gebhart/patrepeval huggingface dataset:
Natural Products as Probes of Cellular Function: Studies of Immunophilins (1992)

Abstract One of the great mysteries of cell biology remains the mechanism of information transfer, or signaling, through the cytoplasm of the cell. Natural products that inhibit this process offer a unique window into fundamental aspects of cytoplasmic signal transduction, the means by which extracellular molecules influence intracellular events. Thus, natural products chemistry, including organic synthesis, conformational analysis, and methods of structure elucidation, is a powerful tool in the study of cell function. This article traces our understanding of a group of natural products from the finding that they inhibit cytoplasmic signaling to their current recognition as mediators of the interaction between widely distributed protein targets. The emphasis of the discussion is primarily structural. The interactions between the natural‐product ligands and their protein receptors are analyzed at a molecular level in order to shed light on the molecular mechanisms of the biological functions of these compounds. In the process we hope to illustrate the power of chemical analysis as applied to biological systems. Through chemistry we can understand the molecular basis of biological phenomena.
Iron-Chelating Therapy and the Treatment of Thalassemia (1997)

THE LAST 3 decades have witnessed profound changes in the management of patients with thalassemia major. Regular red blood cell (RBC) transfusions eliminate the complications of anemia and compensatory bone marrow (BM) expansion, permit normal development throughout childhood, and extend survival.[1
Inducible expression of PTX3, a new member of the pentraxin family, in human mononuclear phagocytes (1994)

The pentraxins C-reactive protein (CRP) and serum amyloid P component (SAP) are acute-phase proteins produced by liver epithelial cells. PTX3 was recently cloned as an interleukin-1 (IL-1)-inducible gene in endothelial cells, with structural similarities to pentraxins in the C- terminal half of the molecule. The present study was designed to investigate the expression of PTX3 in the human leukocyte populations. Human peripheral blood mononuclear cells exposed to lipopolysaccharide (LPS) or IL-1 beta expressed significant levels of PTX3 mRNA. Tumor necrosis factor-alpha (TNF-alpha) was a less-effective inducer of PTX3, whereas IL-6, monocyte chemotactic protein-1, macrophage colony- stimulating factor, granulocyte-macrophage colony-stimulating factor, and interferon-gamma were inactive. Among leukocytes, only monocytes exposed to inflammatory cytokines or LPS expressed the PTX3 transcript, which was undetectable in resting or stimulated polymorphonuclear cells, T or B lymphocytes, and natural killer cells. PTX3 mRNA was also inducible in in vitro monocyte-derived macrophages, in tumor-associated macrophages, and in the myelomonocytic cell lines HL60, U937, and THP1, but not in GFD8, with the latter possibly representative of earlier stages of myelomonocytic differentiation. T- and B-cell lines had no detectable PTX3. Inhibition of transcription by actinomycin D blocked induction of PTX3 in monocytes and nuclear run-on analysis showed that LPS induces the expression of the PTX3 gene at the transcriptional level in isolated monocytes. Cycloheximide had no effect on PTX3 induction in U937 cells, but was inhibitory on monocytes exposed to LPS or IL-1 beta. Monoclonal antibody against TNF and the IL-1 receptor antagonists did not inhibit induction of PTX3 in monocytes by LPS, thus excluding these cytokines as secondary stimulators of PTX3. IL-4, but not dexamethasone or transforming growth factor-beta, inhibited PTX3 expression in monocytes. Using a PTX3-specific antiserum, release of PTX3 protein was demonstrated for the first time in stimulated monocytes as well as in endothelial and fibroblastic cells. Thus, PTX3, unlike the classical pentraxins CRP and SAP, is expressed and released by cells of the monocyte-macrophage lineage exposed to inflammatory signals.
Anemia management: development of a rapid-access anemia and intravenous iron service (2013)

This article describes the initiation and evolution of the Rapid-Access Anemia Clinic (RAAC) at Guy's and St Thomas' Hospitals, London, UK. This clinic was set up to provide diagnosis and treatment, and to coordinate investigative procedures, where necessary, into the underlying causes of anemia. Initially piloted with anemic preoperative orthopedic patients, the clinic now treats a wide range of conditions, deriving from both internal and external referrals. Treatment includes dietary advice, supplementation with iron, vitamin B12 and folate, and blood transfusion. Most patients at the RAAC need iron replacement, the majority of which require intravenous (IV) iron. Therefore the first-line IV iron-administration protocol is carefully considered to ensure viability of the service and patient satisfaction. Four IV irons available in the UK are discussed, with explanation of the benefits and drawbacks of each product and the reasoning behind the IV iron choice at different stages of the RAAC's development. Costs to the service, affected by IV iron price and administration regimen, are considered, as well as the product's contraindications. Finally, the authors reflect on the success of the RAAC and how it has improved patients' quality-of-treatment experience, in addition to benefiting the hospital and National Health Service in achieving specific health-care mandates and directives. Drawing from the authors' experiences, recommendations are given to assist others in setting up and providing a successful rapid-access anemia service or similar facility.
Selective Killing of Normal and Neoplastic Human B Cells with Anti-CD 19- and Anti-CD22-Ricin A Chain Immunotoxins (1986)

Monoclonal antibodies directed against two human B cell-restricted antigens, CD19 and CD22, were conjugated to highly purified ricin A chain. These A chain immunotoxins (A-IT) were specifically cytotoxic to Daudi cells and normal human peripheral blood B cells in vitro. The concentration required for 50% inhibition of protein synthesis (IC50) in these cells ranged from 7.5 X 10(-10) M to 4.2 X 10(-9) M. The specific toxicities of these A-ITs for Daudi cells were augmented 2- to 6-fold in the presence of 20mM NH4Cl. These studies demonstrate that A-ITs specific for CD19 and CD22 may be useful in the clinical treatment of B cell malignancies.
N,N‘-Ethylenedi-l-cysteine (EC) and Its Metal Complexes:  Synthesis, Characterization, Crystal Structures, and Equilibrium Constants (1996)

N,N'-ethylenedi-L-cysteine (EC) and its indium(III) and gallium(III) complexes have been synthesized and characterized. The crystal structures of the ligand and the complexes have been determined by single-crystal X-ray diffraction. EC.2HBr.2H(2)O (C(8)H(22)Br(2)N(2)O(6)S(2)) crystallizes in the orthorhombic space group P2(1)2(1)2 with a = 12.776(3) Å, b = 13.735(2) Å, c = 5.1340 (10) Å, Z = 2, and V = 900.9(3) Å(3). The complexes Na[M(III)EC].2H(2)O (C(8)H(16)MN(2)O(6)S(2)Na) are isostructural for M = In and Ga, crystallizing in the tetragonal space group P4(2)2(1)2 with the following lattice constants for In, (Ga): a = 10.068(2) Å, (9.802(2) Å), b = 10.068(2) Å, (9.802(2) Å), c = 14.932(2) Å, (15.170(11) Å), Z = 4 (4), and V = 1513.6(5) Å(3), (1457.5(11) Å(3)). In both metal complexes, the metal atoms (In and Ga) are coordinated by six donor atoms (N(2)S(2)O(2)) in distorted octahedral coordination geometries in which two sulfur atoms and two nitrogen atoms occupy the equatorial positions, and the axial positions are occupied by two oxygen atoms of two carboxylate groups. The structures of the complexes previously predicted by molecular mechanics are compared with the crystal structures of the Ga(III) and In(III) complexes obtained experimentally. In contrast to the oxygen donors in phenolate-containing ligands, such as 1,2-ethylenebis((o-hydroxyphenyl)glycine) (EHPG) and N,N'-bis(o-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED), the thiolate donors of EC enhances affinity for In(III) relative to Ga(III). The following stability sequence has been obtained: In(III) > Ga(III) >> Ni(II) > Zn(II) > Cd(II) > Pb(II) > Co(II). Evidence was also obtained for several protonated and hydroxo species of the complexes of both divalent and trivalent metals, where the corresponding protonation constants (K(MHL)) decrease with increasing stability of the chelate, ML(n)(-)(4), where M(n)()(+) represent the metal ion.
The pharmacology and distribution of human 5‐hydroxytryptamine2B (5‐HT2b) receptor gene products: comparison with 5‐HT2a and 5‐HT2c receptors (1995)

Full length clones of the human 5‐HT 2B receptor were isolated from human liver, kidney and pancreas. The cloned human 5‐HT 2B receptors had a high degree of homology (∼80%) with the rat and mouse 5‐HT 2B receptors. PCR amplification was used to determine the tissue distribution of human 5‐HT 2B receptor mRNA. mRNA encoding the 5‐HT 2B receptor was expressed with greatest abundance in human liver and kidney. Lower levels of expression were detected in cerebral cortex, whole brain, pancreas and spleen. Expression was not detected in heart. Northern blot analysis confirmed the presence of 5‐HT 2B receptor mRNA (a 2.4 kB sized band) in pancreas, liver and kidney. An additional 3.2 kB sized band of hybridization was detected in liver and kidney. This raises the possibility of a splice variant of the receptor or the presence of an additional homologous receptor. The human 5‐HT 2B receptor was expressed in Cos‐7 cells and its ligand binding characteristics were compared to similarly expressed human 5‐HT 2A and 5‐HT 2C receptors. The ligand specificity of the human 5‐HT 2B receptor (5‐HT &gt; ritanserin &gt; SB 204741 &gt; spiperone) was distinct from that of the human 5‐HT 2A (ritanserin &gt; spiperone &gt; 5‐HT &gt; SB 204741) and 5‐HT 2C (ritanserin &gt; 5‐HT &gt; spiperone = SB 204741) receptors. On the basis of a higher affinity for ketanserin and a lower affinity for yohimbine the human 5‐HT 2B receptor also appeared to differ from the rat 5‐HT 2B receptor. These findings confirm the sequence of the human 5‐HT 2B receptor and they demonstrate that the receptor has a widespread tissue distribution. In addition, these data suggest that there are differences in ligand affinities between different species homologues of the receptor. Finally, the finding of two distinct bands on the Northern blots of liver and kidney raises the possibility of splice variants or subtypes of 5‐HT 2B receptors, within these tissues.
Pathogenesis of Alzheimer's disease. (2007)

Alzheimer's disease (AD) is incredibly common. Increasing longevity ensures its prevalence will rise even further. Ongoing efforts to understand AD pathogenesis reveal numerous tantalizing leads. Formulating a comprehensive AD pathogenesis theory capable of incorporating these disparate leads, though, has proven difficult. This review discusses current attempts to formulate a comprehensive AD pathogenesis theory. In doing so, it focuses on clinical and molecular relationships between AD and aging. A better understanding of these relationships could inform and impact future development of AD-directed treatment strategies.
Influence of Brownian Motion on Blood Platelet Flow Behavior and Adhesive Dynamics near a Planar Wall (2007)

We used the platelet adhesive dynamics computational method to study the influence of Brownian motion of a platelet on its flow characteristics near a surface in the creeping flow regime. Two important characterizations were done in this regard: (1) quantification of the platelet's ability to contact the surface by virtue of the Brownian forces and torques acting on it, and (2) determination of the relative importance of Brownian motion in promoting surface encounters in the presence of shear flow. We determined the Peclet number for a platelet undergoing Brownian motion in shear flow, which could be expressed as a simple linear function of height of the platelet centroid, H from the surface Pe (platelet) = . (1.56H + 0.66) for H > 0.3 microm. Our results demonstrate that at timescales relevant to shear flow in blood Brownian motion plays an insignificant role in influencing platelet motion or creating further opportunities for platelet-surface contact. The platelet Peclet number at shear rates >100 s-1 is large enough (>200) to neglect platelet Brownian motion in computational modeling of flow in arteries and arterioles for most practical purposes even at very close distances from the surface. We also conducted adhesive dynamics simulations to determine the effects of platelet Brownian motion on GPIbalpha-vWF-A1 single-bond dissociation dynamics. Brownian motion was found to have little effect on bond lifetime and caused minimal bond stressing as bond rupture forces were calculated to be less than 0.005 pN. We conclude from our results that, for the case of platelet-shaped cells, Brownian motion is not expected to play an important role in influencing flow characteristics, platelet-surface contact frequency, and dissociative binding phenomena under flow at physiological shear rates (>50 s(-1)).
The preparation of 3-substituted 1-chlorocarbonyl-imidazolidin-2-ones using bis(trichloromethyl) carbonate (2000)

A novel synthesis of 3-substituted 1-chlorocarbonyl-imidazolidin-2-ones using bis(trichloromethyl) carbonate is reported. The bis(trichloromethyl)carbonate is used to generate phosgene in situ in stoichiometric amounts. The yields and purity of the products obtained are better than those obtained by a conventional way using phosgene.
New quinones from a dictyoceratid sponge (1978)

Five new quinones have been isolated from a sponge tentatively classified as Stelospongia conulata. Isospongiaquinone (7) has a rearranged drimane skeleton whereas spongiaquinone (19), cyclo- spongiaquinone-1 (20), cyclospongiaquinone-2 (21) and dehydrocyclospongiaquinone-1 (22) have a normal drimane skeleton. The structures of these were derived from chemical and spectral evidence.
Androgen replacement in menopause. (2001)

Menopause and the years leading to the menopausal transition are associated with significant decline in sex steroid levels. In contrast to the abrupt decline in estrogens at the time of menopause, a fall in the circulating testosterone and the adrenal preandrogens most closely parallel increasing age. Their accelerated decrease occurs in the years preceding menopause. It is now recognized that the decline in androgens plays a significant role in affecting perimenopausal and menopausal symptomatology and quality of life. Loss of circulating levels of androgens affects libido, vasomotor symptoms, mood and well-being, bone structure, muscle mass. Also, it influences cardiovascular profile. In the menopausal female (in whom these symptoms are clearly linked to low levels of bioavailable testosterone levels), hormone replacement therapy may be of benefit. Recently, interest is increasing in the use of androgen replacement not only for women who have undergone premature or surgical menopause but also for those who experience natural menopause and premenopausal loss of libido from diminished free testosterone.
Protective effect of ellagic acid on t-butyl hydroperoxide induced lipid peroxidation in isolated rat hepatocytes. (1999)

Ellagic acid, a plant polyphenol, showed protective effect on isolated rat hepatocytes against destruction due to lipid peroxide formation induced by t-butyl hydroperoxide in vitro. Ellagic acid inhibited the generation of superoxide anions and hydroxyl radicals both in enzymic and non enzymic systems, thus providing protection against oxidative damage.
Recommendations for the treatment of nail psoriasis in patients with moderate to severe psoriasis: a dermatology expert group consensus (2011)

This article provides useful and practical considerations for the management and treatment of patients with moderate to severe skin and nail psoriasis.
FORWARD SCATTERING PROPERTIES OF HUMAN EPIDERMAL LAYERS (1984)

Abstract From an optical point of view the outermost skin layers contain numerous structures by which penetrating radiation may be scattered as well as absorbed. The nature and strength of this scattering may strongly influence the extent of penetration. We illuminated samples of stratum corneum and full‐thickness epidermis with collimated radiation and measured the angular intensity distribution of the transmitted radiation; we did this in the ultraviolet for several angles of incidence, and in the visible for perpendicular incidence only. Skin samples were obtained from the skin of the lower back and upper leg of Caucasian volunteers. Epidermis and subsequently stratum corneum were separated by chemical methods. In the case of stratum corneum, the angular intensity distribution of the transmitted radiation peaks strongly at all wavelengths, in approximately the direction of the incident radiation, that has been refracted at the surface of the sample. With full‐thickness epidermis, the distribution of the transmitted radiation also peaks, though less strongly than with stratum corneum. These features suggest a forward oriented scattering mechanism. Both in the case of stratum corneum and full‐thickness epidermis, the angular distribution flattens towards the shorter wavelengths and with increasing thickness. The wavelength dependence suggests that both scattering and absorption increase towards the shorter wavelengths. The existence of a thickness dependence indicates that volume scattering occurs. Hydration of stratum corneum is found to influence its scattering properties. Dry samples scatter less than hydrated samples. The consequences of our findings for modelling skin optics are briefly discussed.
Ion-Beam Deposition of Thin Films of Diamondlike Carbon (1971)

An ion-beam deposition technique has been developed and was used to deposit thin films of insulating carbon on room-temperature substrates. It was established that the carbon films deposited using this technique are insulating and have the following characteristics similar to that of carbon in the diamond form: (1) transparency, (2) index of refraction greater than 2.0, (3) highly insulating, (4) able to scratch glass, (5) resistant to hydrofluoric acid for long periods of time, (6) at least partially crystalline and with a lattice constant similar to diamond as demonstrated by x-ray diffraction, (7) dielectric constant between about 8 and 14 (diamond is 16.5). A resistance to sodium ion diffusion has been experimentally demonstrated. Preliminary measurements at a dose of 1 Mrad indicated a radiation resistance from the point of view of stability of leakage resistance and of negligibly small flat band voltage shifts. Several coplanar thin-film transistors using the insulating carbon gate have been fabricated.
Mapping and mutagenesis of the amino-terminal transcriptional repression domain of the Drosophila Krüppel protein. (1994)

We previously demonstrated that the Drosophila Krüppel protein is a transcriptional repressor with separable DNA-binding and transcriptional repression activities. In this study, the minimal amino (N)-terminal repression region of the Krüppel protein was defined by transferring regions of the Krüppel protein to a heterologous DNA-binding protein, the lacI protein. Fusion of a predicted alpha-helical region from amino acids 62 to 92 in the N terminus of the Krüppel protein was sufficient to transfer repression activity. This putative alpha-helix has several hydrophobic surfaces, as well as a glutamine-rich surface. Mutants containing multiple amino acid substitutions of the glutamine residues demonstrated that this putative alpha-helical region is essential for repression activity of a Krüppel protein containing the entire N-terminal and DNA-binding regions. Furthermore, one point mutant with only a single glutamine on this surface altered to lysine abolished the ability of the Krüppel protein to repress, indicating the importance of the amino acid at residue 86 for repression. The N terminus also contained an adjacent activation region localized between amino acids 86 and 117. Finally, in accordance with predictions from primary amino acid sequence similarity, a repression region from the Drosophila even-skipped protein, which was six times more potent than that of the Krüppel protein in the mammalian cells, was characterized. This segment included a hydrophobic stretch of 11 consecutive alanine residues and a proline-rich region.
Building Energy Efficiency Trends in China (2013)

The national energy conservation has been focused with increasingly serious energy security situation.Building energy consumption accounts for about the country's energy consumption 20.9% in China.The building energy efficiency is urgent.The low-energy buildings in the future,and even the capacity building is that we need to focus.Energy efficiency of urban public buildings and residential buildings are improved with a modicum of success,but the energy-saving retrofitting projects are not ideal.There are difficulties in rural building energy efficiency.It briefly discusses the building energy efficiency at home and abroad to increase the experience,expecting the building energy efficiency trends.
Measurement of red blood cell mechanics during morphological changes (2010)

The human red blood cell (RBC) membrane, a fluid lipid bilayer tethered to an elastic 2D spectrin network, provides the principal control of the cell's morphology and mechanics. These properties, in turn, influence the ability of RBCs to transport oxygen in circulation. Current mechanical measurements of RBCs rely on external loads. Here we apply a noncontact optical interferometric technique to quantify the thermal fluctuations of RBC membranes with 3 nm accuracy over a broad range of spatial and temporal frequencies. Combining this technique with a new mathematical model describing RBC membrane undulations, we measure the mechanical changes of RBCs as they undergo a transition from the normal discoid shape to the abnormal echinocyte and spherical shapes. These measurements indicate that, coincident with this morphological transition, there is a significant increase in the membrane's shear, area, and bending moduli. This mechanical transition can alter cell circulation and impede oxygen delivery.