gebhart/patrepeval huggingface dataset:
HGF regulates the activation of TGF‐β1 in rat hepatocytes and hepatic stellate cells (2012)

Hepatocyte growth factor (HGF) ameliorates experimental liver fibrosis through many mechanisms, including degradation of accumulated collagen and decreased expression of fibrotic genes. Investigating an upstream mechanism in which HGF could decrease many fibrotic effectors, we asked whether HGF regulates activation of the fibrotic cytokine transforming growth factor-beta 1 (TGF-β1). Specifically, we tested whether HGF decreases the levels of active TGF-β1, and whether such decrease depends on the predominantly hepatocyte-secreted protease plasmin, and whether it depends on the TGF-β1 activator thrombospondin-1 (TSP-1). With hepatocyte monocultures, we found HGF-induced hepatocyte proliferation did increase total levels of plasmin, while decreasing gene expression of fibrotic markers (PAI-1, TGF-β1, and TIMP-2). With in vitro models of fibrotic liver (HSC-T6 hepatic stellate cells, or co-cultures of HSC-T6 and hepatocytes), we found high levels of fibrosis-associated proteins such as TSP-1, active TGF-β1, and Collagen I. HGF treatment on these fibrotic cultures stimulated plasmin levels; increased TSP-1 protein cleavage; and decreased the levels of active TGF-β1 and Collagen I. When plasmin was blocked by the inhibitor aprotinin, HGF could no longer decrease TGF-β1 activation and Collagen I. Meanwhile, the TSP-1-specific peptide inhibitor, LSKL, reduced TGF-β1 to the same level as in the HGF-treated cultures; combining LSKL and HGF treatments caused no further decrease, suggesting that HGF affects the TSP-1 dependent pathway of TGF-β1 activation. Therefore, HGF can decrease TGF-β1 activation and TGF-β1-dependent fibrotic markers, by stimulating hepatocytes to produce plasmin, and by antagonizing TSP-1-dependent activation of TGF-β1.
β-Secretase Protein and Activity Are Increased in the Neocortex in Alzheimer Disease (2002)

The BACE protein and activity levels are increased in brain regions affected by amyloid deposition and remain increased despite significant neuronal and synaptic loss in AD.
Circular resonant structures in microstrip (1969)

Mode patterns of circular disc resonant sections are analysed. Radiation losses are expected to be small for the dominant mode, which would therefore have the highest Q value.
Effect of transition-state analogs on the redox properties of medium-chain acyl-CoA dehydrogenase (1995)

The binding of substrate/product or transition-state intermediates modifies the properties of medium-chain fatty acyl-CoA dehydrogenase (MCAD) by causing the redox potential to shift positive and the oxygen reactivity to slow by 3000-fold. Two ligands, identified as being the most effective in slowing oxygen reactivity, were 2-azaoctanoyl-CoA and 3-thiaoctanoyl-CoA [Wang, R., & Thorpe, C. (1991) Biochemistry 30, 7895-7901]. We have measured the potential shifts caused by the binding of both ligands to determine which is most similar to the potential shift caused by substrate/product mixture, the assumption being that the best transition-state structural intermediate would give the potential shift most similar to that of substrate/product [Lenn, N.D., Stankovich, M.T., & Liu, H. (1990) Biochemistry 29, 10594-10602]. Both ligands shifted the potential positive, but the shift caused by 2-azaoctanoyl-CoA was 65% that of substrate/product, while 3-thiaoctanoyl-CoA was only 20% of that value. This positive shift is proposed to be caused by a resonance form stabilized by the interaction of the catalytically essential carbonyl of the acyl-CoA with two hydrogen bonds from the enzyme, which induces a partial negative charge on the carbonyl and a partial positive charge on carbon 2 of the ligand and carbon 3 of the substrate/product couple. The X-ray structure shows that carbons 2 and 3 of the substrate/product overlap the diazadiene portion of the flavin ring [Kim, J.-J. P., Wang, M., & Paschke, R. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 7523-7527].(ABSTRACT TRUNCATED AT 250 WORDS)
Role of Cholesterol in Human Immunodeficiency Virus Type 1 Envelope Protein-Mediated Fusion with Host Cells (2002)

In this study we examined the effects of target membrane cholesterol depletion and cytoskeletal changes on human immunodeficiency virus type 1 (HIV-1) Env-mediated membrane fusion by dye redistribution assays. We found that treatment of peripheral blood lymphocytes (PBL) with methyl-beta-cyclodextrin (MbetaCD) or cytochalasin reduced their susceptibility to membrane fusion with cells expressing HIV-1 Env that utilize CXCR4 or CCR5. However, treatment of human osteosarcoma (HOS) cells expressing high levels of CD4 and coreceptors with these agents did not affect their susceptibility to HIV-1 Env-mediated membrane fusion. Removal of cholesterol inhibited stromal cell-derived factor-1alpha- and macrophage inflammatory protein 1beta-induced chemotaxis of both PBL and HOS cells expressing CD4 and coreceptors. The fusion activity as well as the chemotactic activity of PBL was recovered by adding back cholesterol to these cells. Confocal laser scanning microscopy analysis indicated that treatment of lymphocytes with MbetaCD reduced the colocalization of CD4 or of CXCR4 with actin presumably in microvilli. These findings indicate that, although cholesterol is not required for HIV-1 Env-mediated membrane fusion per se, its depletion from cells with relatively low coreceptor densities reduces the capacity of HIV-1 Env to engage coreceptor clusters required to trigger fusion. Furthermore, our results suggest that coreceptor clustering may occur in microvilli that are supported by actin polymerization.
The T Cell Receptor/CD3 Complex: A Dynamic Protein Ensemble (1988)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Clinical Efficacy and Safety of SeQuent Please Paclitaxel-Eluting Balloon in a Real-World Single-Center Registry of South-East Asian Patients (2013)

SeQuent Please DEB was a safe and effective treatment modality in our cohort of South-East Asian patients with a low incidence of MACE observed at 9 months follow-up.
Translational Mini-Review Series on Complement Factor H: Structural and functional correlations for factor H (2007)

The 155-kDa glycoprotein, complement factor H (CFH), is a regulator of complement activation that is abundant in human plasma. Three-dimensional structures of over half the 20 complement control protein (CCP) modules in CFH have been solved in the context of single-, double- and triple-module segments. Proven binding sites for C3b occupy the N and C termini of this elongated molecule and may be brought together by a bend in CFH mediated by its central CCP modules. The C-terminal CCP 20 is key to the ability of the molecule to adhere to polyanionic markers on self-surfaces where CFH acts to regulate amplification of the alternative pathway of complement. The surface patch on CCP 20 that binds to model glycosaminoglycans has been mapped using nuclear magnetic resonance (NMR), as has a second glycosaminoglycan-binding patch on CCP 7. These patches include many of the residue positions at which sequence variations have been linked to three complement-mediated disorders: dense deposit disease, age-related macular degeneration and atypical haemolytic uraemic syndrome. In one plausible model, CCP 20 anchors CFH to self-surfaces via a C3b/polyanion composite binding site, CCP 7 acts as a 'proof-reader' to help discriminate self- from non-self patterns of sulphation, and CCPs 1-4 disrupt C3/C5 convertase formation and stability.
The hepatic artery: a reminder of surgical anatomy. (2001)

This study was carried out to document the anatomy of the hepatic artery with the purpose of reminding surgeons of the need for this essential knowledge in order to practice safe hepatobiliary surgery. Repeated surgical mistakes on patients referred to our unit prompted the study. One hundred and eighty consecutive livers procured for transplantation was studied, and the anatomy drawn immediately after dissection. The left hepatic artery arose from the left gastric artery in 15%, and either the splenic, gastroduodenal artery or the aorta in 4% of cases. The right hepatic artery arose from the superior mesenteric artery in 15%, the gastroduodenal, right gastric artery or aorta in 10% of cases. There was a major variation of the coeliac axis in 9% of cases studied. Overall, there was an abnormality in 43% of dissections: 48% were multiple and 27% had more than two vascular variations. A constant pattern of abnormalities occurred in the anatomy of the hepatic artery. Realisation of this vascular pattern should make identification of the anatomy easier. When there is one vascular variation, there is a high chance of there being multiple variations.
Pharmacokinetics of Lidocaine With Epinephrine Following Local Anesthesia Reversal With Phentolamine Mesylate (2008)

Phentolamine mesylate accelerates recovery from oral soft tissue anesthesia in patients who have received local anesthetic injections containing a vasoconstrictor. The proposed mechanism is that phentolamine, an alpha-adrenergic antagonist, blocks the vasoconstriction associated with the epinephrine used in dental anesthetic formulations, thus enhancing the systemic absorption of the local anesthetic from the injection site. Assessments of the pharmacokinetics of lidocaine and phentolamine, and the impact of phentolamine on the pharmacokinetics of lidocaine with epinephrine were performed to characterize this potentially valuable strategy. The blood levels of phentolamine were determined following its administration intraorally and intravenously. Additionally, the effects of phentolamine mesylate on the pharmacokinetics of intraoral injections of lidocaine with epinephrine were evaluated. Sixteen subjects were enrolled in this phase 1 trial, each receiving 4 drug treatments: 1 cartridge lidocaine/epinephrine followed after 30 minutes by 1 cartridge phentolamine (1L1P), 1 cartridge phentolamine administered intravenously (1Piv), 4 cartridges lidocaine/epinephrine followed after 30 minutes by 2 cartridges phentolamine (4L2P), and 4 cartridges lidocaine/epinephrine followed by no phentolamine (4L). Pharmacokinetic parameters estimated for phentolamine, lidocaine, and epinephrine included peak plasma concentration (Cmax), time to peak plasma concentration (Tmax), area under the plasma concentration-time curve from 0 to the last time point (AUClast) or from time 0 to infinity (AUCinf), elimination half-life (t1/2), clearance (CL), and volume of distribution (Vd). The phentolamine Tmax occurred earlier following the intravenous administration of 1Piv (7 minutes than following its submucosal administration in treatment 1L1P (15 minutes) or 4L2P (11 minutes). The phentolamine t1/2, CL, and Vd values were similar for 1L1P, 1Piv, and 4L2P. The Tmax for lidocaine occurred later and the Cmax for lidocaine was slightly higher when comparing the 4L2P treatment and the 4L treatment. The phentolamine-induced delay of the lidocaine Tmax likely represents phentolamine's ability to accelerate the systemic absorption of lidocaine from oral tissues into the systemic circulation.
Genetic and familial considerations of primary biliary cirrhosis (2001)

The genetic basis of human autoimmune diseases is receiving increasing attention. Primary biliary cirrhosis (PBC) is a model autoimmune disease reflective of other organ-specific autoimmune pathology. PBC is an enigmatic autoimmune disease that predominantly affects women and leads to destruction of intrahepatic bile ducts. The serological hallmark of this disease is characterized by antimitochondrial antibodies that specifically react with the E2 components of 2-oxodehydrogenase enzymes, including PDC-E2. There are no clear major histocompatibility complex associations with the development of PBC, despite the observation that first-degree relations of index patients with PBC have a 4-6% prevalence of development of PBC. This risk factor is comparable or higher than any other human autoimmune disease and suggests that a genome-wide approach towards dissection of genetic associations would lead to valuable new insights. In this review, we place these concepts in perspective and highlight in particular the genetic associations in PBC and the importance of studying siblings with PBC who are concordant for disease.
Reflecting telescopes for an orbiting high-resolution camera for Earth observation (2006)

This feasibility study compares several optical configurations for an orbiting high-resolution (<1 m) panchromatic push-broom camera. This is an optical subsystem of the CIA (Camera Iperspettrale Avanzata, Advanced Hyperspectral Camera) project, promoted by the Italian Space Agency (ASI), aimed at high-resolution imaging for applications in Earth observation, mainly for environmental control, geology (especially volcanoes), and coastal and inland water monitoring. The study includes optics and radiometric analyses, used to select a fan of candidate optical configurations, including all the solutions suitable for the specific task, namely, Ritchey-Chretien with and without relay, Korsch, and Schmidt-Cassegrain on axis, off axis, and with relay. The result of a trade-off analysis, considering not only optical performance but also other aspects such as cost, volume, complexity, and technological criticality, shows that the Korsch configuration is currently the best compromise, and it is potentially able to satisfy all project requirements. However, the other configurations have advantages that may be considered in the whole-mission assessment.
Selective binding of actinomycin D and distamycin A to DNA (1982)

The exact sites at which a number of drugs inhibit the nick translation of DNA by E.coli DNA polymerase-I have been pinpointed. In order to do this, a method has been developed for sequencing double-stranded plasmid DNA from the site of a specifically induced nick. The initial experiments have concentrated on analysis of drug inhibition of nick translation in a 200 nucleotide region near the Eco Rl origin of pBR313. Many drugs were found to inhibit nick translation in a highly sequence specific manner. For actinomycin D, significant inhibition occurred at just four sites in the nucleotide sequence under test and only one sequence (pGpCpGpCpGpGp) gave really strong inhibition. Distamycin A gave a different pattern of inhibition with particularly strong stops in just two of the many A-T rich regions in the DNA. Experiments with caffeine suggest that factors in addition to primary sequence are important in determining where major inhibition occurs.
Design of Novel Chimeric Melanotropin−Deltorphin Analogues. Discovery of the First Potent Human Melanocortin 1 Receptor Antagonist (2003)

A number of novel alpha-melanotropin (alpha-MSH) analogues have been designed, synthesized, and assayed for bioactivity at the melanocortin-1 (MC1) receptor from Xenopus frog skin, and selected potent analogues were examined at recombinant human MC1, MC3, and MC4 receptors expressed in human embryonic kidney (HEK) cells. These ligands were designed from Deltorphin-II, by a new hybrid approach, which incorporates the hydrophobic tail and the address sequence of Deltorphin-II (Glu-Val-Val-Gly-NH(2)) and key pharmacophore elements of melanotropins. Some of the ligands designed, c[Xxx-Yyy-Zzz-Arg-Trp-Glu]-Val-Val-Gly-NH(2) [XXX = nothing, Gly, beta-Ala, gamma-Abu, 6-Ahx; YYY = His, His(3-Bom), (S)-cyclopentylglycine (Cpg); ZZZ = Phe, d-Phe; d-Nal(2')], show high potency at melanocortin receptors. One ligand, GXH-32B-c[beta-Ala-His-d-Nal(2')-Arg-Trp-Glu]-Val-Val-Gly-NH(2), the most potent of the chimeric analogues tested, displayed agonist activity at each of the MC receptor subtypes analyzed, with an EC(50) of 2 nM at the amphibian MC1 receptor. In contrast, GXH-38B-c[Gly-Cpg-d-Nal(2')-Arg-Trp-Glu]-Val-Val-Gly-NH(2) (Cpg = cyclopentyl glycine) was an antagonist with a IC(50) of 43 nM at the amphibian receptor, and among the human subtypes tested, was the most potent at the MC1 receptor subtype where it also acted as an antagonist (K(i) = 53 nM), which is the first potent antagonist discovered for the human MC1 receptor. These results provide strong evidence supporting our hypothesis that ligand scaffolds for different G-protein coupled receptors (GPCRs) can be used to design ligands for other GPCRs and to design more potent ligands to treat diseases associated with the human MC1 receptor.
Fee-for-Service Research (1986)

The development of monoclonal antibodies to treat cancer, and\nparticularly the possibility of designing a set unique for each patient, has\nraised the specter of such experimental treatments someday being offered by\nfor-profit companies to those who can afford to underwrite the costs of the\nresearch. Lind discusses some of the scientific, economic, and ethical issues\nraised by this kind of fee-for-service research. These include lack of\npatient protection by ethics committees, government regulation, or informed\nconsent requirements; restriction of information and availability of treatment\ndue to the developer's proprietary interests; conflict of interest for the\nresearcher/physician; unequal access to new treatments; and possible depletion\nof family resources spent to purchase unproven therapies. (KIE abstract)
Heterogeneous ectopic RNP‐derived structures (HERDS) are markers of transcriptional arrest (2000)

We have reviewed the reports in the literature concerning the segregation and clustering of ribonucleoprotein (RNP) -containing nuclear structures in either physiological or experimentally induced conditions (i.e., spermiogenesis and erythropoiesis in mammals, early embryonic development, hibernation, spontaneous and drug-induced apoptosis, treatment with different drugs). Irrespective of the biological system or the experimental conditions, heterogeneous ectopic RNP-derived structures (HERDS) are always found. We hypothesize that the common event at the basis of this phenomenon might be the block in transcription; this is also consistent with our own and others' results on cultured cells after actinomycin D treatment. HERDS may therefore be considered as the morphological sign of transcriptional arrest. Based on the evidence that the restructuring/relocation of RNPs may be reversible, we also hypothesize that HERDS may serve as storage sites from which RNPs may be eventually retrieved, as soon as transcription restarts. Under acute stress conditions or during apoptotic cell death, the same reorganization of RNP-containing structures would be an adaptively suitable mechanism to induce an irreversible arrest in RNA processing, thus effectively blocking protein synthesis.
Total Synthesis and Structural Refinement of the Cyclic Tripyrrole Pigment Nonylprodigiosin (1999)

The first total synthesis of the cyclic prodigiosin derivative 4 is described, which constitutes a potential lead compound for the development of immunosuppressive agents. The key steps of this approach comprise a palladium-catalyzed Suzuki cross coupling reaction of the rather unstable pyrrole boronic acid derivative 17 with the electron rich pyrrolyl triflate 15 followed by a ring-closing metathesis reaction (RCM) of the resulting diene to form the macrocyclic ring of the target molecule. This transformation is best achieved by using the ruthenium indenylidene complex 21 as precatalyst. X-ray data of product 18.HCl thus formed suggest that the tautomeric form B properly describes the electron distribution within the heteroaromatic segment of this alkaloid, in which the central ring constitutes the azafulvene unit of the pyrrolylpyrromethene chromophore.
Efficient power coupling using taper-ended multimode optical fibres (1976)

Highly efficient power coupling of up to 97% between a d.h. laser and a multimode step-index fibre is demonstrated by employing a tapered fibre launcher. Also, it is shown theoretically that a tapered end increases the effective numerical aperture of a fibre. For a Lambertian emitter, the use of a taper launcher permits the maximum coupling efficiency allowed by the Liouville theorem.
An approach to multiobjective optimization of rotational therapy (2009)

Multiobjective optimization is used in radiotherapy, especially IMRT, to generate treatment plans which meet different objectives to varying extents. Trade-off surfaces can be constructed representing the gains and losses of different objectives when switching from one plan to another, and the planner can interactively explore different treatment possibilities without the need for reoptimization. In this work a method for the multiobjective optimization of rotational therapy is introduced. The proposed method is applied slice per slice and uses the geometry of the slice directly to construct several arcs, each conformally irradiating the tumor and blocking a number (0,1,2,...) of different organs at risk present in the treatment. The blocked arc dose distributions so obtained are quite inhomogeneous in the target. An algorithm, based on the iterative reconstruction of images from projections, has been developed to compensate for this inhomogeneity, leading to compensated blocked arcs which deliver more uniform target doses but still block critical structures. Different treatments can be obtained as linear combinations of these arcs, each involving different trade-offs among the objectives involved. The compensatory algorithm substantially improves the target dose uniformity of blocked arcs at the cost of slightly increasing the dose to the rest of the body, allowing delivery of good uniform dose distributions to the target without significantly irradiating the blocked organ(s). Trade-off surfaces are presented for slices containing a target and one or two critical structures. The method is directly implementable using axial or helical tomotherapy. Implementation for conventional linear accelerators will be more difficult because the number of arcs needed to deliver such treatments can be large, an issue to be explored in future work.
Analytics for Metabolic Engineering (2015)

Realizing the promise of metabolic engineering has been slowed by challenges related to moving beyond proof-of-concept examples to robust and economically viable systems. Key to advancing metabolic engineering beyond trial-and-error research is access to parts with well-defined performance metrics that can be readily applied in vastly different contexts with predictable effects. As the field now stands, research depends greatly on analytical tools that assay target molecules, transcripts, proteins, and metabolites across different hosts and pathways. Screening technologies yield specific information for many thousands of strain variants, while deep omics analysis provides a systems-level view of the cell factory. Efforts focused on a combination of these analyses yield quantitative information of dynamic processes between parts and the host chassis that drive the next engineering steps. Overall, the data generated from these types of assays aid better decision-making at the design and strain construction stages to speed progress in metabolic engineering research.