gebhart/patrepeval huggingface dataset:
Nature of the tumor-localizing components of hematoporphyrin derivative. (1987)

Hematoporphyrin derivative linked by ether bonds (HE) was synthesized by unambiguous procedures in order to compare its properties to hematoporphyrin derivative (HpD). Reverse phase high performance liquid and gel filtration chromatography were used to compare the HE derivatives to HpD. The cellular uptake of HE derivatives was compared to HpD using the WEHI 3B (D+) cell line and was shown to be taken up to a degree and in a manner similar to HpD. The efficiency of HE porphyrins as photosensitizers was compared to HpD using the V79 cell line. HE porphyrins were more efficient in sensitizing the V79 cells than was HpD. The in vivo tumor localizing properties of HE porphyrins were compared to HpD in CBA mice bearing the C6 cerebral glioma, and BALB/c mice bearing the EMT6 mammary tumor. HE derivatives localized in both tumor models as effectively as HpD. We conclude that the properties of ether linked hematoporphyrin derivatives are very similar to properties of HpD.
Gene Therapy for Restenosis - What Now, What Next? (2004)

Late luminal loss after coronary angioplasty has resisted pharmacological and physical attempts at prevention for over twenty years. As a consequence of the resistance of restenosis to traditional therapeutic approaches it has become a popular target for DNA-based treatment modalities. In this review we consider what is currently known of the basic pathophysiology of restenosis and briefly outline the previous attempts to influence the long-term outcome after coronary intervention. We then discuss the animal models of vascular injury that have been used for studies of gene therapy and the vectors that have been applied to the setting of vascular gene transfer before considering the many studies in which the effects of specific gene transfer have been studied in the setting of vascular injury. These transgenes are considered in four broad groupings: those that act by the suppression of cellular proliferation in the vessel wall; those that inhibit cell migration; anti-thrombotic transgenes; and transgenes that have multiple effects within the vessel. We finally consider why, although more than eight years have passed since publication of the first studies of gene transfer to inhibit the vascular responses to endoluminal injury, little progress has been made in translating gene therapy for restenosis into the human setting. Principle reasons for the disappointingly slow clinical implementation of gene therapy for restenosis are an incomplete understanding of the vascular biology of restenosis, the difficulty of translating findings in animal models into the human setting and the technical difficulties incumbent upon localised gene delivery into coronary arteries.
Dietary fiber showed no preventive effect against colon and rectal cancers in Japanese with low fat intake: an analysis from the results of nutrition surveys from 23 Japanese prefectures (2001)

This study failed to show any protective effect of dietary fiber in subjects with a low fat intake (Japanese) in this analysis, which supports Fuchs' findings in subjects with a high fat intake (US Americans).
Digital filter design in the quefrency domain (1978)

The desired log magnitude and phase responses are realized by approximating the log frequency response (the complex logarithm of the frequency response). Since the log frequency response is represented by its Fourier series in terms of the quefrency response (the cepstrum of the impulse response), the desired log frequency response is approximated by the filter with a finite length quefrency response. The elemental filter presented in this paper has a component of the quefrency response. Therefore, the quefrency response is realized by a cascade connection of the elemental filters for all its quefrency components. The cascade filter provides the best mean-square approximation to the desired log frequency response. By introducing the elemental filter, digital filters can be designed in the quefrency domain. By designing digital filters in the quefrency domain, the best approximation filter for the desired log frequency response can be easily realized.
A novel vertical DMOS transistor in SOA technology for RF-power applications (2003)

A novel SOI vertical DMOS transistor on glass for RF power applications is proposed. The device has the same advantages as conventional LDMOS transistors over bipolar transistors with respect to the linearity and efficiency for the high-power, high-frequency applications and adds the advantages of silicon-on-anything technology for the integration with high quality passive components. The gate oxide degradation due to hot carrier generation is inherently eliminated. The metalization on the wafer back includes copper electroplating. A thick copper layer on the wafer back serves as an excellent heat spreader and heat sink. Moreover, it can be used to avoid debiasing due to voltage drops over the metalization. The device performance has been investigated using DC and AC MEDICI simulations and the "Smoothie" database model for FET devices. A device with a breakdown of more than 80 V, an f/sub Tmax/ of 8 GHz, a maximum current of more than 10/sup -4/ A//spl mu/m at V/sub DS/=26 V and an R/sub ON/ of 4m/spl Omega/cm/sup 2/ is demonstrated.
Bis-N-heterocyclic Carbene Aminopincer Ligands Enable High Activity in Ru-Catalyzed Ester Hydrogenation (2015)

Bis-N-heterocyclic carbene (NHC) aminopincer ligands were successfully applied for the first time in the catalytic hydrogenation of esters. We have isolated and characterized a well-defined catalyst precursor as a dimeric [Ru2(L)2Cl3]PF6 complex and studied its reactivity and catalytic performance. Remarkable initial activities up to 283,000 h(-1) were achieved in the hydrogenation of ethyl hexanoate at only 12.5 ppm Ru loading. A wide range of aliphatic and aromatic esters can be converted with this catalyst to corresponding alcohols in near quantitative yields. The described synthetic protocol makes use of air-stable reagents available in multigram quantities, rendering the bis-NHC ligands an attractive alternative to the conventional phosphine-based systems.
IL-6 microinjected in the nucleus tractus solitarii attenuates cardiac baroreceptor reflex function in rats (2009)

Recent gene array and molecular studies have suggested that an abnormal gene expression profile of interleukin-6 (IL-6) in the nucleus tractus solitarii (NTS), a pivotal region for regulating arterial pressure, may be related to the development of neurogenic hypertension. However, the precise functional role of IL-6 in the NTS remains unknown. In the present study, we have tested whether IL-6 affects cardiovascular control at the level of the NTS. IL-6 (1, 10, and 100 fmol) was microinjected in the NTS of Wistar rats (280-350 g) under urethane anesthesia. Although the baseline levels of arterial pressure and heart rate did not change following IL-6 injections, the cardiac baroreflex in response to increased arterial pressure was dose-dependently attenuated. In addition, IL-6 (100 fmol) microinjections also attenuated l-glutamate-induced bradycardia at the level of the NTS. Immunohistochemical detection of IL-6 in naïve rats demonstrated that it was predominantly observed in neurons within the brain stem, including the NTS. These findings suggest that IL-6 within the NTS may play an important role for regulating cardiovascular control via modulation of input signals from baroreceptor afferents. Whether the abnormal gene expression of IL-6 in the NTS is associated in a causal way with hypertension remains to be resolved.
Circulating factor VIII immune complexes in patients with type 2 acquired hemophilia A and protection from activated protein C–mediated proteolysis (2001)

Factor VIII (FVIII) inhibitor antibodies are classified into 2 groups according to the kinetic pattern of FVIII inactivation. Type 2 antibodies are more commonly observed in patients with acquired hemophilia A and do not completely inhibit FVIII activity; in most cases, substantial levels of circulating FVIII are detected. Three type 2 autoantibodies from patients who had normal levels of FVIII antigen despite having low levels of FVIII activity were studied. The antibodies reacted exclusively with the light chain of FVIII but not with the C2 domain, and their epitopes were therefore ascribed to the regions in the A3-C1 domains. Heavy and light chains of FVIII were detected in plasma-derived immune complexes extracted by using protein G Sepharose. Direct binding assays using anhydro-activated protein C (anhydro-APC), a catalytically inactive derivative of activated protein C (APC) in which the active-site serine is converted to dehydroalanine, were used to examine the relation between immune complexes and APC. The intact FVIII, 80-kd light chain, and 72-kd light chain bound in a dose-dependent manner to anhydro-APC, with K(d) values of 580, 540, and 310 nM, respectively, whereas no appreciable binding was detected for the heavy chain. The 3 autoantibodies blocked FVIII binding to anhydro-APC by approximately 80% and consequently inhibited APC-induced FVIII proteolytic inactivation. These antibodies also bound to a synthetic peptide, His2009-Val2018, which contains the APC binding site. The findings suggest that binding of type 2 autoantibodies, recognizing residues His2009 to Val2018, protects FVIII from APC-mediated proteolysis and might contribute to the presence of FVIII immune complexes in the circulation.
The Hedgehog signaling pathway – implications for drug targets in cancer and neurodegenerative disorders (2003)

The Hedgehog (Hh) pathway is a highly conserved signaling cascade involved in many developmental processes. Among others, these include patterning of the ventral neural tube and establishment of left-right asymmetry of the embryo. Additionally, the pathway regulates the development of numerous tissues and cell types. Mutations in elements of the pathway are associated with congenital diseases and defects, and ectopic Hh signaling activity is implicated in the development of a number of neoplasms. While little is known of Hh signaling function in the adult organism, a role of the pathway in maintenance of adult organs and cell types, including several neuronal subtypes in the central nervous system, is beginning to emerge. Elements of the Hh pathway are therefore potential drug targets for the treatment of cancers and degenerative diseases like Parkinson's disease, and the recent isolation of synthetic molecules capable of modulating the activity of the Hh cascade through a direct interaction with elements of the pathway is promising.
Implementation of X-ray diffraction in the measurement of residual thermal strains (1996)

Microelectronic systems are multi-material, multi-layer structures, fabricated and exposed to environmental stresses over a wide range of temperatures. Thermal and residual stresses created by thermal mismatches in films and interconnections are a major cause of failure in microelectronic devices. Due to new device materials, increasing die size and the introduction of new materials for enhanced thermal management, differences in thermal expansions of various packaging materials have become exceedingly important and can no longer be neglected. X-ray diffraction is an analytical method using a monochromatic characteristic X-ray beam to characterize the crystal structure of various materials, by measuring the distances between planes in atomic crystalline lattice structures. As a material is strained, this interplanar spacing is correspondingly altered, and this microscopic strain is used to determine the macroscopic strain. This thesis investigates and describes the theory and implementation of X-ray diffraction in the measurement of residual thermal strains. The design of a computer controlled stress attachment stage fully compatible with an Anton Paar heat stage will be detailed. The stress determined by the diffraction method will be compared with bimetallic strip theory and finite element models.
Weighted backprojection approach to cone beam 3D projection reconstruction for truncated spherical detection geometry (1994)

A new analytical three-dimensional cone beam reconstruction algorithm is presented for truncated spherical detection geometry. The basic idea of the proposed algorithm is the formation of spatially invariant 3D blurred back-projected volumetric image by the use of the weighted backprojection of cone beam projection data and subsequent 3D filtering using an acceptance angle dependent rho filter. The backprojection weighting function is calculated on the basis of each given geometrical condition, i.e. detection geometry or degree of truncation, position of cone beam apex, and backprojection point. The proposed algorithm is derived analytically and is computationally efficient. Performance of the algorithm is evaluated by the reconstruction of 3D volumetric images using simulated data from arbitrarily truncated spherical detector geometries.
Porfimer-sodium (Photofrin-II) in combination with ionizing radiation inhibits tumor-initiating cell proliferation and improves glioblastoma treatment efficacy (2013)

Tumor relapse and tumor cell repopulation has been explained partially by the drug-free break period between successive conventional treatments. Strategies to overcome tumor relapse have been proposed, such as the use of chemotherapeutic drugs or radiation in small, frequent fractionated doses without an extended break period between treatment intervals. Yet, tumors usually acquire resistance and eventually escape the therapy. Several mechanisms have been proposed to explain the resistance of tumors to therapy, one of which involves the cancer stem cell or tumor-initiating cell (TIC) concept. TICs are believed to resist many conventional therapies, in part due to their slow proliferation and self-renewal capacities. Therefore, emerging efforts to eradicate TICs are being undertaken. Here we show that treatment with Photofrin II, among the most frequently used photosensitizers, sensitized a TIC-enriched U-87MG human glioblastoma cell to radiation, and improve treatment outcome when used in combination with radiotherapy. A U-87MG tumor cell population enriched with radiation-resistant TICs becomes radio-sensitive, and an inhibition of cell proliferation and an increase in apoptosis are found in the presence of Photofrin II. Furthermore, U-87MG tumors implanted in mice treated with Photofrin II and radiation exhibit a significant reduction in angiogenesis and vasculogenesis, and an increased percentage of apoptotic TICs when compared with tumors grown in mice treated with radiation alone. Collectively, our results offer a new possible explanation for the therapeutic effects of radiosensitizing agents, and suggest that combinatorial treatment modalities can effectively prolong treatment outcome of glioblastoma tumors by inhibiting tumor growth mediated by TICs.
The Prognostic Value of Epigenetic Silencing of p16 Gene in NSCLC Patients: A Systematic Review and Meta-Analysis (2013)

The meta-analysis findings support the hypothesis that p16 methylation is associated with OS and DFS in NSCLC patients. Large well-designed prospective studies are now needed to confirm the clinical utility of p16 methylation as an independent prognostic marker.
Evidence for horizontal transmission of the P transposable element between Drosophila species. (1990)

Several studies have suggested that P elements have rapidly spread through natural populations of Drosophila melanogaster within the last four decades. This observation, together with the observation that P elements are absent in the other species of the melanogaster subgroup, has lead to the suggestion that P elements may have entered the D. melanogaster genome by horizontal transmission from some more distantly related species. In an effort to identify the potential donor in the horizontal transfer event, we have undertaken an extensive survey of the genus Drosophila using Southern blot analysis. The results showed that P-homologous sequences are essentially confined to the subgenus Sophophora. The strongest P hybridization occurs in species from the closely related willistoni group. A wild-derived strain of D. willistoni was subsequently selected for a more comprehensive molecular examination. As part of the analysis, a complete P element was cloned and sequenced from this line. Its nucleotide sequence was found to be identical to the D. melanogaster canonical P, with the exception of a single base substitution at position 32. When the cloned element was injected into D. melanogaster embryos, it was able to both promote transposition of a coinjected marked transposon and induce singed-weak mutability, thus demonstrating its ability to function as an autonomous element. The results of this study suggest that D. willistoni may have served as the donor species in the horizontal transfer of P elements to D. melanogaster.
Quinoline, quinazoline, and acridone alkaloids (1991)

J. P. Michael, Nat. Prod. Rep., 1991, 8, 53 DOI: 10.1039/NP9910800053
The role of the T cell receptor, CD8, and LFA-1 in different stages of the cytolytic reaction mediated by alloreactive T lymphocyte clones. (1987)

The cytotoxic reaction mediated by cytotoxic T lymphocytes (CTL) consists of three phases: first, the CTL binds to the target cell; next, the CTL is triggered to lyse the target cell; and in the third phase, the CTL detaches from the target cell which is lysed in the absence of the CTL. Recently, we obtained evidence that human alloreactive CTL clones initially adhere to target cells without the involvement of the interaction between the T cell receptor (Tcr) and its specific target antigen. In the present study, we investigated the effect of monoclonal antibodies specific for the Tcr on the cytotoxic reaction of three CD8+ HLA-A2-specific CTL clones, using a single cell assay in which the binding event can be distinguished from the post-binding (lytic) phase of the cytolytic reaction. It was found that monoclonal antibodies directed at a variable part of the Tcr do not affect the binding phase but strongly block the lytic phase of the cytotoxic reaction. An anti-constant region Tcr antibody and an anti-CD3 reagent had a similar effect on the two phases of the reaction as the anti-variable part Tcr antibodies. In contrast, antibodies specific for LFA-1 strongly blocked the adhesion phase but did not affect the lytic phase. Antibodies specific for CD-8 had intermediate effects. They could block both the adhesion as well as the lytic phase. The effect of anti-CD8 appeared to be dependent on the CTL clone tested. One clone was found to be inhibited in the adhesion phase, but not in the lytic phase, whereas anti-CD8 hardly blocked the adhesion phase of two other CTL clones, but affected the lytic step of those clones. Our data indicate that LFA-1 is a major adhesion molecule in the CTL reaction, whereas the Tcr/CD3 complex is implicated in a phase after the initial formation of conjugates. CD8 is associated with both steps in the cytolytic reaction. In addition to its minor role in the adhesion phase, our data suggest strongly that CD-8 is involved in the triggering phase of the cytolytic reaction.
Evidence for Acute Central Sensitization to Prolonged Experimental Pain in Posttraumatic Stress Disorder (2014)

These findings are consistent with a significantly higher degree of acute central sensitization in individuals with PTSD. Increased acute central sensitization may underlie increased vulnerability for developing pain-related conditions following combat trauma.
A review of wavelets in biomedical applications (1996)

We present an overview of the various uses of the wavelet transform (WT) in medicine and biology. We start by describing the wavelet properties that are the most important for biomedical applications. In particular we provide an interpretation of the the continuous wavelet transform (CWT) as a prewhitening multiscale matched filter. We also briefly indicate the analogy between the WT and some of the the biological processing that occurs in the early components of the auditory and visual system. We then review the uses of the WT for the analysis of 1-D physiological signals obtained by phonocardiography, electrocardiography (ECG), mid electroencephalography (EEG), including evoked response potentials. Next, we provide a survey of wavelet developments in medical imaging. These include biomedical image processing algorithms (e.g., noise reduction, image enhancement, and detection of microcalcifications in mammograms), image reconstruction and acquisition schemes (tomography, and magnetic resonance imaging (MRI)), and multiresolution methods for the registration and statistical analysis of functional images of the brain (positron emission tomography (PET) and functional MRI (fMRI)). In each case, we provide the reader with same general background information and a brief explanation of how the methods work.
Membrane area and dendritic structure in type‐identified triceps surae alpha motoneurons (1987)

The size and branching structure of the dendritic tree were studied in nine type-identified triceps surae alpha-motoneurons that were labeled intracellularly with horseradish peroxidase and reconstructed from serial sections in the light microscope. The average total membrane area (AN) for motoneurons of type S (slow-twitch) motor units was about 22% smaller than AN for cells of type F units (including both FF and FR motor unit types in this category) (480.1 X 10(3) microns 2 vs. 617.7 X 10(3) microns 2, respectively). Systematic correlations were found between stem dendrite diameter and three measures of dendritic size: dendrite membrane area, combined dendritic length, and number of terminations. All of these correlations were significantly different for the dendrites of F and S motoneurons. Power-function relations between stem diameter and dendritic membrane area were used to estimate AN for a sample of 79 type-identified motoneurons. Mean estimated AN values were significantly different for the F and S motoneuron groups, despite a large overlap in AN values between these groups. The branching structure of dendrites of F and S motoneurons also showed clear differences. Type S motoneuron dendrites showed less-profuse branching and a more-even radial distribution of branch points than found in type F cells. Examination of two forms of the "3/2 power rule" for the relation between the diameters of parent and daughter dendritic branches at branch points showed that the dendrites of type S motoneurons conform less well with the anatomical constraints necessary to represent binary branching trees as equivalent cylinders than do dendrites of type F cells. There was no systematic difference between F and S motoneuron dendrites in the degree of asymmetry of first-order daughter trees. The results overall indicate that the dendrites of F and S motoneuron groups are structurally different, giving rise to a systematic difference in AN between these groups. Such structural differences suggest that the F and S groups of alpha-motoneurons can be viewed as intrinsically distinct cell types and not just large vs. small variants of the same cell species.