gebhart/patrepeval huggingface dataset:
Cat Iris Sphincter Smooth-Muscle Contraction: Comparison of FP-Class Prostaglandin Analog Agonist Activities (2008)

The pharmacologic characteristics of a number of FP-class prostaglandin (PG) analogs were determined by using the cat iris sphincter smooth-muscle-contraction assay. Cumulative concentration-response curves were generated for each compound. The relative agonist potencies (EC(50)) of the compounds were: cloprostenol (0.0012 +/- 0.0004 nM) >> travoprost acid (0.46 +/- 0.13 nM) = bimatoprost acid (0.99 +/- 0.19 nM) > (+/-)-fluprostenol (15.8 +/- 2.6 nM) = PGF(2alpha) (18.6 +/- 1.8 nM) > latanoprost acid (29.9 +/- 1.6 nM) > bimatoprost (140 +/- 45 nM) > S-1033 (588 +/- 39 nM) > unoprostone (UF-021; 1280 +/- 50 nM; n = 4-14). The maximum response induced by travoprost acid (122% +/- 2.3% maximum response relative to PGF(2alpha)) was significantly greater than that induced by all the other PG compounds (P < 0.001 - P < 0.02). Interestingly, the FP-receptor antagonist, AL-8810, behaved as a moderate efficacy partial agonist (EC(50) = 2140 +/- 190 nM; 63 +/- 4.3% maximum response relative to PGF(2alpha)), indicating that the cat iris contains an extremely well-coupled FP-receptor population, and/or the tissue contains an extremely high density of the FP-receptor and/or spare receptors. The cat iris contraction data were well correlated with other FP-receptor-mediated signal-transduction processes, including FP-receptor binding in bovine corpus luteum (r = 0.86), FP-receptor binding in human iris (r = 0.61), phosphoinositide (PI) hydrolysis in human ciliary muscle and trabecular meshwork cells (r = 0.77 - 0.86), PI turnover in rat and mouse cells (r = 0.73 - 0.76) and via cloned human FP-receptor (r = 0.9), and rat uterus contraction (r = 0.84). These data confirm the presence of functional FP-receptors in the cat iris sphincter, which are exquisitely well coupled and which respond to a variety of FP-class PG analogs with differing potencies.
A synthetic HIS4 regulatory element confers general amino acid control on the cytochrome c gene (CYC1) of yeast. (1985)

Hybrid promoters constructed from upstream sequences of the yeast HIS4 promoter and the downstream element of the yeast CYC1 promoter place iso-1-cytochrome c (CYC1) expression under the general amino acid control, typical of HIS4. HIS4 fragments that confer regulation contain at least one copy of the sequence T-G-A-C-T-C that is repeated at HIS4 and other genes subject to the general control. A 14-base-pair synthetic oligonucleotide containing a single copy of the HIS4 repeat places CYC1 under the general control. Two copies of this oligonucleotide produce a derepressed level of expression nearly equivalent to that conferred by the largest HIS4 5' noncoding fragments we examined and direct regulated expression of a set of transcripts with 5' ends typical of the CYC1 promoter. Comparison of the expression levels conferred by the short synthetic repeat and larger HIS4 5' fragments reveals additional promoter elements required for maintaining efficient gene expression under repressing growth conditions.
Introduction: a broad overview of 'value for money' (1996)

If there is a catchphrase which has entered the vocabulary of public sector provision it is 'Does this service provide value for money?' Most readers would say that they understand both the emphasis on 'value for money' and what this term means. The emphasis arises out of political and public concerns in the late 1970s and early 1980s that public expenditure was out of control and that there was little publicly available evidence to show if public services were operating effectively and efficiently. One of the key conclusions which led to the development of this volume was that often there is a failure to agree on what is meant by the term value for money and a failure to appreciate how value for money might be measured and reported up.
Structure−Activity Relationships at the Monoamine Transporters and σ Receptors for a Novel Series of 9-[3-(cis-3,5-Dimethyl-1-piperazinyl)-propyl]carbazole (Rimcazole) Analogues (1999)

9-[3-(cis-3,5-Dimethyl-1-piperazinyl)propyl]carbazole (rimcazole) has been characterized as a sigma receptor antagonist that binds to the dopamine transporter with moderate affinity (K(i) = 224 nM). Although the binding affinities at the dopamine transporter of rimcazole and cocaine are comparable, rimcazole only depressed locomotor activity in mice and antagonized the stimulant effects produced by cocaine. The neurochemical mechanisms underlying the attenuation of cocaine's effects are not understood, although interaction at a low affinity site/state of the dopamine transporter has been suggested. To explore further this class of compounds, a series of rimcazole analogues was designed and synthesized. Displacement of [(3)H]WIN 35,428 binding at the dopamine transporter in rat caudate-putamen revealed that aromatic substitutions on rimcazole were not well tolerated, generally, with significant reductions in affinity for the 3,6-dibromo (5; K(i) = 3890 nM), 1,3, 6-tribromo (6; K(i) = 30300 nM), 3-amino (8; K(i) = 2400 nM), and 3, 6-dinitro (9; K(i) = 174000 nM) analogues. The N-phenylpropyl group was the only terminal piperazine nitrogen substituent that retained moderate affinity at the dopamine transporter (11; K(i) = 263 nM). Analogues in which the carbazole ring was replaced with a freely rotating diphenylamine moiety were also prepared. Although the diphenylamino analogue in which the terminal piperazine nitrogen was unsubstituted, as in rimcazole, demonstrated relatively low binding affinity at the dopamine transporter (24; K(i) = 813 nM), the N-phenylpropyl analogue was found to have the highest affinity for the dopamine transporter within the series (25; K(i) = 61.0 nM). All of the analogues that had affinity for the dopamine transporter inhibited [(3)H]dopamine uptake in synaptosomes, and potencies for these two effects showed a positive correlation (r(2) = 0.7731, p = 0.0018). Several of the analogues displaced [(3)H]paroxetine from serotonin transporters with moderate to high affinity, with the N-phenylpropyl derivative (11) having the highest affinity (K(i) = 44.5 nM). In contrast, none of the analogues recognized the norepinephrine transporter with an affinity of <1.3 microM. Binding affinities for sigma(1) and sigma(2) receptors were also determined, and several of the compounds were more potent than rimcazole with affinities ranging from 97 nM to >6 microM at sigma(1) sites and 145 to 1990 nM at sigma(2) sites. The compound with the highest affinity (25) at sigma(1) sites was also the compound with highest affinity at the dopamine transporter. These novel rimcazole analogues may provide important tools with which to characterize the relationship between the low affinity site or state of the dopamine transporter, sigma receptors, and their potential roles in modulating cocaine's psychostimulant actions.
Selection of sorghum (Sorghum bicolor (L.) Moench) varieties resistant to the parasitic weed Striga hermonthica (Del.) Benth (1991)

Summary: Pot and field experiments were performed in Burkina Faso in 1987 and 1988 to evaluate the resistance of selected ‘low‐stimulant’ sorghum ( Sorghum bicolor (L.) Moench) varieties to the parasitic weed ( Striga hermonthica (Del.) Benth. In a pot experiment, the variety IS‐7777 supported the lowest number and had the latest emergence of Striga , compared with the other varieties tested. The varieties IS‐14825, IS‐6961, IS‐7739, IS‐14928 and IS‐14975 also had signifi cantly lower numbers of emerged Striga per pot than the resistant control Framida. The resist ance of IS‐7777 was confirmed in field experi ments, as was that of IS‐7739, IS‐6961 and IS‐14928. However, the yield potential of these poorly adapted varieties was low in Striga ‐infested fields. The varieties IS‐14975, IS–14825 and Seguetana Niarabougou exhibited a low susceptibility associated with a grain yield equivalent to that of the other varieties in farm fields infested by Striga . As Seguetana is already grown by Sahelian farmers, its use could be recommended in the absence of resistant varieties adapted to Sahelian agroclimatic conditions. The exceptionally high level of restance exhibited by IS‐7777 could be exploited in studies on the genetics and mechanisms of resistance of the host plant to the parasite, as well as in sorghum improvement programmes.
Addressing prejudices (2002)

Dear Editor, Further to the correspondence following the publication of the article ‘Finding Help in a Crisis’ concerning provision of services for people who may find ‘main-stream’ services uncomfortable (MHP, 5, 6, 4-7). I am a member of a minority group that experiences many difficulties in making use of mental health provision.
Successful imaging of human cancer with indium-111-labeled phospholipid vesicles (1988)

Twenty-four patients with proven primary and/or metastatic cancer received single intravenous injections of phospholipid vesicles containing 0.5 mCi of Indium-111. Gamma camera scintigraphy 1 to 72 hours later visualized tumors in 22 patients (92%), including carcinomas of breast, lung, colon, prostate, kidney, cervix, thyroid, and soft tissue sarcoma, lymphoma, and melanoma. Tumor sites that were identified included soft tissues, bone, lung, liver, lymph node, and spinal cord. There were only two false-positive images in metastatic sites and four false-negative images in metastatic sites. Overall sensitivity for tumors in 97 individual sites was 85%, whereas specificity was 96%. Unsuspected areas of malignancy were seen in the lumbar subdural space, pleura, liver, thyroid, and lung. Besides tumor accumulations, homogeneous uptake was observed in normal liver and spleen. Radiation doses to these two organs were 2.2 and 2.9 cGy/0.5 mCi In-111, respectively. Whole body radiation dose was 0.3 cGy/0.5 mCi. The use of Indium-111-labeled vesicles permits a wide variety of human tumors in primary and metastatic sites to be imaged without toxicity and with radiation doses comparable to other radionuclide scanning techniques.
Electrochemically Generated Magnetic Forces. Enhanced Transport of a Paramagnetic Redox Species in Large, Nonuniform Magnetic Fields (1998)

Electrochemically generated magnetic forces at a disk-shaped ultramicroelectrode have been investigated in large, nonuniform magnetic fields. Two sources of magnetic force are simultaneously operative in the electrochemical experiment, both having a significant influence on molecular transport of the electrochemical reactants and products. First, the magnetohydrodynamic (MHD) force, FMHD, described by the Lorentz equation, arises from the diffusion of electrogenerated ions in the magnetic field. The magnitude of FMHD is dependent upon the strength and orientation of the magnetic field. Second, the gradient magnetic force, F∇B, which is proportional to the gradient of the magnetic field, arises from electrogeneration of paramagnetic molecules in a nonuniform magnetic field. F∇B is dependent on the magnetic field strength, its spatial gradient, and the magnetic properties of the redox-active molecules. F∇B and FMHD may be experimentally decoupled and investigated by variation of the field homogeneity and the electrode orientation. Specifically, FMHD is negligibly small when the surface of the ultramicroelectrode is oriented perpendicular to the magnetic field, thus allowing F∇B to be investigated without interference from magnetohydrodynamic flows. Order-of-magnitude theoretical estimates of FMHD and F∇B are correlated with voltammetric data for the electrochemical reduction of nitrobenzene at a 25-μm-radius Pt microdisk electrode in a superconducting cryomagnet. Enhancements in the voltammetric limiting current as large as ∼400% (B = 9.4 T, ∇B = 0 T/m) and ∼100% (B = 6 T, ∇B ∼ 75 T/m) are associated with FMHD and F∇B, respectively.
Dose-guided radiation therapy with megavoltage cone-beam CT (2006)

Recent advances in fractionated external beam radiation therapy have increased our ability to deliver radiation doses that conform more tightly to the tumour volume. The steeper dose gradients delivered in these treatments make it increasingly important to set precisely the positions of the patient and the internal organs. For this reason, considerable research now focuses on methods using three-dimensional images of the patient on the treatment table to adapt either the patient position or the treatment plan, to account for variable organ locations. In this article, we briefly review the different adaptive methods being explored and discuss a proposed dose-guided radiation therapy strategy that adapts the treatment for future fractions to compensate for dosimetric errors from past fractions. The main component of this strategy is a procedure to reconstruct the dose delivered to the patient based on treatment-time portal images and pre-treatment megavoltage cone-beam computed tomography (MV CBCT) images of the patient. We describe the work to date performed to develop our dose reconstruction procedure, including the implementation of a MV CBCT system for clinical use, experiments performed to calibrate MV CBCT for electron density and to use the calibrated MV CBCT for dose calculations, and the dosimetric calibration of the portal imager. We also present an example of a reconstructed patient dose using a preliminary reconstruction program and discuss the technical challenges that remain to full implementation of dose reconstruction and dose-guided therapy.
Risk factors for HIV-2 infection in Guinea-Bissau. (1991)

To define the epidemiology of HIV-2 infection, we conducted a case-control study among hospitalized patients at an acute care hospital in Bissau, Guinea-Bissau, a country with endemic HIV-2 infection. Among 128 patients with various diagnoses, 23 (18%) were positive for HIV-2 by ELISA and Western blot. One of these patients was serologically reactive for HIV-1 also, but PCR and viral culture revealed the presence of HIV-2 only. To study risk factors, behaviors, and AIDS knowledge related to the acquisition of HIV infection, 22 HIV-2-seropositive and 21 seronegative hospitalized patients were given a physical examination and administered a questionnaire. Among women, transfusion was associated with HIV-2 infection (OR = 14.4, p = 0.02); among men, sex with a prostitute was the principal risk factor (OR = undefined, p = 0.02). Although 79% of HIV-infected patients and controls had heard of AIDS, only 17% of all study participants and 50% of males reporting sex with prostitutes had used condoms in the previous year. These data suggest that the risk factors for HIV-2 infection are similar to those for HIV-1 and support previous studies showing that HIV-2 is the predominant HIV in Guinea-Bissau. Efforts to decrease transmission of HIV-2 should include screening for HIV-2 in blood for transfusion in endemic areas (now done in Bissau) and education about the risk of sexual transmission.
Self-Assembly of Chiral DNA Nanotubes (2004)

A system of DNA "tiles" that is designed to assemble to form two-dimensional arrays is observed to form narrow ribbons several micrometers in length. The uniform width of the ribbons and lack of frayed edges lead us to propose that they are arrays that have curled and closed on themselves to form tubes. This proposal is confirmed by the observation of tubes with helical order.
Human amnion collagen for soft tissue augmentation—biochemical characterizations and animal observations (1994)

As bovine collagen is currently being scrutinized as to its immunogenicity in clinical use, a human source collagen, human amnion collagen (HAC), has been developed in our laboratory as an injectable biomaterial for soft tissue augmentation. Pepsin-extracted human amnion collagen was highly purified and reconstituted. Gamma irradiation was employed to ensure complete sterility and to produce cross-linking in collagen chains to improve implant persistence without the use of chemical additives. The purity and characteristics of human amnion collagen were proven by amino acid assay, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immune blotting, and collagenase digestion. Animal studies comparing both irradiated and nonirradiated amnion collagen to bovine collagen (Zyderm and Zyplast) were carried out in a rat model. Humoral immunity was evaluated by examining the sera for antibody reactivity towards the implanted human collagen by the ELISA test. Insignificant antibody levels against human amnion collagen were found. Animal observation revealed fibroplasia, vascular infiltration, and the development of adipocytes with the implant as well as a lack of inflammatory response following up to 12 months of implantation. The persistence rate of our human amnion collagen was equal to, or even longer than, that of both types of bovine collagen implants.
Enhancement of the Long-Wavelength Sensitivity of Optogenetic Microbial Rhodopsins by 3,4-Dehydroretinal (2012)

Electrogenic microbial rhodopsins (ion pumps and channelrhodopsins) are widely used to control the activity of neurons and other cells by light (optogenetics). Long-wavelength absorption by optogenetic tools is desirable for increasing the penetration depth of the stimulus light by minimizing tissue scattering and absorption by hemoglobin. A2 retinal (3,4-dehydroretinal) is a natural retinoid that serves as the chromophore in red-shifted visual pigments of several lower aquatic animals. Here we show that A2 retinal reconstitutes a fully functional archaerhodopsin-3 (AR-3) proton pump and four channelrhodopsin variants (CrChR1, CrChR2, CaChR1, and MvChR1). Substitution of A1 with A2 retinal significantly shifted the spectral sensitivity of all tested rhodopsins to longer wavelengths without altering other aspects of their function. The spectral shift upon substitution of A1 with A2 in AR-3 was close to that measured in other archaeal rhodopsins. Notably, the shifts in channelrhodopsins were larger than those measured in archaeal rhodopsins and close to those in animal visual pigments with similar absorption maxima of their A1-bound forms. Our results show that chromophore substitution provides a complementary strategy for improving the efficiency of optogenetic tools.
Pim-1 Kinase-Dependent Phosphorylation of p21Cip1/WAF1 Regulates Its Stability and Cellular Localization in H1299 Cells (2007)

Previous studies from our laboratory showed that p21Cip1/WAF1 can be phosphorylated by Pim-1 kinase in vitro, implying that part of the function of Pim-1 might involve influencing the cell cycle. In the present study, site-directed mutagenesis and phosphorylated-specific antibodies were used as tools to identify the sites phosphorylated by Pim-1 and the consequences of this phosphorylation. What we found was that Pim-1 can efficiently phosphorylate p21 on Thr145 in vitro using recombinant protein and in vivo in intact cells. Unexpectedly, we found that Ser146 is a second site that is phosphorylated in vivo, but this phosphorylation event seems to be an indirect result of Pim-1 expression. More importantly, the consequences of phosphorylation of either Thr145 or Ser146 are distinct. When p21 is phosphorylated on Thr145, it localizes to the nucleus and results in the disruption of the association between proliferating cell nuclear antigen and p21. Furthermore, phosphorylation of Thr145 promotes stabilization of p21. On the other hand, when p21 is phosphorylated on Ser146, it localizes primarily in the cytoplasm and the effect of phosphorylation on stability is minimal. Cotransfection of wild-type Pim-1 with p21 increases the rate of proliferation compared with cotransfection of p21 with kinase-dead Pim-1. Knocking down Pim-1 expression greatly decreases the rate of proliferation of H1299 cells and their ability to grow in soft agar. These data suggest that Pim-1 overexpression may contribute to tumorigenesis in part by influencing the cellular localization and stability of p21 and by promoting cell proliferation.
Differences amid bone marrow and cord blood hematopoietic stem/progenitor cell division kinetics (2009)

Human hematopoietic stem/progenitor cells (HSC) isolated based upon specific patterns of CD34 and CD38 expression, despite phenotypically identical, were found to be functionally heterogeneous, raising the possibility that reversible expression of these antigens may occur during cellular activation and/or proliferation. In these studies, we combined PKH67 tracking with CD34/CD38 immunostaining to compare cell division kinetics between human bone marrow (BM) and cord blood (CB)-derived HSC expanded in a serum-free/stromal-based system for 14 days (d), and correlated CD34 and CD38 expression with the cell divisional history. CB cells began dividing 24 h earlier than BM cells, and significantly higher numbers underwent mitosis during the time in culture. By d10, over 55% of the CB-cells reached the ninth generation, whereas BM-cells were mostly distributed between the fifth and seventh generation. By d14, all CB cells had undergone multiple cell divisions, while 0.7-3.8% of BM CD34(+) cells remained quiescent. Furthermore, the percentage of BM cells expressing CD34 decreased from 60.8 +/- 6.3% to 30.6 +/- 6.7% prior to initiating division, suggesting that downmodulation of this antigen occurred before commencement of proliferation. Moreover, with BM, all primitive CD34(+)CD38(-) cells present at the end of culture arose from proliferating CD34(+)CD38(+) cells that downregulated CD38 expression, while in CB, a CD34(+)CD38(-) population was maintained throughout culture. These studies show that BM and CB cells differ significantly in cell division kinetics and expression of CD34 and CD38, and that the inherent modulation of these antigens during ex vivo expansion may lead to erroneous quantification of the stem cell content of the expanded graft.
Disintegration of Biomacromolecules by Dielectric Barrier Discharge Plasma in Helium at Atmospheric Pressure (2008)

The inactivation mechanism of microorganisms by plasma has been attracting much attention of researchers in recent years. Some different explanations have been postulated from physical, chemical, and biological views. In this paper, we investigate the inactivation mechanism of cells exposed to dielectric barrier discharge plasma in helium at atmospheric pressure from a biochemical view, i.e., disintegration of biomacromolecules, particularly the polysaccharide on cell wall and membrane-bound proteins. The experimental results showed that a series of complex chemical reactions happened in cell debris suspension and cell suspension, leading to a decrease in the concentration of membrane-bound proteins and an increase in the concentration of proteins released from cells. Cell debris could be effectively decomposed by plasma to amino acid, maltose, glucose, acetic acid, and so on. This might be the main reason for cell lysis and death.
The critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice. (1997)

Angiotensin-converting enzyme (ACE) generates the vasoconstrictor angiotensin II, which plays a critical role in maintenance of blood pressure in mammals. Although significant ACE activity is found in plasma, the majority of the enzyme is bound to tissues such as the vascular endothelium. We used targeted homologous recombination to create mice expressing a form of ACE that lacks the COOH-terminal half of the molecule. This modified ACE protein is catalytically active but entirely secreted from cells. Mice that express only this modified ACE have significant plasma ACE activity but no tissue-bound enzyme. These animals have low blood pressure, renal vascular thickening, and a urine concentrating defect. The phenotype is very similar to that of completely ACE-deficient mice previously reported, except that the renal pathology is less severe. These studies strongly support the concept that the tissue-bound ACE is essential to the control of blood pressure and the structure and function of the kidney.
Single-Conductor Surface-Wave Transmission Lines (1951)

This paper gives general information on single-conductor transmission lines, in particular on lines having a dielectric-coated conductor. A design chart is included and experimental results are presented.