gebhart/patrepeval huggingface dataset:
Recent advances in PEG&ndash;PLA block copolymer nanoparticles (2010)

Due to their small particle size and large and modifiable surface, nanoparticles have unique advantages compared with other drug carriers. As a research focus in recent years, polyethylene glycol-polylactic acid (PEG-PLA) block copolymer and its end-group derivative nanoparticles can enhance the drug loading of hydrophobic drugs, reduce the burst effect, avoid being engulfed by phagocytes, increase the circulation time of drugs in blood, and improve bioavailability. Additionally, due to their smaller particle size and modified surface, these nanoparticles can accumulate in inflammation or target locations to enhance drug efficacy and reduce toxicity. Recent advances in PEG-PLA block copolymer nanoparticles, including the synthesis of PEG-PLA and the preparation of PEG-PLA nanoparticles, were introduced in this study, in particular the drug release and modifiable characteristics of PEG-PLA nanoparticles and their application in pharmaceutical preparations.
Synthesis of a radiotracer for studying nicotinic acetylcholine receptors: 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]A-85380) (1998)

The radiochemical synthesis of 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]A-85380, [18F]1) was accomplished by Kryptofix® 222 assisted nucleophilic no-carrier-added [18F]fluorination of 2-iodo-3((1-tert-butoxycarbonyl-2(S)-azetidinyl)methoxy)pyridine, 2 followed by acidic deprotection. The average radiochemical yield was 10% and the average specific radioactivity was 1050 mCi/μmol, calculated at end-of-synthesis (EOS). © 1998 John Wiley & Sons, Ltd.
Extraction of SSVEP signals of a capacitive EEG helmet for Human Machine Interface (2008)

The use of capacitive electrodes for measuring EEG eliminates the preparation procedure known from classical noninvasive EEG measurements. The insulated interface to the brain signals in combination with steady-state visual evoked potentials (SSVEP) enables a zero prep human machine interface triggered by brain signals. This paper presents a 28-channel EEG helmet system based on our capacitive electrodes measuring and analyzing SSVEPs even through scalp hair. Correlation analysis is employed to extract the stimulation frequency of the EEG signal. The system is characterized corresponding to the available detection time with different subjects. As demonstration of the use of capacitive electrodes for SSVEP measurements, preliminary online Brain-Computer Interface (BCI) results of the system are presented. Detection times lie about a factor of 3 higher than in galvanic EEG SSVEP measurements, but are low enough to establish a proper communication channel for Human Machine Interface (HMI).
A full-color scanning fiber endoscope (2006)

Minimally invasive medical procedures will benefit from flexible endoscopes that are extremely thin yet produce high quality images. Current devices use fiber bundles or silicon image sensors placed in the distal tip where each pixel in the image is derived from an element in the distal tip, such that improving resolution requires increasing distal tip diameter. The University of Washington has developed the scanning fiber endoscope (SFE) to provide full color, high resolution images from a flexible endoscope with a small distal tip diameter. The SFE uses a single mode fiber vibrating in resonance to scan a focused laser spot over the tissue and a detector to record the time-multiplexed backscatter signal. The SFE contains a 400 micron diameter piezoelectric tube through which a length of singlemode optical fiber is placed. The tube drives the fiber tip at its resonant frequency (currently 5 KHz) in an expanding pattern of 250 spirals (500 pixel diameter image) at a frame rate of 15 Hertz. Imaging parameters are determined by the lens system placed in the 1.06 mm diameter distal tip. Prototype systems with 70 degree field-of-view and 10 micron resolution have been developed. Color images are created with red, green, and blue laser sources coupled into the single scanning fiber. Backscattered light is collected with twelve 250 micron multimode fibers placed around the periphery of the microscanner resulting in a total distal tip diameter of 1.6 mm. Frame sequential color, fluorescence, and continuous color imaging modes have been demonstrated in the non-confocal geometry.
Characterization of a Novel Proapoptotic Caspase-2- and Caspase-9-binding Protein (2001)

Caspases play important roles in regulating apoptotic signaling pathways. Here we report the cloning, by the yeast two hybrid system with dominant negative caspase-2 as "bait," of a proapoptotic molecule named proapoptotic caspase adaptor protein (PACAP), encoded by a 372-base pair open reading frame. Binding of this novel protein to caspase-2 (casp-2) was confirmed in yeast two hybrid, in vitro, and in vivo assays. The deduced amino acid sequence revealed homology to functional motifs, including ATP and cytochrome c binding sites. PACAP mRNA was widely expressed in most human tissues; in transfected cells, PACAP was diffusely expressed in the cytoplasm. Bindings studies with the PACAP recombinant protein demonstrated specific binding to casp-2 and casp-9 but not to casp-3, -4, -7, or -8 in cell extracts. Cotransfection experiments showed that PACAP binds to casp-2 and -9 in 293T cells. In addition, studies with truncated PACAP demonstrated a requirement for residues 39-72 of PACAP for specific binding to casp-2 and -9. Transient transfection of PACAP into 293T human kidney cells and rat-1 fibroblasts triggered apoptosis at 24 h, which was at least in part prevented by an inhibitor of casp-3-like enzymes. Transfection of PACAP into human B cell lines using a retroviral system also triggered apoptotic cell death. In addition, transcription of PACAP in primary human B cells was dramatically down-regulated early after cellular activation by CD40L and Staphylococcus aureus and markedly up-regulated as the cells apoptose. These findings identify a novel proapoptotic caspase adaptor protein.
Mycobacteria Induce IFN-γ Production in Human Dendritic Cells via Triggering of TLR2 (2006)

IFN-gamma is of central importance for the induction of robust cell-mediated immunity and for the activation of APC. Recent studies using experimental murine systems have now suggested a fundamental role for APC-derived IFN-gamma during infection with intracellular pathogens. It is currently unknown whether human dendritic cells (DC) can respond to bacterial stimulation with production of IFN-gamma. To test this question, we used human monocyte-derived DC stimulated by Mycobacterium bovis bacillus Calmette-Guérin as a model system. We demonstrate production of IFN-gamma mRNA and protein on the single cell level. IFN-gamma in DC cultures was not simply produced by contaminating lymphocytes because production of DC-IFN-gamma could also be demonstrated in highly purified DC cultures containing virtually no T, B, and NK cells. TLR2 was identified as a key receptor involved in triggering production of DC-IFN-gamma. Interestingly, DC-IFN-gamma seems to participate in an autocrine DC activation loop, and production of DC-IFN-gamma could be enhanced by costimulation of DC with IL-12/IL-15/IL-18. In conclusion, we have demonstrated production of IFN-gamma by human DC on the single cell level, identified TLR2 as a pattern recognition receptor involved in this process, and elucidated some of the functional consequences of autocrine IFN-gamma production by human DC.
Murine B7 antigen provides a sufficient costimulatory signal for antigen-specific and MHC-restricted T cell activation (1992)

We have previously shown that the murine B7 (mB7) molecule, when expressed in Chinese hamster ovary cells in stable fashion, can costimulate with anti-CD3 mAb or Con A to induce T cell activation. We have now derived, by gene transfection, Chinese hamster ovary cell lines that express the I-Ad molecule, either alone or in context with mB7. We have analyzed these transfectants for their capacity to present Ag to murine CD4+ T lymphocytes. I-Ad/mB7-double transfectants were able to stimulate mixed lymphocyte reactions and to present peptide Ag to specific T cells. Chinese hamster ovary cells that expressed only the I-Ad molecule were not able to stimulate T cell proliferation in these systems. Thus, the mB7 protein is a sufficient costimulatory molecule for the physiologic, Ag-dependent/MHC-restricted activation of murine CD4+ T cells. Stimulation of T cell bulk cultures resulted predominantly in the production of IL-2 and not of IL-4. The costimulatory activity of mB7 is not, however, restricted to the IL-2-secreting subset. We have identified one IL-4-secreting T cell clone, CDC35, which is responsive to mB7 triggering. Finally, we present experiments that suggest that mB7 and peptide/MHC complexes need to be expressed on the same cell for optimal induction of T cell activation.
The vitamin D receptor as a therapeutic target (2006)

The vitamin D receptor (VDR) is a member of the large family of nuclear receptor transcription factors and specifically binds the micronutrient-derived hormone 1alpha,25(OH)2D3. A central endocrine role for this receptor in bone health was established at the beginning of the 20th century. Over the last 25 years, additional roles, perhaps through autocrine and paracrine mechanisms, have been established for VDR to regulate cell proliferation and differentiation, and more recently to exert immunomodulatory and antimicrobial functions. These findings, from in vitro and in vivo experiments, have generated considerable interest in targeting the VDR in multiple therapeutic settings. As with many potential therapeutics, it has also become clear that cells and tissues may also display de novo and acquired mechanisms of resistance to these actions. Consequently, a range of experimental and clinical options are being developed to bring about more targeted actions, overcome resistance and enhance efficacy of VDR-centred therapeutics.
High Expression of Wee1 Is Associated with Poor Disease-Free Survival in Malignant Melanoma: Potential for Targeted Therapy (2012)

Notoriously resistant malignant melanoma is one of the most increasing forms of cancer worldwide; there is thus a precarious need for new treatment options. The Wee1 kinase is a major regulator of the G(2)/M checkpoint, and halts the cell cycle by adding a negative phosphorylation on CDK1 (Tyr15). Additionally, Wee1 has a function in safeguarding the genome integrity during DNA synthesis. To assess the role of Wee1 in development and progression of malignant melanoma we examined its expression in a panel of paraffin-embedded patient derived tissue of benign nevi and primary- and metastatic melanomas, as well as in agarose-embedded cultured melanocytes. We found that Wee1 expression increased in the direction of malignancy, and showed a strong, positive correlation with known biomarkers involved in cell cycle regulation: Cyclin A (p<0.0001), Ki67 (p<0.0001), Cyclin D3 (p = 0.001), p21(Cip1/WAF1) (p = 0.003), p53 (p = 0.025). Furthermore, high Wee1 expression was associated with thicker primary tumors (p = 0.001), ulceration (p = 0.005) and poor disease-free survival (p = 0.008). Transfections using siWee1 in metastatic melanoma cell lines; WM239(WTp53), WM45.1(MUTp53) and LOX(WTp53), further support our hypothesis of a tumor promoting role of Wee1 in melanomas. Whereas no effect was observed in LOX cells, transfection with siWee1 led to accumulation of cells in G(1)/S and S phase of the cell cycle in WM239 and WM45.1 cells, respectively. Both latter cell lines displayed DNA damage and induction of apoptosis, in the absence of Wee1, indicating that the effect of silencing Wee1 may not be solely dependent of the p53 status of the cells. Together these results reveal the importance of Wee1 as a prognostic biomarker in melanomas, and indicate a potential role for targeted therapy, alone or in combination with other agents.
Guided mode biosensor based on grating coupled porous silicon waveguide (2011)

Porous silicon waveguide biosensors that utilize grating couplers etched directly into porous silicon are demonstrated for improved molecular detection capabilities. Molecules are infiltrated through the grating couplers into the waveguide where they can interact with a guided waveguide mode. Hybridization of nucleic acids inside the waveguide is shown to significantly perturb the wave vector of the guided mode and is detected through angle-resolved reflectance measurements. A detection sensitivity of 7.3°/mM is demonstrated with selectivity better than 6:1 compared to mismatched sequences. Experimental results are in good agreement with calculations based on rigorous coupled wave analysis. Use of the all-porous silicon grating-coupled waveguide allows improved interaction of the optical field with surface-bound molecules compared to evanescent wave-based biosensors.
DANAZOL TREATMENT AND PLATELET FUNCTION (1980)

Platelet count and platelet function have been studied in detail in 14 women before and during treatment with danazol for endometriosis. A progressive and highly significant increase in platelet count was recorded from the pretreatment value (311 x 10(9)/L) to the value after six months of treatment (366 x 10(9)/L; P less than 0.001). Five patients developed minor platelet release defects, which may have been caused by the drug. However, the abnormalities shown are only likely to be of clinical importance in patients with preexisting platelet abnormalities.
An Improved Harvest andin VitroExpansion Protocol for Murine Bone Marrow-Derived Mesenchymal Stem Cells (2010)

Compared to bone marrow (BM) derived mesenchymal stem cells (MSCs) from human origin or from other species, the in vitro expansion and purification of murine MSCs (mMSCs) is much more difficult because of the low MSC yield and the unwanted growth of non-MSCs in the in vitro expansion cultures. We describe a modified protocol to isolate and expand murine BM derived MSCs based on the combination of mechanical crushing and collagenase digestion at the moment of harvest, followed by an immunodepletion step using microbeads coated with CD11b, CD45 and CD34 antibodies. The number of isolated mMSCs as estimated by colony forming unit-fibroblast (CFU-F) assay showed that this modified isolation method could yield 70.0% more primary colonies. After immunodepletion, a homogenous mMSC population could already be obtained after two passages. Immunodepleted mMSCs (ID-mMSCs) are uniformly positive for stem cell antigen-1 (Sca-1), CD90, CD105 and CD73 cell surface markers, but negative for the hematopoietic surface markers CD14, CD34 and CD45. Moreover the immunodepleted cell population exhibits more differentiation potential into adipogenic, osteogenic and chondrogenic lineages. Our data illustrate the development of an efficient and reliable expansion protocol increasing the yield and purity of mMSCs and reducing the overall expansion time.
Real-Time Nowcasting of GDP: Factor Model versus Professional Forecasters (2010)

This paper performs a fully real-time nowcasting (forecasting) exercise of US real gross domestic product (GDP) growth using Giannone, Reichlin and Small (2008) factor model framework which enables one to handle unbalanced datasets as available in real-time. To this end, we have constructed a novel real-time database of vintages from October 2000 to June 2010 for a panel of US variables, and can hence reproduce, for any given day in that range, the exact information that was available to a real-time forecaster. We track the daily evolution throughout the current and next quarter of the model nowcasting performance. Similarly to Giannone et al. pseudo realtime results, we find that the precision of the nowcasts increases with information releases. Moreover, the Survey of Professional Forecasters (SPF) does not carry additional information with respect to the model best specification, suggesting that the often cited superiority of the SPF, attributable to judgment, is weak over our sample. Then, as one moves forward along the real-time data flow, the continuous updating of the model provides a more precise estimate of current quarter GDP growth and the SPF becomes stale compared to all the model specifications. These results are robust to the recent recession period.
Bone marrow cells adopt the cardiomyogenic fate in vivo (2007)

The possibility that adult bone marrow cells (BMCs) retain a remarkable degree of developmental plasticity and acquire the cardiomyocyte lineage after infarction has been challenged, and the notion of BMC transdifferentiation has been questioned. The center of the controversy is the lack of unequivocal evidence in favor of myocardial regeneration by the injection of BMCs in the infarcted heart. Because of the interest in cell-based therapy for heart failure, several approaches including gene reporter assay, genetic tagging, cell genotyping, PCR-based detection of donor genes, and direct immunofluorescence with quantum dots were used to prove or disprove BMC transdifferentiation. Our results indicate that BMCs engraft, survive, and grow within the spared myocardium after infarction by forming junctional complexes with resident myocytes. BMCs and myocytes express at their interface connexin 43 and N-cadherin, and this interaction may be critical for BMCs to adopt the cardiomyogenic fate. With time, a large number of myocytes and coronary vessels are generated. Myocytes show a diploid DNA content and carry, at most, two sex chromosomes. Old and new myocytes show synchronicity in calcium transients, providing strong evidence in favor of the functional coupling of these two cell populations. Thus, BMCs transdifferentiate and acquire the cardiomyogenic and vascular phenotypes restoring the infarcted heart. Together, our studies reveal that locally delivered BMCs generate de novo myocardium composed of integrated cardiomyocytes and coronary vessels. This process occurs independently of cell fusion and ameliorates structurally and functionally the outcome of the heart after infarction.
Bacteriopurpurinimides:  Highly Stable and Potent Photosensitizers for Photodynamic Therapy (2001)

The in situ conversion of the unstable bacteriochlorophyll a present in Rhodobacter sphaeroides produced highly stable bacteriopurpurin-18 which in a sequence of reactions was converted into a series of alkyl ether analogues of bacteriopurpurin-18-N-alkylimides with long wavelength absorption near 800 nm. The effective photosensitizers were found to localize in mitochondria but did not show any specific displacement of (3)H-PK11195, suggesting that the mitochondrial peripheral benzodiazepine receptor is not the cellular binding site for this class of compounds.
W-band SPST transistor switches (1996)

A single-pole, single-throw (SPST) transistor switch has been developed, Three types of switches, that is, GaAs MESFET, AlGaAs-GaAs HEMT, and pseudomorphic HEMT (PM-HEMT), have been fabricated, and the performances at W-band are compared. To reduce on-state resistance and off-state capacitance, gate length was varied as a parameter. Moreover, an inductance for resonance was installed in parallel to the off-state capacitance between source and drain to obtain a high isolation, A relatively low insertion loss of 1.6 dB and a high isolation over 20 dB at W-band have been obtained from the 0.8-μm gate length PM-HEMT.
Natural killer cells: emerging concepts in immunity to infection and implications for assessment of immunodeficiency (2003)

Natural killer cells are heterogeneous lymphocytes that provide an essential function in host defense. NK cells respond early to microbial assault and interact with other cells of the innate immune system, but they recognize and intercept pathogenic infections through highly specific mechanisms that are similar to T cells. Thus, NK cells are positioned as a cellular bridge between innate and adaptive immunity. It is imperative, then, to include a careful assessment of NK cell populations and functions in most cases of suspected immunodeficiency.
Human NKT Cells Express Granulysin and Exhibit Antimycobacterial Activity (2003)

Abstract Human NKT cells are a unique subset of T cells that express an invariant Vα24 TCR that recognizes the nonclassical Ag-presenting molecule CD1d. Activation of NKT cells is greatly augmented by the marine sponge-derived glycolipid α-galactosylceramide (αGalCer). Because human monocyte-derived cells express CD1d and can harbor the intracellular pathogen Mycobacterium tuberculosis, we asked whether the addition of αGalCer could be used to induce effector functions of NKT cells against infected monocytes, macrophages, and monocyte-derived dendritic cells. NKT cells secreted IFN-γ, proliferated, and exerted lytic activity in response to αGalCer-pulsed monocyte-derived cells. Importantly, αGalCer-activated NKT cells restricted the growth of intracellular M. tuberculosis in a CD1d-dependent manner. NKT cells that exhibited antimycobacterial activity also expressed granulysin, an antimicrobial peptide shown to mediate an antimycobacterial activity through perturbation of the mycobacterial surface. Degranulation of NKT cells resulted in depletion of granulysin and abrogation of antimycobacterial activity. The detection of CD1d in granulomas of tuberculosis patients supports the potential interaction of NKT cells with CD1d-expressing cells at the site of disease activity. These studies provide evidence that αGalCer-activated CD1d-restricted T cells can participate in human host defense against M. tuberculosis infection.
Capsular polysaccharide synthesis in Streptococcus pneumoniae serotype 14: molecular analysis of the complete cps locus and identification of genes encoding glycosyltransferases required for the biosynthesis of the tetrasaccharide subunit (1997)

We have reported previously on seven genes (cps14B-H) of Streptococcus pneumoniae serotype 14, which are part of the type 14 capsular polysaccharide synthesis (cps14) locus. This study describes the cloning and sequencing of the remaining part of the cps14 locus. The entire cps14 gene cluster consists of 12 open reading genes (cps14A to cps14L), which appear to be arranged as a single transcriptional unit. The flanking regions of the cps14 locus contain vestiges of insertion elements. Moreover, a 115-bp-long repeated DNA element, which is also present in several other intergenic regions on the pneumococcal chromosome, has been identified upstream of cps14A. All 12 open reading frames (ORFs) were inactivated by the insertion of a tetracycline resistance cassette. The cps14A to cps14J and cps14L mutants were unencapsulated, whereas only a limited amount of capsular polysaccharide was expressed by a cps14K insertion mutant. Comparison with DNA and protein sequences available in databases allowed us to predict functions for four out of the five new cps14 gene products. The biosynthetic function of Cps14I was determined experimentally by analysis of intermediates in the synthesis of the type 14 tetrasaccharide subunit, catalysed by membrane preparations of Escherichia coli expressing pneumococcal glycosyltransferases. The cps14I gene encodes the beta-1,3-N-acetylglucosaminyltransferase activity necessary for the addition of the third sugar in the synthesis of the type 14 repeating unit. The activity encoded by cps14J was established using a synthetic glycosyltransferase acceptor: cps14J encodes a beta-1,4-galactosyltransferase, which requires beta-linked GlcNAc as an acceptor. Thus, Cps14J is responsible for the addition of the last (fourth) sugar in the synthesis of the type 14 subunit.