gebhart/patrepeval huggingface dataset:
Overview of milling techniques for improving the solubility of poorly water-soluble drugs (2015)

Milling involves the application of mechanical energy to physically break down coarse particles to finer ones and is regarded as a “top–down” approach in the production of fine particles. Fine drug particulates are especially desired in formulations designed for parenteral, respiratory and transdermal use. Most drugs after crystallization may have to be comminuted and this physical transformation is required to various extents, often to enhance processability or solubility especially for drugs with limited aqueous solubility. The mechanisms by which milling enhances drug dissolution and solubility include alterations in the size, specific surface area and shape of the drug particles as well as milling-induced amorphization and/or structural disordering of the drug crystal (mechanochemical activation). Technology advancements in milling now enable the production of drug micro- and nano-particles on a commercial scale with relative ease. This review will provide a background on milling followed by the introduction of common milling techniques employed for the micronization and nanonization of drugs. Salient information contained in the cited examples are further extracted and summarized for ease of reference by researchers keen on employing these techniques for drug solubility and bioavailability enhancement.
Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model (2007)

J. Neurochem. (2008) 104, 1494–1503. Abstract Reduced derivatives of folic acid (folates) play a critical role in the development, function and repair of the CNS. However, the molecular systems regulating folate uptake and homeostasis in the central nervous system remain incompletely defined. Choroid plexus epithelial cells express high levels of folate receptor α (FRα) suggesting that the choroid plays an important role in CNS folate trafficking and maintenance of CSF folate levels. We have characterized 5‐methyltetrahydrofolate (5‐MTHF) uptake and metabolism by primary rat choroid plexus epithelial cells in vitro . Two distinct processes are apparent; one that is FRα dependent and one that is independent of the receptor. FRα binds 5‐MTHF with high affinity and facilitates efficient uptake of 5‐MTHF at low extracellular folate concentrations; a lower affinity FRα independent system accounts for increased folate uptake at higher concentrations. Cellular metabolism of 5‐MTHF depends on the route of folate entry into the cell. 5‐MTHF taken up via a non‐FRα ‐mediated process is rapidly metabolized to folylpolyglutamates, whereas 5‐MTHF that accumulates via FRα remains non‐metabolized, supporting the hypothesis that FRα may be part of a pathway for transcellular movement of the vitamin. The proton‐coupled folate transporter, proton‐coupled folate transporter (PCFT), mRNA was also shown to be expressed in choroid plexus epithelial cells. This is consistent with the role we have proposed for proton‐coupled folate transporter in FRα‐mediated transport as the mechanism of export of folates from the endocytic compartment containing FRα.
Fluoxetine Inhibits Enterovirus Replication by Targeting the Viral 2C Protein in a Stereospecific Manner (2019)

Enteroviruses (family <i>Picornaviridae</i>) comprise a large group of human pathogens against which no licensed antiviral therapy exists. Drug-repurposing screens uncovered the FDA-approved drug fluoxetine as a replication inhibitor of enterovirus B and D species. Fluoxetine likely targets the nonstructural viral protein 2C, but detailed mode-of-action studies are missing because structural information on 2C of fluoxetine-sensitive enteroviruses is lacking. We here show that broad-spectrum anti-enteroviral activity of fluoxetine is stereospecific concomitant with binding to recombinant 2C. (<i>S</i>)-Fluoxetine inhibits with a 5-fold lower 50% effective concentration (EC<sub>50</sub>) than racemic fluoxetine. Using a homology model of 2C of the fluoxetine-sensitive enterovirus coxsackievirus B3 (CVB3) based upon a recently elucidated structure of a fluoxetine-insensitive enterovirus, we predicted stable binding of (<i>S</i>)-fluoxetine. Structure-guided mutations disrupted binding and rendered coxsackievirus B3 (CVB3) resistant to fluoxetine. The study provides new insights into the anti-enteroviral mode-of-action of fluoxetine. Importantly, using only (<i>S</i>)-fluoxetine would allow for lower dosing in patients, thereby likely reducing side effects.
Effect of N‐Acetylsphingosine (C2) and the Ceramidase Inhibitor (1S,2R)‐D‐erythro‐2‐(N‐myristoylamino)‐1‐phenyl‐1‐propanol on the Regulation of Sertoli Cell Function (1999)

In the present study, a possible role of ceramide in the regulation of Sertoli cell function was investigated. Intracellular ceramide levels were increased by adding N-acetylsphingosine (C2) or by inhibiting ceramidase with (1 S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol (MAPP). Cultured Sertoli cells were stimulated for 3 days with different doses of C2, MAPP, and their corresponding inactive analogs. The effect of these drugs was evaluated along four well-known Sertoli cell parameters: lactate and transferrin secretion, gamma-glutamyl transpeptidase (gamma-GTP) activity, and estradiol production. C2 and MAPP increased lactate production and decreased transferrin secretion. The inactive analogs did not produce any effect. In FSH (follicle-stimulating hormone)-stimulated cultures, C2 and MAPP produced a further increment in lactate production and decreased FSH-stimulated transferrin secretion. No effect was observed under basal or FSH-stimulated gamma-GTP activity, and both treatments decreased estradiol production in response to FSH. Results obtained in dbcAMP (dibutyryladenosine 3':5'-cyclic monophosphate)-stimulated cultures suggest that the observed effects of ceramide on transferrin secretion are secondary to a decrease in cAMP production, whereas the effects of ceramide on lactate and estradiol productions are post-cAMP formation regulatory events. In summary, our results show that ceramide can regulate Sertoli cell function. Similar to what has been observed for other signaling molecules, ceramide can interact with the FSH-dependent pathway, but the precise steps involved in this interaction are still unknown.
The first randomized trial of human polymerized hemoglobin as a blood substitute in acute trauma and emergent surgery (1998)

PolyHeme is safe in acute blood loss, maintains total [Hb] in lieu of red cells despite the marked fall in RBC [Hb], and reduces the use of allogeneic blood. PolyHeme appears to be a clinically useful blood substitute.
BisQC: an operational pipeline for multiplexed bisulfite sequencing (2014)

We demonstrate several quality control checkpoints at the library preparation, pre-sequencing, post-sequencing, and post-alignment stages, which should prove useful in determining sample and processing quality. We also determine that including a significant portion of non-bisulfite converted DNA with bisulfite converted DNA has a minimal impact on usable bisulfite read output.
Prostate-Specific Antigen Values at the Time of Prostate Cancer Diagnosis in African-American Men (1995)

As a group, African-American men with newly diagnosed PC have higher PSA values at initial diagnosis than white men. This PSA difference appears to be due to larger tumor volumes within clinical (TNM) stage categories among black patients. Elevated PSA value was a surrogate for larger tumor volume in this cohort of black men. This stage-for-stage tumor volume disparity even in an equal-access health care environment should prompt further study of screening behavior and/or biological differences of PC in the black population.
Pharmacokinetics of intravitreal bevacizumab (Avastin®) in rabbits. (2011)

The vitreous half-life of 1.25 mg/0.05 mL intravitreal bevacizumab was 6.61 days in this rabbit model. Maximum concentrations of bevacizumab were reached at day 1 in both vitreous and aqueous humor of the right eye and at day 8 in the serum. Very low concentrations of bevacizumab were measured in the fellow noninjected eye.
Stable perfluoroalkyl carbanion salts (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStable perfluoroalkyl carbanion saltsBruce E. Smart, William J. Middleton, and William B. FarnhamCite this: J. Am. Chem. Soc. 1986, 108, 16, 4905–4908Publication Date (Print):August 1, 1986Publication History Published online1 May 2002Published inissue 1 August 1986https://pubs.acs.org/doi/10.1021/ja00276a033https://doi.org/10.1021/ja00276a033research-articleACS PublicationsRequest reuse permissionsArticle Views462Altmetric-Citations55LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Studies on polynucleotides. 147. Use of the lipophilic tert-butyldiphenylsilyl protecting group in synthesis and rapid separation of polynucleotides (1978)

To achieve more understanding of the interplay between sustainability and the functional quality of buildings, we should pay more attention to a broad and interdisciplinary approach of building. It means that we must not narrow our vision to the level of the building itself. Instead, we have to go beyond the edges of our discipline and have to change from viewpoint to viewpoint, while we are co-operating in multidisciplinary teams. This could provide a substantial contribution to sustainable development and may solve the complex questions that are posed when developing sustainable building.
A catalyst for educational change: the role of career and technical education in Georgia’s statewide educational improvement efforts (2011)

The Central Educational Center is a product of multiple visions, desires, and hopes. The ideal vision isoutlined in a book entitled "The Eden Conspiracy" (Harless, 1997). Other perspectives include arequirement from local business that basic skills of high school graduates need to be rapidly improved,the desire of a growing local school system to provide costly industry-standard career-technicaleducation to all high school students, the vision of a regional technical college to "dual enroll" highschool students and make technical college a viable post-secondary option, and the hopes of aGovernor looking for a viable model to support his desire to reform education partly through a newinfusion of technical education opportunities.
Analysis of Tryptic Digests Using Microbore HPLC with an Ion Trap Storage/Reflectron Time-of-Flight Detector (1995)

An electrospray ionization source interfaced to an ion trap storage/reflectron time-of-flight mass spectrometer is evaluated as a rapid, sensitive detector for microbore HPLC. Using the total ion storage capabilities of the trap over a broad mass range, total ion chromatograms of tryptic digests of bovine cytochrome c and bovine beta-casein are obtained following microbore HPLC separations with samples in the low picomole range. The digests are analyzed with the aid of software developed in our laboratory, which can display the selected ion chromatogram (SIC) for each chromatographic peak. The SIC mode can be used for enhancement of the S/N and for identification of a chromatographic peak with a particular mass. In addition, the mass spectrum corresponding to each chromatographic peak can be displayed to check for unresolved chromatographic components.
Effects of buffer layer processing on CIGS excess carrier lifetime: application of dual-beam optical modulation to process analysis [of solar cells] (1996)

A new nondestructive contactless dual-beam optical modulation (DBOM) technique has been developed for the characterization of effective excess carrier lifetimes in CuInGaSe/sub 2/ thin-film solar cells. Developed originally for lifetime measurement of SOI wafers, the technique represents a novel tool with the capabilities of direct measurement of the lifetime effects of intermediate processing steps during device fabrication without the confounding effects that subsequent processes might have on the final device characteristics. This is demonstrated in a controlled experiment intended to elucidate the mechanisms whereby CBD CdS processes improve device performance and to compare the CBD process with an MOCVD dry process. Areal mapping of excess carrier lifetimes across the samples is used to exhibit the substantial inhomogeneity of lifetime even within very high quality sample, demonstrating another capability of DBOM applicable to quality assessment and process optimization.
A New Method for Rapidly Generating Gene-Targeting Vectors by Engineering BACs Through Homologous Recombination in Bacteria (2003)

Generating knockout mice is still an expensive and highly time-consuming process. Target construct generation, the first labor-intensive step in this process, requires the manipulation of large fragments of DNA and numerous, and often cumbersome, cloning steps. Here we show the development of a rapid approach for generating targeting constructs that capitalizes on efficient homologous recombination between linear DNA fragments and circular plasmids in Escherichia coli ("recombineering"), the availability of bacterial artificial chromosomes (BACs), and the accessibility of the sequence of the mouse genome. Employing recombineering, we demonstrate with only 1-2 template plasmids, short homologies (40-50bp) between donor and target DNA, and one subcloning step that we can efficiently manipulate BACs in situ to generate a complicated targeting vector. This procedure avoids the need to construct or screen genomic libraries and permits the generation of most standard, conditional, or knock-in targeting vectors, often within two weeks.
BRONCHOCONSTRICTOR ACTION AND ANTAGONISM OF A SLOW‐REACTING SUBSTANCE FROM ANAPHYLAXIS OF GUINEA‐PIG ISOLATED LUNG (1964)

Slow-reacting substance produced in anaphylaxis (SRS-A) increased resistance of the lungs to inflation in the guinea-pig in vivo and caused isolated preparations of its tracheobronchial muscle to contract. SRS-A also contracted human isolated bronchial muscle and some but not all preparations of rabbit trachea. Nonsteroid anti-inflammatory drugs, which antagonize bronchoconstriction induced by kinins, but not that by histamine, acetylcholine, 5-hydroxytryptamine, substance P, angiotensin or lung prostaglandin, also antagonized the bronchoconstrictor action of SRS-A. This antagonism resembled that of kinins in being surmounted by higher doses of agonist, in the potencies of active drugs and in the types of drugs which were inactive. However, receptors in guinea-pig tracheobronchial muscle for SRS-A seem to be distinct from those for bradykinin, since preparations of this muscle could become unresponsive to either agent in vivo and in vitro, while remaining responsive to the other.
Morphological and Histological Effects of Trifluralin on Root Development (1967)

The most obvious external effect of trifluralin on the primary root was an increase in the amount of radial expansion near the root tip. The initial radial expansion of the treated roots occurred in the region of maximum elongation. With increased duration of treatment there was a gradual decrease in the extent of the meristematic tissue zone because of progressive vacuolation and subsequent differentiation. Although trifluralin disrupted the mitotic process, no one type of mitotic figure prevailed. Mitotic activity was not affected in all of the cells, some of which appeared to be undergoing a perfectly normal mitosis. Rates of trifluralin application sufficient to inhibit lateral root emergence without interfering with development of the primary root affected the pericycle and portions of the endodermis. The pericyclic cells were much enlarged in. the regions opposite the protoxylem and had undergone some of the initial phases of lateral root formation. These enlarged pericyclic cells correspond to what have been called primordiomorphs.
Purification and characterization of herpes simplex virus (type 1) thymidine kinase produced in Escherichia coli by a high efficiency expression plasmid utilizing a lambda PL promoter and cI857 temperature-sensitive repressor. (1983)

The structural gene for herpes simplex virus (type 1) thymidine kinase was cloned downstream from the lambda phage high efficiency leftward promotor in a plasmid (pHETK2) also containing the gene for the lambda cI857 temperature-sensitive repressor. Thymidine kinase is synthesized as a run-on product containing the NH2 terminus of the lambda N protein. Heat inactivation of the lambda repressor by growth at 42 degrees C results in the accumulation of thymidine kinase as approximately 4% of the total soluble cellular protein. Thymidine kinase has been purified to greater than 95% homogeneity by high speed centrifugation, ammonium sulfate fractionation, and Sephadex G-100 and hydroxylapatite column chromatography. Thymidine kinase has a subunit Mr = 42,000 determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and behaves as a dimer during Sephadex G-100 chromatography and glycerol gradient centrifugation. Thymidine kinase is enzymatically active from pH 6 to 10 with maximum activity at pH 8.5. The enzyme is protected from heat inactivation by thymidine and has a half-life at 40 degrees C of 30 min in the presence of thymidine and 3 min in its absence. Thymidine kinase displays Michaelis-Menten kinetics with apparent Michaelis constants of 0.6 and 118 microM for thymidine and ATP, respectively. Iododeoxycytidine is a competitive inhibitor of thymidine with an apparent Ki of 14 microM. The anti-herpes drug acyclovir (9-[(2-hydroxyethoxy)methyl]guanine) also appears to be a competitive inhibitor of thymidine (Ki of approximately 300 microM) but requires 3,000-fold higher concentrations than thymidine to give 50% inhibition. Other nucleoside triphosphates can substitute for ATP in the kinase reaction with the exception of dTTP which appears to inhibit thymidine kinase activity by about 50% when present in concentrations equal to that of thymidine.
Staggered striping in multimedia information systems (1994)

Multimedia information systems have emerged as an essential component of many application domains ranging from library information systems to entertainment technology. However, most implementations of these systems cannot support the continuous display of multimedia objects and suffer from frequent disruptions and delays termed hiccups. This is due to the low I/O bandwidth of the current disk technology, the high bandwidth requirement of multimedia objects, and the large size of these objects that almost always requires them to be disk resident. One approach to resolve this limitation is to decluster a multimedia object across multiple disk drives in order to employ the aggregate bandwidth of several disks to support the continuous retrieval (and display) of objects. This paper describes staggered striping as a novel technique to provide effective support for multiple users accessing the different objects in the database. Detailed simulations confirm the superiority of staggered striping.
Cystic Fibrosis Gene Therapy: Looking Back, Looking Forward (2018)

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (<i>CFTR</i>) gene that encodes a cAMP-regulated anion channel. Although CF is a multi-organ system disease, most people with CF die of progressive lung disease that begins early in childhood and is characterized by chronic bacterial infection and inflammation. Nearly 90% of people with CF have at least one copy of the ΔF508 mutation, but there are hundreds of <i>CFTR</i> mutations that result in a range of disease severities. A <i>CFTR</i> gene replacement approach would be efficacious regardless of the disease-causing mutation. After the discovery of the <i>CFTR</i> gene in 1989, the in vitro proof-of-concept for gene therapy for CF was quickly established in 1990. In 1993, the first of many gene therapy clinical trials attempted to rescue the CF defect in airway epithelia. Despite the initial enthusiasm, there is still no FDA-approved gene therapy for CF. Here we discuss the history of CF gene therapy, from the discovery of the <i>CFTR</i> gene to current state-of-the-art gene delivery vector designs. While implementation of CF gene therapy has proven more challenging than initially envisioned; thanks to continued innovation, it may yet become a reality.
Glutamate Excitotoxicity Is Involved in Cell Death Caused by Tributyltin in Cultured Rat Cortical Neurons (2005)

Tributyltin, an endocrine-disrupting chemical, has been used as a heat stabilizer, agricultural pesticide, and component of antifouling paints. In this study, the neurotoxicity of tributyltin was investigated in cultured rat cortical neurons. Tributyltin caused marked time- and dose-dependent increases in the number of trypan blue-stained cells. Measurement of extracellular glutamate concentration showed that glutamate release was induced by tributyltin. Application of the glutamate receptor antagonists MK-801 and CNQX decreased the neurotoxicity. These results suggest that released glutamate and glutamate receptors are involved in tributyltin toxicity. Next, we examined whether various factors, believed to be involved in glutamate excitotoxicity also influence tributyltin toxicity. Cell death induced by tributyltin was found to be reduced by alpha-tocopherol (a membrane-permeable antioxidant), SB202190 (a p38 mitogen-activated protein kinase inhibitor), and U-0126 (an extracellular signal-regulated protein kinase kinase inhibitor). MK-801 and CNQX decreased the phosphorylation of ERK, but not that of p38. A caspase-3 inhibitor had no effect on tributyltin toxicity, and tributyltin did not change the nuclear morphology. These results suggest that the glutamate excitotoxicity caused by tributyltin is unrelated to apoptosis. In conclusion, we demonstrated that tributyltin induced glutamate release and subsequent activation of glutamate receptors, leading to neuronal death. We propose two independent neuronal death pathways by tributyltin; one is glutamate receptor-dependent cell death via ERK phosphorylation, and the other may be glutamate receptor-independent cell death via p38 activation.