrier frequency of 433.92 MHz and an amplitude-shift keying modulation. The signal data rate is 13 kb/s per channel. The digital microcontroller provides good flexibility and interesting performance, such as the threshold monitoring, the transmission error detection, and a low power consumption, thanks to the implementation of a sleep mode. The small overall size (less than 1 cm3), the power density compatible with current regulations for the design of implantable devices, and the dedicated packaging make the system suitable for in vivo monitoring in humans. The design, fabrication, operation, packaging, and performance of the system are described in this paper. An in vivo pressure monitoring case study is described as well.
The Effect of Proteasome Inhibition on the Generation of the Human Leukocyte Antigen (HLA) Peptidome (2013)

The Major histocompatibility complex (MHC) class I peptidome is thought to be generated mostly through proteasomal degradation of cellular proteins, a notion that is based on the alterations in presentation of selected peptides following proteasome inhibition. We evaluated the effects of proteasome inhibitors, epoxomicin and bortezomib, on human cultured cancer cells. Because the inhibitors did not reduce the level of presentation of the cell surface human leukocyte antigen (HLA) molecules, we followed their effects on the rates of synthesis of both HLA peptidome and proteome of the cells, using dynamic stable isotope labeling in tissue culture (dynamic-SILAC). The inhibitors reduced the rates of synthesis of most cellular proteins and HLA peptides, yet the synthesis rates of some of the proteins and HLA peptides was not decreased by the inhibitors and of some even increased. Therefore, we concluded that the inhibitors affected the production of the HLA peptidome in a complex manner, including modulation of the synthesis rates of the source proteins of the HLA peptides, in addition to their effect on their degradation. The collected data may suggest that the current reliance on proteasome inhibition may overestimate the centrality of the proteasome in the generation of the MHC peptidome. It is therefore suggested that the relative contribution of the proteasomal and nonproteasomal pathways to the production of the MHC peptidome should be revaluated in accordance with the inhibitors effects on the synthesis rates of the source proteins of the MHC peptides.
How to Write and Publish a Scientific Paper (1983)

This book includes, in a stylish and readable way, all the information and advice needed to write and publish a scientific paper. This expanded edition contains new information on electronic manuscript preparation and the use of computers to create effective tabulation.
Control of Immunologically Crossreactive Leptospiral Infection by Administration of Lipopolysaccharides from a Nonpathogenic Strain of Leptospira biflexa (2000)

In our previous paper (Matsuo, K., Isogai, E., and Araki, Y., Carbohydr. Res., 328: 517-524, 2000), antigenic polysaccharides obtained from the lipopolysaccharide (LPS) fraction of a nonpathogenic leptospira, Leptospira biflexa patoc Patoc I, are shown to be broadly crossreactable with most rabbit antisera elicited by immunization with various pathogenic leptospires. The result led us to test a protective effect of the same LPS in a hamster model system by heterologously challenging with a pathogenic leptospira, L. interrogans manilae UP-MMG. Firstly, a similarity in the antigenic epitopes of L. biflexa and L. interrogans was confirmed by the following assays. In the microscopic agglutination test (MAT), a hamster antiserum elicited by immunization with the L. biflexa-LPS preparation was shown to agglutinate cells of L. interrogans. Contrarily, in the enzyme-linked immunosorbent assay (ELISA), the L. biflexa-LPS preparation was shown to crossreact with a hamster antiserum elicited by immunization with whole cells of L. interrogans. These results suggest that the same or closely related antigens may be present on the cell surfaces of both L. biflexa patoc Patoc I and L. interrogans manilae UP-MMG. Furthermore, in a protective assay, the prior administration of a L. biflexa-LPS preparation resulted in raising a protective response in hamsters against challenge by L. interrogans without any side effect. The protective effect was strongly dependent on the dose amounts and/or administration times of L. biflexa-LPS. Thus, L. biflexa-LPS preparations can use as a potent vaccine against leptospirosis caused by various leptospires.
Paclitaxel-Functionalized Gold Nanoparticles (2007)

Here we describe the first example of 2 nm gold nanoparticles (Au NPs) covalently functionalized with a chemotherapeutic drug, paclitaxel. The synthetic strategy involves the attachment of a flexible hexaethylene glycol linker at the C-7 position of paclitaxel followed by coupling of the resulting linear analogue to phenol-terminated gold nanocrystals. The reaction proceeds under mild esterification conditions and yields the product with a high molecular weight, while exhibiting an extremely low polydispersity index (1.02, relative to linear polystyrene standards). TGA analysis of the hybrid nanoparticles reveals the content of the covalently attached organic shell as nearly 67% by weight, which corresponds to approximately 70 molecules of paclitaxel per 1 nanoparticle. The presence of a paclitaxel shell with a high grafting density renders the product soluble in organic solvents and allows for detailed (1)H NMR analysis and, therefore, definitive confirmation of its chemical structure. High-resolution TEM was employed for direct visualization of the inorganic core of hybrid nanoparticles, which were found to retain their average size, shape, and high crystallinity after multiple synthetic steps and purifications. The interparticle distance substantially increases after the attachment of paclitaxel as revealed by low-magnification TEM, suggesting the presence of a larger organic shell. The method described here demonstrates that organic molecules with exceedingly complex structures can be covalently attached to gold nanocrystals in a controlled manner and fully characterized by traditional analytical techniques. In addition, this approach gives a rare opportunity to prepare hybrid particles with a well-defined amount of drug and offers a new alternative for the design of nanosized drug-delivery systems.
Reversion of Autocrine Transformation by a Dominant Negative Platelet-Derived Growth Factor Mutant (1993)

A non-receptor-binding mutant of the platelet-derived growth factor (PDGF) A chain, PDGF-0, was generated by exchanging 7 amino acids in the sequence. The mutant chains formed dimers that were similar to wild-type PDGF-AA with regard to stability and rate of processing to the mature 30-kDa secreted forms. Moreover, the mutant chains formed disulfide-bonded heterodimers with the PDGF B chain in NIH 3T3 cells heterodimer underwent the same processing and secretion as PDGF-AB. Transfection of c-sis-expressing 3T3 cells with PDGF-0 significantly inhibited the transformed phenotype of these cells, as determined by the following criteria. (i) Compared with PDGF-0-negative clones, PDGF-0-producing clones showed a reverted morphology. (ii) Clones producing PDGF-0 grew more slowly than PDGF-0-negative clones, with a fivefold difference in cell number after 14 days in culture. (iii) The expression of PDGF-0 completely inhibited the ability of the c-sis-expressing 3T3 cells to form colonies in soft agar; this inhibition was overcome by the addition of recombinant PDGF-BB to the culture medium, showing that the lack of colony formation of these cells was not due to a general unresponsiveness to PDGF. The specific expression of a PDGF-0/PDGF wild-type heterodimer in COS cells revealed that the affinity of the mutant heterodimer for the PDGF alpha receptor was decreased by approximately 50-fold compared with that of PDGF-AA. Thus, we show that a non-receptor-binding PDGF A-chain mutant neutralizes in a trans-dominant manner the autocrine transforming potential of the c-sis/PDGF B chain by forming low-affinity heterodimers with wild-type PDGF chains. This method of specifically antagonizing the effect of PDGF may be useful in investigations of the role of PDGF in normal and pathological conditions.
Treatment of Dry Age-Related Macular Degeneration (2014)

A number of different approaches are under development for treating nonexudative manifestations of age-related macular degeneration (AMD). Some interventions target specific pathways that are believed to play a role in AMD pathogenesis, e.g. oxidative damage, lipofuscin accumulation, chronic inflammation (including complement activation), extracellular matrix changes (e.g. β-amyloid accumulation), impaired choroidal blood flow, and apoptosis. In principle, these therapies can be combined ('combination therapy'), which may lead to synergistic effects that include better visual outcome, less likelihood for 'escape' (i.e. drug resistance), and less frequent treatment.
Phase 1 studies of central memory–derived CD19 CAR T–cell therapy following autologous HSCT in patients with B-cell NHL (2016)

Myeloablative autologous hematopoietic stem cell transplantation (HSCT) is a mainstay of therapy for relapsed intermediate-grade B-cell non-Hodgkin lymphoma (NHL); however, relapse rates are high. In phase 1 studies designed to improve long-term remission rates, we administered adoptive T-cell immunotherapy after HSCT, using ex vivo-expanded autologous central memory-enriched T cells (TCM) transduced with lentivirus expressing CD19-specific chimeric antigen receptors (CARs). We present results from 2 safety/feasibility studies, NHL1 and NHL2, investigating different T-cell populations and CAR constructs. Engineered TCM-derived CD19 CAR T cells were infused 2 days after HSCT at doses of 25 to 200 × 10(6) in a single infusion. In NHL1, 8 patients safely received T-cell products engineered from enriched CD8(+) TCM subsets, expressing a first-generation CD19 CAR containing only the CD3ζ endodomain (CD19R:ζ). Four of 8 patients (50%; 95% confidence interval [CI]: 16-84%) were progression free at both 1 and 2 years. In NHL2, 8 patients safely received T-cell products engineered from enriched CD4(+) and CD8(+) TCM subsets and expressing a second-generation CD19 CAR containing the CD28 and CD3ζ endodomains (CD19R:28ζ). Six of 8 patients (75%; 95% CI: 35-97%) were progression free at 1 year. The CD4(+)/CD8(+) TCM-derived CD19 CAR T cells (NHL2) exhibited improvement in expansion; however, persistence was ≤28 days, similar to that seen by others using CD28 CARs. Neither cytokine release syndrome nor delayed hematopoietic engraftment was observed in either trial. These data demonstrate the safety and feasibility of CD19 CAR TCM therapy after HSCT. Trials were registered at www.clinicaltrials.gov as #NCT01318317 and #NCT01815749.