gebhart/patrepeval huggingface dataset:
Optical Imaging of PKH‐Labeled Hematopoietic Cells in Recipient Bone Marrow In Vivo (2002)

This work describes an optical technique for characterization of the early stages of hematopoietic stem cell (HSC) engraftment under physiological conditions and in real time. Bone marrow cells (BMCs) labeled with PKH membrane linkers were injected into conditioned recipients (B10-->B10.BR mice) preoperated for placement of optical windows over femoral epiphyses. Labeled cells were tracked in vivo by fluorescence microscopy. Cellular adhesion to the BM stroma was tested with laser tweezers, and viability was assayed by the propidium iodide (PI) exclusion test, as determined from energy-transfer measurements of the pair PKH67-PI in freshly excised femurs in situ. At optimal concentrations for in vivo tracking, 1-4 micro M PKH dyes neither impaired the viability of BMCs nor the capacity of allogeneic HSCs to reconstitute hematopoiesis in myeloablated recipients. The optical window allowed in vivo visualization of 23%-26% of the PKH-labeled BMCs in the femur. The homing efficiencies at 16 hours posttransplantation were quantified as 1.77% +/- 0.15% and 0.21% +/- 0.02% for syngeneic and allogeneic BMCs, respectively. In femurs excised 16 hours after transplantation, 70% +/- 9% of the cells were adherent to the BM stroma, and two-thirds of the cells were PI negative (viable). In vivo tracking and in situ assessment of labeled HSCs in recipient BM provide important quantitative and qualitative insights into the early stages of engraftment. Correlation of early events and the efficiency of durable engraftment serve as the basis for a systematic approach toward optimization of the conditions for transplantation.
Inhibition of HIV-1 Tat-Dependent Trans Activation by Steric Block Chimeric 2‘-O-Methyl/LNA Oligoribonucleotides (2001)

The HIV-1 trans-activation responsive element (TAR) RNA 59-residue stem-loop interacts with the HIV trans-activator protein Tat and other cellular factors to stimulate transcriptional elongation from the viral long terminal repeat (LTR). Inhibition of these interactions blocks full-length HIV transcription and hence replication. We have found that three types of 12-residue oligonucleotide analogues, namely, a 2'-O-methyl oligoribonucleotide (OMe), a chimeric oligonucleotide containing 7xOMe and 5x5-methyl C locked nucleic acid (LNA) residues, and a peptide nucleic acid (PNA), inhibit Tat-dependent in vitro transcription in HeLa cell nuclear extract equally efficiently (50% inhibition at 100-200 nM) and sequence specifically. The results are correlated with surprisingly similar binding strengths to a model 39-residue TAR under transcription conditions. A 12-mer containing 11 contiguous LNA residues was less effective in both Tat-dependent transcription inhibition and TAR 39 binding. Anti-TAR 3'-carboxyfluorescein- (FAM-) labeled OMe and OMe/LNA chimeric 12-mers were also efficient Tat-dependent in vitro transcription inhibitors as were 3'-FAM-labeled OMe oligonucleotides containing some phosphorothioate (PS) linkages. By use of a HeLa cell line containing stably integrated plasmids expressing firefly luciferase under HIV-LTR/Tat dependence as well as a Renilla luciferase constitutive control, we showed submicromolar, selective, dose-dependent, and sequence-dependent intracellular inhibition of Tat-TAR trans activation by the anti-TAR 3'-FAM 12-residue 7xOMe/5xLNA oligonucleotide when delivered by cationic lipid. No intracellular activity was observed for the corresponding anti-TAR 3'-FAM OMe 12-mer. An alternating PS-containing 3'-FAM OMe 12-mer oligonucleotide exhibited partial inhibition of trans-activation activity, but this was correlated with a similar effect on control gene expression, suggesting nonspecific inhibition.
Antibody to intercellular adhesion molecule 1 protects the kidney against ischemic injury. (1994)

The pathophysiology of ischemic acute renal failure is complex, and the role of leukocyte adhesion in this process is not well defined. A monoclonal antibody (mAb) against intracellular adhesion molecule 1 (anti-ICAM-1), administered at the time of bilateral renal ischemia in the rat, prevented both functional impairment and histologic changes of acute renal failure. Plasma creatinine measured (mg/dl) 24 hr after 30 min of ischemia was 0.61 +/- 0.05 in the anti-ICAM-1-treated animals compared with 2.4 +/- 0.14 (P < 0.0001) in the vehicle-treated ischemic group. Forty-eight hours after ischemia, creatinine values were 0.46 +/- 0.05 and 2.03 +/- 0.22 (P < 0.0001) in anti-ICAM-1 and vehicle-treated groups, respectively. A low dose of anti-ICAM-1 that was itself nonprotective, when given with partially protective doses of a mAb against lymphocyte function-associated antigen-1 (anti-LFA-1), acted synergistically to prevent renal failure. Anti-ICAM-1 mAb also protected the kidney when administered 0.5 or 2 hr but not 8 hr after restoration of blood flow and when the ischemic period was extended to 40 min. Ischemia-induced increases in tissue myeloperoxidase, a marker of neutrophil infiltration, were mitigated with anti-ICAM-1 treatment. Thus, anti-ICAM-1 mAb protected the kidney against ischemic renal failure, even when the antibody was administered after the ischemic period. These results suggest a critical role for leukocytes and adhesion molecules in the pathophysiology of ischemic injury and may have important therapeutic implications.
Near-IR imaging of atheromas in living arterial tissue (1993)

A near-IR imaging system and parallel vector supercomputer are used with a fiber-optic probe to produce chemical maps of the intimal surface of living arteries. Spectrometric information collected at hundreds of near-IR wavelengths is assembled into color pictures of the lipoprotein and apolipoprotein composition of atheromas using a vectorized 3-D cellular automaton-based algorithm that operates in parallel. The nonparametric mathematics developed to identify and quantify the constituents of each voxel in the artery wall avoid the matrix factorizations that generate excess error in other pattern recognition methods and permit analysis in a wavelength space of over 1000 dimensions using fewer than 100 calibration samples. A surface feature resolution of 5.5 microns and depth resolution of 6.5 microns are achieved with the system. Data from the fiber optics confirm the injury hypothesis of lesion formation and the differing roles of HDL and LDL in cholesterol transport. In clinical studies, approximately 1/2 of human arterial lesions appear fibrous and contain little or no lipid. As such, these lesions would not be expected to regress in response to cholesterol-lowering agents such as lovastatin. Identification of lesion types in vivo will enhance the efficacy of treatment programs.
Increased disease susceptibility of transgenic tobacco plants with suppressed levels of preformed phenylpropanoid products. (1994)

It has been proposed that natural products synthesized by plants contribute to their resistance to pests and pathogens. We show here that transgenic tobacco plants with suppressed levels of the phenylpropanoid biosynthetic enzyme phenylalanine ammonia-lyase (L-phenylalanine ammonia-lyase, EC 4.3.1.5) and correspondingly low levels of chlorogenic acid, the major soluble leaf phenylpropanoid product, exhibit more rapid and extensive lesion development than wild-type plants after infection by the virulent fungal pathogen Cercospora nicotianae. These observations provide direct evidence that phenylpropanoid products contribute to disease limitation. No induction of transcripts encoding phenylalanine ammonia-lyase or the lignin branch pathway enzyme caffeic acid O-methyltransferase was observed during the infection and there was no perturbation in the pattern of soluble phenylpropanoids. Hence, increased disease susceptibility does not involve inhibition of a pathogen-induced response but likely reflects inhibition of the developmental accumulation of chlorogenic acid. Demonstration of the contribution of such preformed protectants to plant health identifies attractive targets for manipulation by breeding or gene transfer to reduce the quantitative impact of disease.
Adsorption of Branched-Linear Polyethyleneimine–Ethylene Oxide Conjugate on Hydrophilic Silica Investigated by Ellipsometry and Monte Carlo Simulations (2011)

The adsorption of and conformation adopted by a branched-linear polymer conjugate to the hydrophilic silica-aqueous solution interface have been studied by in situ null ellipsometry and Monte Carlo simulations. The conjugate is a highly branched polyethyleneimine structure with ethyleneoxide chains grafted to its primary and secondary amino groups. In situ null ellipsometry demonstrated that the polymer conjugate adsorbs to the silica surface from water and aqueous solution of 1 mM asymmetric divalent salt (calcium and magnesium chloride to emulate hard water) over a large pH range. The adsorbed amount is hardly affected by pH and large charge reversal on the negatively charged silica surface occurred at pH = 4.0, due to the adsorption of the cationic polyelectrolyte. The Monte Carlo simulations using an appropriate coarse-grained model of the polymer in solution predicted a core-shell structure with no sharp boundary between the ethyleneimine and ethyleneoxide moieties. The structure at the interface is similar to that in solution when the polymer degree of protonation is low or moderate while at high degree of protonation the strong electrostatic attraction between the ethyleneimine core and oppositely charged silica surface distorts the ethyleneoxide shell so that an "anemone"-like configuration is adopted. The adsorption of alkyl benzene sulfonic acid (LAS) to a preadsorbed polymer layer was also investigated by null ellipsometry. The adsorption data brought additional support for the existence of a strong polymer adsorption and showed the presence of a binding which was further enhanced by the decreased solvency of the surfactant in the salt solution and confirmed the surface charge reversal by the polymer adsorption at pH = 4.0.
Research in practice: Substance P antagonism in chronic pruritus (2014)

Pruritus is an unpleasant sensation of the skin, which triggers a desire to scratch or rub. The chronic form (≥6 weeks' duration) often occurs as a side effect of many diseases and is usually accompanied by a high loss in quality of life for patients, especially in cases in which the symptom is chronic without adequate treatment options. In recent years, the situation improved continuously, guidelines for chronic pruritus have been defined and standard medications have been proposed. For many reasons, there are still patients who are unable to obtain relief. New therapeutic approaches are therefore urgently needed. Blocking the neuropeptide substance P is a promising strategy; substance P mediates clinically relevant pro-inflammatory effects by binding to the neurokinin 1 receptor (NK-1R). This led us to hypothesize that NK-1R antagonists are promising therapeutic options for chronic pruritus. Several international case series have meanwhile proven the antipruritic effect of the NK-1R antagonist aprepitant for various forms of chronic pruritus. Initiation of clinical trials with new NK-1R-antagonists as a new therapeutic option continues this trend.
Bio based fuels and fuel additives from lignocellulose feedstock via the production of levulinic acid and furfural (2011)

Abstract The demand for biomass-derived fuels and fuel additives, particularly in the transportation sector, has stimulated intense research efforts in the chemistry of levulinic acid and levulinic acid secondary products over the past decade. Additionally, recent technological progress in lignocellulosic feedstock (LCF) chemistry has also increased attention in this regard. As a result, several oxygenating fuel additives with potential applications in both gasoline and diesel fuels have been identified. Some of the chemicals, such as ethyl valerate, appear to be viable alternatives to the currently used branched, short-chain ethers that are derived from side products of petrol refining. Cost-effective applications of lignocellulosic biomass are a crucial aspect of its feasibility. In consideration of the LCF biorefinery concept, the feasibility must also include the chemical pulping of LCF and the comprehensive utilisation of its main constituents cellulose, hemicelluloses, and lignin. The present study focuses on cellulose and hemicelluloses as viable sources for the production of biofuels and biofuel additives. Multifunctional catalysis, including hydrogenation and acid catalysis are the primary instruments used for the conversion of the monomeric carbohydrate building blocks, i.e., mainly C5 sugars, such as xylose and arabinose, and C6 sugars in the form of glucose and their respective secondary products, furfural and levulinic acid. Lignin utilisation is not addressed in this paper.
Surface polymerization of poly(γ‐alkyl‐l‐glutamate) on solid substrates (1997)

Abstract Surface polymerization of poly(γ‐methyl‐L‐glutamate) and a copolymer of γ‐methyl and γ‐stearyl‐L‐glutamate are conducted on aminopropyl triethoxysilane modified silicon(100) native oxide substrates. The film formation is monitored by X‐ray photoelectron spectroscopy, and the conformation and orientation of surface‐bound polypeptides are characterized by transmission Fourier transform infrared spectroscopy. Both films are formed as β‐sheet material, and the film orientations are tilted from the solid substrate.
Functional neuroanatomical correlates of electrodermal activity: A positron emission tomographic study (1998)

To reveal areas in the central nervous system of importance for electrodermal control, regional cerebral blood flow (rCBF) was correlated to nonspecific skin conductance fluctuations (NSF) during aversive and nonaversive conditions. Participants viewed a TV screen displaying white noise or snake videotapes presented both with and without electric shocks given to the right hand. H2 15 O positron emission tomography was used to measure rCBF, and the constant voltage technique was used to measure NSF from the left hand. Electrodermal activity was positively related to rCBF in the left primary motor cortex (MI, Brodmann's Area 4) and bilaterally in the anterior (Areas 24 and 32) and posterior cingulate cortex (Area 23). Negative relations were observed bilaterally in the secondary visual cortex (Areas 18 and 19) and the right inferior parietal cortex (Area 39), with a tendency also for the right insular cortex (Areas 13, 15, and 16). Because results from lesion and stimulation studies in humans converge with the present imaging results, we conclude that the cingulum and the motor cortex, in addition to the parietal and possibly the insular cortex, form part of one or several distributed neural network(s) involved in electrodermal control. Because these areas also support anticipation, affect, and locomotion, electrodermal responses seem to reflect cognitively or emotionally mediated motor preparation.
Hierarchical Reinforcement Learning with the MAXQ Value Function Decomposition (2000)

This paper presents a new approach to hierarchical reinforcement learning based on decomposing the target Markov decision process (MDP) into a hierarchy of smaller MDPs and decomposing the value function of the target MDP into an additive combination of the value functions of the smaller MDPs. The decomposition, known as the MAXQ decomposition, has both a procedural semantics---as a subroutine hierarchy---and a declarative semantics---as a representation of the value function of a hierarchical policy. MAXQ unifies and extends previous work on hierarchical reinforcement learning by Singh, Kaelbling, and Dayan and Hinton. It is based on the assumption that the programmer can identify useful subgoals and define subtasks that achieve these subgoals. By defining such subgoals, the programmer constrains the set of policies that need to be considered during reinforcement learning. The MAXQ value function decomposition can represent the value function of any policy that is consistent with the given hierarchy. The decomposition also creates opportunities to exploit state abstractions, so that individual MDPs within the hierarchy can ignore large parts of the state space. This is important for the practical application of the method. This paper defines the MAXQ hierarchy, proves formal results on its representational power, and establishes five conditions for the safe use of state abstractions. The paper presents an online model-free learning algorithm, MAXQ-Q, and proves that it converges with probability 1 to a kind of locally-optimal policy known as a recursively optimal policy, even in the presence of the five kinds of state abstraction. The paper evaluates the MAXQ representation and MAXQ-Q through a series of experiments in three domains and shows experimentally that MAXQ-Q (with state abstractions) converges to a recursively optimal policy much faster than flat Q learning. The fact that MAXQ learns a representation of the value function has an important benefit: it makes it possible to compute and execute an improved, non-hierarchical policy via a procedure similar to the policy improvement step of policy iteration. The paper demonstrates the effectiveness of this non-hierarchical execution experimentally. Finally, the paper concludes with a comparison to related work and a discussion of the design tradeoffs in hierarchical reinforcement learning.
A cyclophilin-related protein involved in the function of natural killer cells. (1993)

Natural killer cells are non-major histocompatibility complex-restricted large granular lymphocytes that can recognize and destroy tumor cells without prior stimulation. A 150-kDa molecule on the surface of human natural killer cells was identified as a component of a putative tumor-recognition complex. We report here the isolation of cDNAs coding for the 150-kDa tumor-recognition molecule from human and mouse cDNA libraries. The amino terminus of the predicted protein contains a large hydrophobic region followed by a domain that is highly homologous to cyclophilin/peptidylprolyl cis-trans isomerase. The remainder of the protein is extremely hydrophilic and contains three homologous positively charged clusters. There are also three regions that contain extensive arginine- and serine-rich repeats. Comparison of the human and mouse predicted amino acid sequences revealed > 80% homology.
Phorbol esters cause sequential activation and deactivation of complement receptors on polymorphonuclear leukocytes. (1986)

Phorbol myristate acetate (PMA) exerts a biphasic effect on receptors for C3b and C3bi of human polymorphonuclear leukocytes (PMN). The addition of PMA for 10 min enhances the capacity of these receptors to promote binding and phagocytosis of C3b- and C3bi-coated erythrocytes. Upon additional incubation for 60 min, the capacity of these receptors to bind and ingest ligand-coated erythrocytes decreases to levels below those of resting cells. Although PMA does cause increased expression of cell surface C3b and C3bi receptors, the sequential rise and fall of receptor activity cannot be accounted for by alterations in the number of surface receptors. It appears, rather, that PMA causes qualitative changes in these receptors, first an increase in receptor activity (activation) and then a decrease in receptor activity (deactivation). In contrast with its effects on C3 receptors, PMA causes only a reduction in the capacity of Fc receptors to bind and ingest IgG-coated erythrocytes. Deactivation of Fc receptors also appears to involve a qualitative alteration in receptors, because the binding affinity of soluble immune complexes is sharply reduced upon stimulation of PMN with PMA. To explore the role of phosphorylation in the sequential activation and deactivation of phagocytosis-promoting receptors, we loaded PMN with thiophosphate (thioP). This compound is incorporated into cellular nucleotides and proteins, and the resultant (thio)phosphorylated proteins are resistant to phosphatases. thioP-loaded cells show enhanced receptor activity, suggesting that activation of receptors is mediated by a phosphorylation event. Cells loaded with thioP and treated with PMA for 70 min do not deactivate C3 or Fc receptors, suggesting that the deactivation is the result of a dephosphorylation event.
BRAF and Melanoma (2002)

Every so often, the cancer genetics community gets excited about the discovery of a gene that is found to be frequently mutated in a specific cancer. One such gene, BRAF, is selectively mutated in cutaneous melanoma. Investigators examined a panel of 15 cancer cell lines (6 breast cancers, 1 small-cell lung cancer, 6 non-small-cell lung cancers, 1 melanoma, and 1 mesothelioma) and found 3 missense mutations in the gene for the …
Ensembl 2012 (2011)

The Ensembl project (http://www.ensembl.org) provides genome resources for chordate genomes with a particular focus on human genome data as well as data for key model organisms such as mouse, rat and zebrafish. Five additional species were added in the last year including gibbon (Nomascus leucogenys) and Tasmanian devil (Sarcophilus harrisii) bringing the total number of supported species to 61 as of Ensembl release 64 (September 2011). Of these, 55 species appear on the main Ensembl website and six species are provided on the Ensembl preview site (Pre!Ensembl; http://pre.ensembl.org) with preliminary support. The past year has also seen improvements across the project.
Fuzzy PID control of a flexible-joint robot arm with uncertainties from time-varying loads (1997)

This paper presents the design and experiment of a fuzzy proportional integral derivative (PID) controller for a flexible-joint robot arm with uncertainties from time-varying loads. Experimental results have shown remarkable tracking performance of this fuzzy PID controller, and have convincingly demonstrated that fuzzy logic control can be used for flexible-joint robot arms with uncertainties and it is quite robust. In this paper, the fuzzy PID controller is first described briefly, using a simple and practical PD+I controller configuration. This configuration preserves the linear structure of the conventional PD+I controller, but has nonconstant gains: the proportional, integral, and derivative gains are nonlinear functions of their input signals, which have self-tuning (adaptive) capabilities in set-point tracking performance. Moreover, these variable gains make the fuzzy PID controller robust with faster response time and less overshoot than its conventional counterpart. The proposed design was tested using a flexible-joint robot arm driven by a DC motor in a laboratory, where the arm was experienced with time-varying loads. Control performance by the conventional and fuzzy PID controllers for such a laboratory robotic system are both included in this paper for comparison.
Ocular Examination For Trauma; Clinical Ultrasound Aboard The International Space Station (2005)

A comprehensive, high-quality ultrasound examination of the eye was performed with a multipurpose imager aboard the ISS by a non-expert operator using remote guidance. Ocular ultrasound images were of diagnostic quality despite the 2-second communication latency and the unconventional setting of a weightless spacecraft environment. The remote guidance techniques developed to facilitate this successful NASA research experiment will support wider applications of ultrasound for remote medicine on Earth including the assessment of pupillary reactions in patients with severe craniofacial trauma and swelling.
Age-Dependent Impairment of Angiogenesis (1999)

Angiogenesis responsible for collateral development in limb ischemia is impaired with aging; responsible mechanisms include age-related endothelial dysfunction and reduced VEGF expression. Advanced age, however, does not preclude augmentation of collateral vessel development in response to exogenous angiogenic cytokines.