gebhart/patrepeval huggingface dataset:
A 19‐year‐old Male with Generalized Seizures, Unconsciousness and a Deviation of Gaze (2006)

Light chain deposition disease (LCDD) is a form of monoclonal immunoglobulin deposition diseases (MIDD) which in contrast to light-chain derived (AL) amyloidosis is characterized by non-congophilic, non-fibrillary monoclonal protein deposits. Systemic organ deposits are common with the kidney being a major target organ. A clonal lymphoplasmocytic proliferation, e.g. plasmacytoma, is present in the majority of cases. Here we report on a 19-year-old male who presented with generalized seizures and an enhancing white matter lesion on MRI scans. A stereotactic brain biopsy revealed a low-grade B cell lymphoma with plasmacellular differentiation as well as lambda light chain deposits without birefringence under polarized microscopy. No systemic lymphoma manifestations or systemic light chain deposits were found, nor was a monoclonal gammopathy detectable in serum and urine. After systemic chemotherapy with three courses high-dose methotrexate the size of the lesion and the condition of the patient have remained stable for 24 months now. This is the first description of cerebral LCDD developing without systemic disease in conjunction with the diagnosis of a cerebral low-grade B cell lymphoma. We present the clinical, laboratory and radiological findings and discuss the pathogenesis of this unusual LCDD manifestation.
Naptumomab Estafenatox: Targeted Immunotherapy with a Novel Immunotoxin (2014)

Improvement of cancer therapy by introducing new concepts is still urgent even though there have been major advancements lately. Immunotherapy is well on the way to becoming an established tool in the cancer treatment armory. It seems that a combination of (1) activation of immune effector cells and selective targeting of them to tumors and (2) the inhibition of immune suppression often induced by the tumor itself are necessary to achieve the therapeutic goal. The immunotoxin naptumomab estafenatox was developed in an effort to activate and target the patient's own T cells to their tumor, by fusing a superantigen (SAg) variant that activates T lymphocytes to the Fab moiety of a tumor-reactive monoclonal antibody. Naptumomab estafenatox targets the 5T4 tumor antigen, a 72-kDa oncofetal trophoblast protein expressed on many carcinomas, including renal cell carcinoma. The therapeutic effect is associated with activation of SAg-binding T cells. The SAg-binding T lymphocytes expand, differentiate to effector cells, and infiltrate the tumor. The therapeutic efficacy is most likely related to the dual mechanism of tumor cell killing: (1) direct lysis by cytotoxic T lymphocytes of tumor cells expressing the antigen recognized by the antibody moiety of the fusion protein and (2) secretion of cytokines eliminating antigen-negative tumor cell variants. Naptumomab estafenatox has been clinically tested in a range of solid tumors with focus on renal cell carcinoma. This review looks at the clinical experience with the new immunotoxin and its potential.
SLV-306. Solvay. (2003)

SLV-306 is an orally active mixed neutral endopeptidase/endothelin converting enzyme inhibitor under development by Solvay SA for the potential treatment of essential hypertension and congestive heart failure. The compound is currently undergoing phase II clinical trials in Belgium.
Injury-induced innate immune response in human skin mediated by transactivation of the epidermal growth factor receptor (2006)

We found that sterile wounding of human skin induced epidermal expression of the antimicrobial (poly)peptides human beta-defensin-3, neutrophil gelatinase-associated lipocalin, and secretory leukocyte protease inhibitor through activation of the epidermal growth factor receptor. After skin wounding, the receptor was activated by heparin-binding epidermal growth factor that was released by a metalloprotease-dependent mechanism. Activation of the epidermal growth factor receptor generated antimicrobial concentrations of human beta-defensin-3 and increased the activity of organotypic epidermal cultures against Staphylococcus aureus. These data demonstrate that sterile wounding initiates an innate immune response that increases resistance to overt infection and microbial colonization.
K+-Channel Openers for Relaxation of Isolated Penile Erectile Tissue from Rabbit (1990)

The effects of the K(+)-channel openers (KCOs) cromakalim (BRL 34915) and pinacidil were investigated and compared with those of papaverine on isolated corpus cavernosum from rabbit. Preparations were mounted in organ baths and isometric tension was recorded. Spontaneous contractile activity was effectively abolished by the KCOs tested, cromakalim being the most potent of them. The KCOs concentration-dependently and effectively depressed electrically induced contractions and also contractions induced by exogenously applied noradrenaline and by low (less than or equal to 20 mM) concentrations of K+. Cromakalim was three to four times more potent than pinacidil. Pinacidil and cromakalim were shown to cause increases in the efflux of 86Rb from preloaded cavernous tissue. Papaverine also effectively depressed spontaneous contractile activity, and contractions evoked by electrical stimulation and noradrenaline. It had a potency 19 to 36 times lower than that of cromakalim. However, papaverine did not increase 86Rb efflux from preloaded tissue. The results show that cromakalim and pinacidil effectively relax penile erectile tissue, probably by the opening of K(+)-channels and subsequent hyperpolarization. Further investigations on human material seems motivated in order to elucidate if the principle of K(+)-channel opening offers any therapeutic advantages to other drugs in the diagnosis and treatment of penile erectile dysfunction.
Bcl2 is the guardian of microtubule integrity. (1997)

We have investigated the ability of several drugs commonly used in the treatment of human cancer to induce bcl2 phosphorylation and cell death in human cell lines derived from acute leukemia, lymphoma, breast cancer, and prostate cancer. The results of this analysis indicate that drugs affecting the integrity of microtubules induce bc12 phosphorylation, whereas anticancer drugs damaging DNA do not. Comparison of the effects of taxol and its analogue, taxotere, indicates that taxotere is capable of inducing bcl2 phosphorylation and apoptotic cell death at 100-fold lower concentrations than taxol. Induction of cancer cell death through phosphorylation of bcl2 thus provides an opportunity not only for more refined targeting of therapeutic drugs but for understanding of an important pathway leading to apoptosis. Phosphorylation of bcl2 in drug-treated cancer cells occurs in G2-M, the phase of the cell cycle in which this class of drugs is active. No induction of bcl2 phosphorylation occurs in chronic lymphocytic leukemia cells that overexpress bcl2 but are blocked at G0-G1. Thus, prevention of polymerization or depolymerization of cellular microtubules by this class of cancer therapeutic drugs causes phosphorylation of bcl2, abrogating the normal antiapoptotic function of bcl2 and initiating the apoptotic program in the cycling cancer cells; these results are consistent with a normal physiological role of bcl2 as "guardian of microtubule integrity."
Extension of the biological effective dose to the MIRD schema and possible implications in radionuclide therapy dosimetry (2008)

In dosimetry-based treatment planning protocols, patients with rapid clearance of the radiopharmaceutical require a larger amount of initial activity than those with slow clearance to match the absorbed dose to the critical organ. As a result, the dose-rate to the critical organ is higher in patients with rapid clearance and may cause unexpected toxicity compared to patients with slow clearance. In order to account for the biological impact of different dose-rates, radiobiological modeling is beginning to be applied to the analysis of radionuclide therapy patient data. To date, the formalism used for these analyses is based on kinetics derived from activity in a single organ, the target. This does not include the influence of other source organs to the dose and dose-rate to the target organ. As a result, only self-dose irradiation in the target organ contributes to the dose-rate. In this work, the biological effective dose (BED) formalism has been extended to include the effect of multiple source organ contributions to the net dose-rate in a target organ. The generalized BED derivation has been based on the Medical Internal Radionuclide Dose Committee (MIRD) schema assuming multiple source organs following exponential effective clearance of the radionuclide. A BED-based approach to determine the largest safe dose to critical organs has also been developed. The extended BED formalism is applied to red marrow dosimetry, as well as kidney dosimetry considering the cortex and the medulla separately, since both those organs are commonly dose limiting in radionuclide therapy. The analysis shows that because the red marrow is an early responding tissue (high alpha/beta), it is less susceptible to unexpected toxicity arising from rapid clearance of high levels of administered activity in the marrow or in the remainder of the body. In kidney dosimetry, the study demonstrates a complex interplay between clearance of activity in the cortex and the medulla, as well as the initial activity ratio and the S value ratio between the two. In some scenarios, projected BED based on both the cortex and the medulla is a more appropriate constraint on the administered activity than the BED based on the cortex only. Furthermore, different fractionated regimens were considered to reduce renal toxicity. The MIRD-based BED formalism is expected to be useful for patient-specific adjustments of activity and to facilitate the investigation of dose-toxicity correlations with respect to dose-rate and tissue repair mechanism.
Assess Carefully Before Intervening (1994)

Sandra D. John, RN, MS, MDiv,a clinical specialist in psychiatric-mental health nursing, is the spiritual care coordinator at Hospice Care of DC in Washington, DC. Along with twenty years of working and teaching in psychiatric nursing, she has also served as an American Baptist pastor for ten years.
New advances in three-dimensional controlled-source electromagnetic inversion (2008)

New techniques for improving both the computational and imaging performance of the three-dimensional (3-D) electromagnetic inverse problem are presented. A non-linear conjugate gradient algorithm is the framework of the inversion scheme. Full wave equation modelling for controlled sources is utilized for data simulation along with an efficient gradient computation approach for the model update. Improving the modelling efficiency of the 3-D finite difference (FD) method involves the separation of the potentially large modelling mesh, defining the set of model parameters, from the computational FD meshes used for field simulation. Grid spacings and thus overall grid sizes can be reduced and optimized according to source frequencies and source–receiver offsets of a given input data set. Further computational efficiency is obtained by combining different levels of parallelization. While the parallel scheme allows for an arbitrarily large number of parallel tasks, the relative amount of message passing is kept constant. Image enhancement is achieved by model parameter transformation functions, which enforce bounded conductivity parameters and thus prevent parameter overshoots. Further, a remedy for treating distorted data within the inversion process is presented. Data distortions simulated here include positioning errors and a highly conductive overburden, hiding the desired target signal. The methods are demonstrated using both synthetic and field data.
Multi-Rate High-Throughput LDPC Decoder: Tradeoff Analysis Between Decoding Throughput and Area (2006)

In order to achieve high decoding throughput (hundreds of MBits/sec and above) for multiple code rates and moderate codeword lengths, several LDPC decoder solutions with different levels of processing parallelism are possible. Selection between these solutions is based on a threefold criterion: hardware complexity, decoding throughput, and error-correcting performance. In this work, we determine the multi-rate LDPC decoder architecture with the best tradeoff in terms of area cost, error-correcting performance, and decoding throughput. The prototype architecture of this decoder is implemented on an FPGA
Polylactide‐cyclosporin A nanoparticles for targeted immunosuppression (2010)

Polymeric nanoparticles (NPs), prepared via coprecipitation of drugs and polymers, are promising drug delivery vehicles for treating diseases with improved efficacy and reduced toxicity. Here, we report an unprecedented strategy for preparing polylactide-cyclosporine A (PLA-CsA) NPs (termed CsA-NPs) through CsA-initiated ring-opening polymerization of lactide (LA) followed by nanoprecipitation. The resulting CsA-NPs have sub-100 nm sizes and narrow particle size distributions, and release CsA in a sustained manner without a "burst"-release effect. Both free CsA and CsA-NPs displayed comparable suppression of T-cell proliferation and production of inflammatory cytokines in various T-cell assays in a dose-dependent manner. The IC(50) values for CsA and CsA-NPs were 27.5 and 72.0 ng/ml, respectively. As lymph nodes are the main loci for T-cell activation, we coupled dendritic cells (DCs) with CsA-NPs and successfully delivered CsA selectively to the lymph nodes. Our studies indicated that CsA-NPs could be internalized in the DCs with a sustained release of CsA to the culture medium, suppressing alloreactive T-cell proliferation. Allogeneic DCs loaded with CsA-NPs were able to migrate to the draining lymph nodes where the T-cell priming was significantly reduced without any systemic release. This innovative nanoparticulate CsA delivery technology constitutes a strong basis for future targeted delivery of immunosuppressive drugs with improved efficiency and reduced toxicity.
Efficient coupling in integrated twin-waveguide lasers using waveguide tapers (1999)

We demonstrate a 1.55-μm wavelength, InGaAsP-InP, twin-waveguide (TG) laser integrated with passive ridge waveguides using low-loss taper couplers. The lateral taper on the laser waveguide induces efficient resonant coupling of light between the active and passive layers. The device is fabricated using low-cost conventional photolithography and reactive ion etching of a TG structure grown by gas-source molecular beam epitaxy. This structure is suitable for integrating a variety of photonic devices without requiring epitaxial regrowth.
Printed fractal antennas (1999)

One aspect of this paper is to describe the possibilities for reducing the overall size of a monopole so that they can be hidden within a system rather than protrude from it. Improved bandwidth results from the bow-tie monopole but there are instances where individual bands rather than a single band is preferable, for example for rejection of unwanted signals. One class of antenna to replace the monopole is the printed fractal antenna. Two types of fractal antennas are discussed, the Koch fractal patterns and the Sierpinski gasket which is akin to a printed bow-tie antenna. In both classes of antenna their radiation patterns, efficiency and frequency response as well as dimensions are discussed and compared. The principal application for the work described here is to provide hidden antennas on vehicles for multiband radio and television services. These include AM, FM and DAB services.
Human extramedullary bone marrow in mice: a novel in vivo model of genetically controlled hematopoietic microenvironment (2012)

The interactions between hematopoietic cells and the bone marrow (BM) microenvironment play a critical role in normal and malignant hematopoiesis and drug resistance. These interactions within the BM niche are unique and could be important for developing new therapies. Here, we describe the development of extramedullary bone and bone marrow using human mesenchymal stromal cells and endothelial colony-forming cells implanted subcutaneously into immunodeficient mice. We demonstrate the engraftment of human normal and leukemic cells engraft into the human extramedullary bone marrow. When normal hematopoietic cells are engrafted into the model, only discrete areas of the BM are hypoxic, whereas leukemia engraftment results in widespread severe hypoxia, just as recently reported by us in human leukemias. Importantly, the hematopoietic cell engraftment could be altered by genetical manipulation of the bone marrow microenvironment: Extramedullary bone marrow in which hypoxia-inducible factor 1α was knocked down in mesenchymal stromal cells by lentiviral transfer of short hairpin RNA showed significant reduction (50% ± 6%; P = .0006) in human leukemic cell engraftment. These results highlight the potential of a novel in vivo model of human BM microenvironment that can be genetically modified. The model could be useful for the study of leukemia biology and for the development of novel therapeutic modalities aimed at modifying the hematopoietic microenvironment.
Action of Nucleases on Double‐Stranded RNA (1976)

Double-stranded RNAs from Penicillium chrysogenum virus have been treated with RNAse III, pancreatic RNAse A and RNAse T1 and the degradation of the RNAs has been studied under different conditions. It was found that only the two former enzymes cut across both strands, RNase T1 cannot cleave double strands. RNase III was shown to digest double-stranded RNA by a two step process: an initial phase of specific cleavage is followed by random degradation. In the first phase the enzyme exhibited a definite preference for some specific base pattern. Partial or complete degradation with pancreatic RNase A could also be achieved in media with high salt concentration provided that the enzyme: substrate ratio was increased together with the salt concentration. By combining different assay techniques, the process of degradation was followed from the early stages to complete digestion and the breakdown products were characterised. It is suggested that a structural change in the enzyme molecules enables them to act on double-stranded RNA. RNAse T1, being unable to cleave double strands, provides a useful tool for studying the secondary structure of RNA molecules. Treatment with different nucleases yielded some new information on the structure of different RNA species in Penicillium stoloniferum virus.
Masquerader: High Mobility Group Box-1 and Cancer (2007)

Since its identification a third of a century ago, the high-mobility group box-1 (HMGB1) protein has been linked to varied diverse cellular processes, including release from necrotic cells and secretion by activated macrophages engulfing apoptotic cells. Initially described as solely chromatin-associated, HMGB1 was additionally discovered in the cytoplasm of several types of cultured mammalian cells 6 years later. In addition to its intracellular role, HMGB1 has been identified extracellularly as a putative leaderless cytokine and differentiation factor. In the years since its discovery, HMGB1 has also been implicated in disease states, including Alzheimer's, sepsis, ischemia-reperfusion, arthritis, and cancer. In cancer, overexpression of HMGB1, particularly in conjunction with its receptor for advanced glycation end products, has been associated with the proliferation and metastasis of many tumor types, including breast, colon, melanoma, and others. This review focuses on current knowledge and speculation on the role of HMGB1 in the development of cancer, metastasis, and potential targets for therapy.
Staphylococcal multidrug efflux protein QacA. (2001)

The QacA multidrug exporter from Staphylococcus aureus mediates resistance to a wide array of monovalent or divalent cationic, lipophilic, antimicrobial compounds. QacA provides resistance to these various compounds via a proton motive force-dependent antiport mechanism that conforms to classical Michaelis-Menten kinetics. Fluorescent transport analyses have demonstrated that this QacA:substrate interaction occurs with high affinity and competition studies have shown that QacA-mediated ethidium export is competitively inhibited by other monovalent cations, and non-competitively inhibited by divalent cations, suggesting that monovalent and divalent cations bind at distinct sites on the QacA protein. The closely related export protein QacB, mediates lower levels of resistance to divalent cations, and lacks a high affinity-binding site for divalent cations. The cell membrane has been identified as the origin of QacA-mediated efflux; substrates are bound and expelled from within this hydrophobic environment. Regulation of qacA expression is achieved via the transacting repressor protein, QacR. QacR belongs to the TetR family of transcriptional repressor proteins, which all possess a helix-turn-helix DNA-binding domain at their N-terminal ends, and have highly divergent C-termini postulated to be involved in the binding of inducing compounds. QacR specifically binds to an inverted repeat, IR1, which has been identified as the qacA operator region, and overlaps the identified promoter sequence for qacA. QacR, like the multidrug export protein whose expression it regulates, has been shown to interact directly with a number of structurally-dissimilar compounds.
Molecular Regulation of Mirnas and Potential Biomarkers in the Progression of Hepatic Steatosis to NASH (2015)

Increasing evidence suggests that microRNAs regulate diverse biological functions in the liver and play a very important function in metabolic-related disorders such as nonalcoholic fatty liver disease via regulating their target genes expression. In this review, we summarized the most recent progress in identification of miRNAs involving in the progression of liver steatosis and discussed the possible mechanisms by which miRNAs contribute to the diverse pathogenic liver injuries. We provide insights into the functional network of miRNAs by connecting miRNAs, their targets and biological pathways associated to hepatic steatosis and fibrosis, with important implications for our understanding of phenotypic-based disease pathogenesis. We also discuss the possible roles and challenges of miRNAs as biomarkers for drug-induced liver injury.