gebhart/patrepeval huggingface dataset:
1,3-Di(2-[5-3H]tolyl)guanidine: a selective ligand that labels sigma-type receptors for psychotomimetic opiates and antipsychotic drugs. (1986)

Brain sigma-type receptors are thought to mediate hallucinogenic effects of certain benzomorphan opiates in humans. The biochemical characterization of sigma receptors has been difficult because of the lack of potent and selective ligands. We report here the synthesis and characterization of a tritiated, symmetrically substituted guanidine derivative, 1,3-di(2-[5-3H]tolyl)guanidine ([3H]Tol2Gdn), that binds with high affinity to a single population of binding sites in guinea pig brain membrane preparations. The [3H]Tol2Gdn binding site displays stereoselectivity for dextrorotatory optical isomers of benzomorphan opiates known to have sigma-type behavioral effects. Furthermore, the [3H]Tol2Gdn binding site has a high affinity for haloperidol and for phenothiazine antipsychotics, which have antihallucinatory properties in humans. The drug-selectivity profile of [3H]Tol2Gdn binding closely correlates with the drug-selectivity profile of tritiated (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [+)-[3H]3-PPP) binding to guinea pig brain membrane receptors. (+)-[3H]3-PPP has been proposed to be a selective sigma-receptor ligand [Largent, B. L., Gundlach, A. L. & Snyder, S. H. (1984) Proc. Natl. Acad. Sci. USA 82, 4983-4987]. Receptor autoradiography using [3H]Tol2Gdn on slide-mounted rat and guinea pig brain sections reveals a heterogeneous distribution pattern of enriched binding in limbic and sensorimotor structures of the brain. These results indicate that [3H]Tol2Gdn is a selective ligand for the sigma-site. Availability of this sigma-receptor probe should greatly facilitate the physiological, biochemical, and pharmacological characterization of sigma receptors in brain.
Slow Hot-Carrier Relaxation in Colloidal Graphene Quantum Dots (2010)

Reducing hot-carrier relaxation rates is of great significance in overcoming energy loss that fundamentally limits the efficiency of solar energy utilization. Semiconductor quantum dots are expected to have much slower carrier cooling because the spacing between their discrete electronic levels is much larger than phonon energy. However, the slower carrier cooling is difficult to observe due to the existence of many competing relaxation pathways. Here we show that carrier cooling in colloidal graphene quantum dots can be 2 orders of magnitude slower than in bulk materials, which could enable harvesting of hot charge carriers to improve the efficiency of solar energy conversion.
Cutting Edge: Mast Cells Express IL-17A in Rheumatoid Arthritis Synovium (2010)

The proinflammatory cytokine IL-17A is considered a crucial player in rheumatoid arthritis (RA) pathogenesis. In experimental models of autoimmune arthritis, it has been suggested that the cellular source of IL-17A is CD4(+) T cells (Th17 cells). However, little is known about the source of IL-17 in human inflamed RA tissue. We explored the cellular sources of IL-17A in human RA synovium. Surprisingly, only a small proportion of IL-17-expressing cells were T cells, and these were CCR6 negative. Unexpectedly, the majority of IL-17A expression colocalized within mast cells. Furthermore, we demonstrated in vitro that mast cells produced RORC-dependent IL-17A upon stimulation with TNF-alpha, IgG complexes, C5a, and LPS. These data are consistent with a crucial role for IL-17A in RA pathogenesis but suggest that in addition to T cells innate immune pathways particularly mediated via mast cells may be an important component of the effector IL-17A response.
Psoralen photo-crosslinked mRNA-puromycin conjugates: a novel template for the rapid and facile preparation of mRNA-protein fusions (2000)

We describe the synthesis of a novel type of mRNA template and its use in the preparation of mRNA-protein fusions. A light-induced psoralen crosslinking reaction was used to attach a puromycin-containing oligonucleotide to the 3'-end of an mRNA template. The photo-crosslinked template was found to undergo efficient mRNA-protein fusion formation in rabbit reticulocyte lysate. Fusion formation was subsequently tested with templates carrying puromycin linkers of different length and chemical composition. Short linkers with multiple triethyleneglycol phosphate building blocks allowed the most efficient fusion formation under a wide range of salt conditions. The present method simplifies the preparation of mRNA-protein fusions and thus significantly accelerates the in vitro protein evolution procedure which involves repetitive cycles of fusion production and selection.
Reduced surface: an efficient way to compute molecular surfaces. (1996)

Because of their wide use in molecular modeling, methods to compute molecular surfaces have received a lot of interest in recent years. However, most of the proposed algorithms compute the analytical representation of only the solvent-accessible surface. There are a few programs that compute the analytical representation of the solvent-excluded surface, but they often have problems handling singular cases of self-intersecting surfaces and tend to fail on large molecules (more than 10,000 atoms). We describe here a program called MSMS, which is shown to be fast and reliable in computing molecular surfaces. It relies on the use of the reduced surface that is briefly defined here and from which the solvent-accessible and solvent-excluded surfaces are computed. The four algorithms composing MSMS are described and their complexity is analyzed. Special attention is given to the handling of self-intersecting parts of the solvent-excluded surface called singularities. The program has been compared with Connolly's program PQMS [M.L. Connolly (1993) Journal of Molecular Graphics, Vol. 11, pp. 139-141] on a set of 709 molecules taken from the Brookhaven Data Base. MSMS was able to compute topologically correct surfaces for each molecule in the set. Moreover, the actual time spent to compute surfaces is in agreement with the theoretical complexity of the program, which is shown to be O[n log(n)] for n atoms. On a Hewlett-Packard 9000/735 workstation, MSMS takes 0.73 s to produce a triangulated solvent-excluded surface for crambin (1 crn, 46 residues, 327 atoms, 4772 triangles), 4.6 s for thermolysin (3tln, 316 residues, 2437 atoms, 26462 triangles), and 104.53 s for glutamine synthetase (2gls, 5676 residues, 43632 atoms, 476665 triangles).
Persistent clonal expansions of peripheral blood CD4+ lymphocytes in chronic inflammatory bowel disease (1996)

It is increasingly recognized that chronic Ag exposure may lead to clonal expansions of T cells, including those within the peripheral blood. Inflammatory bowel disease is a chronic, multisystemic disease of unknown origin that predominantly affects the intestine. We sought to determine whether clonal expansions of T cells are present in the peripheral blood of patients with inflammatory bowel disease by an examination of TCR usage. Positively selected CD4+ and CD8+ peripheral blood T cells were isolated from subjects with active ulcerative colitis, Crohn's disease, and diverticulitis and from normal controls. Analysis of complementarity determining region 3 lengths of 24 TCR-beta chain V region families from CD4+ and CD8+ peripheral blood T cells showed a skewed distribution in the three inflammatory groups, consistent with expansion of T cell clones, in comparison to the normally distributed pattern observed among the control donors. Random sequencing of the PCR amplification products of CD4+ peripheral blood T cells from the subjects with ulcerative colitis, Crohn's disease, and diverticulitis revealed reiterative TCR-beta chain sequences that were not found in the normal donors. In subjects with Crohn's disease, the reiterative TCR-beta chain sequences from the CD4+ peripheral blood T cells were persistent over at least a 1-yr period. The persistently expanded TCR-beta chain sequences of CD4+ peripheral blood T cells were identifiable in genomic DNA isolated from archival tissue of intestine from subjects with Crohn's disease and ulcerative colitis by Southern blotting and direct DNA sequencing. An identical twin pair, concordant for Crohn's disease, shared the same reiterative TCR-beta chain sequences in their CD4+ peripheral blood T cells. These studies show that chronic intestinal inflammation is associated with expansions of CD4+ peripheral blood T cells. Furthermore, in inflammatory bowel disease these T cell clonal expansions are persistent and shared among HLA-identical individuals, implicating a response to specific, persistent, and stimulating Ags in these diseases.
Mechanism of the stabilization of ribonuclease a by sorbitol: Preferential hydration is greater for the denatured than for the native protein (1997)

The effect of interactions of sorbitol with ribonuclease A (RNase A) and the resulting stabilization of structure was examined in parallel thermal unfolding and preferential binding studies with the application of multicomponent thermodynamic theory. The protein was stabilized by sorbitol both at pH 2.0 and pH 5.5 as the transition temperature, Tm, was increased. The enthalpy of the thermal denaturation had a small dependence on sorbitol concentration, which was reflected in the values of the standard free energy change of denaturation, delta delta G(o) = delta G(o) (sorbitol) - delta G(o)(water). Measurements of preferential interactions at 48 degrees C at pH 5.5, where protein is native, and pH 2.0 where it is denatured, showed that sorbitol is preferentially excluded from the denatured protein up to 40%, but becomes preferentially bound to native protein above 20% sorbitol. The chemical potential change on transferring the denatured RNase A from water to sorbitol solution is larger than that for the native protein, delta mu(2D) > delta mu(2N), which is consistent with the effect of sorbitol on the free energy change of denaturation. The conformity of these results to the thermodynamic expression of the effect of a co-solvent on denaturation, delta G(o)(W) + delta mu(D)(2)delta G(o)(S) + delta mu(2D), indicates that the stabilization of the protein by sorbitol can be fully accounted for by weak thermodynamic interactions at the protein surface that involve water reversible co-solvent exchange at thermodynamically non-neutral sites. The protein structure stabilizing action of sorbitol is driven by stronger exclusion from the unfolded protein than from the native structure.
Tat protein induces self-perpetuating permissivity for productive HIV-1 infection (1997)

We report that human immunodeficiency virus type 1 (HIV-1) has evolved a self-perpetuating mechanism to actively generate cells permissive for productive and cytopathic infection. Only activated T cells can be productively infected, which leads to their rapid depletion (2 x 10(9)/day in an infected individual). Establishment of productive HIV-1 infection therefore requires continual activations from the large pool of quiescent T cells. Tat protein, which is secreted by infected cells, activated uninfected quiescent T cells in vitro and in vivo. These Tat-activated uninfected cells became highly permissive for productive HIV-1 infection. Activation of primary T cells by Tat protein involved integrin receptors and was associated with activation of mitogen-activated protein kinases, including ERK1 and JNK kinase. Accordingly, these primary T cells progressed from G0 to the late G1 phase of the cell cycle.
Nuclear Targeting of Transforming Growth Factor-β-activated Smad Complexes (2005)

Upon stimulation by the transforming growth factor beta (TGF-beta), Smad2 and Smad3 are phosphorylated at their C termini and assemble into stable heteromeric complexes with Smad4. These complexes are the functional entities that translocate into the nucleus and regulate the expression of TGF-beta target genes. Here we report that the TGF-beta-activated phospho-Smad3/Smad4 complex utilizes an importin-independent mechanism for nuclear import and engages different nucleoporins for nuclear import compared with the monomeric Smad4. Within the heteromeric complex, phospho-Smad3 appears to dominate over Smad4 in the nuclear import process and guides the complex to its nuclear destination. We also demonstrate that the binding of phospho-Smad3 to Smad4 prevents Smad4 from interacting with the nuclear export receptor chromosome region maintenance 1. In this way, TGF-beta signaling suppresses nuclear export of Smad4 by chromosome region maintenance 1 and thereby targets Smad4 into the nucleus. Indeed tumorigenic mutations in Smad4 that affect its interaction with Smad2 or Smad3 impair nuclear accumulation of Smad4 in response to TGF-beta.
Cosmetic Contact Lenses and Iris Recognition Spoofing (2014)

Automatically detecting novel types of cosmetic contact lenses in iris images is a very difficult pattern-recognition problem, but experimental datasets that enable researchers to study this problem have recently become available.
Maskless patterning of silicon surface based on scanning tunneling microscope tip-induced anodization and chemical etching (1994)

A microprocessing method for silicon (Si) without photolithography is proposed. The method consists of only two processes. Hydrogen-terminated Si surfaces (Si-H) were first locally anodized using scanning tunneling microscopy (STM). The non-anodized surfaces were then etched chemically in potassium hydroxide solution. The anodic oxide produced with the first process performed as an etching mask. The height of the etched pattern of approximately 50 nm was much larger than the thickness of the anodic oxide. Humidity effect on STM tip-induced anodization of Si-H is also shown. The area of the anodization was enlarged with increasing humidity, and the spatial resolution became worse.
Adaptive execution techniques for SMT multiprocessor architectures (2005)

In simultaneous multithreading (SMT) multiprocessors, using all the available threads (logical processors) to run a parallel loop is not always beneficial due to the interference between threads and parallel execution overhead. To maximize performance in an SMT multiprocessor, finding the optimal number of threads is important. This paper presents adaptive execution techniques to find the optimal execution mode for SMT multiprocessor architectures. A compiler preprocessor generates code that, based on dynamic feedback, automatically determines at run time the optimal number of threads for each parallel loop in the application. Using 10 standard numerical applications and running them with our techniques on an Intel 4-processor Hyper-Threading Xeon SMP with 8 logical processors, our code is, on average, about 2 and 18 times faster than the original code executed on 4 and 8 logical processors, respectively.
Hemoglobin A1c in Diabetes: Panacea or Pointless? (2012)

Glycation is the nonenzymatic attachment of a monosaccharide to amino groups of proteins. The reaction has been recognized for many years in the food industry, where it is known as browning (also termed the Maillard reaction) and is responsible for the formation of commonly ingested items, such as toast. In patients with diabetes, glucose accumulation results in enhanced glycation of many proteins, both in tissues (e.g., the lens) and in the blood. Of these, glycated hemoglobin (GHb) is by far the most frequently measured in patient care. Hemoglobin (Hb) in healthy adults consists predominantly of HbA, which has 2α- and 2β-chains. Glucose can attach to several amino acid residues in these chains. HbA1c is formed when glucose attaches specifically to the NH2-terminal valine of the β-chain. Formation of HbA1c is essentially irreversible, and its concentration in the blood depends on both the life span of the red blood cell (RBC), which averages ∼120 days, and the blood glucose concentration. Because the rate of formation of HbA1c is directly proportional to the concentration of glucose in the blood, HbA1c represents integrated values for glucose over the preceding 8 to 12 weeks (Table 1).

View this table:

TABLE 1 
Selected attributes of HbA1c



Initially described 57 years ago (1), GHb was first reported to be increased in patients with diabetes in the late 1960s (2). The clinical value of GHb was soon realized and the American Diabetes Association (ADA) began encouraging the routine measurement of GHb in all patients with diabetes (3).

The fundamental role of GHb in diabetes was accentuated by the publication in 1993 of the Diabetes Control and Complications Trial (DCCT) (4). The study, which compared intensive to conventional insulin therapy in patients with type 1 diabetes, documented a direct relationship between blood glucose concentrations …
Synthesis of Macrobi- and Macrotricyclic Compounds Comprising Pyrimidyl Substituted Cyclen and Cyclam (2010)

The synthesis of novel N 1 ,N 7 -bis(bromobenzyl)cyclens and N 1 ,N 8bis(bromobenzyl)cyclams is described.Arylation of these compounds with excess 4,6-dichloropyrimidine and 2-chloropyrimidine gave corresponding tetrasubstituted cyclen and cyclam in good yields.Bis(bromobenzyl)bis(pyrimidyl) substituted cyclens and cyclams were used in the Pd-catalyzed reactions with polyamines to give macrobi-and macrotricycles.The yields of macropolycyclic compounds were shown to be dependent on the nature of starting tetraazamacrocycles and polyamines.In the case of cyclam monopyrimidyl derivatives were also obtained and macropolycyclic compounds were synthesized on their base.
Rod Photoreceptors Protect from Cone Degeneration-Induced Retinal Remodeling and Restore Visual Responses in Zebrafish (2013)

Humans are largely dependent upon cone-mediated vision. However, death or dysfunction of rods, the predominant photoreceptor subtype, results in secondary loss of cones, remodeling of retinal circuitry, and blindness. The changes in circuitry may contribute to the vision deficit and undermine attempts at restoring sight. We exploit zebrafish larvae as a genetic model to specifically characterize changes associated with photoreceptor degenerations in a cone-dominated retina. Photoreceptors form synapses with two types of second-order neurons, bipolar cells, and horizontal cells. Using cell-specific reporter gene expression and immunolabeling for postsynaptic glutamate receptors, significant remodeling is observed following cone degeneration in the pde6c(w59) larval retina but not rod degeneration in the Xops:mCFP(q13) line. In adults, rods and cones are present in approximately equal numbers, and in pde6c(w59) mutants glutamate receptor expression and synaptic structures in the outer plexiform layer are preserved, and visual responses are gained in these once blind fish. We propose that the abundance of rods in the adult protects the retina from cone degeneration-induced remodeling. We test this hypothesis by genetically manipulating the number of rods in larvae. We show that an increased number and uniform distribution of rods in lor/tbx2b(p25bbtl) or six7 morpholino-injected larvae protect from pde6c(w59)-induced secondary changes. The observations that remodeling is a common consequence of photoreceptor death across species, and that in zebrafish a small number of surviving photoreceptors afford protection from degeneration-induced changes, provides a model for systematic analysis of factors that slow or even prevent the secondary deteriorations associated with neural degenerative disease.
Inhibition of Bone Morphogenetic Protein Signaling Reduces Vascular Calcification and Atherosclerosis (2012)

These results definitively implicate BMP signaling in atherosclerosis and calcification, while uncovering a previously unidentified role for BMP signaling in LDL cholesterol metabolism. BMP inhibition may be helpful in the treatment of atherosclerosis and associated vascular calcification.
Antibody Capture of Soluble Aβ Does Not Reduce Cortical Aβ Amyloidosis in the PDAPP Mouse (2008)

Reversing and preventing Alzheimer's type amyloidosis is most effectively accomplished with anti-amyloid antibodies that avidly bind plaque.
Malignant Skin Tumours (1984)

Part 1 Epidemiology and skin examination: living with the sun - history of the occurrence and treatment of skin tumours, A.J.J.Emmett and M.G.E.O'Rourke, epidemiology, M.G.E.O'Rourke and A.J.J.Emmett, epidemiology of malignant melanoma, A.Green ultraviolet radiation and the skin, G.A.Groves cell and molecular biology of cancer cells, K.A.O.Ellem assessment of the tumour, examination and recording of the skin tumour, A.J.J.Emmett and M.G.O'Rourke, interface between pathologist and surgeon, J.R.Bell, the surgeon's approach to the pathologist, A.J.J.Emmett and M.G.E.O'Rourke other diagnostic techniques - nuclear magnetic resonance imaging, C.R.Rayner, nuclear medicine for diagnosis and therapy of malignant skin tumours, J.M.Egerton-Vernon. Part 2 Tumours: malignant melanoma - clinical presentation and differential diagnosis, N.C.Davis, pathology, D.Weedon and G.Strutton, primary treatment, G.R.C.McLeod, elective and therapeutic lymph node dissection, G.R.C.McLeod, metastic malignant melanoma, G.G.E.O'Rourke, dyplastic naevi, D.Weedon, desmoplastic melanoma, M.G.E.O'Rourke and A.J.J.Emmett, melanoma in children and congenital melanocytic naevi, M.G.E.O'Rourke and A.J.J.Emmmett, regression in melanomas, J.Triscott basal cell carcinoma - clinical presentation, A.J.J.Emmett, pathology, D.Weedon, differential diagnosis, A.J.J.Emmett, surgical treatment, A.J.J.Emmett squamous cell carcinoma - clinical presentation, T.J.Harris, pathology, D.Weedon, treatment, T.J.Harris merkel cell or neuro endocrine tumour of skin - M.G.E.O'Rourke, D.Weedon, keratoacanthoma, keratoses, bowen's disease - keratoacanthoma, J.T.Hueston, pathology of keratoacanthoma, J.J.Sullivan, keratoses, G.L.Beardmore, Bowen's disease, G.L.Beardmore, pathology of Bowen's disease, D.Weedon kaposi's sarcoma sarcoma and lymphoma - sarcoma - clinical, M.G.E.O'Rourke, primary cutaneous malignant lymphoma, S.J.C.Roberts, pathology, R.Duhig appendageal tumours - B.Gutteridge. Part 3 Therapeutic techniques: dermatological treatment - cryosurgery in the treatment of cutaneous malignancies, M.Deakin, curettage and electrosurgery, R.C.Needham, tropical cytotoxic therapy for solar and other lesions, V.Hart, Moh's chemosurgery or microscopically controlled excision for skin cancer, M.M.Stewart radiation treatment, R.G.Bourne chemo-immune therapy - chemotherapy and immunotherapy, G.J.A.Clunie, regional cytotoxic arterial perfusion for recurrent malignant melanoma, W.S.Egerton. Part 4 Surgical techniques: excision and repair of small lesions, A.J.J.Emmett repair by skin grafting, A.J.J.Emmett flap repair of defects after surgery, A.J.J.Emmett large flap repair, T.J.Harris composite free flap repairs, D.N.Robinson radical node dissection, M.G.E.O'Rourke, inguinal node dissection, M.G.E.O'Rourke, axillary node dissection, M.G.E.O'Rourke, radical neck dissection, M.G.E.O'Rourke and G.R.C.McLeod.