gebhart/patrepeval huggingface dataset:
Sex Differences in the Twenty-Four-Hour Mean Plasma Concentrations of Dehydroisoandrosterone (DHA) and Dehydroisoandrosterone Sulfate (DHAS) and the DHA to DHAS Ratio in Normal Adults* (1980)

The 24-h mean plasma concentrations of dehydroisoandrosterone (DHA) and dehydroisoandrosterone sulfate (DHAS) and the DHA to DHAS ratio were determined in 37 normal women, aged 21-75 yr, and 32 normal men, aged 21-72 yr. As predicted from our study of sex differences in the metabolism of DHAS, women showed a markely higher DHA to DHAS ratio than men at all ages; the geometric mean for women was 7.5 x 10(-3) and that for men was 3.9 x 10(-3) (P less than 0.0001); and the mean for premenopausal women (6.7 x 10(-3) did not differ significantly from that for postmenopausal women (8.6 x 10(-3)). The two steroids showed a clear-cut linear inverse correlation between concentration and age in both sexes, and menopause was "nonevent" in the age progression for both steroids in the women. The slopes of the concentration vs. age curves were considerably greater in the women, as a reuslt of which the sex differences in concentrations of these steroids changed with age. Under age 50 yr, the plasma DHA concentration of women was considerably higher than that of men [462 +/- 187 (mean +/- SD) vs. 336 +/- 103; P less than 0.025], while the concentrations of DHAS showed no significant sex difference ((77 +/- 38 vs. 101 +/- 67; P greater than 0.1). In persons 50 yr of age or over, plasma DHA concentrations were about the same in women and men (238 +/- 119 vs. 287 +/- 121; P greater than 0.1), but plasma DHAS concentrations were very much lower in women (31 +/- 21 vs. 83 +/- 49; P less than 0.0001).
THE PATHOPHYSIOLOGY OF ACUTE OPTIC NEURITIS (1991)

Eighteen patients with acute optic neuritis underwent optic nerve magnetic resonance imaging (MRI) before and after injection of gadolinium-diethylene triamine pentacetic acid (Gd-DTPA). Ten were re-examined 4 weeks later. Leakage of Gd-DTPA across the blood-optic nerve barrier was a consistent finding in the acute lesion, and its presence was associated with abnormal visual acuity and colour vision, retro-ocular pain on eye movement, and afferent pupillary defect, and a reduced amplitude of the P100 component of the visual evoked potential. Gd-DTPA leakage had ceased in 9/11 nerves when restudied 4 wks later, and this evolution was associated with improved visual acuity and an increased P100 amplitude. Leakage is likely to reflect inflammation, and we conclude that the latter plays an important part in the production of conduction block and clinical deficit, and that its resolution is an important step in clinical remission from acute episodes of demyelination.
Chemical Kinetics of Methane Pyrolysis in Microwave Plasma at Atmospheric Pressure (2013)

Results of chemical kinetics modeling in methane subjected to the microwave plasma at atmospheric pressure are presented in this paper. The reaction mechanism is based on the methane oxidation model without reactions involving nitrogen and oxygen. For the numerical calculations 0D and 1D models were created. 0D model uses Calorimetric Bomb Reactor whereas 1D model is constructed either as Plug Flow Reactor or as a chain of Plug Flow Reactor and Calorimetric Bomb Reactor. Both models explain experimental results and show the most important reactions responsible for the methane conversion and production of H2, C2H2, C2H4 and C2H6 detected in the experiment. Main conclusion is that the chemical reactions in our experiment proceed by a thermal process and the products can be defined by considering thermodynamic equilibrium. Temperature characterizing the methane pyrolysis is 1,500–2,000 K, but plasma temperature is in the range of 4,000–5,700 K, which means that methane pyrolysis process is occurring outside the plasma region in the swirl gas flowing around the plasma.
Computational design gains momentum in enzyme catalysis engineering (2013)

Computational protein design is becoming a powerful tool for tailoring enzymes for specific biotechnological applications. When applied to existing enzymes, computational re-design makes it possible to obtain orders of magnitude improvement in catalytic activity towards a new target substrate. Computational methods also allow the design of completely new active sites that catalyze reactions that are not known to occur in biological systems. If initial designs display modest catalytic activity, which is often the case, this may be improved by iterative cycles of computational design or by follow-up engineering through directed evolution. Compared to established protein engineering methods such as directed evolution and structure-based mutagenesis, computational design allows for much larger jumps in sequence space; for example, by introducing more than a dozen mutations in a single step or by introducing loops that provide new functional interactions. Recent advances in the computational design toolbox, which include new backbone re-design methods and the use of molecular dynamics simulations to better predict the catalytic activity of designed variants, will further enhance the use of computational tools in enzyme engineering.
Chemical modification potentiates the biological activities of 2-5A and its congeners. (1982)

Chemical modification of p5'A2'(p5'A2')np5'A by a periodate oxidation/Schiff base formation/borohydride reduction cycle gave a series of 2-5A analogues in which the ribose of the 2'-terminal nucleotide was transformed to an N-substituted morpholine (azahexapyranose). 2',5'-Oligoriboadenylate 5'-monophosphates bearing this modification were 5-10 times more potent as antagonists of the action of 2-5A or poly(I).poly(C) than was unmodified p5'A2'p5'A2'p5'A. Application of this modification to the tetramer triphosphate ppp5'A2'p5'A2'p5'A2'p5'A resulted in an analogue with 10 times the activity of ppp5'A2'p5'A2'p5'A (2-5A trimer triphosphate) as an inhibitor of protein synthesis or activator of the 2-5A-dependent endoribonuclease. This activator of the 2-5A-dependent endoribonuclease. This new 2-5A analogue, the most potent 2-5A derivative reported to date, inhibited translation in extracts of mouse L-cells programmed with encephalomyocarditis virus RNA at a concentration of 10(-10) M (concentration for half-maximal inhibition). All such N-substituted morpholine modified 2',5'-oligoriboadenylates were found to be extremely resistant to degradation by L-cell extracts under conditions where unmodified 2-5A or its derivatives were quickly destroyed. These data demonstrate the necessity for an intact terminal ribose ring for the action of the 2-5A phosphodiesterase. Thus, extensive chemical modification of 2' terminus of 2-5A may be possible without adversely affecting its biological activity while endowing it with other favorable properties such as resistance to degradation.
Efficacy of several antibiotic combinations against Brucella melitensis Rev 1 experimental infection in BALB/c mice (2006)

Gentamicin may be used along with doxycycline when the classical combination is considered the first choice in the treatment of patients with brucellosis due to B. melitensis vaccine strain Rev 1.
Modular and Dynamic Functionalization of Polymeric Scaffolds (2006)

The design and synthesis of multifunctionalized, architecturally controlled polymers is a prerequisite for a variety of future applications of polymeric materials. On the basis of Nature's use of self-assembly in the creation of biomaterials, this Account describes concepts that were developed over the past 5 years that utilize noncovalent interactions such as hydrogen bonding, ionic interactions, electrostatic interactions, metal coordination, and pi-pi stacking in modification of copolymer side-chains to obtain multifunctional polymeric materials, induce polymer morphology changes, and influence bulk-polymer properties.
Preequalizer Design for Spatial Multiplexing SIMO-UWB TR Systems (2010)

A spatial multiplexing single-input-multiple-output (SM-SIMO) ultrawideband (UWB) communication system using the time-reversal (TR) technique is proposed in this paper. The system with only one transmit antenna, using a spatial multiplexing scheme, can transmit several independent data streams to achieve a very high data rate. To cope with the long delay spread of the UWB channel, the TR technique is adopted. TR can mitigate not only the intersymbol interference (ISI) but the multistream interference (MSI) caused by multiplexing several data streams simultaneously as well. Preequalization using the channel state information (CSI), which is already available at the transmitter in TR systems, is proposed to further eliminate the ISI and MSI. Simulation results show that the preequalization based on shortened equivalent channels can considerably improve the bit error rate (BER) performance of the system.
Peak-to-Average Power Ratio Reduction in MIMO OFDM (2007)

Peak-to-average power ratio (PAR) reduction in OFDM using antenna arrays (MIMO OFDM) is considered. In particular, generalizations of selected mapping (SLM) recently proposed in literature, are studied, and a new version, we call it <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">directed</i> <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SLM</i> ( <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">dSLM</i> ), is introduced. It is shown that, in contrast to the other schemes, dSLM utilizes the potential offered by MIMO transmission-the complementary distribution function of the PAR exhibits a steeper (increased by a factor equal to the number of transmit antennas) decay. This effect is similar to the diversity gain in error performance when using MIMO transmission. We show that dSLM is very flexible and not restricted to any modulation format or OFDM frame size. Moreover, a variant of dSLM which does not require any side information to recover data at the receiver is presented.
Clinicopathological significance of S100 protein expression in cholangiocarcinoma (2013)

These results suggest that S100P may be useful for the detection of cholangiocarcinoma as tissue and bile biomarkers, and the immunohistochemical expression of S100A2 is a potential prognostic marker in cholangiocarcinoma patients.
Towards software defined persistent memory (2015)

The emergence of persistent memories promises a sea-change in application and data center architectures, with efficiencies and performance not possible with today's volatile DRAM and persistent slow storage. We present Software Defined Persistent Memory, an approach that enables applications to use persistent memory in a variety of local and remote configurations. The heterogeneity is managed by a middleware that manages hardware specific needs and optimizations. We present the first ever design and implementation of such an architecture, and illustrate the key abstractions that are needed to hide hardware specific details from applications while exposing necessary characteristics for performance optimization. We evaluate the performance of our implementation on a set of microbenchmarks and database workloads using the MySQL database. Through our evaluation, we show that it is possible to apply Software Defined concepts to persistent memory, to improve performance while retaining functionality and optimizing for different hardware architectures.
Morphological variability of the trabecular meshwork in glaucoma patients: implications for non-perforating glaucoma surgery (2000)

From the morphological point of view the risk of inadvertent perforation during deep sclerectomy in older, white glaucoma patients should be taken into account even by an experienced surgeon, because the anterior meshwork in these cases is very thin and trabecular pigmentation that can be used as a topographic landmark is often lacking. The functional success of non-perforating glaucoma surgery in many patients may be limited by endothelial covering of the trabecular meshwork.
Pulmonary Hypoplasia in Neonatal Hypophosphatasia (1988)

Morphological, biophysical, and biochemical parameters of lung growth were studied at autopsy on a male infant with hypophosphatasia who died with asphyxia immediately after birth. The lungs were hypoplastic because of a marked decrease in airspace formation but lung maturation was normal for gestational age by all the parameters used. Diaphragmatic development, assessed by weight and fiber measurement, was in keeping with the decreased chest size. The proposed mechanism for this late onset type of pulmonary hypoplasia, attributed to decreased thoracic volume, is correlated with antenatal ultrasonographic observations of normal fetal breathing movements in the affected infant.
Gold Nanorods as Contrast Agents for Biological Imaging: Optical Properties, Surface Conjugation and Photothermal Effects† (2009)

Gold nanorods (NRs) have plasmon-resonant absorption and scattering in the near-infrared (NIR) region, making them attractive probes for in vitro and in vivo imaging. In the cellular environment, NRs can provide scattering contrast for darkfield microscopy, or emit a strong two-photon luminescence due to plasmon-enhanced two-photon absorption. NRs have also been employed in biomedical imaging modalities such as optical coherence tomography or photoacoustic tomography. Careful control over surface chemistry enhances the capacity of NRs as biological imaging agents by enabling cell-specific targeting, and by increasing their dispersion stability and circulation lifetimes. NRs can also efficiently convert optical energy into heat, and inflict localized damage to tumor cells. Laser-induced heating of NRs can disrupt cell membrane integrity and homeostasis, resulting in Ca(2+) influx and the depolymerization of the intracellular actin network. The combination of plasmon-resonant optical properties, intense local photothermal effects and robust surface chemistry render gold NRs as promising theragnostic agents.
Pharmacokinetics of morphine loaded into erythrocyte in rabbits (2006)

Aim:To study the pharmacokinetics in the rabbits of morphine hydrochloride loaded into erythrocyte(M-RBC).Methods:The hyperosmotic resealing method was employed to load morphine hydrochloride into erythrocyte(M-RBC).Latin square crossover design was used to evaluate the pharmacokinetics of M-RBC and Morphine Injection.Blood samples after administration were collected at predetermined intervals and analyzed for plasma levels by RP-HPLC.After curve-fitting performed by the computer program pkbp-n1,the obtained pharmacokinetic parameters were used to compare M-RBC and Morphine Injection.Results:AUC and t_(1/2) of morphine obtained from dosing of M-RBC were significantly greater than that from dosing of the injection but the clearance of the M-RBC was significantly less than that of the injection(P0.05).Conclusion:M-RBC might be a potential drug delivery system.
The Ret Receptor Tyrosine Kinase Pathway Functionally Interacts with the ERα Pathway in Breast Cancer (2008)

A limited number of receptor tyrosine kinases (e.g., ErbB and fibroblast growth factor receptor families) have been genetically linked to breast cancer development. Here, we investigated the contribution of the Ret receptor tyrosine kinase to breast tumor biology. Ret was expressed in primary breast tumors and cell lines. In estrogen receptor (ER)alpha-positive MCF7 and T47D lines, the ligand (glial-derived neurotrophic factor) activated signaling pathways and increased anchorage-independent proliferation in a Ret-dependent manner, showing that Ret signaling is functional in breast tumor cells. Ret expression was induced by estrogens and Ret signaling enhanced estrogen-driven proliferation, highlighting the functional interaction of Ret and ER pathways. Furthermore, Ret was detected in primary cancers, and there were higher Ret levels in ERalpha-positive tumors. In summary, we showed that Ret is a novel proliferative pathway interacting with ER signaling in vitro. Expression of Ret in primary breast tumors suggests that Ret might be a novel therapeutic target in breast cancer.
β-Sheet Side Chain Polymers Synthesized by Atom-Transfer Radical Polymerization (2004)

Silks are a widely studied class of naturally occurring structural proteins. Dragline spider silk, in particular, is considered to be nature's high-performance material due to its remarkable combination of strength and toughness. These mechanical properties stem from the protein secondary structure, a combination of well-defined beta-sheets in a less well-defined glycine-rich matrix. The translation of this structure into a synthetic polymer was the aim of this investigation. To achieve this, a peptide-based monomer containing the sequence alanine-glycine-alanine-glycine, a well-known beta-sheet-forming sequence found in silk, was synthesized. Using atom-transfer radical polymerization and a bifunctional initiator, a well-defined peptide-based polymer was prepared. This was then used as the macroinitiator for the polymerization of methyl methacrylate. The resulting well-defined triblock copolymer was analyzed using IR spectroscopy, which clearly showed beta-sheet secondary structure had been introduced.
Prognosis in Acute Organ-System Failure (1985)

This prospective study describes the current prognosis of patients in acute Organ System Failure (OSF). Objective definitions were developed for five OSFs, and then 5677 ICU admissions from 13 hospitals were monitored. The number and duration of OSF were linked to outcome at hospital discharge for each of the 2719 ICU patients (48%) who developed OSF. For all medical and most surgical admissions, a single OSF lasting more than 1 day resulted in a mortality rate approaching 40%. Among both medical and surgical patients, two OSFs for more than 1 day increased death rates to 60%. Advanced chronologic age increased both the probability of developing OSF and the probability of death once OSF occurred. Mortality for 99 patients with three or more OSFs persisting after 3 days was 98%. The two patients who survived were both young, in prior excellent health, and had severe but limited primary diseases. These results emphasize the high death rates associated with acute OSF and the rapidity with which mortality increases over time. The prognostic estimates provide reference data for physicians treating similar patients.
Regulation of Epidermal Growth Factor Receptor Signaling by Phosphorylation of the Ras Exchange Factor hSOS1 (1996)

In response to stimulation with epidermal growth factor (EGF), the guanine nucleotide exchange factor human SOS1 (hSOS1) promotes the activation of Ras by forming a complex with Grb2 and the human EGF receptor (hEGFR). hSOS1 was phosphorylated in cells stimulated with EGF or phorbol 12-myristate 13-acetate or following co-transfection with activated Ras or Raf. Co-transfection with dominant negative Ras resulted in a decrease of EGF-induced hSOS1 phosphorylation. The mitogen-activated protein kinase (MAPK) phosphorylated hSOS1 in vitro within the carboxyl-terminal proline-rich domain. The same region of hSOS1 was phosphorylated in vivo, in cells stimulated with EGF. Tryptic phosphopeptide mapping showed that MAPK phosphorylated hSOS1 in vitro on sites which were also phosphorylated in vivo. Phosphorylation by MAPK did not affect hSOS1 binding to Grb2 in vitro. However, reconstitution of the hSOS1-Grb2-hEGFR complex showed that phosphorylation by MAPK markedly reduced the ability of hSOS1 to associate with the hEGFR through Grb2. Similarly, phosphorylated hSOS1 was unable to form a complex with Shc through Grb2. Thus phosphorylation of hSOS1, by affecting its interaction with the hEGFR or Shc, down-regulates signal transduction from the hEGFR to the Ras pathway.
Do Cryopreserved Mesenchymal Stromal Cells Display Impaired Immunomodulatory and Therapeutic Properties? (2014)

We have recently reported that therapeutic mesenchymal stromal cells (MSCs) have low engraftment and trigger the instant blood mediated inflammatory reaction (IBMIR) after systemic delivery to patients, resulting in compromised cell function. In order to optimize the product, we compared the immunomodulatory, blood regulatory, and therapeutic properties of freeze-thawed and freshly harvested cells. We found that freeze-thawed MSCs, as opposed to cells harvested from continuous cultures, have impaired immunomodulatory and blood regulatory properties. Freeze-thawed MSCs demonstrated reduced responsiveness to proinflammatory stimuli, an impaired production of anti-inflammatory mediators, increased triggering of the IBMIR, and a strong activation of the complement cascade compared to fresh cells. This resulted in twice the efficiency in lysis of thawed MSCs after 1 hour of serum exposure. We found a 50% and 80% reduction in viable cells with freshly detached as opposed to thawed in vitro cells, indicating a small benefit for fresh cells. In evaluation of clinical response, we report a trend that fresh cells, and cells of low passage, demonstrate improved clinical outcome. Patients treated with freshly harvested cells in low passage had a 100% response rate, twice the response rate of 50% observed in a comparable group of patients treated with freeze-thawed cells at higher passage. We conclude that cryobanked MSCs have reduced immunomodulatory and blood regulatory properties directly after thawing, resulting in faster complement-mediated elimination after blood exposure. These changes seem to be paired by differences in therapeutic efficacy in treatment of immune ailments after hematopoietic stem cell transplantation.
DNA Methyltransferase Inhibitors and the Development of Epigenetic Cancer Therapies (2005)

Epimutations, such as the hypermethylation and epigenetic silencing of tumor suppressor genes, play a role in the etiology of human cancers. In contrast to DNA mutations, which are passively inherited through DNA replication, epimutations must be actively maintained because they are reversible. In fact, the reversibility of epimutations by small-molecule inhibitors provides the foundation for the use of such inhibitors in novel cancer therapy strategies. Among the compounds that inhibit epigenetic processes, the most extensively studied are DNA methyltransferase inhibitors. In this review, we examine the literature on DNA methyltransferase inhibitors and discuss the efficacy of such compounds as antitumor agents, as evaluated in phase I-III clinical trials. We also discuss future areas of research, including the development of nonnucleoside inhibitors, the application of novel bioanalytical tools for DNA methylation analysis (which will be important for the clinical application of these compounds by allowing rational approaches to trial design), the need to optimize treatment schedules for maximal biologic effectiveness, and the need to define molecular endpoints so that changes induced by demethylating drugs in patients can be monitored during treatment. Assays for genome-wide and tumor-specific DNA methylation also need to be further developed to establish the pharmacodynamic parameters of DNA methyltransferase inhibitors in patients and to provide rational approaches to maximizing the therapeutic efficacy of these compounds.