gebhart/patrepeval huggingface dataset:
Highly potent mRNA based cancer vaccines represent an attractive platform for combination therapies supporting an improved therapeutic effect (2012)

Direct vaccination with mRNA encoding tumor antigens is a novel and promising approach in cancer immunotherapy. CureVac's mRNA vaccines contain free and protamine-complexed mRNA. Such two-component mRNA vaccines support both antigen expression and immune stimulation. These self-adjuvanting RNA vaccines, administered intradermally without any additional adjuvant, induce a comprehensive balanced immune response, comprising antigen specific CD4+ T cells, CD8+ T cells and B cells. The balanced immune response results in a strong anti-tumor effect and complete protection against antigen positive tumor cells. This tumor inhibition elicited by mRNA vaccines is a result of the concerted action of different players. After just two intradermal vaccinations, we observe multiple changes at the tumor site, including the up-regulation of many genes connected to T and natural killer cell activation, as well as genes responsible for improved infiltration of immune cells into the tumor via chemotaxis. The two-component mRNA vaccines induce a very fast and boostable immune response. Therefore, the vaccination schedules can be adjusted to suit the clinical situation. Moreover, by combining the mRNA vaccines with therapies in clinical use (chemotherapy or anti-CTLA-4 antibody therapy), an even more effective anti-tumor response can be elicited. The first clinical data obtained from two separate Phase I/IIa trials conducted in PCA (prostate cancer) and NSCLC (non-small cell lung carcinoma) patients have shown that the two-component mRNA vaccines are safe, well tolerated and highly immunogenic in humans.
Macrophage Migration Inhibitory Factor and Host Innate Immune Responses to Microbes (2003)

Among innate immune cells, macrophages play an essential role in the sensing and elimination of invasive microorganisms. Binding of microbial products to pathogen-recognition receptors stimulates macrophages to release cytokines and other effector molecules that orchestrate the host innate and adaptive immune responses. Recently, the protein known as macrophage migration inhibitory factor (MIF) has emerged as a pivotal mediator of innate immunity. First identified as a T-cell cytokine, MIF was rediscovered as a protein released by pituitary cells after exposure to endotoxin [lipopolysaccharide (LPS)] or bacteria and in response to stress. Monocytes, macrophages and lymphocytes constitutively express MIF, which is rapidly released after stimulation with bacterial endotoxins and exotoxins, and cytokines. MIF induces powerful proinflammatory biological responses and has been shown to be an important effector molecule of septic shock. High levels of MIF have been detected in the circulation of patients with severe sepsis and septic shock. Inhibition of MIF activity with neutralizing anti-MIF antibodies or deletion of the Mif gene led to a marked reduction in cytokine production and protected mice from lethal bacterial sepsis and toxic shock induced by Gram-negative endotoxin or Gram-positive exotoxins. Investigations into the mechanisms whereby MIF modulates innate immune responses to endotoxin and Gram-negative bacteria have shown that MIF up-regulates the expression of Toll-like receptor 4 (TLR4), the signal-transducing molecule of the LPS receptor complex. Thus, MIF enables cells, such as the macrophage, that are at the forefront of the host antimicrobial defences, to sense promptly the presence of invading Gram-negative bacteria and mount an innate immune response. Given that it is a pivotal regulator of innate immune responses to bacterial infections, MIF appears to be a perfect target for novel therapeutic interventions in patients with severe sepsis.
Hybrid multi-wavelength photoacoustic imaging (2018)

Multi-wavelength photoacoustic (PA) imaging has been studied extensively to explore the spectroscopic absorption contrast of biological tissues. To generate strong PA signals, a high-power wavelength-tunable pulsed laser source has to be employed, which is bulky and quite expensive. In this paper, we propose a hybrid multi-wavelength PA imaging (hPAI) method based on combination of single-wavelength pulsed and multi-wavelength continuous-wave (CW) laser sources. By carefully controlling laser illumination sequence (pulse-CW-pulse), and extracting the PA signals' difference before and after heating of CW lasers, the optical absorption property of multi-wavelength CW lasers could be obtained. Compared with conventional PA imaging, the proposed hPAI shows much lower system cost due to the usage of single-wavelength pulsed laser and cheap CW lasers. Theoretical analysis and analytical model are presented in this paper, followed by proof-of-concept experimental results.
Dispersion in graded single-mode fibres (1979)

The normalised frequency for zero waveguide dispersion of the HE11 mode, called VOD, is highly dependent on profile shape. The more the profile departs from a step, the greater the increase of VOD above the effective single-moded region until, for example, VOD becomes infinite for profiles that fall off at a rate greater than or equal to the parabola.
Antisense RNA Strategies for Metabolic Engineering of Clostridium acetobutylicum (1999)

We examined the effectiveness of antisense RNA (as RNA) strategies for metabolic engineering of Clostridium acetobutylicum. Strain ATCC 824(pRD4) was developed to produce a 102-nucleotide asRNA with 87% complementarity to the butyrate kinase (BK) gene. Strain ATCC 824(pRD4) exhibited 85 to 90% lower BK and acetate kinase specific activities than the control strain. Strain ATCC 824(pRD4) also exhibited 45 to 50% lower phosphotransbutyrylase (PTB) and phosphotransacetylase specific activities than the control strain. This strain exhibited earlier induction of solventogenesis, which resulted in 50 and 35% higher final concentrations of acetone and butanol, respectively, than the concentrations in the control. Strain ATCC 824(pRD1) was developed to putatively produce a 698-nucleotide asRNA with 96% complementarity to the PTB gene. Strain ATCC 824(pRD1) exhibited 70 and 80% lower PTB and BK activities, respectively, than the control exhibited. It also exhibited 300% higher levels of a lactate dehydrogenase activity than the control exhibited. The growth yields of ATCC 824(pRD1) were 28% less than the growth yields of the control. While the levels of acids were not affected in ATCC 824(pRD1) fermentations, the acetone and butanol concentrations were 96 and 75% lower, respectively, than the concentrations in the control fermentations. The lower level of solvent production by ATCC 824(pRD1) was compensated for by approximately 100-fold higher levels of lactate production. The lack of any significant impact on butyrate formation fluxes by the lower PTB and BK levels suggests that butyrate formation fluxes are not controlled by the levels of the butyrate formation enzymes.
Highly Efficient CdS Quantum Dot-Sensitized Solar Cells Based on a Modified Polysulfide Electrolyte (2011)

A modified polysulfide redox couple, [(CH(3))(4)N](2)S/[(CH(3))(4)N](2)S(n), in an organic solvent (3-methoxypropionitrile) was employed in CdS quantum dot (QD)-sensitized solar cells (QDSSCs), and an unprecedented energy conversion efficiency of up to 3.2% was obtained under AM 1.5 G illumination. The QDs were linked to nanoporous TiO(2) via covalent bonds by using thioglycolic acid, and chemical bath deposition in an organic solvent was then used to prepare the QDSSCs, facilitating high wettability and superior penetration capability of the TiO(2) films. A very high fill factor of 0.89 was observed with the optimized QDSSCs.
The Desferrithiocin Pharmacophore (1994)

The (S)-desferrithiocin (DFT) skeleton is shown to be a useful pharmacophore on which to design orally effective iron chelators. While the study clearly indicates that formal reduction of the desazadesmethyldesferrithiocin thiazoline to a thiazolidine (6), expansion of the desmethyldesferrithiocin thiazoline to a thiazine (7), or substitution of the thiazoline sulfur of of desazedes-methyldesferrithiocin by an oxygen (8 and 9) lead to a substantial loss of activity, conversion of (S)-desmethyldesferrithiocin (1) to an N-methylhydroxamate (4) or to the hexacoordinate dihydroxamate ligand (5) results in active compounds. This investigation thus demonstrates which structural components of the siderophore are required for iron clearance after oral administration and suggests the use of the desferrithiocin platform as a vector for other chelators.
Magnetic resonance monitoring of focused ultrasound/magnetic nanoparticle targeting delivery of therapeutic agents to the brain (2010)

The superparamagnetic properties of magnetic nanoparticles (MNPs) allow them to be guided by an externally positioned magnet and also provide contrast for MRI. However, their therapeutic use in treating CNS pathologies in vivo is limited by insufficient local accumulation and retention resulting from their inability to traverse biological barriers. The combined use of focused ultrasound and magnetic targeting synergistically delivers therapeutic MNPs across the blood-brain barrier to enter the brain both passively and actively. Therapeutic MNPs were characterized and evaluated both in vitro and in vivo, and MRI was used to monitor and quantify their distribution in vivo. The technique could be used in normal brains or in those with tumors, and significantly increased the deposition of therapeutic MNPs in brains with intact or compromised blood-brain barriers. Synergistic targeting and image monitoring are powerful techniques for the delivery of macromolecular chemotherapeutic agents into the CNS under the guidance of MRI.
FDSOI Floating Body Cell eDRAM Using Gate-Induced Drain-Leakage (GIDL) Write Current for High Speed and Low Power Applications (2009)

A Capacitorless IT-DRAM cell using gate-induced drain leakage (GIDL) current for write operation was demonstrated for the first time on FDSOI substrate, 9.5 nm silicon film and 19 nm BOX. 20 nm gate scaling improves 20% memory effect amplitude. GIDL mechanism allows low bias, low power, fast write time and does not affect intrinsic retention time. A similar value of 10 ms at 85degC is obtained like for impact ionization (II) optimised devices.
Electroactive Block Copolymer Brushes on Multiwalled Carbon Nanotubes (2009)

ADVERTISEMENT RETURN TO ISSUEPREVCommunication to the...Communication to the EditorNEXTElectroactive Block Copolymer Brushes on Multiwalled Carbon NanotubesDaisuke Izuhara and Timothy M. Swager*View Author Information Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139*Corresponding author. E-mail: [email protected]Cite this: Macromolecules 2009, 42, 15, 5416–5418Publication Date (Web):July 15, 2009Publication History Received22 March 2009Revised18 June 2009Published online15 July 2009Published inissue 11 August 2009https://pubs.acs.org/doi/10.1021/ma9006076https://doi.org/10.1021/ma9006076rapid-communicationACS PublicationsCopyright © 2009 American Chemical SocietyRequest reuse permissionsArticle Views1680Altmetric-Citations15LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Carbon nanotubes,Copolymers,Mixtures,Nanotubes,Polymers Get e-Alerts
Inhibition by interferon of herpes simplex virus type 1-activated transcription of tat-defective provirus. (1991)

The herpes simplex virus type 1 (HSV-1)-mediated transactivation of human immunodeficiency virus type 1 (HIV-1) provirus was studied in cell lines containing either integrated tat-defective HIV-1 provirus (HNHIVdt4 cells) or the tat-defective HIV-1 provirus, and a plasmid in which the expression of human alpha 2 interferon (HuIFN-alpha 2) was under the control of the HIV-1 long terminal repeat (LTR) (HNHIV alpha 1 cells). In both cell lines, transcription of the HIV-1 provirus was below the limits of detection, but it could be induced effectively by transfection with a HIV-1 tat-expression plasmid. In HNHIV alpha 1 cells, HuIFN-alpha 2 was induced concomitantly with HIV-1 provirus, although these cells synthesized only low levels of IFN constitutively. In contrast, infections with HSV-1 activated transcription of HIV-1 provirus only in HNHIVdt4 cells but not in HNHIV alpha 1 cells. Similarly in a transient expression assay, HSV-1 up-regulated expression of a HIV LTR-CAT (chloramphenicol acetyltransferase gene) plasmid in HNHIVdt4 but not in HNHIV alpha 1 cells. No major differences could be detected in the expression of HSV-1 immediate-early (IE) genes IE175 and IE110 (which are essential for the activation of HIV-1 LTR) in HNHIVdt4 and HNHIV alpha 1 cells to account for the inability of HSV-1 to induce HIV-1 in HNHIV alpha 1 cells. However, major differences were observed in the binding pattern of NF-kappa B-specific nuclear proteins to the enhancer region of the HIV-1 LTR: whereas binding of the 45-kDa NF-kappa B-specific nuclear protein was detected in nuclear extracts from HNHIVdt4 cells, no protein binding was seen in extracts from HNHIV alpha 1 cells. These results suggest an alternate mechanism by which IFN may alter the expression of cellular and viral genes.
Generalization of distance to higher dimensional objects (2007)

The measurement of distance between two objects is generalized to the case where the objects are no longer points but are one-dimensional. Additional concepts such as nonextensibility, curvature constraints, and noncrossing become central to the notion of distance. Analytical and numerical results are given for some specific examples, and applications to biopolymers are discussed.
A Comparative Analysis of Localized and Propagating Surface Plasmon Resonance Sensors:  The Binding of Concanavalin A to a Monosaccharide Functionalized Self-Assembled Monolayer (2004)

A comparative analysis of the properties of two optical biosensor platforms: (1) the propagating surface plasmon resonance (SPR) sensor based on a planar, thin film gold surface and (2) the localized surface plasmon resonance (LSPR) sensor based on surface confined Ag nanoparticles fabricated by nanosphere lithography (NSL) are presented. The binding of Concanavalin A (ConA) to mannose-functionalized self-assembled monolayers (SAMs) was chosen to highlight the similarities and differences between the responses of the real-time angle shift SPR and wavelength shift LSPR biosensors. During the association phase in the real-time binding studies, both SPR and LSPR sensors exhibited qualitatively similar signal vs time curves. However, in the dissociation phase, the SPR sensor showed an approximately 5 times greater loss of signal than the LSPR sensor. A comprehensive set of nonspecific binding studies demonstrated that this signal difference was not the consequence of greater nonspecific binding to the LSPR sensor but rather a systematic function of the Ag nanoparticle's nanoscale structure. Ag nanoparticles with larger aspect ratios showed larger dissociation phase responses than those with smaller aspect ratios. A theoretical analysis based on finite element electrodynamics demonstrates that this results from the characteristic decay length of the electromagnetic fields surrounding Ag nanoparticles being of comparable dimensions to the ConA molecules. Finally, an elementary (2 x 1) multiplexed version of an LSPR carbohydrate sensing chip to probe the simultaneous binding of ConA to mannose and galactose-functionalized SAMs has been demonstrated.
Quantification of circulating plasma DNA fragments as tumor markers in patients with esophageal cancer. (2007)

qPCR assays for plasma DNA concentrations and their integrity can serve as new diagnostic markers for screening and monitoring patients with esophageal cancer.
An Analysis of Phase Transition in NK Landscapes (2002)

In this paper, we analyze the decision version of the NK landscape model from the perspective of threshold phenomena and phase transitions under two random distributions, the uniform probability model and the fixed ratio model. For the uniform probability model, we prove that the phase transition is easy in the sense that there is a polynomial algorithm that can solve a random instance of the problem with the probability asymptotic to 1 as the problem size tends to infinity. For the fixed ratio model, we establish several upper bounds for the solubility threshold, and prove that random instances with parameters above these upper bounds can be solved polynomially. This, together with our empirical study for random instances generated below and in the phase transition region, suggests that the phase transition of the fixed ratio model is also easy.
Identification of a key element for hydrogen‐bonding patterns between protein kinases and their inhibitors (2008)

In this article, we report crystal structures for inhibitor-kinase complexes in which the inhibitor has different binding orientations and hydrogen-bonding patterns with extracellular-signal regulated kinase 2 and insulin receptor tyrosine kinase. Our crystallographic studies, and sequence and structural analyses of 532 coordinates of kinases held in the Protein Data Bank, suggest that the length of the "specificity linker" described here is a key structural element of the hydrogen-bonding patterns between protein kinases and their inhibitors.
Current concepts in oral cancer (1999)

Over 750 new intra-oral squamous cell carcinomas are registered in Australia each year. In this article, the authors review the epidemiology, aetiology, genetics and spread of intra-oral squamous cell carcinoma. The mechanisms of field cancerization are discussed. The prevention of intra-oral squamous cell carcinoma is highlighted and future treatments are presented.
Cloning, expression and characterization of a blood group B active recombinant α‐D‐galactosidase from soybean (Glycine max) (1996)

Abstract A cDNA encoding soybean α‐D‐galactosidase [E.C. 3.2.1.22] was obtained by screening a soybean library with Phaseolus α‐D‐galactosidase cDNA. The Glycine max α‐D‐galactosidase cDNA is 1.75 kb long and contains untranslated 5′ and 3′ sequences. The deduced amino acid sequence of the soybean gene has a high degree of homology with other eucaryotic α‐D‐galactosidases. Recombinant α‐D‐galactosidase (rGal) was expressed in Pichia pastoris and purified by affinity chromatography. Purified rGal was homogeneous as judged by SDS‐PAGE analysis with the relative molecular mass under reducing conditions of 39.8, and under nonreducing conditions 38.0 kDa. The expressed protein contained the sequence NGLGHTPPMG at the N‐terminus, corresponding to the deduced amino acid sequence of the soybean gene. The relative native molecular mass by Sephacryl S‐200 chromatography was determined to be 33.1 kDa. The specific activity was 295.6 μmoles of PNP‐α‐D‐galactopyranoside hydrolyzed per mg pure rGal per min. rGal was highly specific for α‐D‐galactosyl residues. No detectable hemagglutinin or protease activity was present in the preparations. Furthermore, rGal was active against the blood group B antigen in native human erythrocyte cell suspension assays. The only detectable erythrocyte phenotypic change was loss of the B and P1 epitopes. Consequently, recombinant Glycine max α‐D‐galactosidase may have useful biotechnical applications in the potential mass production of universally transfusable type O erythrocytes by enzymatic conversion.
HLA-DQB1*02–Restricted HPV-16 E7 Peptide–Specific CD4+ T-Cell Immune Responses Correlate with Regression of HPV-16–Associated High-Grade Squamous Intraepithelial Lesions (2007)

The HPV-16 E7 peptide-specific CD4+ T-cell immune response correlates with spontaneous regression of established HPV16+ HSILs. Thus, this E7 epitope may be useful for the characterization of HPV-specific immune responses in patients infected with HPV-16 or immunized with HPV vaccines.
A bilayer cell‐free protein synthesis system for high‐throughput screening of gene products (2002)

A high-throughput cell-free protein synthesis method has been described. The methodology is based on a bilayer diffusion system that enables the continuous supply of substrates, together with the continuous removal of small byproducts, through a phase between the translation mixture and substrate mixture. With the use of a multititer plate the system was functional for a prolonged time, and as a consequence yielded more than 10 times that of the similar batch-mode reaction. Combining this method with a wheat germ cell-free translation system developed by us, the system could produce a large amount of protein sufficient for carrying out functional analyses. This novel bilayer-based cell-free protein synthesis system with its simplicity, minimum time and low cost may be useful practical methodology in the post-genome era.
High Preoperative Plasma D-dimer Level is Associated with Advanced Tumor Stage and Short Survival After Curative Resection in Patients with Colorectal Cancer (2001)

Elevated plasma D-dimer levels in patients with colorectal cancer are associated with relatively advanced tumor stage and short postoperative survival after curative resection. It appears that measurement of preoperative D-dimer level would be useful in the preoperative diagnosis of tumor stage and prediction of postoperative survival.
Functional analysis of the endothelin-1 gene promoter. Evidence for an endothelial cell-specific cis-acting sequence. (1990)

Endothelin-1 (ET-1) is a peptide synthesized by endothelial cells both in culture and in vivo. ET-1 induces contraction of smooth muscle cells and stimulates growth in a variety of mesenchymal cell types. We have previously characterized the genomic organization of the ET-1 gene and described its chromosomal localization and promoter region sequence. In this report, we describe the use of fusion plasmids containing ET-1 5'-flanking sequence and the chloramphenicol acetyltransferase gene to identify cis-acting sequences that direct transcription of the ET-1 gene. When transfected into bovine aortic endothelial cells, constructs containing 143 base pairs of ET-1 5'-flanking sequence allowed maximal transcription, whereas constructs containing 129 base pairs of sequence had 40-fold lower rates of transcription. A synthetic DNA fragment encoding the region delineated by these deletion mutants was found to have a positive effect on transcription when placed in either orientation upstream of short inactive ET-1 promoter constructs. However, this increase in transcription was noted only when a second region containing an AP1 consensus sequence was also included in the constructs. In experiments with a heterologous promoter and a 119-base pair DNA fragment containing these two functional regions, this 119-base pair sequence acted in a positive and endothelial cell-specific fashion. Taken together, these data localize cis-acting sequences important in determining the rate and tissue specificity of ET-1 gene transcription and should allow the study of protein-DNA interactions which mediate transcription of this gene in endothelial cells.