gebhart/patrepeval huggingface dataset:
Levodopa pharmacokinetic mechanisms and motor fluctuations in Parkinson's disease (1987)

The contribution of the peripheral and central pharmacokinetic mechanisms of levodopa to the pathogenesis of the motor fluctuations that complicate its long-term administration was studied in 28 parkinsonian patients. The rate of levodopa clearance from the general circulation, its plasma half-life, and apparent volume of distribution were indistinguishable between patients with the on-off or the wearing-off phenomenon and those with a stable response to levodopa or those who had not been previously treated with levodopa. Peripheral pharmacokinetic factors are thus unlikely to account for the development of these response fluctuations. Conversely, the efficacy half-time of levodopa differed markedly among the four response groups studied and may provide a quantitative index of central mechanisms that favor the development of the wearing-off and on-off phenomena. Although symptom duration was the best predictor of the severity of untreated parkinsonism, levodopa dose correlated best with response half-time. The wearing-off phenomenon may primarily reflect the loss of buffering capacity caused by degeneration of the dopamine neurons, while the development of the on-off phenomenon appears to require additional postsynaptic changes, possibly at the receptor level.
Partial transmit sequences for PAPR reduction of OFDM signals with stochastic optimization techniques (2010)

This paper considers the use of the partial transmit sequence (PTS) technique in reducing the peak-to-average power ratio (PAPR) of an orthogonal frequency division multiplexing (OFDM) signal. The conventional PTS technique is highly successful in PAPR reduction for OFDM signals, but the considerable computational complexity for the required search through a high-dimensional vector space is a potential problem for practical implementation. To reduce the search complexity while still improving the PAPR statistics, stochastic optimization techniques such as the simulated annealing (SA) algorithm, Cross-Entropy (CE) method, and particle swarm optimization (PSO) have recently been proposed to search for a phase factor that reduces both the PAPR statistics and the computational load. In this paper, a novel stochastic optimization approach, that is, the electromagnetism-like (EM) algorithm, is applied to reduce the PAPR of an OFDM signal. The computer simulation results show that compared with the various stochastic search techniques developed previously, the proposed EM method obtains the most desirable PAPR reduction with low computational complexity.
Molecular mechanisms triggered by low-calcium diets (2009)

Ca is not only essential for bone mineralisation, but also for regulation of extracellular and intracellular processes. When the Ca2+ intake is low, the efficiency of intestinal Ca2+ absorption and renal Ca2+ reabsorption is increased. This adaptive mechanism involves calcitriol enhancement via parathyroid hormone stimulation. Bone is also highly affected. Low Ca2+ intake is considered a risk factor for osteoporosis. Patients with renal lithiasis may be at higher risk of recurrence of stone formation when they have low Ca2+ intake. The role of dietary Ca2+ on the regulation of lipid metabolism and lipogenic genes in adipocytes might explain an inverse relationship between dairy intake and BMI. Dietary Ca2+ restriction produces impairment of the adipocyte apoptosis and dysregulation of glucocorticosteroid metabolism in the adipose tissue. An inverse relationship between hypertension and a low-Ca2+ diet has been described. Ca2+ facilitates weight loss and stimulates insulin sensitivity, which contributes to the decrease in the blood pressure. There is also evidence that dietary Ca2+ is associated with colorectal cancer. Dietary Ca2+ could alter the ratio of faecal bile acids, reducing the cytotoxicity of faecal water, or it could activate Ca2+-sensing receptors, triggering intracellular signalling pathways. Also it could bind luminal antigens, transporting them into mucosal mononuclear cells as a mechanism of immunosurveillance and promotion of tolerance. Data relative to nutritional Ca2+ and incidences of other human cancers are controversial. Health professionals should be aware of these nutritional complications and reinforce the dairy intakes to ensure the recommended Ca2+ requirements and prevent diseases.
Taxol-dependent mutants of Chinese hamster ovary cells with alterations in alpha- and beta-tubulin. (1986)

Chinese hamster ovary cell mutants resistant to the microtubule stabilizing drug taxol were isolated in a single step. Of these 139 drug-resistant mutants, 59 exhibit an absolute requirement for taxol for normal growth and division, 13 have a partial requirement, and 69 grow normally without the drug. Two-dimensional gel analysis of whole cell proteins reveal "extra" spots representing altered tubulins in 13 of the mutants. Six of these have an altered alpha-tubulin and seven have an altered beta-tubulin. Cells with an absolute dependence on taxol become large and multinucleated when deprived of the drug. In contrast, partially dependent cells exhibit some multinucleation, but most cells appear normal. In one mutant that has an absolute dependence on taxol, the cells appear to die more quickly and their nuclei do not increase in size or number. As previously found for another taxol-dependent mutant (Cabral, F., 1983, J. Cell. Biol., 97:22-29), the taxol dependence of the mutants described in this paper behaves recessively in somatic cell hybrids, and the cells are more susceptible to being killed by colcemid than are the wild-type parental cells. When compared with wild-type cells, taxol-dependent mutants have normal arrays of cytoplasmic microtubules but form much smaller mitotic spindles in the presence of taxol. When deprived of the drug, however, these mutants cannot complete assembly of the mitotic spindle apparatus, as judged by tubulin immunofluorescence. Thus, the defects leading to taxol dependence in these mutants with defined alterations in alpha- and beta-tubulin appear to result from the cell's inability to form a functional mitotic spindle. Reversion analysis indicates that the properties of at least one alpha-tubulin mutant are conferred by the altered tubulin seen on two-dimensional gels.
Development and characterization of a simple perfused oral microcosm (2005)

This study demonstrates the utility of the MSD for studying the micro-ecology of the oral cavity.
Clinical evaluation of tumor targeting with the anticarcinoembryonic antigen murine monoclonal antibody fragment, MN-14 F(ab)2 (1996)

MN-14 F(ab)2 exhibits a similar targeting sensitivity and tumor dose as reported previously for the IgG form. The lower red marrow doses combined with lower immunogenicity expected for this agent, may make it a suitable alternative for future imaging and therapeutic applications.
Low-temperature growth of silicon dioxide films: A study of chemical bonding by ellipsometry and infrared spectroscopy (1987)

This paper presents a spectroscopic study using the techniques of ellipsometry and infrared (IR) absorption spectroscopy of the chemical bonding in silicon dioxide (SiO2) films grown in dry oxygen ambients at temperatures between 550 and 1000 °C. We find that the index of refraction at 632.8 nm increases and the frequency of the dominant IR active bond-stretching vibration at about 1075 cm−1 decreases as the growth temperature is decreased below 1000 °C. Comparing the properties of these films with suboxides (SiOx, x&amp;lt;2) grown by plasma-enhanced chemical vapor deposition, and compacted bulk silica has lead us to conclude: (i) that films grown at temperatures at or below 1000 °C are homogeneous stoichiometric oxides (SiO2); and (ii) that the systematic and correlated variations in the index of refraction and the IR frequency result from increases in the film density with decreasing growth temperature. We present a microscopic model that accounts for (i) the increases in the density and the index of refraction; and (ii) the accompanying decrease in the IR stretching frequency in terms of a decrease in the Si–O–Si bond angle.
Polydepsipeptides. 5. Experimental Conformational Analysis of Poly(L-alanyl-L-lactic acid) and Related Model Compounds (1976)

In this paper we report an experimental conformational analysis of the depsipeptide model compounds acetyl-L-alanine methyl ester, acetyl-L-lactic acid N-methylamide, and acetyl-L-alanyl-L-lactic acid N-methylamide and of the sequential polydepsipeptide poly(L-alanyl-L-lactic acid). The model depsipeptides were examined in dilute organic solutions by infrared and nuclear magnetic resonance spectroscopy. Neither acetyl-L-alanine methyl ester nor acetyl-L-lactic acid N-methylamide assumes an intramolecularly hydrogen-bonded conformation. Acetyl-L-alanyl-L-lactic acid N-methylamide, on the other hand, in dilute chloroform or dilute carbon tetrachloride solutions, strongly favors a conformation with an intramolecular hydrogen bond between the N-H hydrogen atom of its N-methylamide group and the carbonyl oxygen atom of its acetyl group. Comparison of theoretical and experimental circular dichroism suggests that poly(L-alanyl-L-lactic acid) is partially ordered in chloroform solution with approximately 50% of its repeat units in the R10 helix, an ordered conformation found by our previous theoretical analysis to have a low intramolecular conformational energy.
A Single Intramuscular Injection of Recombinant Plasmid DNA Induces Protective Immunity and Prevents Japanese Encephalitis in Mice (2000)

Plasmid vectors containing Japanese encephalitis virus (JEV) premembrane (prM) and envelope (E) genes were constructed that expressed prM and E proteins under the control of a cytomegalovirus immediate-early gene promoter. COS-1 cells transformed with this plasmid vector (JE-4B clone) secreted JEV-specific extracellular particles (EPs) into the culture media. Groups of outbred ICR mice were given one or two doses of recombinant plasmid DNA or two doses of the commercial vaccine JEVAX. All mice that received one or two doses of DNA vaccine maintained JEV-specific antibodies 18 months after initial immunization. JEVAX induced 100% seroconversion in 3-week-old mice; however, none of the 3-day-old mice had enzyme-linked immunosorbent assay titers higher than 1:400. Female mice immunized with this DNA vaccine developed plaque reduction neutralization antibody titers of between 1:20 and 1:160 and provided 45 to 100% passive protection to their progeny following intraperitoneal challenge with 5,000 PFU of virulent JEV strain SA14. Seven-week-old adult mice that had received a single dose of JEV DNA vaccine when 3 days of age were completely protected from a 50, 000-PFU JEV intraperitoneal challenge. These results demonstrate that a recombinant plasmid DNA which produced JEV EPs in vitro is an effective vaccine.
Discovering regulatory elements in non-coding sequences by analysis of spaced dyads (2000)

The application of microarray and related technologies is currently generating a systematic catalog of the transcriptional response of any single gene to a multiplicity of experimental conditions. Clustering genes according to the similarity of their transcriptional response provides a direct hint to the regulons of the different transcription factors, many of which have still not been characterized. We have developed a new method for deciphering the mechanism underlying the common transcriptional response of a set of genes, i.e. discovering cis -acting regulatory elements from a set of unaligned upstream sequences. This method, called dyad analysis, is based on the observation that many regulatory sites consist of a pair of highly conserved trinucleotides, spaced by a non-conserved region of fixed width. The approach is to count the number of occurrences of each possible spaced pair of trinucleotides, and to assess its statistical significance. The method is highly efficient in the detection of sites bound by C(6)Zn(2)binuclear cluster proteins, as well as other transcription factors. In addition, we show that the dyad and single-word analyses are efficient for the detection of regulatory patterns in gene clusters from DNA chip experiments. In combination, these programs should provide a fast and efficient way to discover new regulatory sites for as yet unknown transcription factors.
Team terramax and the DARPA grand challenge: a general overview (2004)

The Defense Advanced Research Projects Agency (DARPA), is an agency of the United States Government, has issued a challenge to developers of off-road autonomous ground vehicles to design and build a vehicle that can complete a lengthy and difficult off road course across desert southwest areas of the United States. A one million dollar US prize is available to the team that completes the 200-250 mile course first and in less than 10 hours. This paper describes the Team TerraMax entry to the March, 2004 race event. Vehicle hardware and drive by wire actuators, internal and external sensing systems, sensor fusion, and high and low level control systems are described.
Converting Peptides into Drug Leads by Lipidation (2012)

Lipidation is a posttranslational modification of proteins that has also found its use in designing peptide drugs. The presence of a lipid group in peptides modulates their hydrophobicity, secondary structures and self-assembling propensities while retaining their abilities to bind to target receptors. Lipidation improves peptides' metabolic stability, membrane permeability, bioavailability, and changes peptides' pharmacokinetic and pharmacodynamic properties. Herein, we review the applications of various lipidation strategies in peptide drug design, the effects of the chain length and anchor position of fatty acids in peptide lipidation, the physicochemical and biological properties of selected lipidated peptides and the synthesis strategies for peptide lipidation.
Vision‐aided inertial navigation for pin‐point landing using observations of mapped landmarks (2007)

Abstract In this paper we describe an extended Kalman filter algorithm for estimating the pose and velocity of a spacecraft during entry, descent, and landing. The proposed estimator combines measurements of rotational velocity and acceleration from an inertial measurement unit (IMU) with observations of a priori mapped landmarks, such as craters or other visual features, that exist on the surface of a planet. The tight coupling of inertial sensory information with visual cues results in accurate, robust state estimates available at a high bandwidth. The dimensions of the landing uncertainty ellipses achieved by the proposed algorithm are three orders of magnitude smaller than those possible when relying exclusively on IMU integration. Extensive experimental and simulation results are presented, which demonstrate the applicability of the algorithm on real‐world data and analyze the dependence of its accuracy on several system design parameters. © 2007 Wiley Periodicals, Inc.
Sensing increased image resolution using aperture masks (2008)

We present a technique to construct increased-resolution images from multiple photos taken without moving the camera or the sensor. Like other super-resolution techniques, we capture and merge multiple images, but instead of moving the camera sensor by sub-pixel distances for each image, we change masks in the lens aperture and slightly defocus the lens. The resulting capture system is simpler, and tolerates modest mask registration errors well. We present a theoretical analysis of the camera and image merging method, show both simulated results and actual results from a crudely modified consumer camera, and compare its results to robust ‘blind’ methods that rely on uncontrolled camera displacements.
Nonsteroidal Selective Androgen Receptor Modulator Ostarine ™ in Cancer Cachexia (2009)

Cancer cachexia is a complex syndrome, affecting up to 60% of the approximately 1.4 million patients diagnosed with cancer each year in the USA. This condition is characterized by progressive deterioration of a patient's nutritional status, weight loss, anorexia, diminished quality of life and increased mortality and morbidity. Current therapy with progestational, anti-inflammatory and anabolic agents is often ineffective and has a large number of undesirable effects. The newly developed nonsteroidal selective androgen receptor modulator Ostarine has demonstrated promising results in Phase I and II clinical trials, increasing total lean body mass, enhancing functional performance and decreasing total tissue percent fat. This selective androgen receptor modulator may have the ability to perform as a potent anabolic agent with minimal side effects on other organs (prostate and hair follicles), thus presenting a new strategy in managing cancer cachexia. However, more extensive data is required before its efficacy is confirmed.
PNA-RELATED OLIGONUCLEOTIDE MIMICS AND THEIR EVALUATION FOR NUCLEIC ACID HYBRIDIZATION STUDIES AND ANALYSIS (2001)

DNA mimics containing phosphonate analogues of PNAs (pPNAs), particularly PNA-pPNA hybrids as well as hetero-oligomers consisted of pPNA units and PNA-like molecules on the base of trans-4-hydroxy-L-proline (HypNA) have been synthesized. The evaluation of their effectiveness in assays based on the hybridization technique in the comparison with natural oligonucleotides and classical PNAs has shown a high potential of these mimics as sensor molecules for nucleic acid based diagnostics and as molecular probes for mRNA isolation.
Stability of converging shock waves (1979)

A computer program that determines the position of converging shocks and monitors the decay of radial perturbations of the shock fronts, described by their amplitude Δr and their center angle γ has been developed. With this program a region of stability for spherical and cylindrical shocks of different Mach numbers has been found, where perturbations will disappear before the wave has collapsed. The model was tested by comparison with an experiment and an analytically approximate model.
Synthesis of quinazoline analogs of folic acid modified at position 10 (1977)

&lt;p&gt;E-cadherin is a cell-cell adhesion protein that plays a prominent role in cancer invasion. Inactivation of E-cadherin in breast cancer can arise from gene promoter hypermethylation or genetic mutation. Depending on their E-cadherin status, breast cancer cells adopt different morphologies with distinct invasion modes. The tumor microenvironment (TME) can also affect the cell morphology and invasion mode. In this paper, we used a previously developed microfluidic system to quantify the three-dimensional invasion of breast cancer cells with different E-cadherin status, namely MCF-7, CAMA-1 and MDA-MB-231 with wild type, mutated and promoter hypermethylated E-cadherin, respectively. The cells migrated into a stable and reproducible microfibrous polycaprolactone mesh in the chip under a programmed stable chemotactic gradient. We observed that the MDA-MB-231 cells invaded the most, as single cells. MCF-7 cells collectively invaded into the matrix more than CAMA-1 cells, maintaining their E-cadherin expression. The CAMA-1 cells exhibited multicellular multifocal infiltration into the matrix. These results are consistent with what is seen in vivo in the cancer biology literature. In addition, comparison between complete serum and serum gradient conditions showed that the MDA-MB-231 cells invaded more under the serum gradient after one day, however this behavior was inverted after 3 days. The results showcase that the microfluidic system can be used to quantitatively assess the invasion behavior of cancer cells with different E-cadherin expression, for a longer period than conventional invasion models. In the future, it can be used to quantitatively investigate effects of matrix structure and cell treatments on cancer invasion.&lt;/p&gt;
Induction of an Antibody That Catalyzes the Hydrolysis of an Amide Bond (1988)

Catalysis of amide bond hydrolysis is of singular importance in enzymology. An antibody was induced to an analog of a high-energy intermediate anticipated along the reaction coordinate of amide hydrolysis. This antibody is an amidase with high specificity and a large rate enhancement (250,000) relative to the uncatalyzed reaction. This reaction represents the kinetically most difficult hydrolysis reaction yet catalyzed by an antibody.
Development of an in vivo method to identify mutants of phage T4 lysozyme of enhanced thermostability (1993)

An M13 bacteriophage-based in vivo screening system has been developed to identify T4 lysozyme mutants of enhanced thermal stability. This system takes advantage of easy mutagenesis in an M13 host, the production of functional T4 lysozyme during M13 growth, and the ability to detect lysozyme activity on agar plates. Of several mutagenesis procedures that were tested, the most efficient was based on misincorporation by avian myeloma virus reverse transcriptase. This one-step mutagenesis and screening system has been used to find 18 random single-site mutant lysozymes, of which 11 were heat resistant. Each of these had a melting temperature within 0.8-1.4 degrees C of wild type, suggesting that the screening system is quite sensitive.
Comprehensive pharmacokinetics of a humanized antibody and analysis of residual anti-idiotypic responses. (1995)

A murine antibody to human tumour necrosis factor-alpha (TNF-alpha) (CB0010) was complementarity-determining region (CDR)-grafted using human IgG4 heavy and kappa light chain constant regions. In cynomolgus monkeys, the grafted antibody (CDP571) was eliminated with a half-life of 40-90 hr, two to three times longer than CB0010, and immunogenicity was reduced by > 90%. Responses to the constant regions were almost entirely eliminated and responses to the CDR loop (anti-idiotype) were lowered. CDP571 was given to 24 human volunteers in doses from 0.1 to 10.0 mg/kg. It was well tolerated, with a half-life of approximately 13 days. Anti-CDP571 antibodies were low or undetectable at higher doses. At lower doses, anti-CDP571 peaked at 2 weeks and then declined. The response was primarily IgM (in contrast to the cynomolgus monkey, where by 5 weeks IgG predominated) and was against a conformational epitope comprising heavy and light chain CDR loops. No antibodies were detected against the gamma 4/kappa domains or frameworks. The response had little or no effect on CDP571 binding to TNF-alpha or on plasma clearance.
AVP ‐825 Breath‐Powered Intranasal Delivery System Containing 22 mg Sumatriptan Powder vs 100 mg Oral Sumatriptan in the Acute Treatment of Migraines (The COMPASS Study): A Comparative Randomized Clinical Trial Across Multiple Attacks (2015)

AVP-825 (containing 22 mg sumatriptan nasal powder) provided statistically significantly greater reduction of migraine pain intensity over the first 30 minutes following treatment, and greater rates of pain relief and pain freedom within 15 minutes, compared with 100 mg oral sumatriptan. Sustained pain relief and pain freedom through 24 and 48 hours was achieved in a similar percentage of attacks for both treatments, despite substantially lower total systemic drug exposure with AVP-825. Treatment was well tolerated, with statistically significantly fewer atypical sensations with AVP-825.