gebhart/patrepeval huggingface dataset:
Comparative bioavailability of three commercial acetaminophen tablets. (1987)

Three brands of acetaminophen tablets marketed in Turkey were evaluated for their in vitro properties, and their in vivo bioavailabilities were determined in comparison to a standard acetaminophen solution containing an equivalent amount of the drug. The total amount of acetaminophen in urine or in tablets was determined by the colorimetric method of Welch and Conney [1965]. No significant difference between the manufacturing parameters, namely the assay, hardness, diameter and thickness of the brands was observed except that the coefficients of variation for brand A were greater than the other two brands. Brand A also disintegrated more slowly and its dissolution time (80% of the drug dissolved in 45 min) did not meet the requirements of USP XX. In vivo bioavailability studies were carried out in six healthy volunteers who received the tablets or the standard solution in a single dose, cross-over study. The urine was collected for 24 h and the total acetaminophen excreted was determined according to the method of Welch and Conney. The relative bioavailabilities for Brands A, B and C were found to be 97.87, 95.41 and 98.78%, respectively, with respect to the solution. The differences were not statistically significant and it can be concluded that all tablets were rapidly and almost completely absorbed. This study also demonstrates that there is not always a good correlation between the in vitro disintegration and dissolution tests and the in vivo bioavailability of a drug.
Laser treatment of tattoos. A preliminary survey of three year's clinical experience (1967)

Preliminary experiences with lasers in the treatment of tattoos over a period of more than three years have shown that this is a safe procedure, both for the patient and for the operating personnel, when conducted in specially designed laboratories and with planned safety programs. The laser treatment of tattoos is still, and will continue to be for some time, an investigative treatment and not a conventional treatment.
Arabidopsis CLV3 Peptide Directly Binds CLV1 Ectodomain (2008)

CLV1, which encodes a leucine-rich repeat receptor kinase, and CLV3, which encodes a secreted peptide, function in the same genetic pathway to maintain stem cell populations in Arabidopsis shoot apical meristem. Here, we show biochemical evidence, by ligand binding assay and photoaffinity labeling, that the CLV3 peptide directly binds the CLV1 ectodomain with a dissociation constant of 17.5 nM. The CLV1 ectodomain also interacts with the structurally related CLE peptides, with distinct affinities depending on the specific amino acid sequence. Our results provide direct evidence that CLV3 and CLV1 function as a ligand-receptor pair involved in stem cell maintenance.
Establishment of a foreign antigen secretion system in mycobacteria (1990)

In order to develop recombinant Mycobacterium bovis BCG into a useful multivaccine vehicle, we established a foreign antigen secretion system in mycobacteria in which an extracellular alpha antigen of Mycobacterium kansasii was utilized as a carrier. By using this system, a B-cell epitope (Glu-12-Leu-Asp-Arg-Trp-Glu-Lys-Ile-19) of human immunodeficiency virus type 1 p17gag, which was identified by a fusion protein-based method, has been successfully obtained from BCG along with the alpha antigen. This is the first report of expression and secretion of a foreign viral antigen from BCG. It is possible that the system can become a universal vaccination vehicle applicable to protection against various infectious diseases.
Synthesis and Fermentation Properties of Novel Galacto-Oligosaccharides by β-Galactosidases from Bifidobacterium Species (2001)

beta-Galactosidase enzymes were extracted from pure cultures of Bifidobacterium angulatum, B. bifidum BB-12, B. adolescentis ANB-7, B. infantis DSM-20088, and B. pseudolongum DSM-20099 and used in glycosyl transfer reactions to synthesize oligosaccharides from lactose. At a lactose concentration of 30% (wt/wt) oligosaccharide yields of 24.7 to 47.6% occurred within 7 h. Examination of the products by thin-layer chromatography and methylation analysis revealed distinct product derived spectra from each enzyme. These were found to be different to that of Oligomate 55, a commercial prebiotic galacto-oligosaccharide. Fermentation testing of the oligosaccharides showed an increase in growth rate, compared to Oligomate 55, with products derived from B. angulatum, B. bifidum, B. infantis, and B. pseudolongum. However B. adolescentis had a lower growth rates on its oligosaccharide compared with Oligomate 55. Mixed culture testing of the B. bifidum BS-4 oligosaccharide showed that the overall prebiotic effect was equivalent to that of Oligomate 55.
CMOS-Integrated Film Bulk Acoustic Resonators for Label-Free Biosensing (2010)

The throughput is an important parameter for label-free biosensors. Acoustic resonators like the quartz crystal microbalance have a low throughput because the number of sensors which can be used at the same time is limited. Here we present an array of 64 CMOS-integrated film bulk acoustic resonators. We compare the performance with surface plasmon resonance and the quartz crystal microbalance and demonstrate the performance of the sensor for multiplexed detection of DNA.
Novel cellulose derivatives. III. Thermal analysis of mixed esters with butyric and hexanoic acid (1995)

Abstract Cellulose derivatives with low degrees of substitution (i.e., DS &lt; 1.5) often fail to reveal glass transition temperatures ( T g ) by virtue of their tenacious adherence to moisture, thus preventing systematic analysis of substituent effects (size and DS) on T g and T m transitions. On the other hand, cellulose triesters have T m s that decline with acyl substituent size except when the substituent size becomes very large (i.e., &gt; C 6 ), and they have T g s within 5–20°C of their T m s. This proximity is unusual for a semicrystalline material, and it interferes with the crystallization process that occurs between T m and T g . Triesters of cellulose with mixed acyl substituents (one smaller and one larger) allow not only unambiguous observation of T g s and T m s but also an adjustable Δ( T m − T g ) window that depends upon the size and the DS of the larger substituent. The materials studied including cellulose acetate butyrate triesters (DS bu 0.8–2.6), cellulose acetate hexanoate triesters (DS hex 0–3.0), and cellulose acetate (DS ac 2.44), revealed that only the mixed esters, in which the bulkier acyl group is in the range of DS 0.3–1.0, had a Δ( T m − T g ) value in excess of 40°C. Although the T m of cellulose acetate hexanoate declined by ca. 150°C per unit of DS hex as DS hex rose from 0 to 1, this was only ca. 25°C between DS hex of 1 and 3. Frequently observed dual‐melt endotherms were attributed to two separate crystal morphologies. ©1995 John Wiley &amp; Sons, Inc.
Hemoconcentration by ultrafiltration during open-heart surgery (1988)

Ultrafiltration was used during extracorporeal circulation (ECC) with heart-lung machine in 17 critically ill cardiac patients. In ultrafiltration (hemofiltration), water and small molecules (e.g. urea, creatinine and electrolytes), are separated from the blood by hydrostatic pressure generated on the blood side of a semipermeable membrane. The patients had severe water overload for three reasons, viz. congestive heart failure (10), renal failure (6) or iatrogenic extreme hemodilution (1). On average 2090 (800-5700) ml water was filtered off, increasing the hematocrit from 25 to 33%. Three indications for ultrafiltration during ECC and two modes of such treatment are exemplified in three case reports. No negative effect of the treatment was observed. Ultrafiltration during ECC thus may help to improve the postoperative course in patients with severe water overload due to congestive heart failure, renal failure or iatrogenic extreme hemodilution.
Functional study of hepatitis delta virus large antigen in packaging and replication inhibition: role of the amino-terminal leucine zipper (1992)

The large hepatitis delta antigen (HDAg) has been found to be essential for the assembly of the hepatitis delta virion. Furthermore, in a cotransfection experiment, the large HDAg itself, without the hepatitis delta virus (HDV) genome and small HDAg, could be packaged into hepatitis B surface antigen (HBsAg) particles. By deletion analysis, it was shown that the amino-terminal leucine zipper domain was dispensable for packaging. The large HDAg could also help in copackaging of the small HDAg into HBsAg particles without the need for HDV RNA. This process was probably mediated through direct interaction of the two HDAgs as a mutated large HDAg whose leucine zipper domain was deleted such that it could not help in copackaging of the small HDAg. This mutated large HDAg did not suppress HDV replication, suggesting that this effect is probably also via protein interaction. These results indicated that functional domains of the large HDAg responsible for packaging with HBsAg particles and for the trans-negative effect on HDV replication can be separated.
Real-time spectral domain Doppler optical coherence tomography and investigation of human retinal vessel autoregulation (2007)

Investigation of the autoregulatory mechanism of human retinal perfusion is conducted with a real-time spectral domain Doppler optical coherence tomography (SDOCT) system. Volumetric, time-sequential, and Doppler flow imaging are performed in the inferior arcade region on normal healthy subjects breathing normal room air and 100% oxygen. The real-time Doppler SDOCT system displays fully processed, high-resolution [512 (axial) x 1000 (lateral) pixels] B scans at 17 frames/sec in volumetric and time-sequential imaging modes, and also displays fully processed overlaid color Doppler flow images comprising 512 (axial) x 500 (lateral) pixels at 6 frames/sec. Data acquired following 5 min of 100% oxygen inhalation is compared with that acquired 5 min postinhalation for four healthy subjects. The average vessel constriction across the population is -16+/-26% after oxygen inhalation with a dilation of 36+/-54% after a return to room air. The flow decreases by -6+/-20% in response to oxygen and in turn increases by 21+/-28% as flow returns to normal in response to room air. These trends are in agreement with those previously reported using laser Doppler velocimetry to study retinal vessel autoregulation. Doppler flow repeatability data are presented to address the high standard deviations in the measurements.
The genome of Cryptosporidium hominis (2004)

Cryptosporidium species cause acute gastroenteritis and diarrhoea worldwide. They are members of the Apicomplexa--protozoan pathogens that invade host cells by using a specialized apical complex and are usually transmitted by an invertebrate vector or intermediate host. In contrast to other Apicomplexans, Cryptosporidium is transmitted by ingestion of oocysts and completes its life cycle in a single host. No therapy is available, and control focuses on eliminating oocysts in water supplies. Two species, C. hominis and C. parvum, which differ in host range, genotype and pathogenicity, are most relevant to humans. C. hominis is restricted to humans, whereas C. parvum also infects other mammals. Here we describe the eight-chromosome approximately 9.2-million-base genome of C. hominis. The complement of C. hominis protein-coding genes shows a striking concordance with the requirements imposed by the environmental niches the parasite inhabits. Energy metabolism is largely from glycolysis. Both aerobic and anaerobic metabolisms are available, the former requiring an alternative electron transport system in a simplified mitochondrion. Biosynthesis capabilities are limited, explaining an extensive array of transporters. Evidence of an apicoplast is absent, but genes associated with apical complex organelles are present. C. hominis and C. parvum exhibit very similar gene complements, and phenotypic differences between these parasites must be due to subtle sequence divergence.
Systematic identification of essential genes by in vitro mariner mutagenesis (1998)

Although the complete DNA sequences of several microbial genomes are now available, nearly 40% of the putative genes lack identifiable functions. Comprehensive screens and selections for identifying functional classes of genes are needed to convert sequence data into meaningful biological information. One particularly significant group of bacterial genes consists of those that are essential for growth or viability. Here, we describe a simple system for performing transposon mutagenesis on naturally transformable organisms along with a technique to rapidly identify essential or conditionally essential DNA segments. We show the general utility of this approach by applying it to two human pathogens, Haemophilus influenzae and Streptococcus pneumoniae, in which we detected known essential genes and assigned essentiality to several ORFs of unknown function.
Re-expression of the Mannose 6-Phosphate Receptors in Receptor-deficient Fibroblasts (1996)

We have previously generated primary embryonic fibroblasts lacking either the cation-independent mannose 6-phosphate/insulin-like growth factor II receptor (MPR) or the cation-dependent MPR, two trans-membrane proteins that bind the mannose 6-phosphate (Man-6-P) recognition marker on soluble lysosomal enzymes (Ludwig, T., Munier-Lehmann, H., Bauer, U., Hollinshead, M., Ovitt, C., Lobel, P., and Hoflack, B.(1994) EMBO J. 13, 3430-3437). These two cell types partially missort phosphorylated lysosomal enzymes. Using two-dimensional gel electrophoresis, we show here that they secrete, in a large part, different phosphorylated ligands. In order to better understand the sorting function of the MPRs, we have re-expressed each MPR in MPR-negative fibroblasts. We show that the MPRs have similar capacities for transporting the bulk of the newly synthesized lysosomal enzymes and that they target individual ligands with various efficiencies. However, high levels of one MPR do not fully compensate for the absence of the other, demonstrating that the two MPRs have complementary targeting functions, perhaps by recognizing different features on lysosomal enzymes. The analysis of the phosphorylated oligosaccharides shows that the ligands missorted in the absence of the cation-dependent MPR are slightly but significantly depleted in oligosaccharides with two Man-6-P residues, when compared with those missorted in the absence of the cation-independent MPR. While these results could explain some differences between the structure and the sorting function of the two MPRs, they strongly suggest that the reason why cells express two different but related MPRs is to maintain an efficient Man-6-P-dependent targeting process that could be potentially regulated by MPR expression.
Two-dimensional multiwavelength surface emittinglaser arraysfabricated by nonplanar MOCVD (1994)

The authors demonstrate two dimensional multiwavelength vertical cavity surface emitting laser (VCSEL) arrays fabricated by using nonplanar metal organic chemical vapour deposition (MOCVD). The resonance wavelength of GaInAs/GaAs VCSELs grown on a patterned substrate is successfully controlled in the wavelength range over 45 nm on wafer. The threshold of multiwavelength VCSELs formed on the patterned substrate is as low as 3 mA.
A Method for Chemical Shift Imaging (1984)

A new method for chemical shift imaging is described. In this method the spin-echo signals are collected with the field gradient switched on, which reduces the imaging time considerably. A human bone marrow pathology is demonstrated by proton chemical shift imaging.
Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study (2013)

Autologous T cells expressing a CD19-specific chimeric antigen receptor (CD19.CAR) are active against B-cell malignancies, but it is unknown whether allogeneic CD19.CAR T cells are safe or effective. After allogeneic hematopoietic stem cell transplantation (HSCT), infused donor-derived virus-specific T cells (VSTs) expand in vivo, persist long term, and display antiviral activity without inducing graft-vs-host disease; therefore, we determined whether donor VSTs, engineered to express CD19.CAR, retained the characteristics of nonmanipulated allogeneic VSTs while gaining antitumor activity. We treated 8 patients with allogeneic (donor-derived) CD19.CAR-VSTs 3 months to 13 years after HSCT. There were no infusion-related toxicities. VSTs persisted for a median of 8 weeks in blood and up to 9 weeks at disease sites. Objective antitumor activity was evident in 2 of 6 patients with relapsed disease during the period of CD19.CAR-VST persistence, whereas 2 patients who received cells while in remission remain disease free. In 2 of 3 patients with viral reactivation, donor CD19.CAR-VSTs expanded concomitantly with VSTs. Hence CD19.CAR-VSTs display antitumor activity and, because their number may be increased in the presence of viral stimuli, earlier treatment post-HSCT (when lymphodepletion is greater and the incidence of viral infection is higher) or planned vaccination with viral antigens may enhance disease control.
Integrating multiple ‘omics’ analysis for microbial biology: application and methodologies (2009)

Recent advances in various 'omics' technologies enable quantitative monitoring of the abundance of various biological molecules in a high-throughput manner, and thus allow determination of their variation between different biological states on a genomic scale. Several popular 'omics' platforms that have been used in microbial systems biology include transcriptomics, which measures mRNA transcript levels; proteomics, which quantifies protein abundance; metabolomics, which determines abundance of small cellular metabolites; interactomics, which resolves the whole set of molecular interactions in cells; and fluxomics, which establishes dynamic changes of molecules within a cell over time. However, no single 'omics' analysis can fully unravel the complexities of fundamental microbial biology. Therefore, integration of multiple layers of information, the multi-'omics' approach, is required to acquire a precise picture of living micro-organisms. In spite of this being a challenging task, some attempts have been made recently to integrate heterogeneous 'omics' datasets in various microbial systems and the results have demonstrated that the multi-'omics' approach is a powerful tool for understanding the functional principles and dynamics of total cellular systems. This article reviews some basic concepts of various experimental 'omics' approaches, recent application of the integrated 'omics' for exploring metabolic and regulatory mechanisms in microbes, and advances in computational and statistical methodologies associated with integrated 'omics' analyses. Online databases and bioinformatic infrastructure available for integrated 'omics' analyses are also briefly discussed.
Cancer Immunotherapy by Targeting IDO1/TDO and Their Downstream Effectors (2015)

The tryptophan (TRP) to kynurenine (KYN) metabolic pathway is now firmly established as a key regulator of innate and adaptive immunity. A plethora of preclinical models suggests that this immune tolerance pathway - driven by the key and rate-limiting enzymes indoleamine-2,3-dioxygenase and TRP-2,3-dioxygenase - is active in cancer immunity, autoimmunity, infection, transplant rejection, and allergy. Drugs targeting this pathway, specifically indoleamine-2,3-dioxygenase, are already in clinical trials with the aim at reverting cancer-induced immunosuppression. In the past years, there has been an increase in our understanding of the regulation and downstream mediators of TRP metabolism, such as the aryl hydrocarbon receptor as a receptor for KYN and kynurenic acid. This more detailed understanding will expand our opportunities to interfere with the pathway therapeutically on multiple levels. Here, we discuss the perspective of targeting TRP metabolism at these different levels based on reviewing recent insight into the regulation of TRP metabolism and its downstream effectors.
Prognostic Value and Link to Atrial Fibrillation of Soluble Klotho and FGF23 in Hemodialysis Patients (2014)

Deranged calcium-phosphate metabolism contributes to the burden of morbidity and mortality in dialysis patients. This study aimed to assess the association of the phosphaturic hormone fibroblast growth factor 23 (FGF23) and soluble Klotho with all-cause mortality. We measured soluble Klotho and FGF23 levels at enrolment and two weeks later in 239 prevalent hemodialysis patients. The primary hypothesis was that low Klotho and high FGF23 are associated with increased mortality. The association between Klotho and atrial fibrillation (AF) at baseline was explored as secondary outcome. AF was defined as presence of paroxysmal, persistent or permanent AF. During a median follow-up of 924 days, 59 (25%) patients died from any cause. Lower Klotho levels were not associated with mortality in a multivariable adjusted analysis when examined either on a continuous scale (HR 1.25 per SD increase, 95% CI 0.84-1.86) or in tertiles, with tertile 1 as the reference category (HR for tertile two 0.65, 95% CI 0.26-1.64; HR for tertile three 2.18, 95% CI 0.91-2.23). Higher Klotho levels were associated with the absence of AF in a muItivariable logistic regression analysis (OR 0.66 per SD increase, 95% CI 0.41-1.00). Higher FGF23 levels were associated with mortality risk in a multivariable adjusted analysis when examined either on a continuous scale (HR 1.45 per SD increase, 95% CI 1.05-1.99) or in tertiles, with the tertile 1 as the reference category (HR for tertile two 1.63, 95% CI 0.64-4.14; HR for tertile three 3.91, 95% CI 1.28-12.20). FGF23 but not Klotho levels are associated with mortality in hemodialysis patients. Klotho may be protective against AF.
Molecular cloning, expression, and chromosomal localization of the human earliest lymphocyte activation antigen AIM/CD69, a new member of the C-type animal lectin superfamily of signal-transmitting receptors. (1993)

The activation of T lymphocytes, both in vivo and in vitro, induces the expression of CD69. This molecule, which appears to be the earliest inducible cell surface glycoprotein acquired during lymphoid activation, is involved in lymphocyte proliferation and functions as a signal transmitting receptor in lymphocytes, natural killer (NK) cells, and platelets. To determine the structural basis for CD69 function, the cDNA coding for CD69 was isolated by a polymerase chain reaction-based strategy using oligonucleotides deduced from peptide sequences of the purified protein. The isolated cDNA exhibited a single open reading frame of 597 bp coding for CD69, and predicted a 199-amino acid protein of type II membrane topology, with extracellular (COOH-terminal), transmembrane, and intracellular domains. The CD69 clone hybridized to a 1.7-kb mRNA species, which was rapidly induced and degraded after lymphocyte stimulation, consistent with the presence of rapid degradation signals at the 3' untranslated region. Transient expression of the polypeptide encoded by CD69 cDNA in COS-7 cells demonstrated that it presented properties comparable to native CD69 protein. The CD69 gene was regionally mapped to chromosome 12 p13-p12 by both somatic cell hybrid DNA analysis and fluorescence in situ hybridization coupled with GTG banding (G bands by trypsin using Giemsa). Protein sequence homology search revealed that CD69 is a new member of the Ca(2+)-dependent (C-type) lectin superfamily of type II transmembrane receptors, which includes the human NKG2, the rat NKR-P1, and the mouse NKR-P1 families of NK cell-specific genes. CD69 also has a structural homology with other type II lectin cell surface receptors, such as the T cell antigen Ly49, the low avidity immunoglobulin E receptor (CD23), and the hepatic asialoglycoprotein receptors. The CD69 protein also shares functional characteristics with most members of this superfamily, which act as transmembrane signaling receptors in early phases of cellular activation.