gebhart/patrepeval huggingface dataset:
Effect of Once Daily Intravenous and Oral Omeprazole on 24-Hour Intragastric Acidity in Healthy Subjects (1993)

The effect of repeated once daily administration of 20 mg omeprazole orally and 10 mg and 40 mg intravenously on 24-h intragastric acidity was studied in nine healthy subjects. On day 1, 20 mg orally and 10 mg intravenously reduced integrated intragastric acidity by 18% and 15%, respectively (NS). On day 5 the reduction had increased to 60% and 53%, respectively (p < 0.05). The first dose of 40 mg intravenously produced a reduction of 71% (p < 0.05) with no further increase during continued administration. An increase in plasma omeprazole concentrations by 56% (p < 0.05) was seen during repeated dosing with 40 mg intravenously, while no significant change occurred with the two other doses. Thus once daily administration of 10 mg omeprazole intravenously produced an effect on 24-h intragastric acidity comparable to that of once daily administration of 20 mg omeprazole orally. However, for both these dosage regimens it took a few days before their maximal effect was obtained. Parenteral administration of 40 mg omeprazole produced, already on the first day of treatment, an effect similar to that seen after 5 days of oral administration of 20 mg omeprazole or intravenous administration of 10 mg and can therefore overcome this initial delay in drug action. The reduction of 24-h intragastric acidity seen in the present study appeared to be lower than that seen in a similar study in duodenal ulcer patients, a finding not explained by differences in age or pharmacokinetics.
Chronic administration of OB protein decreases food intake by selectively reducing meal size in male rats (1998)

The potent hypophagic effect of OB protein (OB) is well established, but the mechanism of this effect is largely unknown. We investigated the effects of chronic administration of a novel modified recombinant human OB (Mod-OB) with a prolonged half-life (>48 h) on ad libitum food intake, spontaneous meal patterns, and body weight in 24 adult, male Sprague-Dawley rats (body weight at study onset: 292 g). Single daily subcutaneous injections of Mod-OB (4 mg/kg daily) for 8 consecutive days significantly reduced ad libitum food intake compared with vehicle injections from injection day 3 through postinjection day 3. Mod-OB-injected rats ate between 4.5 and 7.1 g (or 13-20%) per day less than controls, with the reduction primarily occurring during the dark period. Body weight gain was significantly decreased in response to Mod-OB from injection day 8 until postinjection day 4, with a maximum difference of 24 g on postinjection day 3. The reduction of food intake by Mod-OB was mainly due to a 21-34% decrease in nocturnal spontaneous meal size. There was no significant effect of Mod-OB on nocturnal meal frequency or duration. Mod-OB also did not reliably affect the size, duration, or frequency of diurnal meals. Mod-OB-injected rats displayed no compensatory hyperphagia after the injection period. These results indicate that chronically administered OB selectively affects the mechanisms controlling meal size in male rats.
The Use of Near-Infrared Reflectance Spectroscopy to Predict the Moisture, Nitrogen, Calcium, Total Phosphorus, Gross Energy, and Phytate Phosphorus Contents of Broiler Excreta (2001)

One hundred forty-three broiler chick excreta samples were obtained from previous experiments dealing with phytate phosphorus utilization. The air-dried samples were ground in a Cyclotech 1093 sample mill and analyzed for the following: moisture, N, Ca, energy, total P, and phytate P. By chemical assay, the sample compositions were moisture: mean = 9.62, SD = 1.27% (range = 7.37-13.59); N: mean = 5.31, SD = 0.37% (range = 4.28 to 6.48); Ca: mean = 1.66, SD = 0.32% (range = 0.85 to 2.6); total P: mean = 1.13, SD = 0.28% (range = 0.66 to 1.75); gross energy: mean = 3,560, SD = 120 kcal/kg (range = 3,309 to 3,882); phytate P: mean = 0.63, SD = 0.17% (range = 0.32 to 0.97). The samples were scanned in a Feed & Forage Analyzer Model 5000 with near-infrared reflectance spectroscopy (NIRS)-2 Software. One hundred twenty-three samples were used to create the calibration curves (20 randomly selected samples were set aside for validating the calibration). The combination of math treatments and scatter corrections that provided the best standard error of cross validation (and its correlation coefficient) was chosen for the standard curves. The coefficients of determination (R2) were moisture, 0.96; N, 0.88; Ca, 0.84; total P, 0.91; gross energy, 0.86; and phytate P, 0.86. The standard errors of prediction were moisture, 0.342%; N, 0.193%; Ca, 0.143%; total P, 0.134%; gross energy, 74.66 kcal; and phytate P, 0.91%. We concluded that it is possible to predict the moisture, N, Ca, gross energy, total P, and phytate P in broiler excreta by using NIRS.
Impedance matching and tuning of non-resonant mobile terminal antennas (2013)

The volume reserved for antennas in a mobile handset is very limited. Furthermore, the laws of physics state that the efficiency and/or the bandwidth of a small antenna are also limited. Despite this fact, the antennas of the future mobile terminals should operate efficiently at increasingly many frequency bands. This doctoral thesis contributes to solving some of the main challenges arising from the theoretical and practical limitations of handset antennas.&#13;\nNon-resonant capacitive coupling element (CCE) based antennas are an attractive option for future mobile handsets, having many useful characteristics such as compact size and broad frequency tunability. A circuit model improving the physical understanding of the operation of a capacitive coupling element antenna is developed in the thesis work. This work also advances the usability of CCE antennas by developing impedance matching and tuning solutions as enablers of future mobile communication systems, including software defined radio. The properties of non-self-resonant antennas are utilized in developing novel multi-band antennas for mobile terminals. A method for implementing simultaneous multi-band operation of single-element CCE antennas is developed, based on a novel diplexing impedance matching circuit and a distributed CCE feeding structure. The realized prototypes operate at 4th generation mobile communication system (LTE-A) frequency bands 698—960 MHz and 1710—2690 MHz, reaching state-of-the-art performance. This versatile CCE structure is shown to operate equally well with single- or dual-feed RF front-end interfaces. Broadband tunable antenna prototypes are realized as a proof of concept regarding CCE tunability. Also design rules for avoiding excess losses and nonlinearity in tuning circuits are given, based on numerical and experimental analyses.&#13;\nAn antenna in a mobile terminal is also subject to electromagnetic interaction with the user of the handset. This interaction deteriorates the operation of the antenna through absorption of power and detuning of the antenna impedance. In this work, methods for avoiding the impedance detuning are developed. CCE geometry design and antenna selection diversity areshown to decrease the impedance mismatch and improve radiation efficiency by up to 4 dB in total in the case of some typical hand grips. Also matching circuits that result in improved robustness against the mistuning are studied and developed.
Molecular characterization of 4-hydroxyphenylacetate 3-hydroxylase of Escherichia coli. A two-protein component enzyme. (1994)

The nucleotide sequences of the hpaB and hpaC genes encoding the 4-hydroxyphenylacetate 3-hydroxylase from Escherichia coli W ATCC 11105 have been determined. These genes appear to be part of an operon and encode two proteins of 58,781 and 18,679 Da, respectively, that are required for hydroxylase activity. This aromatic hydroxylase is NADH-dependent and uses FAD as the redox chromophore. The largest component (HpaB) has been purified by affinity chromatography in Cibacron blue. E. coli cells that express exclusively hpaB showed only a very low hydroxylase activity that was enhanced in the presence of extracts containing the smallest protein HpaC. This behavior resembles that of the coupling protein of the 4-hydroxyphenylacetate 3-hydroxylase from Pseudomonas putida, and it might prevent the wasteful oxidation of NADH in the absence of substrate. Using a promoter-probe plasmid we have demonstrated that the hpaBC operon is expressed by a promoter inducible by 4-hydroxyphenylacetic acid. A gene, named hpaA, encoding a protein homologous to the XylS/AraC family of regulators, was identified upstream of the hydroxylase operon. The role played by HpaA in the regulation of the hpaBC operon remains to be elucidated. Since HpaB is not homologous to other aromatic hydroxylases, we suggest that the E. coli 4-hydroxyphenylacetate 3-hydroxylase is the first member of a new family of two-component aromatic hydroxylases sequenced so far.
Changes in the platelet membrane glycoprotein IIb.IIIa complex during platelet activation. (1985)

Platelet activation is accompanied by the appearance on the platelet surface of approximately 45,000 receptor sites for fibrinogen. The binding of fibrinogen to these receptors is required for platelet aggregation. Although it is established that the fibrinogen receptor is localized to a heterodimer complex of the membrane glycoproteins, IIb and IIIa, little is known about the changes in this complex during platelet activation that result in the expression of the receptor. In the present studies, we have developed and characterized a murine monoclonal anti-platelet antibody, designated PAC-1, that binds to activated platelets, but not to unstimulated platelets. PAC-1 is a pentameric IgM that binds to agonist-stimulated platelets with an apparent Kd of 5 nM. Binding to platelets is dependent on extracellular Ca2+ (KCa = 0.4 microM) but is not dependent on platelet secretion. Platelets stimulated with ADP or epinephrine bind 10,000-15,000 125I-PAC-1 molecules/platelet while platelets stimulated with thrombin bind 20,000-25,000 molecules/platelet. Several lines of evidence indicate that PAC-1 is specific for the glycoprotein IIb.IIIa complex. First, PAC-1 binds specifically to the IIb.IIIa complex on Western blots. Second, PAC-1 does not bind to thrombasthenic platelets or to platelets preincubated with ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid at 37 degrees C, both of which lack the intact IIb.IIIa complex. Third, PAC-1 competitively inhibits the binding of 125I-A2A9, and IgG monoclonal antibody that is specific for the IIb.IIIa complex. Fourth, the antibody inhibits fibrinogen-mediated platelet aggregation. These data demonstrate that PAC-1 recognizes an epitope on the IIb.IIIa complex that is located near the platelet fibrinogen receptor. Platelet activation appears to cause a Ca2+-dependent change involving the glycoprotein IIb.IIIa complex that exposes the fibrinogen receptor and, at the same time, the epitope for PAC-1.
C5a receptor antagonists for the treatment of inflammation. (2004)

The anaphylatoxin C5a is a classic, potent inflammatory mediator, with biological activities that have been implicated in a variety of diseases. As a result of two decades of study, C5a receptor antagonists that prevent high-affinity binding of C5a to its receptor have been discovered, which show therapeutic effects in various inflammatory disease models. Moreover, the involvement of C5a in disease models has been demonstrated in various experiments using C5/C5a receptor-deficient mice and anti-C5/C5a antibodies. It is therefore anticipated that these antagonists will have potential as novel anti-inflammatory therapeutics.
Kinetic characterization of ribonuclease S mutants containing photoisomerizable phenylazophenylalanine residues (2001)

Incorporation of the photoisomerizable amino acid phenylazophenylalanine (PAP) into enzyme structures has been proposed as a strategy for photoswitching enzyme activity. To evaluate the strengths and limitations of this approach to enzyme photo-control, we performed a kinetic analysis of RNase S analogues containing PAP in positions 4, 7, 8, 10, 11 or 13. For an enzyme containing a single PAP group, the maximum extent of photoconversion (between approximately 96% trans/4% cis and 10% trans/90% cis under standard conditions) sets a limit on the maximum fold change in the initial rate of approximately 25-fold, if the cis form is the more active isomer, and approximately 10-fold if the trans form is more active. This extent of photoswitching was not realized in the present case because the effects of photoisomerization on kinetic constants were small and distributed among effects on S-peptide binding, substrate binding and the rate of the chemical step. These results suggest that photoisomerization could substantially alter enzyme kinetic constants but that a directed combinatorial approach might be required for realizing maximal photo-control in such systems. The limit set by the extent of photoconversion might be overcome by coupling multiple PAP groups to one enzyme or by altering the behaviour of a system that required oligomerization for activity.
Identical 3′-terminal octanucleotide sequence in 18S ribosomal ribonucleic acid from different eukaryotes. A proposed role for this sequence in the recognition of terminator codons (1974)

The 3'-terminal sequence of 18S ribosomal RNA from Drosophila melanogaster and Saccharomyces cerevisiae was determined by stepwise degradation from the 3'-terminus and labelling with [(3)H]isoniazid. The sequence G-A-U-C-A-U-U-A(OH) was found at the 3'-terminus of both 18S rRNA species. Less extensive data for 18S RNA from a number of other eukaryotes are consistent with the same 3'-terminal sequence, and an identical sequence has previously been reported for the 3'-end of rabbit reticulocyte 18S rRNA (Hunt, 1970). These results suggest that the base sequence in this region is strongly conserved and may be identical in all eukaryotes. As the 3'-terminal hexanucleotide is complementary to eukaryotic terminator codons we discuss the possibility that the 3'-end of 18S rRNA may have a direct base-pairing role in the termination of protein synthesis.
Genomics and proteomics tools for the clinic. (2000)

The sequencing of the human genome was only made possible by the massively parallel use of automated high-throughput technologies. These technologies have required the development and interfacing of new hardware and software in a way which would have been hardly conceivable only ten years ago. As a consequence, an unbroken trend to more 'industrialized science' is apparent. The wealth of information generated by intensive sequencing efforts is now being further exploited by using complex tools to comprehensively analyze complex systems at the DNA, RNA and protein level. A landmark innovation was the introduction of the biochip principle, best exemplified with the development of the DNA chip, mainly used for RNA expression profiling. The chip principle, together with miniaturization, has now become the dominating theme for a number of new genomics and proteomics technologies, culminating in the lab-on-a-chip concept which, in the next five to ten years, could advance at a comparable rate to that of computers over the last 50 years. Some of the new technologies are already used for comprehensive analysis of clinical samples in an attempt to describe disease and disease risk at the molecular level. However, all of these technologies are far from routine in clinical use and it is also too early to decide whether molecular fingerprints or signature profiles will have the diagnostic and prognostic power currently predicted.
The Role of the Chemokines in Myocardial Ischemia and Reperfusion (2004)

Chemokines critically regulate basal and inflammatory leukocyte trafficking and may play a role in angiogenesis. This review summarizes our current understanding of the regulation and potential role of the chemokines in myocardial ischemia and reperfusion. Reperfused myocardial infarction is associated with an inflammatory response leading to leukocyte recruitment, healing and scar formation. Neutrophil chemoattractants, such as the CXC chemokine CXCL8/Interleukin (IL)-8, are upregulated in the infarcted area inducing polymorphonuclear leukocyte infiltration. In addition, mononuclear cell chemoattractants, such as the CC chemokine CCL2/Monocyte Chemoattractant Protein (MCP)-1, are expressed, leading to monocyte and lymphocyte recruitment in the ischemic area. However, chemokines may have additional effects in healing infarcts beyond their leukotactic properties. We have recently described a marked transient induction of the angiostatic CXC chemokine CXCL10/Interferon-gamma inducible Protein (IP)-10 in the infarct. Upregulation of angiostatic factors, such as IP-10, in the first few hours following injury may inhibit premature angiogenesis, until the infarct is debrided and appropriate supportive matrix is formed. Suppression of IP-10 synthesis during the healing phase may allow formation of the wound neovessels, a critical process for infarct healing. Chemokine expression is also noted after a single brief ischemic insult in the absence of myocardial infarction, suggesting a potential role for a chemokine-induced inflammatory response in noninfarctive ischemic cardiomyopathy. Unlike cytokines, which have pleiotropic effects, chemokines have more specific cellular targets. Understanding of their role in myocardial infarction may allow us to design specific therapeutic strategies aiming at optimizing cardiac repair and preventing ventricular remodeling.
New perspectives on APC control of cell fate and proliferation in colorectal cancer (2009)

Aberrant Wnt/beta-catenin signaling following loss of the tumor suppressor adenomatous polyposis coli (APC) is thought to initiate colon adenoma formation. Considerable evidence for this model has come from mouse models of Apc truncation where nuclear beta-catenin is detectable soon after loss of Apc. However, examination of tumors from familial adenomatous polyposis coli (FAP) patients has failed to confirm the presence of nuclear beta-catenin in early lesions following APC loss despite robust staining in later lesions. This observation presents the possibility that colon adenomas arise through a beta-catenin-independent function of APC. Additionally, there is a well established role for inflammation and specifically COX-2 and prostaglandin E2 in the progression of colorectal cancer. Here we review the current literature regarding the functions of APC in regulating WNT/beta-catenin signaling as well as its control of intestinal cell fate and differentiation. Further, we provide a brief commentary on our current understanding of the role that inflammation plays in colorectal tumorigenesis and how it fits in with APC dysfunction. Though there are currently contrasting models to explain colon tumorigenesis, our goal is to begin to reconcile data from multiple different model systems and provide a functional view into the initiation and progression of colon cancer.
Genetic analysis of the low calcium response in Yersinia pestis mu d1(Ap lac) insertion mutants (1984)

Yersinia pestis strain KIM requires plasmid pCD1 for expression of the low calcium response, plague virulence antigen V, and virulence. We constructed Mu d1(Ap lac) insertion mutants of this plasmid which were unable to express the low calcium response. The insertions mapped to a 17-kilobase region of the plasmid. By determining the orientation of the insertions and examining beta-galactosidase production from the Mu d1 lac genes, we determined that this region contains three units of transcription, one of which is transcribed in a direction opposite the direction of transcription of the other two. Transcription of at least two of these units was induced significantly at 37 degrees C compared with 26 degrees C. Ca2+ (2.5 mM) and ATP (18 mM) had no significant effect on the level of expression of the Mu d1 lac genes of these mutants. All insertions in the region strongly reduced production of the V antigen. Insertions from each unit of transcription also reduced virulence in mice.
Mode of Action of Interleukin-6 on Mature Osteoclasts. Novel Interactions with Extracellular Ca2+ Sensing in the Regulation of Osteoclastic Bone Resorption (1998)

We describe a physiologically significant mechanism through which interleukin-6 (IL-6) and a rising ambient Ca2+ interact to regulate osteoclastic bone resorption. VOXEL-based confocal microscopy of nonpermeabilized osteoclasts incubated with anti- IL-6 receptor antibodies revealed intense, strictly peripheral plasma membrane fluorescence. IL-6 receptor expression in single osteoclasts was confirmed by in situ reverse transcriptase PCR histochemistry. IL-6 (5 ng/l to 10 microg/l), but not IL-11 (10 and 100 microg/l), reversed the inhibition of osteoclastic bone resorption induced by high extracellular Ca2+ (15 mM). The IL-6 effect was abrogated by excess soluble IL-6 receptor (500 microg/l). Additionally, IL-6 (5 pg/l to 10 microg/l) inhibited cytosolic Ca2+ signals triggered by high Ca2+ or Ni2+. In separate experiments, osteoclasts incubated in 10 mM Ca2+ or on bone released more IL-6 than those in 1.25 mM Ca2+. Furthermore, IL-6 mRNA histostaining was more intense in osteoclasts in 10 or 20 mM Ca2+ than cells in 1.25 mM Ca2+. Similarly, IL-6 receptor mRNA histostaining was increased in osteoclasts incubated in 5 or 10 mM Ca2+. Thus, while high Ca2+ enhances IL-6 secretion, the released IL-6 attenuates Ca2+ sensing and reverses inhibition of resorption by Ca2+. Such an autocrine-paracrine loop may sustain osteoclastic activity in the face of an inhibitory Ca2+ level generated locally during resorption.
Panoptic DVS: A fine-grained dynamic voltage scaling framework for energy scalable CMOS design (2009)

The energy efficiency of a CMOS architecture processing dynamic workloads directly affects its ability to provide long battery lifetimes while maintaining required application performance. Existing scalable architecture design approaches are often limited in scope, focusing either only on circuit-level optimizations or architectural adaptations individually. In this paper, we propose a circuit/architecture co-design methodology called Panoptic Dynamic Voltage Scaling (PDVS) that makes more efficient use of common circuit structures and algorithm-level processing rate control. PDVS expands upon prior work by using multiple component-level PMOS header switches to enable fine-grained rate control, allowing efficient dithering among statically scheduled algorithms with sub-block energy savings. This way, PDVS is able to achieve a wide variety of processing rates to match incoming workload as closely as possible, while each iteration takes less energy to process than on architectures with coarser levels of rate control. Measurements taken from a fabricated 90 nm test chip characterize both savings and overheads and are used to inform PDVS synthesis decisions. Results show that PDVS consumes up to 34% and 44% less energy than Multi-VDD and Single-VDD systems, respectively.