gebhart/patrepeval huggingface dataset:
Comparative pharmacokinetics and pharmacodynamics of lansoprazole oral capsules and suspension in healthy subjects (2001)

The pharmacokinetics and pharmacodynamics of lansoprazole suspension and lansoprazole capsules were studied. Thirty-six healthy males and females were randomized in a single-dose, open-label, two-period crossover study. Lansoprazole 30 mg was administered via a nasogastric tube as simplified lansoprazole suspension (in 8.4% sodium bicarbonate) or orally as the intact capsule after a minimum 12-hour fast and 5 hours before lunch. Ambulatory 24-hour intragastric pH was monitored at baseline and on day 1 of each treatment period to assess lansoprazole's pharmacodynamics. Blood samples were collected before drug administration and at predetermined intervals up to 24 hours after each dose to assess lansoprazole's pharmacokinetics. Both formulations effectively raised the mean 24-hour intragastric pH (mean 24-hour pH of 3.75 with suspension and 3.52 with intact capsule) and maintained it above threshold values of 3 and 4 for more than 40% of the 24-hour postdose period. The suspension was associated with a significantly shorter mean time to the maximum observed concentration (tmax) compared with the intact capsule. The mean maximum observed plasma concentration (Cmax) of the suspension was significantly higher and the mean area under the concentration-time curve from time zero to infinity (AUC infinity) was significantly lower than those of the intact capsule (879 versus 810 ng/mL and 1825 versus 2229 ng.hr/mL). The 90% confidence intervals obtained by two one-sided tests for both Cmax and AUC infinity were contained within the 0.80 to 1.25 range, confirming the bioequivalence of the two regimens. Simplified lansoprazole suspension effectively controls intragastric pH, is bioequivalent to the intact capsule, and represents an effective therapeutic option for patients who have difficulty swallowing or are unable to swallow lansoprazole capsules.
Detection of clonal B cell populations in paraffin-embedded tissues by polymerase chain reaction. (1993)

A method was established to detect clonal B cell populations in frozen and paraffin-embedded tissues. The method is based on the polymerase chain reaction amplification of rearranged VH and V kappa genes using V gene family-specific primers. Monoclonal B cell populations could be detected in peripheral blood lymphocyte DNA in all 16 cases of B-CLL and immunocytoma investigated and in 8 of 10 cases of B cell non-Hodgkin's lymphoma using frozen and paraffin sections. The amplification of V kappa rearrangements in addition to the VH amplification is a useful tool to verify the results of the heavy chain rearrangement and to detect proliferation of a B cell clone in cases in which no VH product was obtained. In spite of the degradation of DNA in paraffin-embedded tissues, we were able to find amplified polymerase chain reaction products of about 350 bp length in 8 of 10 cases analyzed. The method presented here may be helpful in routine diagnosis of B cell non-Hodgkin's lymphoma using frozen or paraffin-embedded specimens.
A low complexity ML channel estimator for OFDM (2002)

Orthogonal frequency-division multiplexing (OFDM) with cyclic prefix enables low cost frequency-domain mitigation of multipath distortion. However, to determine the equalizer coefficients, knowledge of the channel frequency response is required. While a straightforward approach is to measure the response to a known pilot symbol sequence, existing literature reports a significant performance gain when exploiting the frequency correlation properties of the channel. Expressing this correlation by the finite delay spread, we build a deterministic model parametrized by the channel impulse response and, based on this model, derive the maximum likelihood (ML) channel estimator. In addition to being optimal, this estimator receives an elegant time-frequency interpretation. As a result, it has a significantly lower complexity than previously published methods.
Relation of markers of inflammation (C-reactive protein, white blood cell count, and lipoprotein-associated phospholipase A2) to the ankle brachial index (2004)

Markers of inflammation are predictive of cardiovascular events but their association with atherosclerotic burden remains poorly defined. We hypothesized that markers of inflammation, including C-reactive protein (CRP), white blood cell (WBC) count, and lipoprotein-associated phospholipase A2 (Lp-PLA2), would be associated with the ankle-brachial index (ABI), a marker of atherosclerotic burden. Subjects were 247 patients referred for lower extremity arterial evaluation to the non-invasive vascular laboratory excluding those with active infection or lower extremity revascularization within the previous year. ABI was measured at two sites in both legs and the lowest of four measurements was used in the analyses. CRP was measured by a high-sensitivity immunoturbidimetric assay and Lp-PLA2 was measured by ELISA. The mean patient age was 68+/-11 years, and 54% were men. Mean ABI was 0.84+/-0.31 and 49% had an ABI < 0.9. Age, hypertension, fasting plasma glucose, and 'ever' smoking were independently associated with the ABI. Spearman correlation coefficients of inflammatory markers with the ABI were: CRP (r = -0.15, p= 0.02), WBC count (r = -0.27, p = 0.001), and Lp-PLA2 (r = -0.09, p = 0.21). In a multiple regression model that included conventional risk factors and statin use, CRP and WBC count were no longer significantly associated with ABI, whereas Lp-PLA2 was a borderline-significant predictor of lower ABI (p = 0.05). These data indicate that CRP and WBC count are not independently associated with ABI, a marker of atherosclerotic burden in subjects referred for non-invasive lower extremity arterial evaluation. The association of Lp-PLA2 with ABI merits further study.
Structural characterization of the oligosaccharide chains of native and crystallized boar seminal plasma spermadhesin PSP‐I and PSP‐II glycoforms (1999)

The PSP-I/PSP-II heterodimer is the major protein of boar seminal plasma. Both subunits are glycoproteins of the spermadhesin family and each contains a single N-glycosylation site. After enzymatic release of the oligosaccharides from isolated PSP-I and PSP-II, mainly neutral and monosialylated oligosaccharides, and small amounts of disialylated oligosaccharides, were recovered from both proteins. Twenty-two neutral oligosaccharides, 11 monosialylated glycans and three disialylated carbohydrate chains were characterized using mass spectrometric and NMR techniques. PSP-I and PSP-II share the same glycans but differ in their relative molar ratios. Most glycan structures are proximally alpha1-6-fucosylated, diantennary complex-type bearing nonsialylated or alpha2-6-sialylated N-acetyllactosamine or di-N-acetyllactosamine antennae. The majority of nonsialylated N-acetyllactosamine antennae bear terminal alpha1-3-linked Gal residues. In addition, the N-acetylglucosamine residue of nonsialylated N-acetyl and di-N-acetyllactosamine antennae can be modified by an alpha1-3-linked fucose residue. Structures of higher antennarity, as well as structures 3,6-branched at galactose residues, were found in smaller amounts. In one oligosaccharide, N-acetylneuraminic acid is substituted by N-glycolylneuraminic acid. Mass spectrometric analysis of PSP-I and PSP-II glycoforms isolated from crystallized PSP-I/PSP-II heterodimer showed the coexistence of major PSP-I and PSP-II glycoforms in the hexagonal crystals. Oligosaccharides with the NeuNAcalpha2-6GalNAcbeta1-4GlcNAc-R motif block adhesive and activation-related events mediated by CD22, suggesting a possible immunoregulatory activity for PSP-I/PSP-II.
Favorable Effects of Hyaluronidase on Electrocardiographic Evidence of Necrosis in Patients with Acute Myocardial Infarction (1977)

To evaluate hyaluronidase's effect in reducing post-infarction myocardial necrosis, we randomized 91 patients with anterior infarction to control (45) or to hyaluronidase-treatment (46) groups. A 35-lead precordial electrocardiogram was recorded on admission and seven days later. Hyaluronidase was administered intravenously after the first electrocardiogram and every six hours for 48 hours. QRS-complex changes were analyzed to assess the drug's effect. Precordial sites with ST-segment elevation (larger than or equal to 0.15 mV) on the initial electrocardiogram that retained an R wave were considered vulnerable for the development of electrocardiographic signs of necrosis. The sum of R-wave voltages of vulnerable sites fell more in the control group than in the hyaluronidase group (70.9 +/- 3.6 per cent [+/- 1 S.E.M.] vs 54.2 +/- 5.0 per cent P less than 0.01). Q waves appeared in 59.3 +/- 4.9 per cent of the vulnerable sites in control versus 46.4 +/- 4.9 per cent in hyaluronidase-treated patients (P less than 0.05). Thus, hyaluronidase reduced the frequency of electrocardiographic signs of myocardial necrosis.
Epstein-Barr Virus Latent Membrane Protein 1 Induces Cellular MicroRNA miR-146a, a Modulator of Lymphocyte Signaling Pathways (2007)

The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is a functional homologue of the tumor necrosis factor receptor family and contributes substantially to the oncogenic potential of EBV through activation of nuclear factor kappaB (NF-kappaB). MicroRNAs (miRNAs) are a class of small RNA molecules that are involved in the regulation of cellular processes such as growth, development, and apoptosis and have recently been linked to cancer phenotypes. Through miRNA microarray analysis, we demonstrate that LMP1 dysregulates the expression of several cellular miRNAs, including the most highly regulated of these, miR-146a. Quantitative reverse transcription-PCR analysis confirmed induced expression of miR-146a by LMP1. Analysis of miR-146a expression in EBV latency type III and type I cell lines revealed substantial expression of miR-146a in type III (which express LMP1) but not in type I cell lines. Reporter studies demonstrated that LMP1 induces miR-146a predominantly through two NF-kappaB binding sites in the miR-146a promoter and identified a role for an Oct-1 site in conferring basal and induced expression. Array analysis of cellular mRNAs expressed in Akata cells transduced with an miR-146a-expressing retrovirus identified genes that are directly or indirectly regulated by miR-146a, including a group of interferon-responsive genes that are inhibited by miR-146a. Since miR-146a is known to be induced by agents that activate the interferon response pathway (including LMP1), these results suggest that miR-146a functions in a negative feedback loop to modulate the intensity and/or duration of the interferon response.
Silica-based single-mode waveguides on silicon and their application to guided-wave optical interferometers (1988)

Low-loss silica-based single-mode waveguides and directional couplers are fabricated on silicon substrates. Their application to Mach-Zehnder interferometer type guided-wave devices is demonstrated. Optical switches or tunable optical couplers are fabricated using the thermooptic effect. Asymmetrical Mach-Zehnder interferometers are successfully applied to multi/demultiplexers for optical FDM transmission systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Effects of molecular organization on exciton diffusion in thin films of bioinspired light-harvesting molecules (2009)

Efficient exciton diffusion in light-harvesting organic materials is of great importance for the development of cheap and flexible photovoltaic devices. Bioinspired molecular materials such as derivatives of phthalocyanine and porphyrin offer promising prospects for the realization of efficient exciton diffusion. The chemical composition of these molecules is found to strongly affect the molecular organization in thin films and in turn the efficiency of exciton diffusion. High singlet exciton diffusion coefficients exceeding 10−6 m2 s−1 have been found. This value is similar to that for the natural chlorosomal bacterio-chlorophyll, which exhibits the highest exciton diffusion coefficient for self-assembled systems.
Molecular cytogenetics in metaphase and interphase cells for cancer and genetic research, diagnosis and prognosis. Application in tissue sections and cell suspensions. (2002)

As the pioneer among molecular cytogenetics techniques, fluorescence in situ hybridization (FISH) allows identification of specific sequences in a structurally preserved cell, in metaphase or interphase. This technique, based on the complementary double-stranded nature of DNA, hybridizes labeled specific DNA (probe). The probe, bound to the target, will be developed into a fluorescent signal. The fact that the signal can be detected clearly, even when fixed in interphase, improves the accuracy of the results, since in some cases it is extremely difficult to obtain mitotic samples. FISH is still used mostly in research, but there are diagnostic applications. New nomenclature is being developed in order to define many of the aberrations that were not distinguished before FISH. Prenatal diagnosis of aneuploidies and malignancies are promptly detected with FISH, which is very useful in critical cases. In some tumors, where chromosomal abnormalities are too complicated to classify manually, the technique of comparative genomic hybridization (CGH), a competitive FISH, allows examiners to determine complete or partial gain or loss of chromosomes. CGH results allow the classification of many tumor cell lines and along with other complementary techniques, like microdissection-FISH, PRINS, etc., increase the possibility of choosing an appropriate treatment for cancer patients.
Enhanced sialylation of EPO by overexpression of UDP‐GlcNAc 2‐epimerase/ManAc kinase containing a sialuria mutation in CHO cells (2007)

Sialylation (e.g. expression of sialic acid) plays a crucial role for function and stability of most glycoproteins. The key enzyme for the biosynthesis of sialic acid is the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine-kinase (GNE). Mutations in the binding site of the feedback inhibitor CMP-sialic acid of the GNE leads to sialuria, a disease in which patients produce sialic acid in gram scale. Here, we report on the use in biotechnology of sialuria-mutated GNE. Expression of the sialuria-mutated GNE in CHO-cells leads to increased sialylation of recombinant expressed erythropoietin (EPO). Our data show that sialuria-mutated-GNE over-expressing cells are the perfect platform to express highly sialylated therapeutic proteins, such as EPO.
Involvement of aspartic and glutamic residues in kringle-2 of tissue-type plasminogen activator in lysine binding, fibrin binding and stimulation of activity as revealed by chemical modification and oligonucleotide-directed mutagenesis (1990)

Modification of glutamic and aspartic acid residues of tissue-type plasminogen activator (t-PA) with 1-ethyl-3(3-dimethyl-aminopropyl)-carbodiimide leads to a decrease in affinity for lysine and fibrin, to a decrease of plasminogen activation activity in the presence of a fibrin mimic, but leaves amidolytic activity and plasminogen activation without fibrin mimic unaffected. Experiments with kringle-2 ligands and a deletion mutant of t-PA (K2P) suggests that glutamic or aspartic acid residues in K2 of t-PA are involved in stimulation of activity, lysine binding and fibrin binding. Mutant t-PA molecules were constructed by site-directed mutagenesis in which one or two of the five aspartic or glutamic acid residues in K2 were changed to asparagine or glutamine respectively. Mutation of Asp236 and/or Asp238 leads to t-PA molecules with 3- to 4-fold lower specific activity in the presence of fibrin mimic and having no detectable affinity for lysine analogs. However, fibrin binding was not influenced. Mutation of Glu254 also leads to a 3- to 4-fold lower activity, but to a much smaller reduction of lysine or fibrin binding. Residues Asp236 and Asp238 are both essential for binding to lysine derivatives, while Glu254 might be involved but is not essential. Residues Asp236, Asp238 and Glu254 are all three involved in stimulation of activity. Remarkably, mutation of residues Asp236 and/or Asp238 appears not to influence fibrin binding of t-PA whereas that of Glu254 does.
Sacral neuromodulation in diabetic patients: Success and complications in the treatment of voiding dysfunction (2009)

No difference in long-term success rates was seen in diabetic patients when compared with similar, non-diabetic patients. Diabetic patients did, however, have a higher incidence of device explantation due to infection.
Adaptive query processing in data stream management systems (2005)

SPECT/CT imaging provides regional quantification of skeletal muscle perfusion reserve which is significantly associated with exercise tolerance and cardiovascular fitness. Future application of SPECT/CT may elucidate the underlying skeletal muscle adapations to exercise therapy in patients with cardiovascular diseases.
The Double Life of the Ku Protein: Facing the DNA Breaks and the Extracellular Environment (2005)

The Ku heterodimer (Ku70/Ku80) plays a central role in DNA double strand break recognition and repair. It has been shown, more than ten years ago, that Ku is also expressed at the cell surface of different cells types along with its intracellular pool within the nucleus and the cytoplasm but involvement of Ku in cell-cell and cell-extracellular matrix adhesion has been only recently demonstrated. In addition, we have shown that Ku may have a second and unexpected activity in cell/microenvironment interaction. Indeed, Ku appears to be involved in extracellular proteolytic processes through its specific interaction, on the cell surface, with the matrix metalloprotease 9. Taken together, these results suggest that Ku function at the cell surface is likely to be important in tumour invasion. Various fundamental questions arise from these observations. How Ku is expressed on the cell surface, why a protein with completely unrelated functions also serve as an integrin-like molecule once expressed at the cell surface and is this functional moonlighting of Ku related to cell transformation remain open issues that will be discussed here.
Neurotrophins in healthy and diseased skin (2011)

Neurotrophins (NT) belong to a family of structurally and functionally related proteins that, depending on the tissue context and the receptors involved, promote either neuronal cell survival and differentiation or cell death. NT, and in particular NGF, were first identified as neurotrophic factors supporting the synthesis and development of sensory neurons in the central and peripheral nervous system. It is now widely accepted that NT also act as growth factors in non-neuronal cells, including the skin. In the skin, most cell types are able to secrete and/or to respond to stimulation by NT, creating a unique network of molecular signaling in the cutaneous microenvironment. Moreover, many skin diseases have been associated with an involvement of a number of neural factors including NT, but less attention has been given to the role of NT as growth factors in the development of skin pathologies. This review summarizes currently data on the expression and function of NT and their receptors in several cell types in the skin. Moreover it focuses on the role of the skin NT network in two cutaneous conditions, melanoma and psoriasis where NT are clearly involved.
Superparamagnetic Iron Oxide Nanoparticles Function as a Long-Term, Multi-Modal Imaging Label for Non-Invasive Tracking of Implanted Progenitor Cells (2014)

The purpose of this study was to determine the ability of superparamagnetic iron oxide (SPIO) nanoparticles to function as a long-term tracking label for multi-modal imaging of implanted engineered tissues containing muscle-derived progenitor cells using magnetic resonance imaging (MRI) and X-ray micro-computed tomography (μCT). SPIO-labeled primary myoblasts were embedded in fibrin sealant and imaged to obtain intensity data by MRI or radio-opacity information by μCT. Each imaging modality displayed a detection gradient that matched increasing SPIO concentrations. Labeled cells were then incorporated in fibrin sealant, injected into the atrioventricular groove of rat hearts, and imaged in vivo and ex vivo for up to 1 year. Transplanted cells were identified in intact animals and isolated hearts using both imaging modalities. MRI was better able to detect minuscule amounts of SPIO nanoparticles, while μCT more precisely identified the location of heavily-labeled cells. Histological analyses confirmed that iron oxide particles were confined to viable, skeletal muscle-derived cells in the implant at the expected location based on MRI and μCT. These analyses showed no evidence of phagocytosis of labeled cells by macrophages or release of nanoparticles from transplanted cells. In conclusion, we established that SPIO nanoparticles function as a sensitive and specific long-term label for MRI and μCT, respectively. Our findings will enable investigators interested in regenerative therapies to non-invasively and serially acquire complementary, high-resolution images of transplanted cells for one year using a single label.
Formation of experimental murine AA amyloid fibrils in SAP-deficient mice: High resolution ultrastructural study (2005)

Previously, the role of the serum amyloid P component (SAP) in the deposition of murine AA amyloid has been examined in SAP-deficient mice in which the deposition was significantly retarded. In this study, AA amyloid fibrillogenesis in SAP-deficient mice was examined ultrastructurally. The fibrils of wild type mice were made up of a microfibril-like main body composed of SAP, chondroitin sulfate proteoglycan (CSPG), and outermost heparan sulfate proteoglycan (HSPG), and associated on its surface were 3 nm wide AA protein 'helical rods', a possible suitable form for Congo red staining. In SAP-deficient mice, fibrils of a similar appearance were also noted among an overwhelming amount of amorphous material, but the AP-containing main body of the fibril was replaced by elongated irregular aggregates of CSPG. The mechanism of retardation of AA amyloid induction in SAP-deficient mice has not yet been clear. It may be caused by possible slower formation of a 'substitute' core. Also, slower formation of AA helical rods may be possible due to the difference in the core material to which AA protein is attached. If it is so, it may limit the extent of Congo red staining, resulting in underestimation of the actual amount of AA protein.