gebhart/patrepeval huggingface dataset:
Common Telomere Changes during In Vivo Reprogramming and Early Stages of Tumorigenesis (2017)

Reprogramming of differentiated cells into induced pluripotent stem cells has been recently achieved in vivo in mice. Telomeres are essential for chromosomal stability and determine organismal life span as well as cancer growth. Here, we study whether tissue dedifferentiation induced by in vivo reprogramming involves changes at telomeres. We find telomerase-dependent telomere elongation in the reprogrammed areas. Notably, we found highly upregulated expression of the TRF1 telomere protein in the reprogrammed areas, which was independent of telomere length. Moreover, TRF1 inhibition reduced in vivo reprogramming efficiency. Importantly, we extend the finding of TRF1 upregulation to pathological tissue dedifferentiation associated with neoplasias, in particular during pancreatic acinar-to-ductal metaplasia, a process that involves transdifferentiation of adult acinar cells into ductal-like cells due to K-Ras oncogene expression. These findings place telomeres as important players in cellular plasticity both during in vivo reprogramming and in pathological conditions associated with increased plasticity, such as cancer.
Reversal of long-term sepsis-induced immunosuppression by dendritic cells (2004)

Severe sepsis leads to long-term systemic and local immunosuppression, which is the cause of a number of complications, including pulmonary infection. A therapeutic strategy that reverses this immunosuppression is required, given the ongoing high mortality rate of patients who have survived a severe sepsis. The present study demonstrates that experimental severe sepsis renders the lung susceptible to a normally innocuous Aspergillus fumigatus fungus challenge, due to a dominant lung type 2 cytokine profile. Dendritic cells (DCs) obtained from the lungs of mice subjected to cecal ligation and puncture (CLP) model were skewed toward type 2 cytokine profile, which occurred with exaggerated expression of Toll-like receptor 2 (TLR2). The intrapulmonary transfer of bone marrow-derived DCs (BMDCs) in postseptic mice prevented fatal Aspergillus infection. This therapy reduced the overall inflammatory response and fungal growth in the lung, and promoted the balance of proinflammatory and suppressive cytokines in the lung. Thus, intrapulmonary DC supplementation appears to restore the pulmonary host response in the postseptic lung in our animal model. These data strongly suggest that lung DCs are profoundly affected as a consequence of the systemic impact of severe sepsis, and the identification of mechanisms that restore their function may serve as a key strategy to reverse sepsis-induced immunosuppression.
Cytotoxic T Lymphocytes Responding to Low Dose TRP2 Antigen are Induced Against B16 Melanoma by Liposome-encapsulated TRP2 Peptide and CpG DNA Adjuvant (2006)

The induction of a potent and specific T cell response is a major challenge in the development of efficacious cancer vaccine strategies. We applied a novel liposomal formulation (AVE3) for efficient delivery of antigenic peptides into APCs of the skin. These liposomes resulted in a long-lasting deposition of encapsulated compounds at the injection site and the draining lymph nodes. Using a peptide from the melanocyte differentiation antigen tyrosinase-related protein (TRP2) 2 we could show that vaccination with liposome-encapsulated peptide in combination with oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODNs) as adjuvant leads to the induction of tumor cell-specific cytotoxic T cells. The most potent immune response was observed when both, TRP2 peptide and CpG ODNs, were encapsulated into AVE3. Importantly, in contrast to vaccination with free TRP2 liposomal TRP2 peptide generated T cells which respond to 1000-fold lower antigen concentration. Using the poorly immunogenic B16 melanoma model we could demonstrate that vaccination with liposomal TRP2 peptide plus CpG ODNs but not vaccination with free peptide or adjuvant alone resulted in tumor protection in subcutaneous and metastatic tumor models. In summary, vaccination with liposome-encapsulated peptide antigen and CpG ODN allows for the in vivo loading and activation of DC, thereby generating reactive CTL populations even against poorly immunogenic self-peptide presenting tumors resulting in a potent anti-tumor immune response.
Direction finding for wideband signals using an interpolated array (2002)

The authors derive a novel direction finding algorithm for multiple wideband signals received by an arbitrary array, and analyze its performance. Using an interpolation technique, a set of virtual arrays is generated, each for a different frequency band, having the same array manifold. The covariance matrices of these arrays are added to produce a composite covariance matrix. Direction of arrival (DOA) estimates are obtained by eigendecomposition of this composite covariance matrix using the narrowband MUSIC algorithm or its variants. By choosing the virtual arrays to be linear and equally spaced the root-MUSIC algorithm can be applied to this problem. Closed form expressions for the asymptotic covariance matrix of the DOA estimation errors are derived using perturbation analysis.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
SCORING SYSTEMS AND BLOOD LACTATE CONCENTRATIONS IN RELATION TO THE DEVELOPMENT OF ADULT RESPIRATORY DISTRESS SYNDROME AND MULTIPLE ORGAN FAILURE IN SEVERELY TRAUMATIZED PATIENTS (1993)

In 56 patients with multiple trauma with ISSs > or = 33 we prospectively collected data of seven scoring systems (ISS, TS, TRISS, GCS, PTS, APACHE II, SSS) and sequentially determined blood lactate concentrations. These data were analyzed in relation to the patients later developing adult respiratory distress syndrome (ARDS) and multiple organ failure (MOF). Twenty-two patients developed ARDS, and 18 developed MOF. Of the mentioned scoring systems only ISS, PTS, and SSS were predictive of subsequent ARDS, and only ISS and SSS were predictive of subsequent MOF. Lactate concentrations at days 2, 3, and 4 were significantly different between patients with and without subsequent ARDS, MOF, or both. Surprisingly, APACHE II scores did not correlate with subsequent ARDS or MOF, nor did they show any significant relation with lactate concentrations at any time. By stepwise regression analysis ISS, SSS, and lactate level at day 3 were the most significant variables toward the development of ARDS and MOF. It is concluded that scoring systems directly grading the severity of groups of trauma patients have predictive value for late and remote complications such as ARDS and MOF, whereas scoring systems that grade the physiologic response to trauma--although clearly related to mortality--have no such predictive value.
Hepatitis C virus kinetics and host responses associated with disease and outcome of infection in chimpanzees (2004)

To study determinants of clinical outcome following HCV infection, viral kinetics, immune events, and intrahepatic cytokine markers were compared in 10 naive chimpanzees. Four of the animals cleared HCV; 6 developed persistent infections. All animals developed similar acute infections with increasing viremia from 1 to 2 weeks, followed by alanine aminotransferase (ALT) elevations and seroconversion. This viremia pattern consisted of a biphasic increase, a rapid slope (mean doubling time [t(2)] = 0.5 days) followed by a slower slope after the second week (t(2) = 7.5 days). This slowing of virus replication correlated in all animals with increased intrahepatic 2'5' oligoadenylate synthetase 1 (2OAS-1) messenger RNA (mRNA) levels and was independent of disease outcome. An effective control of virus replication was observed following increases in intrahepatic interferon gamma (IFN-gamma) mRNA and ALT levels. Although this control was associated in all animals with a 2-log decrease in virus titer, the timing occurred approximately 2 weeks later in the chronic group (P <.05). Additionally, while cleared infections were characterized by a continual decrease in virus titer, the titers in the persistent infections reached a steady state level of 10(4) to 10(5) RNA copies/mL. This inability of the immune response to sustain viral clearance in the persistent infections was associated with a reduced intrahepatic CD3e and monocyte-induced protein 1alpha (MIP-1alpha) mRNA induction. In conclusion, these data indicate that, regardless of outcome, chimpanzees generate responses that control HCV replication during the early and late acute phase. However, the pathogenesis of HCV may be determined by a more rapid onset of the induced response and the cell population that migrates to the liver.
Distribution of proteoglycans antigenically related to corneal keratan sulfate proteoglycan. (1987)

Three antibodies reacting with corneal keratan sulfate proteoglycan were used to detect antigenically related molecules in 11 bovine and 13 embryonic chick tissues. Two monoclonal antibodies recognized sulfated epitopes on the keratan sulfate chain and a polyclonal antibody bound antigenic sites on the core protein of corneal keratan sulfate proteoglycan. Competitive immunoassay detected core protein and keratan sulfate antigens in guanidine HCl extracts of most tissues. Keratan sulfate antigens of most bovine tissues were only partially extracted with guanidine HCl, but the remainder could be solubilized by CNBr treatment of the guanidine-extracted residue. Keratan sulfate and core protein antigens co-eluted with purified corneal keratan sulfate proteoglycan on ion exchange high-performance liquid chromatography (HPLC). Endo-beta-galactosidase digestion of the HPLC-purified keratan sulfate antigens eliminated the binding of monoclonal anti-keratan sulfate antibodies in enzyme-linked immunosorbent assay. Extracts of all 11 bovine tissues, except those from brain and cartilage, could bind both anti-keratan sulfate monoclonal antibodies and anti-core protein polyclonal antibody simultaneously. Binding was sensitive to competition with keratan sulfate and to digestion with endo-beta-galactosidase. These results suggest widespread occurrence of a proteoglycan or sulfated glycoprotein bearing keratan sulfate-like carbohydrate and a core protein resembling that of corneal keratan sulfate proteoglycan.
Review of inductively coupled plasmas for plasma processing (1992)

The need for large-area, high-density plasma sources for plasma-aided manufacturing of integrated circuits has created a renewed interest in inductively coupled plasmas (ICPs). Several ICP reactor geometries are briefly reviewed. Typically, inductive coupling of RF power (0.5-28 MHz) can produce ion densities in excess of 1012 cm-3 even at submillitorr pressures. Existing electromagnetic field models of ICPs are examined and found to be in reasonable agreement with experimental results. Sputter deposition, anodic silicon oxidation and polymer etching using ICPs are also described. It is concluded that ICPs are promising candidates for meeting the future requirements of plasma processing, although considerable process development, plasma characterization and modelling are still needed.
Collagen nerve conduits – Assessment of biocompatibility and axonal regeneration (2005)

Bridging of nerve gaps is still a major problem in peripheral nerve surgery. Alternatively to autologous nerve grafts tissue engineering of peripheral nerves focuses on biocompatible conduits to reconstruct nerves. Such non-neural conduits fail to support regeneration over larger gaps due to lacking viable Schwann cells that promote regeneration by producing growth factors and cell guiding molecules. This problem may be overcome by implantation of cultivated Schwann cells into suitable scaffolds. In the present experiments we tested a collagen type I/III tube as a potential nerve guiding matrix. Revascularization, tolerance and Schwann cell settlement were evaluated by light, fluorescence and scanning electron microscopy after different implantation times. The conduits were completely revascularized between day 5 and 7 post-operatively and well integrated into the host tissue. Implanted Schwann cells adhered, survived and proliferated on the inner surface of the conduits. Nevertheless, bridging a 2 cm gap of the sciatic nerve of adult Wistar rats with these collagen/Schwann cell conduits led to a disappointing regeneration compared to controls with autologous grafts. From these results, we conclude that a sufficient biocompatibility of bioartificial nerve conduits is a necessary prerequisite, however, it remains only one of several parameters important for peripheral nerve regeneration.
Concurrent reading and writing of clocks (1990)

As an exercise in synchronization without mutual exclusion, algorithms are developed to implement both a monotonic and a cyclic multiple-word clock that is updated by one process and read by one or more other processes.
Approximative Matrix Inverse Computations for Very-large MIMO and Applications to Linear Pre-coding Systems (2013)

In very-large multiple-input multiple-output (MIMO) systems, the BS (base station) is equipped with very large number of antennas as compared to previously considered systems. There are various advantages of increasing the number of antennas, and some schemes would require handling large matrices for joint processing (pre-coding) at the base station. The dirty paper coding (DPC) is an optimal pre-coding scheme and has a very high complexity. However with increasing number of BS antennas linear pre-coding performance tends to that of the optimal DPC. Although linear pre-coding is less complex than DPC, there is a need to compute pseudo inverses of large matrices. In this paper we present a low complexity approximation of down-link Zero Forcing linear pre-coding for very-large multi-user MIMO systems. Approximation using a Neumann series expansion is opted for inversion of matrices over traditional exact computations, by making use of special properties of the matrices, thereby reducing the cost of hardware. With this approximation of linear pre-coding, we can significantly reduce the computational complexity for large enough systems, i.e., where we have enough BS antenna elements. For the investigated case of 8 users, we obtain 90% of the full ZF sum rate, with lower computational complexity, when the number of BS antennas per user is about 20 or more.
Clathrin, adaptors and eps15 in endosomes containing activated epidermal growth factor receptors (1999)

Activation of the epidermal growth factor receptor (EGFR) by EGF results in binding of clathrin adaptor protein complex AP-2 to the receptor cytoplasmic tail. The transient interaction with AP-2 is thought to be responsible for the selective recruitment of the EGFR into coated pits during endocytosis. In this study we found that EGF-induced EGFR/AP-2 association, measured by co-immunoprecipitation, persists after receptor internalization. Double-label immunofluorescence of EGF-treated A-431 and COS-1 cells revealed the presence of AP-2, clathrin and eps15, another component of the plasma membrane coated pits, in the large perinuclear endosomes loaded with EGFRs. By optical sectioning and image deconvolution, the immunoreactivities were seen to be distributed within vesicular and tubular elements of these endosomes. In addition, these compartments contained the transferrin receptors and a EEA.1 protein, markers of early endosomes. Furthermore, Golgi clathrin adaptor complex AP-1 was found in EGFR-containing endosomes and EGFR immunoprecipitates in A-431 cells. The direct interaction of the EGFR with micro1 as well as micro2 subunits of AP-1 and AP-2, correspondingly, was shown using the yeast two-hybrid assay. Brefeldin A, a drug that releases AP-1 from the trans-Golgi membranes, had no effect on AP-1 association with endosomes and its co-precipitation with EGFR. Taken together, the data suggest that endosomal EGFR-AP complexes make up a significant portion of the total amount of these complexes detectable by co-immunoprecipitation. It can be proposed that APs are capable of binding to the endosomal membrane via a mechanism that requires AP interaction with the intracellular tails of multimeric receptors like activated EGFR, which in turn allows recruitment of clathrin and eps15. The hypothesis that the competition between adaptor complexes for binding to the receptor tails in endosomes may regulate of the sorting of receptors is discussed.
Memory-Prediction Framework for Pattern Recognition: Performance and Suitability of the Bayesian Model of Visual Cortex. (2007)

This paper explores an inferential system for recognizing visual patterns. The system is inspired by a recent memoryprediction theory and models the high-level architecture of the human neocortex. The paper describes the hierarchical architecture and recognition performance of this Bayesian model. A number of possibilities are analyzed for bringing the model closer to the theory, making it uniform, scalable, less biased and able to learn a larger variety of images and their transformations. The effect of these modifications on recognition accuracy is explored. We identify and discuss a number of both conceptual and practical challenges to the Bayesian approach as well as missing details in the theory that are needed to design a scalable and universal model.
Linear group II intron RNAs can retrohome in eukaryotes and may use nonhomologous end-joining for cDNA ligation (2009)

Mobile group II introns retrohome by an RNP-based mechanism in which the excised intron lariat RNA fully reverse splices into a DNA site via 2 sequential transesterification reactions and is reverse transcribed by the associated intron-encoded protein. However, linear group II intron RNAs, which can arise by either hydrolytic splicing or debranching of lariat RNA, cannot carry out both reverse-splicing steps and were thus expected to be immobile. Here, we used facile microinjection assays in 2 eukaryotic systems, Xenopus laevis oocyte nuclei and Drosophila melanogaster embryos, to show that group II intron RNPs containing linear intron RNA can retrohome by carrying out the first step of reverse splicing into a DNA site, thereby ligating the 3' end of the intron RNA to the 5' end of the downstream exon DNA. The attached linear intron RNA is then reverse transcribed, yielding an intron cDNA whose free end is linked to the upstream exon DNA. Some of these retrohoming events result in the precise insertion of full-length intron. Most, however, yield aberrant 5' junctions with 5' exon resections, 5' intron truncations, and/or extra nucleotide residues, hallmarks of nonhomologous end-joining. Our findings reveal a mobility mechanism for linear group II intron RNAs, show how group II introns can co-opt different DNA repair pathways for retrohoming, and suggest that linear group II intron RNAs might be used for site-specific DNA integration in gene targeting.
High-Linear Energy Transfer Irradiation Targeted to Skeletal Metastases by the α-Emitter 223Ra: Adjuvant or Alternative to Conventional Modalities? (2006)

The bone-seeking, alpha-particle-emitting radiopharmaceutical Alpharadin, 223RaCl2 (half-life=11.4 days), is under clinical development as a novel treatment for skeletal metastases from breast and prostate cancer. This article summarizes the current status of preclinical and clinical research on 223RaCl2. Potential advantages of 223Ra to that of external beam irradiation and registered beta-emitting bone seekers are discussed. Published data of 223Ra dosimetry in mice and a therapeutic study in a skeletal metastases model in nude rats have indicated significant therapeutic potential of bone-seeking alpha-emitters. This article provides short-term and long-term results from the first clinical single dosage trial. We also present data from a repeated dosage study of five consecutive injections of 50 kBq/kg body weight, once every 3rd week, or two injections of 125 kBq/kg body weight, 6 weeks apart. Furthermore, interim results are described for a randomized phase 2 trial involving 64 patients with hormone-refractory prostate cancer and painful skeletal metastases who received four monthly injections of 223Ra or saline as an adjuvant to external beam radiotherapy. Lastly, we present preliminary dose estimates for 223Ra in humans. Results indicate that repeated dosing is feasible and toxicity is low, and that opportunities are available for combined treatment strategies.
Structure‐activity relationship study: short antimicrobial peptides (1999)

Many short antimicrobial peptides (< 18mer) have been identified for the development of therapeutic agents. However, Structure-activity relationship (SAR) studies about short antimicrobial peptides have not been extensively performed. To investigate the relationship between activity and structural parameters such as an alpha-helical structure, a net positive charge and a hydrophobicity, we synthesized and characterized diastereomers, scramble peptides and substituted peptides of the short antimicrobial peptide identified by combinatorial libraries. Circular dichroism (CD) spectra and in vitro activity indicated that an alpha-helical structure correlated with the antimicrobial activity and a beta-sheet structure also satisfied a structural requirement for antimicrobial activity. Most peptides consisting of L-amino acids lost antifungal activity in the presence of heat-inactivated serum, while active diastereomers and a scramble peptide with the beta-sheet structure retained antifungal activity in the same condition.
The Inflammatory versus Constitutive Trafficking of Mononuclear Phagocytes into the Alveolar Space of Mice Is Associated with Drastic Changes in Their Gene Expression Profiles (2005)

Mononuclear phagocytes enter the lungs both constitutively to maintain alveolar macrophage and dendritic cell homeostasis, as well as during lung inflammation, where the role of these cells is less well defined. We used a transgenic mouse strain (CX3CR1(+/GFP)) that harbors a GFP label in circulating monocytes to identify and sort these cells from the vascular and alveolar compartments under both constitutive and acute lung inflammatory conditions. Using nylon arrays combined with real-time RT-PCR for gene expression profiling, we found that flow-sorted, highly purified mononuclear phagocytes recruited to acutely inflamed mouse lungs showed strongly up-regulated mRNA levels of the neutrophil chemoattractants KC, MIP-2, and IP-10, which contrasted with alveolar mononuclear phagocytes that immigrated in steady state. Similar observations were made for the lysosomal cathepsins B, L, and K being strongly up-regulated in mononuclear phagocytes upon recruitment to inflamed lungs but not during constitutive alveolar immigration. Inflammatory elicited mononuclear phagocytes also demonstrated significantly increased mRNA levels of the cytokine TNF-alpha and the PRR-associated molecules CD14, TLR4, and syndecan-4. Together, inflammatory elicited mononuclear phagocytes exhibit strongly increased neutrophil chemoattractants, lysosomal proteases, and LPS signaling mRNA transcripts, suggesting that these cells may play a major role in acute lung inflammatory processes.