gebhart/patrepeval huggingface dataset:
MER-101 tablets: A pilot bioavailability study of a novel oral formulation of zoledronic acid (2007)

B194 Introduction  The purpose of the study was to compare the absorption of two strengths of an investigational oral dosage form of MER-101, a tablet form of zoledronic acid, to the parenteral reference product, commercially-available zoledronic acid intravenous infusion. MER-101 was developed by Merrion Pharmaceuticals using GIPET™ I technology to improve the oral bioavailability of zoledronic acid and thereby enable the development of an oral dosage form. GIPET™ I is based on proprietary penetration enhancers which improve the absorption of such drugs in the small intestine. There is no chemical modification to the active drug. The enhancer system is comprised of food based material which is on the US GRAS list. These are important factors in reducing regulatory requirements and the time to market. GIPET™ technology is equally applicable to small molecules, macromolecules and biologics, and is broadly applicable over a wide range of marketed and emerging products.  Zoledronic acid is a bisphosphonate used in the treatment of bone metastases. Bisphosphonates are synthetic analogs of pyrophosphate that bind to the hydroxyapatite found in bone. The current marketed dosage form of zoledronic acid is a given as an infusion to overcome the limitations of oral dosing of bisphosphonates, including low bioavailability, gastric irritation, and gastric reflux.  Experimental Procedures  The study was a single-dose, three-way crossover bioequivalence study in 13 postmenopausal female subjects with osteoporosis. There was a washout period of at least 7 days between dosing days. Cumulative urinary excretion of zoledronic acid over a 48-hour period was used as the basis for the pharmacokinetic analysis. Eleven subjects successfully completed all treatment periods of the study and were included in the final analysis.  The treatments administered during the clinical trial were: MER-101 10mg and 20mg enteric coated tablets and zoledronic acid injection 1mg, administered as a 15-minute infusion in 100mL of normal saline. The treatments were well tolerated in all cases.  Data Summary  The MER-101 20mg tablet had a mean 48-hour urinary excretion of zoledronic acid approximately 44% greater than the MER-101 10mg tablet. The MER-101 20mg tablet had a mean zoledronic acid excretion that was similar to the zoledronic acid 1mg Injection (0.514mg and 0.541mg respectively).  Conclusions  A tablet dosage form of zoledronic acid has been successfully developed which will allow once weekly treatment of patients. The dose administered via a 20mg tablet equals that of a 1mg intravenous infusion. MER-101 was well tolerated and there were no serious adverse events associated with its administration.
Three-dimensional image processing in the future of immersive media (2004)

This survey paper discusses the three-dimensional image processing challenges posed by present and future immersive telecommunications, especially immersive video conferencing and television. We introduce the concepts of presence, immersion, and co-presence and discuss their relation to virtual collaborative environments in the context of communications. Several examples are used to illustrate the current state of the art. We highlight the crucial need of real-time, highly realistic video with adaptive viewpoint for future immersive communications and identify calibration, multiple-view analysis, tracking, and view synthesis as the fundamental image-processing modules addressing such a need. For each topic, we sketch the basic problem and representative solutions from the image processing literature.
Interaction with CD4 and Antibodies to CD4-Induced Epitopes of the Envelope gp120 from a Microglial Cell-Adapted Human Immunodeficiency Virus Type 1 Isolate (2005)

We previously showed that the envelope glycoprotein from an in vitro microglia-adapted human immunodeficiency virus type 1 isolate (HIV-1(Bori-15)) is able to use lower levels of CD4 for infection and demonstrates greater exposure of the CD4-induced epitope recognized by the 17b monoclonal antibody than the envelope of its parental, peripheral isolate (HIV-1(Bori)). We investigated whether these phenotypic changes were related to a different interaction of their soluble monomeric gp120 proteins with CD4 or 17b. Equilibrium binding analyses showed no difference between Bori and Bori-15 gp120s. However, kinetic analysis of surface plasmon resonance-based, real-time binding experiments showed that while both proteins have similar association rates, Bori-15 gp120 has a statistically significant, 3-fold-lower dissociation rate from immobilized CD4 than Bori and a statistically significant, 14-fold-lower dissociation rate from 17b than Bori in the absence of soluble CD4. In addition, using the sensitivity to inhibition by anti-CD4 antibodies as a surrogate for CD4:trimeric envelope interaction, we found that Bori-15 envelope-pseudotyped viruses were significantly less sensitive than Bori pseudotypes, with four- to sixfold-higher 50% inhibitory concentration values for the three anti-CD4 antibodies tested. These differences, though small, suggest that adaptation to microglia correlates with the generation of a gp120 that forms a more stable interaction with CD4. Nonetheless, the observation of limited binding changes leaves open the possibility that HIV-1 adaptation to microglia and HIV-associated dementia may be related not only to diminished CD4 dependence but also to changes in other molecular factors involved in the infection process.
Using Positively Charged Magnetic Nanoparticles to Capture Bacteria at Ultralow Concentration (2019)

Detecting bacteria at low concentrations without time-consuming culture processes would allow rapid diagnoses. Since electrostatic attraction exists between negatively charged bacterial cells and positively charged magnetic nanoparticles (NP+), capture of bacteria holds great promise towards achieving this goal. Here, we present a rapid and highly efficient approach to capture Escherichia coli, which was used as a model for gram-negative bacteria. Capture of E. coli at very low concentrations of 10 and 100 CFU/mL using NP+ is rapidly and efficiently achieved within 1 h. Moreover, the capture efficiency of NP+ was over 90% by analyzing the number of bacterial colonies on the plate. Optical and transmission electron microscopy confirmed the bacterial capture abilities of electrically charged nanoparticles (NPs). In contrast, negatively charged magnetic nanoparticles (NP-) did not show affinities towards E. coli. These results showed that bacterial cells, such as E. coli, carry a negative charge. Unlike a ligand-dependent capture system, our designed NP+ has potentials to capture a broad range of bacteria via electrostatic attractions.
New Technologies in Spine (2002)

Nucleus replacement offers several benefits over other surgical options. Several design criteria need to be met. Nucleus prostheses can be either preformed or formed in situ. Preclinical evaluations should include biomechanical testing, biocompatibility testing, and surgical technique evaluation. Indications and contraindications of nucleus prosthesis are largely determined by the benefit-to-risk ratio and benefit-to-cost ratio.
Xylulokinase Overexpression in Two Strains ofSaccharomyces cerevisiaeAlso Expressing Xylose Reductase and Xylitol Dehydrogenase and Its Effect on Fermentation of Xylose and Lignocellulosic Hydrolysate (2001)

Fermentation of the pentose sugar xylose to ethanol in lignocellulosic biomass would make bioethanol production economically more competitive. Saccharomyces cerevisiae, an efficient ethanol producer, can utilize xylose only when expressing the heterologous genes XYL1 (xylose reductase) and XYL2 (xylitol dehydrogenase). Xylose reductase and xylitol dehydrogenase convert xylose to its isomer xylulose. The gene XKS1 encodes the xylulose-phosphorylating enzyme xylulokinase. In this study, we determined the effect of XKS1 overexpression on two different S. cerevisiae host strains, H158 and CEN.PK, also expressing XYL1 and XYL2. H158 has been previously used as a host strain for the construction of recombinant xylose-utilizing S. cerevisiae strains. CEN.PK is a new strain specifically developed to serve as a host strain for the development of metabolic engineering strategies. Fermentation was carried out in defined and complex media containing a hexose and pentose sugar mixture or a birch wood lignocellulosic hydrolysate. XKS1 overexpression increased the ethanol yield by a factor of 2 and reduced the xylitol yield by 70 to 100% and the final acetate concentrations by 50 to 100%. However, XKS1 overexpression reduced the total xylose consumption by half for CEN.PK and to as little as one-fifth for H158. Yeast extract and peptone partly restored sugar consumption in hydrolysate medium. CEN.PK consumed more xylose but produced more xylitol than H158 and thus gave lower ethanol yields on consumed xylose. The results demonstrate that strain background and modulation of XKS1 expression are important for generating an efficient xylose-fermenting recombinant strain of S. cerevisiae.
A comparison of HIPERLAN/2 and IEEE 802.11a physical and MAC layers (2002)

At present, wireless local area networks (WLANs) supporting broadband multimedia communication are being developed and standardized. Two such standards are HIPERLAN/2, defined by ETSI BRAN and the IEEE's 802.11a. These WLAN standards will provide data rates up to 54 Mbps (in a channel spacing of 20 MHz) in the 5.2 GHz band. In this paper, an overview of the the standards is presented together with software simulated physical layer performance results for each of the transmission modes defined in the two standards. Furthermore, the differences between the standards (protocol data unit-PDU-size, upper protocol layers etc.) and the effects on applications are discussed.
Electrochemical decomposition of choline chloride based ionic liquid analogues (2009)

Ionic liquids are studied intensively for electrochemical applications and more specifically for the electrodeposition of metals. In this paper the electrochemical stability of a deep-eutectic solvent based on choline chloride and ethylene glycol is studied over longer periods of electrolysis. The formation of several decomposition products such as 2-methyl-1,3-dioxolane was observed. Possible mechanisms for the formation of these products are given: some products involve a reaction at either the anode or the cathode, while others can be explained by consecutive reactions of reaction products formed at both electrodes. A range of chlorinated products like chloromethane, dichloromethane and chloroform could be detected as well. This is remarkable as evolution of chlorine gas at the anode is not observed. The formation of the chlorinated products is ascribed to the existence of the Cl3− ion in the solution. The presence of the Cl3− ion was observed photometrically. The presence of chlorinated products gives rise to a larger environmental impact and higher risks for health and safety, and it questions the “greenness” of these ionic liquid analogues. To reduce the decomposition of the solvent, water and easily oxidizable acids were added as ‘sacrificial agents’. Their influence on the formation of 2-methyl-1,3-dioxolane was quantified. However, the addition of the sacrificial agents did not improve the stability of the solvent. Addition of formic acid reduced the formation of 2-methyl-1,3-dioxolane but chlorinated products could still be detected. Water reduced the formation of chlorinated products.
Functional Label-Free Assays for Characterizing the in Vitro Mechanism of Action of Small Molecule Modulators of Capsid Assembly (2015)

HIV capsid protein is an important target for antiviral drug design. High-throughput screening campaigns have identified two classes of compounds (PF74 and BI64) that directly target HIV capsid, resulting in antiviral activity against HIV-1 and HIV-2 laboratory strains. Using recombinant proteins, we developed a suite of label-free assays to mechanistically understand how these compounds modulate capsid activity. PF74 preferentially binds to the preassembled hexameric capsid form and prevents disruption of higher-order capsid structures by stabilizing capsid intersubunit interactions. BI64 binds only the monomeric capsid and locks the protein in the assembly incompetent monomeric form by disrupting capsid intersubunit interactions. We also used these assays to characterize the interaction between capsid and the host protein cleavage and polyadenylation specific factor 6 (CPSF6). Consistent with recently published results, our assays revealed CPSF6 activates capsid polymerization and preferentially binds to the preassembled hexameric capsid form similar to the small molecule compound, PF74. Furthermore, these label-free assays provide a robust method for facilitating the identification of a different class of small molecule modulators of capsid function.
(-)-Phenylahistin Arrests Cells in Mitosis by Inhibiting Tubulin Polymerization. (1999)

(-)-Phenylahistin, a fungal diketopiperazine metabolite composed of phenylalanine and isoprenylated dehydrohistidine, arrested cells in mitosis and inhibited the proliferation of A549 cells. The microtubule network in A549 cells was disrupted by (-)-phenylahistin, which also inhibited the polymerization of both microtubule protein from bovine brain and phosphocellulose-purified tubulin in vitro. Competitive binding studies indicated that (-)-phenylahistin interacted with the colchicine binding site on tubulin but not with the vinblastine binding site.
The Usefulness and Applicability of a Basic Headache Diary Before First Consultation: Results of a Pilot Study Conducted In Two Centres (2008)

We tested the usefulness and applicability of a simplified headache diary in the diagnosis of migraine (M), tension-type headache (TTH) and medication overuse headache (MOH). The diary was given to headache patients before their first consultation at the headache centre. Seventy-six naive headache patients completed the study. Their understanding of the diary proved highly satisfactory. The patients' level of compliance was also good, with 71% returning the diary completely filled in. The data entered in the diary were deemed complete for the diagnostic purpose in 93% of cases. The level of agreement between headache information gathered through clinical interview and the headache diary was satisfactory. When comparing the diary with the clinical interview, sensitivity was 92% for M, 75% for TTH and MOH. Specificity was 58% for M and TTH, 87% for MOH. Combined use of a diagnostic diary and clinical interview is recommended from the first consultation for headache.
A New Low Density Lipoprotein Receptor Homologue with 8 Ligand Binding Repeats in Brain of Chicken and Mouse (1996)

The blood-brain barrier necessitates disparate macromolecular transport systems in the brain and central nervous system. We now report the discovery of a new member of the low density lipoprotein receptor (LDLR) family whose expression is highly restricted to the brain. The full-length cDNA specifying the chicken receptor (open reading frame, 2754 base pairs) as well as a cDNA for the major portion of its murine homologue have been obtained. The novel receptor shows the greatest similarity to the group of LDLR relatives with 8 ligand binding repeats, in chicken termed LR8 and in mammals, very low density lipoprotein receptors. Thus, in addition to 8 tandemly arranged ligand binding repeats, the five-domain receptor contains an O-linked sugar region and the internalization signal, Phe-Asp-Asn-Pro-Val-Tyr, typical for all LDLR gene family members. In chicken, the 6.5-kb receptor transcript is present at high levels in brain and at much lower levels in extraoocytic cells of the ovary; in mouse, the same transcript of 6.5 kb was detected in brain, but not in heart (the major site of very low density lipoprotein receptor expression), lung, liver, kidney, and ovary. An antibody directed against the predicted carboxyl terminus of the avian receptor detected a 130-kDa protein in brain extracts. The apparent size of the immunoreactive protein is compatible with extensive glycosylation of the 894-residue mature form of the receptor. The presence of this novel receptor in brain of a bird and a rodent suggests an important and evolutionary conserved function.
Pim‐2 upregulation: Biological implications associated with disease progression and perinueral invasion in prostate cancer (2005)

Pim-2 is an important prosurvival gene, which might result in activation of enhanced anti-apoptotic pathway, leading to a more aggressive phenotype of PCa. Pim-2 may become a target for novel therapeutic strategies.
Cloning and Targeted Disruption of MLG1 , a Gene Encoding Two of Three Extracellular Mixed-Linked Glucanases of Cochliobolus carbonum (1998)

Mixed-linked glucanases (MLGases), which are extracellular enzymes able to hydrolyze beta 1,3-1,4-glucans (also known as mixed-linked glucans or cereal beta-glucans), were identified in culture filtrates of the plant-pathogenic fungus Cochliobolus carbonum. Three peaks of MLGase activity, designated Mlg1a, Mlg1b, and Mlg2, were resolved by cation-exchange and hydrophobic-interaction high-performance liquid chromatography (HPLC). Mlg1a and Mlg1b also hydrolyze beta 1,3-glucan (laminarin), whereas Mlg2 does not degrade beta 1,3-glucan but does degrade beta 1,4-glucan to a slight extent. Mlg1a, Mlg1b, and Mlg2 have monomer molecular masses of 33.5, 31, and 29.5 kDa, respectively. The N-terminal amino acid sequences of Mlg1a and Mlg1b are identical (AAYNLI). Mlg1a is glycosylated, whereas Mlg1b is not. The gene encoding Mlg1b, MLG1, was isolated by using PCR primers based on amino acid sequences of Mlg1b. The product of MLG1 has no close similarity to any known protein but does contain a motif (EIDI) that occurs at the active site of MLGases from several prokaryotes. An internal fragment of MLG1 was used to create mlg1 mutants by transformation-mediated gene disruption. The total MLGase and beta 1,3-glucanase activities in culture filtrates of the mutants were reduced by approximately 50 and 40%, respectively. When analyzed by cation-exchange HPLC, the mutants were missing the two peaks of MLGase activity corresponding to Mlg1a and Mlg1b. Together, the data indicate that Mlg1a and Mlg1b are products of the same gene, MLG1. The growth of mlg1 mutants in culture medium supplemented with macerated maize cell walls or maize bran and the disease symptoms on maize were identical to the growth and disease symptoms of the wild type.
Imaging Microglial Activation with TSPO PET: Lighting Up Neurologic Diseases? (2015)

Neuroinflammation is implicated in the pathogenesis of a wide range of neurologic and neuropsychiatric diseases. For over 20 years, (11)C-PK11195 PET, which aims to image expression of the translocator protein (TSPO) on activated microglia in the brain, has been used in preclinical and clinical research to investigate neuroinflammation in vivo in patients with brain diseases. However, (11)C-PK11195 suffers from two major limitations: its low brain permeability and high nonspecific and plasma binding results in a low signal-to-noise ratio, and the use of (11)C restricts its use to PET research centers and hospitals with an on-site cyclotron. In recent years, there has been a great deal of work into the development of new TSPO-specific PET radiotracers. This work has focused on fluorinated radiotracers, which would enable wider use and improved signal-to-noise ratios. These radiotracers have been utilized in preclinical and clinical studies of several neurologic diseases with varying degrees of success. Unfortunately, the application of these second-generation TSPO radiotracers has revealed additional problems, including a polymorphism that affects TSPO binding. In this review, the developments in TSPO imaging are discussed, and current limitations and suggestions for future directions are explored.
Coding nucleotide sequence of rat NADPH-cytochrome P-450 oxidoreductase cDNA and identification of flavin-binding domains. (1985)

The coding nucleotide sequence of the mRNA for NADPH-cytochrome P-450 oxidoreductase (NADPH:ferricytochrome oxidoreductase, EC 1.6.2.4) from rat liver was determined from two overlapping cDNA clones, pOR-7 and pOR-8, which together contain 2401 nucleotides complementary to rat liver oxidoreductase mRNA. The single open reading frame of 2034 nucleotides spanning these cDNAs codes for a 678 amino acid polypeptide with a molecular weight of 76,962. The deduced amino acid composition is in excellent agreement with that determined by direct amino acid analysis of purified rat liver P-450 oxidoreductase, and the amino-terminal region (residues 1-80) largely coincides with the amino-terminal sequence of the oxidoreductase isolated from rabbit liver. Comparison of the amino acid sequence to those of other flavoproteins revealed two separate domains that are likely to be involved in flavin binding: a long segment (residues 77-228) homologous with Desulfovibrio vulgaris flavodoxin, an FMN-containing protein, and a shorter segment (residues 452-477) homologous with the FAD-binding segment of fumarate reductase from Escherichia coli.
Global Gene Expression Analysis to Identify Molecular Markers of Uterine Receptivity and Embryo Implantation (2001)

Infertility and spontaneous pregnancy losses are an enduring problem to women's health. The establishment of pregnancy depends on successful implantation, where a complex series of interactions occurs between the heterogeneous cell types of the uterus and blastocyst. Although a number of genes are implicated in embryo-uterine interactions during implantation, genetic evidence suggests that only a small number of them are critical to this process. To obtain a global view and identify novel pathways of implantation, we used a dual screening strategy to analyze the expression of nearly 10,000 mouse genes by microarray analysis. Comparison of implantation and interimplantation sites by a conservative statistical approach revealed 36 up-regulated genes and 27 down-regulated genes at the implantation site. We also compared the uterine gene expression profile of progesterone-treated, delayed implanting mice to that of mice in which delayed implantation was terminated by estrogen. The results show up-regulation of 128 genes and down-regulation of 101 genes after termination of the delayed implantation. A combined analysis of these experiments showed specific up-regulation of 27 genes both at the implantation site and during uterine activation, representing a broad diversity of molecular functions. In contrast, the majority of genes that were decreased in the combined analysis were related to host immunity or the immune response, suggesting the importance of these genes in regulating the uterine environment for the implanting blastocyst. Collectively, we identified genes with recognized roles in implantation, genes with potential roles in this process, and genes whose functions have yet to be defined in this event. The identification of unique genetic markers for the onset of implantation signifies that genome-wide analysis coupled with functional assays is a promising approach to resolve the molecular pathways required for successful implantation.
A Threshold Cryptosystem without a Trusted Party (Extended abstract) (1991)

In a threshold cryptosystem n members share the necret key of an organization such that k members (1 5 k 5 n) must cooperate in order to decipher a given uphertext. In this note it is shown how to implement such a scheme without having a trusted party, which selects the secret key and distributes it to the members. In stead, the members choose the secret key and distribute it verifiably among themselves. Subsequently, this key can be used for authentication as well as secret communication.