gebhart/patrepeval huggingface dataset:
Pharmacokinetics, pharmacodynamics, safety and tolerability of APG101, a CD95-Fc fusion protein, in healthy volunteers and two glioma patients (2012)

APG101 is a glycosylated fusion protein consisting of the extracellular domain of human CD95 (APO-1/Fas) and the Fc domain of human IgG1. Administration of APG101 blocks the interaction between CD95 and its cognate ligand CD95L, thereby inhibiting various pathways involved in e.g. proliferation, migration, differentiation and apoptosis induction. The safety and tolerability of ascending single doses of intravenously applied APG101 was examined in a randomized, double-blind, placebo-controlled, mono-centre "first in man" dose escalation study in 34 healthy male volunteers. Pharmacokinetics and pharmacodynamics were also assessed. The maximum serum concentration of 460 μg/ml was achieved following 1h infusion of the highest dose of 20 mg/kg. The systemic clearance was low (0.4 to 0.5 ml/hkg). Mean terminal elimination half-life was 12 to 15 days. Two patients suffering from malignant glioma received APG101 intravenously under compassionate use conditions. They received doses ranging from 5mg to 600 mg APG101. No adverse events and no clinical significant changes in laboratory parameters related to APG101 were reported. The presence of anti-drug-antibodies (ADA) was investigated and revealed no detectable levels of ADA. Overall, single ascending doses of APG101 up to 20 mg/kgbody weight (bw) administered as infusion over 1h were considered as safe and well tolerated in healthy volunteers. After the application of multiple doses of 400 mg in two glioma patients, steady state for APG101 seemed to be reached. These results support further clinical evaluation of APG101 at a dose of 400 mg per week in glioblastoma patients.
Lung capacity estimation through acoustic signal of breath (2012)

Breathing disorders are generally associated with the lung cancer disease. Through daily treatment, lung cancer patients often use a traditional spirometer to measure their lung capacity. However, the use of a spirometer device for accurate measurement requires some sort of training and adjustment, which may be inconvenient for certain groups of patients, especially the elderly. In addition, the spirometer readings can become unreliable if the measurements are not taken as instructed. On the other hand, a microphone, say the microphone on a hand-held device such as a smart-phone, can easily capture the acoustic signal of breath without certain instructions. This signal can then be processed to estimate the lung capacity. In this paper, we propose a methodology through the simply recorded acoustic signal of breath, splitting the breathing cycle to inhale, pause, exhale and pause phases to measure the depth of the breath along with the time duration and signal energy of the breathing phases. We show how these computed parameters are used to estimate the lung size with a high degree of accuracy. This work is part of a virtual reality platform embedded within a smart-phone to assist lung cancer patients regulate their breath. Furthermore, the lung capacity estimation methodology proposed in this paper can also be used to aid patients with other breathing disorders.
Renal Denervation Abolishes Hypertension in Low-Birth-Weight Offspring From Pregnant Rats With Reduced Uterine Perfusion (2005)

Low birth weight is a risk factor for the subsequent development of hypertension in humans. We previously reported that reduced uterine perfusion in the pregnant rat results in growth-restricted offspring predisposed to the development of hypertension. The purpose of this study was to determine whether the sympathetic nervous system plays a role in mediating hypertension in this model of low birth weight. Weight at birth was significantly decreased in male growth-restricted offspring (5.9+/-0.1 grams) as compared with male control offspring (6.5+/-0.2 grams; P<0.05). At 10 weeks of age, growth-restricted offspring and control offspring were randomly assigned to either an intact group (sham-denervated) or a group subjected to bilateral renal denervation. For sham-denervated offspring, mean arterial pressure was significantly elevated in growth-restricted offspring (145+/-4 mm Hg; n=7) as compared with control offspring (134+/-3 mm Hg; P<0.05; n=9) at 12 weeks of age. Bilateral renal denervation resulted in a marked reduction in arterial pressure in growth-restricted offspring (125+/-3 mm Hg; P<0.01; difference of 20 mm Hg versus sham growth-restricted; n=8) but no significant decrease in control offspring (127+/-3 mm Hg; difference of 7 mm Hg versus sham control; n=9). Adequacy of renal denervation was verified by >90% reduction in renal norepinephrine content. Therefore, these findings indicate the renal nerves play an important role in mediating hypertension in adult growth-restricted offspring.
Chromatography : fundamentals and applications of chromatographic and electrophoretic methods (1983)

Chromatography: fundamentals and applications of chromatographic and electrophoretic methods , Chromatography: fundamentals and applications of chromatographic and electrophoretic methods , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Genistein suppresses the invasive potential of human breast cancer cells through transcriptional regulation of metalloproteinases and their tissue inhibitors (2005)

Progression of breast cancer implicates the degradation of extracellular matrix (ECM) by metallo-proteinases (MMPs), a process with important consequences on the growth and invasiveness of cancer cells in adjacent and distant sites. The isoflavone, genistein--a natural inhibitor of protein tyrosine kinase pathway--inhibits the growth of a wide range of cancer cells in vitro. The aim of this study was to investigate: i) the expression of mRNAs encoded for MMPs and their endogenous inhibitors (TIMPs) associated with pathogenesis and metastatic potential of breast cancer cells; and ii) the effect of genistein on the transcription of MMPs and TIMPs and the invasive potential of breast cancer cells. Gene expression at transcriptional level was examined in cell cultures of two epithelial breast cancer cell lines, the high invasive (ER-negative) MDA-MB-231 and the low invasive (ER-positive) MCF-7, as well as the normal mammary cells (MCF-12A) following RNA isolation and reversed transcriptase polymerase chain reaction (RT-PCR). The inhibitory effect of genistein on functional invasiveness was examined by a cell invasion assay. Cell cycle distribution showed that genistein arrested breast cancer MDA-MB-231, MCF-7 and BT-20 cells in the G2/M phase. Both normal and breast cancer cell lines express the genes of MMP-2, -9, MT1-, MT2-, MT3-MMP and TIMP-1, -2 and -3. MCF-7 express notably less MMPs than MDA-MB-231 cell line. The addition of genistein resulted in down-regulation of the transcription of all MMP genes in MDA-MB-231 and most of MMPs in MCF-7 cells. The inhibitory effect of genistein on MMPs was functionally confirmed, since it significantly reduced the invasion properties of cancer cells in vitro. The obtained results indicate that genistein may be of great value in prevention of breast cancer cell metastasis, since it represents both a transcriptional modulator of genes involved in this pathogenetic process and a suppressor of breast cancer cell invasiveness.
Beyond superquenching: Hyper-efficient energy transfer from conjugated polymers to gold nanoparticles (2003)

Gold nanoparticles quench the fluorescence of cationic polyfluorene with Stern-Volmer constants (KSV) approaching 1011 M-1, several orders of magnitude larger than any previously reported conjugated polymer-quencher pair and 9-10 orders of magnitude larger than small molecule dye-quencher pairs. The dependence of KSV on ionic strength, charge and conjugation length of the polymer, and the dimensions (and thus optical properties) of the nanoparticles suggests that three factors account for this extraordinary efficiency: (i) amplification of the quenching via rapid internal energy or electron transfer, (ii) electrostatic interactions between the cationic polymer and anionic nanoparticles, and (iii) the ability of gold nanoparticles to quench via efficient energy transfer. As a result of this extraordinarily high KSV, quenching can be observed even at subpicomolar concentrations of nanoparticles, suggesting that the combination of conjugated polymers with these nanomaterials can potentially lead to improved sensitivity in optical biosensors.
History and progress of hypotheses and clinical trials for Alzheimer’s disease (2019)

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss along with neuropsychiatric symptoms and a decline in activities of daily life. Its main pathological features are cerebral atrophy, amyloid plaques, and neurofibrillary tangles in the brains of patients. There are various descriptive hypotheses regarding the causes of AD, including the cholinergic hypothesis, amyloid hypothesis, tau propagation hypothesis, mitochondrial cascade hypothesis, calcium homeostasis hypothesis, neurovascular hypothesis, inflammatory hypothesis, metal ion hypothesis, and lymphatic system hypothesis. However, the ultimate etiology of AD remains obscure. In this review, we discuss the main hypotheses of AD and related clinical trials. Wealthy puzzles and lessons have made it possible to develop explanatory theories and identify potential strategies for therapeutic interventions for AD. The combination of hypometabolism and autophagy deficiency is likely to be a causative factor for AD. We further propose that fluoxetine, a selective serotonin reuptake inhibitor, has the potential to treat AD.
Challenges to targeting epidermal growth factor receptor in glioblastoma: escape mechanisms and combinatorial treatment strategies (2014)

Epidermal growth factor receptor (EGFR) gene amplification and activating mutations are common findings in glioblastomas. EGFR is at the top of a downstream signaling cascade that regulates important characteristics of glioblastoma cells, including cellular proliferation, migration, and survival. Targeting EGFR has therefore been regarded as a promising therapeutic strategy in glioblastoma for decades. However, although various pharmacological inhibitors and anti-EGFR antibodies are available, the antiglioma activity of these agents has been largely limited to preclinical models, whereas their administration to glioblastoma patients was characterized by lack of clinical benefit. Comprehensive efforts have been made within the last years to understand the underlying mechanisms that confer resistance to EGFR inhibition in glioma cells. The absence of well-known mutations that predict response to EGFR tyrosine kinase inhibitors (TKIs) in gliomas as well as the presence of redundant and alternative compensatory pathways are among the most important escape mechanisms that prevent potent antiglioma effects of EGFR-targeting drugs. Accordingly, an increasing number of in vitro and in vivo studies are aimed at overcoming this resistance by combinatorial approaches using anti-EGFR treatment together with one or more additional drugs. Novel insights into the molecular mechanisms mediating resistance to anti-EGFR treatment and promising combinatorial approaches may help to better define a future role for EGFR inhibition in the treatment of glioblastoma.
Decreased ability of HIV-1 Tat protein-treated accessory cells to organize cellular clusters is associated with partial activation of T cells (1997)

It has been shown in several animal models that HIV infection of accessory cells (ACs) plays an important role in development of AIDS. Here, we report that ACs treated with HIV-1 Tat protein (Tat-ACs) have a decreased ability to organize cellular aggregates as compared with untreated ACs, resulting in incomplete activation of T cells in responses to anti-CD3 mAb or staphylococcal enterotoxin B stimulation. The T cells failed to up-regulate adhesion molecules CD11a and CD2 on the cell surface and had reduced proliferative responses, as determined by [3H]thymidine incorporation, but they obtained lymphoblast-like morphology and expressed early activation antigens on the cell surface such as Fas and CD69 and interleukin 2 receptor, at comparable levels as those T cells undergoing a maximal proliferation. These results suggest that the Tat-AC-induced defect occurs in the late, but not in the early, phases of T cell activation. Normal expression of cell surface Fas antigen accompanied by defects in late activation thus may result in the susceptibility of these T cells to apoptosis. Our studies suggest that dysfunction, hyperactivation, and susceptibility to apoptosis, as observed with T cells isolated from HIV-infected individuals, may be, at least in part, a consequence of abnormal functions of ACs.
When pain after surgery doesn't go away… (2009)

Chronic post-surgical pain is a common, under-recognized and important clinical problem which affects millions of patients worldwide. It results from a series of neuroplastic changes associated most commonly with peripheral nerve injury at the time of surgery. Predisposing factors include the type of surgery, pre-operative and acute post-operative pain intensity, and probably psychological (e.g. pain-catastrophizing) and genetic factors [e.g. GCH1 (GTP cyclohydrolase 1) haplotype]. Preventive measures which are currently available include selection of a minimally invasive surgical technique and an aggressive multimodal perioperative analgesic regimen. Very promising therapeutic agents which target the sensitization process are currently in development.
Structure solution by minimal-function phase refinement and Fourier filtering. II. Implementation and applications (1994)

The minimal function, R(psi), has been used to provide the basis for a new computer-intensive direct-methods procedure that shows potential for providing fully automatic routine solutions for structures in the 200-400 atom range. This procedure, which has been called shake-and-bake, is an iterative process in which real-space filtering is alternated with phase refinement using a technique that reduces the value of R(psi). It has been successfully tested using experimental data for a dozen known structures ranging in size from 25 to 317 atoms and crystallizing in a variety of space groups. The details of this procedure, the parameters used and the results of these applications are described.
Extended-range optical low-coherence reflectometry using a recirculating delay technique (1993)

We propose a novel technique allowing for a substantial increase in the distance measurement range for optical low-coherence reflectometry. By introducing a recirculating delay into the interferometer reference path, we achieve a 100 times increase in range compared to previous optical low-coherence reflectometry techniques. At this extended range, a reflection sensitivity greater than -80 dB is demonstrated at a probe wavelength of 1.55 mu m.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Reduced complexity equalizers for zero-padded OFDM transmissions (2002)

The widespread application of OFDM for local area mobile wireless broadband systems is strongly motivated by the simple equalization it affords. OFDM's bottleneck of channel-dependent performance was only previously addressed by replacing the cyclic prefix (CP) with trailing zeros (TZ). Such zero-padded OFDM transmissions enable FIR channel-irrespective symbol recovery which results in significant BER gains. The price paid is increased receiver complexity compared to the classical CP-OFDM. To reduce complexity, this paper proposes two novel equalizers for TZ-OFDM. One is based on an overlap and add approach and exhibits exactly the same performance and complexity as CP-OFDM. The second offers BER performance close to the TZ-OFDM MMSE equalizer and incurs a moderate complexity increase. An extension of an existing CP-OFDM pilot-based channel estimation method is also derived for the proposed equalization schemes. Simulations are conducted in a realistic HiperLAN/2 scenario comparing the various OFDM transceivers.
The clinical significance of B-cell maturation antigen as a therapeutic target and biomarker (2018)

B-cell maturation antigen (BCMA) is a cell membrane bound tumor necrosis factor receptor family member that is expressed exclusively on late stage normal and malignant B-cells and plasma cells. Addition of two of its ligands, B-cell activating factor and a proliferation inducting ligand, to normal B-cells cause B-cell proliferation and antibody production. Serum BCMA is elevated among patients with multiple myeloma (MM) and chronic lymphocytic leukemia (CLL), and is a prognostic and monitoring tool for these patients. The first anti-BCMA antibody (Ab) was developed in 2007. Recently, biotech and pharmaceutical companies have created various forms of BCMA-directed Abs (naked Abs, Ab drug conjugates, and bispecific Abs) and cellular therapies (chimeric antigen receptor T-cells) with promising clinical results. Areas covered: This BCMA review encompasses full-text publications of original research articles and abstracts presented at hematology/oncology meetings. Expert commentary: The limited preclinical and ongoing clinical studies published to date evaluating BCMA-directed therapies have shown great promise. It has also been demonstrated that BCMA is solubilized and elevated in the blood of MM, Waldenstrom's macroglobulinemia and CLL patients, and is also responsible for the immune deficiency in MM. Reducing circulating levels may improve the efficacy of these treatments.
Evolution of Layer Based Neural Networks (2016)

Modern applications of Artificial Neural Networks (ANNs)largely feature networks organized into layers of nodes. Each layer contains an arbitrary number of nodes, and these nodes only share edges with nodes in certain other layers, as determined by the network's topology. Topologies of ANNs are frequently designed by human intuition, due to the lack of a versatile method of determining the best topology for any given problem. Previous attempts at creating a system to automate the discovery of network topologies have utilized evolutionary computing [6]. The evolution in these systems built networks on a node-by-node basis, limiting the probability of larger, layered topologies. This paper provides on overview of Growth from Embryo of Layered Neural Networks (GELNN), which attempts to evolve topologies ofneural networks in terms of layers, and inter-layer connections, instead of individual nodes and edges.
Development of a hammerhead ribozyme against BCL-2. II. Ribozyme treatment sensitizes hormone-resistant prostate cancer cells to apoptotic agents. (1998)

The results obtained strongly support the ability of a potential anti-bcl-2 ribozyme therapy to synergize with other agents in inducing apoptosis of hormone-resistant human prostate cancer cells.
HomER: a review of time-series analysis methods for near-infrared spectroscopy of the brain (2009)

Near-infrared spectroscopy (NIRS) is a noninvasive neuroimaging tool for studying evoked hemodynamic changes within the brain. By this technique, changes in the optical absorption of light are recorded over time and are used to estimate the functionally evoked changes in cerebral oxyhemoglobin and deoxyhemoglobin concentrations that result from local cerebral vascular and oxygen metabolic effects during brain activity. Over the past three decades this technology has continued to grow, and today NIRS studies have found many niche applications in the fields of psychology, physiology, and cerebral pathology. The growing popularity of this technique is in part associated with a lower cost and increased portability of NIRS equipment when compared with other imaging modalities, such as functional magnetic resonance imaging and positron emission tomography. With this increasing number of applications, new techniques for the processing, analysis, and interpretation of NIRS data are continually being developed. We review some of the time-series and functional analysis techniques that are currently used in NIRS studies, we describe the practical implementation of various signal processing techniques for removing physiological, instrumental, and motion-artifact noise from optical data, and we discuss the unique aspects of NIRS analysis in comparison with other brain imaging modalities. These methods are described within the context of the MATLAB-based graphical user interface program, HomER, which we have developed and distributed to facilitate the processing of optical functional brain data.
Production of Antibodies by Single DNA Immunization: Comparison of Various Immunization Routes (2002)

DNA immunization is a recent vaccination method that induces humoral and cellular immune responses in a range of hosts. Different immunization routes induce a different degree of the immune response. In the present report, we demonstrate that multiple intramuscular immunizations of plasmid DNA encoding various leukocyte surface molecules induced a specific antibody response. In contrast, a single intramuscular immunization could not induce antibody production. To study the induction of antibody response after a single immunization of plasmid DNA, mice were single-dose intramuscularly, intraperitoneally, intravenously and intrasplenically immunized, simultaneously, with the same preparation of plasmid DNA encoding CD147 membrane protein. We observed that only the intrasplenic route induced specific antibody production. The induction of antibody by intrasplenic immunization was confirmed by using plasmid DNA encoding CD54 molecule. By this single-dose DNA intrasplenic immunization, the generated antibodies could be detected in mice up to 6 months. These results suggest that the injected DNA is expressing the relevant protein antigen in the spleen for several months after injection. Our results demonstrate that direct immunization of antigen-encoding DNA into the spleen is a more effective method for induction of antibody production. This finding may support future investigations of DNA vaccination strategies that specifically promote the uptake of plasmid by splenocytes. Intrasplenic immunization may also be helpful in the understanding of the early events of the immune response to DNA vaccine and be useful as an effective route for the induction of immune responses.
Energy Release in Earthquakes (1958)

The notion of applying methods of static elasticity to the study of energy differences in two states of a given structure was extended by Starr to yield the solution to problems involving the propagation of cracks in shear fields. This technique may be modified to include the solution of the problem of the energy release upon the introduction of a tear fault, such as the San Andreas fault, into an otherwise homogeneous medium subjected to a uniform shear stress. The idealized properties of such a fault are a structure elongated compared with its depth and a strike-slip motion along the fault. This configuration, by symmetry, may be imaged in the Earth's surface so that the problem is reducible to that of a strip fault of infinite length in a homogeneous, isotropic, elastic, infinite medium. The medium is subjected to a uniform shear stress at infinity and the shear stress is assumed to vanish upon the strip. This two-dimensional problem has a vector solution rather than a tensor one, and thus it has an analogue in the electrical problem of a perfectly conducting strip placed in a uniform electric field or that of a strip obstacle placed in a uniform hydrodynamic stream field. The stress distribution and the relative motion throughout the medium before and after faulting can be obtained. For the case of the 1906 San Francisco earthquake, this model yields an energy difference of the shear fields before and after faulting of 4 × 1023 ergs. This value must exceed the elastic wave energy.