gebhart/patrepeval huggingface dataset:
Nitric oxide inhibits the transcription of E6 gene of human papillomavirus (2018)

High-risk human papillomavirus (HPV) is an important pathogenic factor for cervical cancer and understanding the mechanism of HPV gene transcription is important for the prevention and therapy of HPV related cervical cancer. This study aimed to investigate the role of nitric oxide (NO) in the regulation of HPV gene transcription. SiHa cells containing integrated HPV16 were treated with NO donor DETA-NO and cell proliferation and cytotoxicity were determined. HPV gene transcription was detected by real-time PCR. We found no significant cytotoxic effects on SiHa cells when the concentration of DETA-NO was less than 0.5 mmol/l. The transcription of HPV E6 gene was inhibited by DETA-NO in a dose-dependent manner and the best inhibitory effect was observed at 0.5 mmol/l DETA-NO. In addition, ERK inhibitor U0126 decreased the transcription of HPV E6 gene at the concentration of 30 μmol/l. In conclusion, NO inhibits the transcription of HPV E6 gene and probably involves MAPK signaling pathway. Keywords: SiHa cells; nitric oxide; MAPK pathway; HPV transcription.
Ultrasound Microbubble Contrast Agents: Fundamentals and Application to Gene and Drug Delivery (2006)

This review offers a critical analysis of the state of the art of medical microbubbles and their application in therapeutic delivery and monitoring. When driven by an ultrasonic pulse, these small gas bubbles oscillate with a wall velocity on the order of tens to hundreds of meters per second and can be deflected to a vessel wall or fragmented into particles on the order of nanometers. While single-session molecular imaging of multiple targets is difficult with affinity-based strategies employed in some other imaging modalities, microbubble fragmentation facilitates such studies. Similarly, a focused ultrasound beam can be used to disrupt delivery vehicles and blood vessel walls, offering the opportunity to locally deliver a drug or gene. Clinical translation of these vehicles will require that current challenges be overcome, where these challenges include rapid clearance and low payload. The technology, early successes with drug and gene delivery, and potential clinical applications are reviewed.
Phase I Clinical and Pharmacokinetic Study of Flavopiridol Administered as a Daily 1-Hour Infusion in Patients With Advanced Neoplasms (2002)

The recommended phase II doses of flavopiridol as a 1-hour infusion are 37.5 mg/m(2)/d for 5 days, 50 mg/m(2)/d for 3 days, and 62.5 mg/m(2)/d for 1 day. Flavopiridol as a daily 1-hour infusion can be safely administered and can achieve concentrations in the micromolar range, sufficient to inhibit cyclin-dependent kinases in preclinical models. Further studies to determine the optimal schedule of flavopiridol as a single agent and in combination with chemotherapeutic agents are underway.
Polarity and Patterning in the Neural Tube: The Origin and Function of the Floor Plate (2007)

Little is known about the cellular and molecular mechanisms that determine neuronal cell fate and the patterning of neuronal connections in the vertebrate central nervous system. In this paper we summarize evidence which indicates that some aspects of neuronal differentiation and axon guidance are regulated by specialized epithelial cells that occupy the medial region of the neural plate and, later, the ventral midline of the spinal cord. This cell group, termed the notoplate/floor plate appears to constitute a distinct compartment within the neural plate that is more closely related in lineage and perhaps also in function to axial mesodermal cells of the underlying notochord than to other neural plate cells. Cells of the notoplate exhibit specialized mechanical and adhesive properties that may contribute to neurulation. At later stages of development, the floor plate appears to guide developing axons in the embryonic spinal cord by releasing a diffusible chemoattractant factor and by virtue of its specialized cell surface properties. The floor plate may also play a role in the determination of cell identity and patterning at earlier stages of neural tube development.
Antiparallel DNA Double Crossover Molecules As Components for Nanoconstruction (1996)

Double crossover molecules are DNA structures containing two Holliday junctions connected by two double helical arms. There are several types of double crossover molecules, differentiated by the relative orientations of their helix axes, parallel or antiparallel, and by the number of double helical half-turns (even or odd) between the two crossovers. We have examined these molecules from the viewpoint of their potential utility in nanoconstruction. Whereas the parallel double helical molecules are usually not well behaved, we have focused on the antiparallel molecules; antiparallel molecules with an even number of half turns between crossovers (termed DAE molecules) produce a reporter strand when ligated, so these have been characterized in a ligation cyclization assay. In contrast to other molecules that contain branched junctions, we find that these molecules cyclize rarely or not at all. The double crossover molecules cyclize no more readily than the linear molecule containing the same sequence as the ligation domain. We have tested both a conventional DAE molecule and one containing a bulged three-arm branched junction between the crossovers. The conventional DAE molecule appears to be slightly stiffer, but so few cyclic products are obtained in either case that quantitative comparisons are not possible. Thus, it appears that these molecules may be able to serve as the rigid components that are needed to assemble symmetric molecular structures, such as periodic lattices. We suggest that they be combined with DNA triangles and deltahedra in order to accomplish this goal.
Biphasic materials for bone grafting and hyperthermia treatment of cancer (2003)

Three biphasic materials have been synthesized from a magnetic glass-ceramic (Si-Ca-Fe) and a bioactive sol-gel glass (Si-P-Ca). The ratios of glass-ceramic:sol-gel glass used in this work were 1:1, 2:1, and 5:1. These materials show bioactive and magnetic properties and can be used as thermoseeds for hyperthermia treatment of bone tumors. The sol-gel glass content affects the textural properties of the glass-ceramic, giving rise to porosity, which plays a fundamental role in the formation of an apatite-like layer on the surface. On the other hand, as the sol-gel glass content increases, the magnetic properties change due to the diffusion of Fe ions to the glassy phases of the biphasic materials. The biphasic nature of these materials allows the changing of both properties, depending on the requirements of the patient.
Dry Powder Inhaler Formulation (2005)

A drug product combines pharmacologic activity with pharmaceutical properties. Desirable performance characteristics are physical and chemical stability, ease of processing, accurate and reproducible delivery to the target organ, and availability at the site of action. For the dry powder inhaler (DPI), these goals can be met with a suitable powder formulation, an efficient metering system, and a carefully selected device. This review focuses on the DPI formulation and development process. Most DPI formulations consist of micronized drug blended with larger carrier particles, which enhance flow, reduce aggregation, and aid in dispersion. A combination of intrinsic physicochemical properties, particle size, shape, surface area, and morphology affects the forces of interaction and aerodynamic properties, which in turn determine fluidization, dispersion, delivery to the lungs, and deposition in the peripheral airways. When a DPI is actuated, the formulation is fluidized and enters the patient's airways. Under the influence of inspiratory airflow, the drug particles separate from the carrier particles and are carried deep into the lungs, while the larger carrier particles impact on the oropharyngeal surfaces and are cleared. If the cohesive forces acting on the powder are too strong, the shear of the airflow may not be sufficient to separate the drug from the carrier particles, which results in low deposition efficiency. Advances in understanding of aerosol and solid state physics and interfacial chemistry are moving formulation development from an empirical activity to a fundamental scientific foundation.
Sexually Transmitted Diseases (1998)

Dr. Holmes is Director, Center for AIDS and STD, University of Washington, Seattle, and Section Head, Division of Allergy and Infectious Diseases, Harborview Medical Center, Seattle.
Regions of the Molecule Responsible for Substrate Specificity of Monoamine Oxidase A and B: A Chimeric Enzyme Analysis (1995)

To examine regions of the monoamine oxidase (MAO, EC 1.4.3.4) molecule responsible for substrate recognition, a series of these enzymes, in which discrete regions in one molecule were substituted by corresponding sequences of the other, were constructed from the cDNAs of rat liver MAO A and MAO B and were expressed in yeast, Saccharomyces cerevisiae. Substrate specificities of the original and chimeric enzymes were examined in terms of the maximum activity (Vmax) and the affinity (Km) for serotonin, beta-phenylethylamine (PEA), and benzylamine. Chimeric enzymes with the amino-terminal portion (about 220 residues) and the amino-terminal and middle portions (about 400 residues) of MAO A and MAO B, respectively, exhibited substantially the same Km values as those of the parent enzymes. Extension of the substitution in the middle portion of a chimeric enzyme to the second half of the amino-terminal portion resulted in conversion of the Km values for serotonin to those of the counterpart. Data on relative Vmax values of the chimeric enzymes for the three substrates revealed that the relative catalytic activities were mainly determined by the presence of the middle portion. We conclude from these observations that the region between about residues 120-220 and about residues 50-400 is responsible for determination of the substrate specificity of MAO A and MAO B, respectively, while the middle portion, of about residues 220-400, may relate to the relative catalytic activity towards substrates.
Hyperhidrosis Treated by Botulinum A Exotoxin (1998)

Intracutaneous injections of botulinum toxin offer a simple, safe, and effective alternative to other conservative and surgical options.
High-Dimensional Probability Estimation with Deep Density Models (2013)

One of the fundamental problems in machine learning is the estimation of a probability distribution from data. Many techniques have been proposed to study the structure of data, most often building around the assumption that observations lie on a lower-dimensional manifold of high probability. It has been more difficult, however, to exploit this insight to build explicit, tractable density models for high-dimensional data. In this paper, we introduce the deep density model (DDM), a new approach to density estimation. We exploit insights from deep learning to construct a bijective map to a representation space, under which the transformation of the distribution of the data is approximately factorized and has identical and known marginal densities. The simplicity of the latent distribution under the model allows us to feasibly explore it, and the invertibility of the map to characterize contraction of measure across it. This enables us to compute normalized densities for out-of-sample data. This combination of tractability and flexibility allows us to tackle a variety of probabilistic tasks on high-dimensional datasets, including: rapid computation of normalized densities at test-time without evaluating a partition function; generation of samples without MCMC; and characterization of the joint entropy of the data.
정보 ; 제21회 학술대회 강연 요지 ; 일반연제 ; 생약 제제의 처방에 따른 성분 추출량에 관한 연구 (IV) . 숙지황 및 그 함유제제의 분석법에 관한 연구 (1991)

종전까지 숙지황의 품질관리를 위한 지표물질로서 catalpol, D-mannitol, rehmannioside A-D등이 사용되어 왔는데 이는 건지황과 생지황에도 존재하는 물질이며 산지 또는 계절 별도 함량의 차이가 있기 때문에 지표물질로 삼는데는 문제점이 많았다.
숙지황 중의 5-HMF는 숙지황의 조제 과정에서 생기는 물질로 건지황과 생지황에는 거의 존재하지 않고 정량성이 있으므로 복합 생약제제에 적용하여 H.P.L.C로 시험했다. H.P.L.C의 조건은 다음과 같다.
Colume : μ Bondapak＾(TM) C_(18) 3.9㎜, id 30㎝ long; Mobile phase : 5% CH₃CN in H₂O; Detector: UV 280 ㎚; Injection volume : 20㎕; Sensitivity : 1.0 AuFS.
Modeling and simulation of polycrystalline ZnO thin-film transistors (2010)

Thin-film transistors (TFTs) made of transparent channel semiconductors such as ZnO are of great technological importance because their insensitivity to visible light makes device structures simple. In fact, there have been several demonstrations of ZnO TFTs achieving reasonably good field effect mobilities of 1-10 cm2/V s, but the overall performance of ZnO TFTs has not been satisfactory, probably due to the presence of dense grain boundaries. We modeled grain boundaries in ZnO TFTs and performed simulation of a ZnO TFT by using a two-dimensional device simulator in order to determine the grain boundary effects on device performance. Polycrystalline ZnO TFT modeling was started by considering a single grain boundary in the middle of the TFT channel, formulated with a Gaussian defect distribution localized in the grain boundary. A double Schottky barrier was formed in the grain boundary, and its barrier height was analyzed as a function of defect density and gate bias. The simulation was extended to TFTs with many grain boundaries to quantitatively analyze the potential profiles that developed along the channel. One of the main differences between a polycrystalline ZnO TFT and a polycrystalline Si TFT is that the much smaller nanoscaled grains in a polycrystalline ZnO TFT induces a strong overlap of the double Schottky barriers with a higher activation energy in the crystallite and a lower barrier potential in the grain boundary at subthreshold or off-state region of its transfer characteristics. Through the simulation, we were able to estimate the density of total trap states localized in the grain boundaries for polycrystalline ZnO TFT by determining the apparent mobility and grain size in the device.
In situ detection of single micron-sized magnetic beads using magnetic tunnel junction sensors (2005)

We have demonstrated the use of highly sensitive magnetic tunnel junction (MTJ) sensors for the detection of individual micron-sized magnetic labels. By integrating the MTJ sensor into a microfluidic channel, we were able to detect the presence of moving superparamagnetic beads (Dynabeads® M-280) in real time by direct measurement of the magnetic dipole fields associated with single beads. The dipolar fields of a single bead were sufficient to obtain a signal of 80μV with signal to noise ratio of 24dB in an applied field of 15Oe. Our data show conclusively that MTJ sensors are very promising candidates for future applications involving the accurate detection and identification of biomolecules with magnetic labels.
Optimal filter banks for multiple description coding: analysis and synthesis (2002)

Multiple description (MD) coding is a source coding technique for information transmission over unreliable networks. In MD coding, the coder generates several different descriptions of the same signal and the decoder can produce a useful reconstruction of the source with any received subset of these descriptions. In this paper, we study the problem of MD coding of stationary Gaussian sources with memory. First, we compute an approximate MD rate distortion region for these sources, which we prove to be asymptotically tight at high rates. This region generalizes the MD rate distortion region of El Gamal and Cover (1982), and Ozarow (1980) for memoryless Gaussian sources. Then, we develop an algorithm for the design of optimal two-channel biorthogonal filter banks for MD coding of Gaussian sources. We show that optimal filters are obtained by allocating the redundancy over frequency with a reverse "water-filling" strategy. Finally, we present experimental results which show the effectiveness of our filter banks in the low complexity, low rate regime.
The Effect of Topical Fluticasone on Nasal Nitric Oxide Levels in a Patient with Allergic Rhinitis (2003)

Nitric oxide (NO) in exhaled breath is produced primarily by the upper respiratory airway mucosa. The nasal output of this gas is increased in patients with allergic rhinitis. We performed a study on a 41-year-old nonsmoking male volunteer with allergic rhinitis to investigate the effect of fluticasone nasal spray on nasal NO output (VNO). A total of 28 nasal NO measurements from both nostrils were taken during the 2-month period of June and July 2002. During the second half of the study period (treatment phase), the patient took fluticasone in doses of 100 micrograms per nostril once a day. During the treatment phase, nasal NO measurements were taken 10 days after the initiation of treatment. In addition, we also recorded the patient's nasal symptom scores and the grass pollen counts in the greater Pittsburgh area. The patient's mean VNO was 989.9 nl/min prior to treatment and 787.7 nl/min following treatment--a statistically significant 20.4% decrease (p < 0.01). The findings of our study support the observation that topical nasal steroid treatment decreases NO production in sinonasal mucosa.
Human Leukocyte Antigen-G (HLA-G) Expression in Cancers: Roles in Immune Evasion, Metastasis and Target for Therapy (2015)

Aberrant induction of human leukocyte antigen-G (HLA-G) expression has been observed in various malignancies and is strongly associated with tumor immune escape, metastasis and poor prognosis. To date, great achievements have been made in understanding the underlying mechanisms of HLA-G involved in tumor progression. HLA-G could lead to tumor evasion by inhibition of immune cell cytolysis, differentiation and proliferation and inhibition of cytokine production, induction of immune cell apoptosis, generation of regulatory cells and expansion of myeloid-derived suppressive cells and by impairment of chemotaxis. Moreover, HLA-G could arm tumor cells with a higher invasive and metastatic potential with the upregulation of tumor-promoting factor expression such as matrix metalloproteinases (MMPs), indicating that ectopic HLA-G expression could render multiple effects during the progression of malignancies. In this review, we summarized the mechanisms of HLA-G involved in promoting tumor cell immune escaping, metastasis and disease progression. Special attention will be paid to its significance as an attractive therapeutic target in cancers.
Midkine: A Promising Molecule for Drug Development to Treat Diseases of the Central Nervous System (2011)

Midkine (MK) is a heparin-binding cytokine, and promotes growth, survival, migration and other activities of target cells. After describing the general properties of MK, this review focuses on MK and MK inhibitors as therapeutics for diseases in the central nervous system. MK is strongly expressed during embryogenesis especially at the midgestation period, but is expressed only at restricted sites in adults. MK expression is induced upon tissue injury such as ischemic brain damage. Since exogenously administered MK or the gene transfer of MK suppresses neuronal cell death in experimental systems, MK has the potential to treat cerebral infarction. MK might become important also in the treatment of neurodegenerative diseases such as Alzheimer's disease. MK is involved in inflammatory diseases by enhancing migration of leukocytes, inducing chemokine production and suppressing regulatory T cells. Since an aptamer to MK suppresses experimental autoimmune encephalitis, MK inhibitors are promising for the treatment of multiple sclerosis. MK is overexpressed in most malignant tumors including glioblastoma, and is involved in tumor invasion. MK inhibitors may be of value in the treatment of glioblastoma. Furthermore, an oncolytic adenovirus, whose replication is under the control of the MK promoter, inhibits the growth of glioblastoma xenografts. MK inhibitors under development include antibodies, aptamers, glycosaminoglycans, peptides and low molecular weight compounds. siRNA and antisense oligoDNA have proved effective against malignant tumors and inflammatory diseases in experimental systems. Practical information concerning the development of MK and MK inhibitors as therapeutics is described in the final part of the review.
Distortion/Interaction Energy Control of 1,3-Dipolar Cycloaddition Reactivity (2007)

Computations of activation barriers and reaction energies for 1,3-dipolar cycloadditions by a high-accuracy quantum mechanical method (CBS-QB3) now reveal previously unrecognized quantitative trends in activation barriers. The distortion/interaction theory explains why (1) there is a monotonic decrease of ∼6 kcal/mol in the barrier height along the series oxides, imine, and ylide, for each class of 1,3-dipoles; (2) the corresponding nitrilium and azomethine betaines have almost identical cycloaddition barrier heights; (3) cycloadditions of a given 1,3-dipole with ethylene and acetylene have the same activation energies, in spite of very different reaction thermodynamics and frontier orbital gaps. There is a linear correlation between distortion energies (ΔEd⧧) and the activation barrier (ΔE⧧ = 0.75ΔEd⧧ − 2.9 kcal/mol) that is general for substituted and unsubstituted 1,3-dipoles in these cycloadditions. The energy to distort the 1,3-dipole to the geometry favorable for interaction with the dipolarophile, that is, the transition state geometry, rather than frontier molecular orbital (FMO) interactions or reaction thermodynamics, controls reactivity. Interaction energies between the 1,3-dipole and the dipolarophile differentiate dipolarophile reactivity, and FMO interactions influence this.
Technological considerations for genome-guided diagnosis and management of cancer (2016)

Technological, methodological, and analytical advances continue to improve the resolution of our view into the cancer genome, even as we discover ways to carry out analyses at greater distances from the primary tumor sites. These advances are finally making the integration of cancer genomic profiling into clinical practice feasible. Formalin fixation and paraffin embedding, which has long been the default pathological biopsy medium, is now being supplemented with liquid biopsy as a means to profile the cancer genomes of patients. At each stage of the genomic data generation process-sample collection, preservation, storage, extraction, library construction, sequencing, and variant calling-there are variables that impact the sensitivity and specificity of the analytical result and the clinical utility of the test. These variables include sample degradation, low yields of nucleic acid, and low variant allele fractions (proportions of assayed molecules carrying variant allele(s)). We review here the most common pre-analytical and analytical factors relating to routine cancer patient genome profiling, some solutions to common challenges, and the major sample preparation and sequencing technology choices available today.