gebhart/patrepeval huggingface dataset:
Double-illumination photoacoustic microscopy (2012)

Recent developments of optical-resolution photoacoustic microscopy (OR-PAM) have improved its spatial resolution and imaging speed. However, the penetration depth of OR-PAM is still limited to ~1 mm in tissue, owing to the strong tissue scattering. Here, we have developed double-illumination PAM (DI-PAM), which illuminates the sample from both top and bottom sides simultaneously. Through phantom and in vivo experiments, we have demonstrated for thin targets that DI-PAM has a penetration depth of ~2 mm in tissue at 532 nm and a focal zone of 260 μm, both significant improvements over traditional reflection or transmission-mode OR-PAM.
Sustained proliferation of PDX-1+ cells derived from human islets. (1999)

Ex vivo expansion of human beta-cells is an important step toward the development of cell-based insulin delivery systems in type 1 diabetes. Here, we report that human pancreatic endocrine cells can be expanded through 15 cell doublings in vitro for an estimated total 30,000-fold increase in cell number. We believe that the cells resulting from these cultures are of beta-cell origin, since they uniformly express the transcription factor PDX-1 (STF-1, IDX-1, IPF-1), which is initially seen only in cells positive for insulin and negative for the ductal cell marker cytokeratin (CK)-19. To rule out the possibility that PDX-1 expression might be induced by the culture conditions used here, cells from isolated human pancreatic ducts were cultured under the same conditions as the islet cells. Cells in these cultures expressed CK-19 but not PDX-1. Although the expanded beta-cells continued to express PDX-1, insulin expression was lost over time. Whether reexpression of islet-specific genes in vitro is essential for successful cell transplantation remains to be determined.
Cutting Edge: An In Vivo Requirement for STAT3 Signaling in TH17 Development and TH17-Dependent Autoimmunity (2007)

STAT3 activation has been observed in several autoimmune diseases, suggesting that STAT3-mediated pathways promote pathologic immune responses. We provide in vivo evidence that the fundamental role of STAT3 signaling in autoimmunity relates to its absolute requirement for generating T(H)17 T cell responses. We show that STAT3 is a master regulator of this pathogenic T cell subtype, acting at multiple levels in vivo, including T(H)17 T cell differentiation and cytokine production, as well as induction of RORgamma t and the IL-23R. Neither naturally occurring T(H)17 cells nor T(H)17-dependent autoimmunity occurs when STAT3 is ablated in CD4 cells. Furthermore, ablation of STAT3 signaling in CD4 cells results in increased T(H)1 responses, indicating that STAT3 signaling skews T(H) responses away from the T(H)1 pathway and toward the T(H)17 pathway. Thus, STAT3 is a candidate target for T(H)17-dependent autoimmune disease immunotherapy that could selectively inhibit pathogenic immune pathways.
Localizing α-Helices in Human Tropoelastin:  Assembly of the Elastin “Puzzle” (2006)

Polyalanine cross-linking domains encoded by exons 6, 15, 17, 19, 21, 23, 25, 27, 29, 31 of human tropoelastin were synthesized, and their conformations were studied in different solutions and at different temperatures by CD and (1)H NMR. The results demonstrated the presence of poly-proline II helix (PPII) in aqueous solvent and of alpha-helical conformation in TFE. The (1)H NMR results allowed the precise localization of the helices along the peptide sequence. These data were further refined by prediction algorithms in order to take into account the reduced helix stability at the end of the peptides. Furthermore, the influence of flanking residues was checked by synthesizing and by determining the structure of a peptide spanning exon 31 coded domain and the first five residues of the following exon 32 coded domain. These studies, together with those previously published [Tamburro, A. M., Bochicchio, B., and Pepe, A. (2003) Biochemistry 42, 13147-62], are used to propose a coherent recomposition of the elastin pieces (domains) in order to give an acceptable solution to the elastin structure-function problem.
A hybrid network of synthetic polymer mesh and collagen sponge (2000)

A novel hybrid network of synthetic polymer mesh and collagen sponge was prepared by forming collagen sponges with interconnected microporous structures in the interstices of the synthetic polymer mesh.
Nuclear Magnetic Resonance-Based Screening Methods for Drug Discovery (2006)

Nuclear magnetic resonance (NMR) techniques are widely used in the drug discovery process. The primary feature exploited in these investigations is the large difference in mass between drugs and receptors (usually proteins) and the effect that this has on the rotational or translational correlation times for drugs bound to their targets. Many NMR parameters, such as the diffusion coefficient, spin diffusion, nuclear Overhauser enhancement, and transverse and longitudinal relaxation times, are strong functions of either the overall tumbling or translation of molecules in solution. This has led to the development of a wide variety of NMR techniques applicable to the elucidation of protein and nucleic acid structure in solution, the screening of drug candidates for binding to a target of choice, and the study of the conformational changes that occur in a target on drug binding. High-throughput screening by NMR methods has recently received a boost from the introduction of sophisticated computational techniques for reducing the time needed for the acquistion of the primary NMR data for multidimensional studies.
Roles of Tyrosine 158 and Lysine 165 in the Catalytic Mechanism of InhA, the Enoyl-ACP Reductase fromMycobacterium tuberculosis (1999)

The role of tyrosine 158 (Y158) and lysine 165 (K165) in the catalytic mechanism of InhA, the enoyl-ACP reductase from Mycobacterium tuberculosis, has been investigated. These residues have been identified as putative catalytic residues on the basis of structural and sequence homology with the short chain alcohol dehydrogenase family of enzymes. Replacement of Y158 with phenylalanine (Y158F) and with alanine (Y158A) results in 24- and 1500-fold decreases in k(cat), respectively, while leaving K(m) for the substrate, trans-2-dodecenoyl-CoA, unaffected. Remarkably, however, replacement of Y158 with serine (Y158S) results in an enzyme with wild-type activity. Kinetic isotope effect studies indicate that the transfer of a solvent-exchangeable proton is partially rate-limiting for the wild-type and Y158S enzymes, but not for the Y158A enzyme. These data indicate that Y158 does not function formally as a proton donor in the reaction but likely functions as an electrophilic catalyst, stabilizing the transition state for hydride transfer by hydrogen bonding to the substrate carbonyl. A conformational change involving rotation of the Y158 side chain upon binding of the enoyl substrate to the enzyme is proposed as an explanation for the inverse solvent isotope effect observed on V/K(DD-CoA) when either NADH or NADD is used as the reductant. These data are consistent with the recently published structure of a C16 fatty acid substrate bound to InhA that shows Y158 hydrogen bonded to the substrate carbonyl group and rotated from the position it occupies in the InhA-NADH binary complex [Rozwarski, D. A., Vilcheze, C., Sugantino, M., Bittman, R., and Sacchettini, J. C. (1999) J. Biol. Chem. 274, 15582-15589]. Finally, the role of K165 has been analyzed using site-directed mutagenesis. Replacement of K165 with glutamine (K165Q) and arginine (K165R) has no effect on the enzyme's catalytic ability or on its ability to bind NADH. However, the K165A and K165M enzymes are unable to bind NADH, indicating that K165 has a primary role in cofactor binding.
Identification and characterization of a novel peptide ligand of epidermal growth factor receptor for targeted delivery of therapeutics (2005)

Epidermal growth factor receptor (ErbB1, EGFR) is overexpressed in a variety of human cancer cells. It has been considered as a rational target for drug delivery. To identify novel ligands with specific binding capabilities to EGFR, we screened a phage display peptide library and found an enriched phage clone encoding the amino acid sequence YHWYGYTPQNVI (designated as GE11). Competitive binding assay and Scatchard analysis revealed that GE11 peptide bound specifically and efficiently to EGFR with a dissociation constant of approximately 22 nM, but with much lower mitogenic activity than with EGF. We showed that the peptides were internalized preferentially into EGFR highly expressing cells, and they accumulated in EGFR overexpressing tumor xenografts after i.v. delivery in vivo. In gene delivery studies, GE11-conjugated polyethylenimine (PEI) vectors were less mitogenic, but still quite efficient at transfecting genes into EGFR highly expressing cells and tumor xenografts. Taken together, GE11 is a potentially safe and efficient targeting moiety for selective drug delivery systems mediated through EGFR.
Small intestinal bacterial overgrowth: a comprehensive review. (2007)

Small intestinal bacterial overgrowth (SIBO), defined as excessive bacteria in the small intestine, remains a poorly understood disease. Initially thought to occur in only a small number of patients, it is now apparent that this disorder is more prevalent than previously thought. Patients with SIBO vary in presentation, from being only mildly symptomatic to suffering from chronic diarrhea, weight loss, and malabsorption. A number of diagnostic tests are currently available, although the optimal treatment regimen remains elusive. Recently there has been renewed interest in SIBO and its putative association with irritable bowel syndrome. In this comprehensive review, we will discuss the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of SIBO.
Cell-Based Therapeutics: The Next Pillar of Medicine (2013)

Two decades ago, the pharmaceutical industry-long dominated by small-molecule drugs-was revolutionized by the the advent of biologics. Today, biomedicine sits on the cusp of a new revolution: the use of microbial and human cells as versatile therapeutic engines. Here, we discuss the promise of this "third pillar" of therapeutics in the context of current scientific, regulatory, economic, and perceptual challenges. History suggests that the advent of cellular medicines will require the development of a foundational cellular engineering science that provides a systematic framework for safely and predictably altering and regulating cellular behaviors.
Structures ofC-mannosylated anti-adhesives bound to the type 1 fimbrial FimH adhesin (2016)

Selective inhibitors of the type 1 fimbrial adhesin FimH are recognized as attractive alternatives for antibiotic therapies and prophylaxes against Escherichia coli infections such as urinary-tract infections. To construct these inhibitors, the α-d-mannopyranoside of high-mannose N-glycans, recognized with exclusive specificity on glycoprotein receptors by FimH, forms the basal structure. A hydrophobic aglycon is then linked to the mannose by the O1 oxygen inherently present in the α-anomeric configuration. Substitution of this O atom by a carbon introduces a C-glycosidic bond, which may enhance the therapeutic potential of such compounds owing to the inability of enzymes to degrade C-glycosidic bonds. Here, the first crystal structures of the E. coli FimH adhesin in complex with C-glycosidically linked mannopyranosides are presented. These findings explain the role of the spacer in positioning biphenyl ligands for interactions by means of aromatic stacking in the tyrosine gate of FimH and how the normally hydrated C-glycosidic link is tolerated. As these new compounds can bind FimH, it can be assumed that they have the potential to serve as potent new antagonists of FimH, paving the way for the design of a new family of anti-adhesive compounds against urinary-tract infections.
HDAC inhibitors in HIV (2011)

Combination antiretroviral therapy (cART) has led to a very substantial reduction in morbidity and mortality in HIV-infected patients; however, cART alone is unable to cure HIV and therapy is lifelong. Therefore, a new strategy to cure HIV is urgently needed. There is now a concerted effort from scientists, clinicians and funding agencies to identify ways to achieve either a functional cure (long-term control of HIV in the absence of cART) or a sterilizing cure (elimination of all HIV-infected cells). Multiple strategies aiming at achieving a cure for HIV are currently being investigated, including both pharmacotherapy and gene therapy. In this review, we will review the rationale as well as in vitro and clinical trial data that support the role of histone deacetylase inhibitors as one approach to cure HIV.
Metal‐Assisted Chemical Etching of Silicon: A Review (2010)

This article presents an overview of the essential aspects in the fabrication of silicon and some silicon/germanium nanostructures by metal-assisted chemical etching. First, the basic process and mechanism of metal-assisted chemical etching is introduced. Then, the various influences of the noble metal, the etchant, temperature, illumination, and intrinsic properties of the silicon substrate (e.g., orientation, doping type, doping level) are presented. The anisotropic and the isotropic etching behaviors of silicon under various conditions are presented. Template-based metal-assisted chemical etching methods are introduced, including templates based on nanosphere lithography, anodic aluminum oxide masks, interference lithography, and block-copolymer masks. The metal-assisted chemical etching of other semiconductors is also introduced. A brief introduction to the application of Si nanostructures obtained by metal-assisted chemical etching is given, demonstrating the promising potential applications of metal-assisted chemical etching. Finally, some open questions in the understanding of metal-assisted chemical etching are compiled.
Preparation of tetrazoles from organic nitriles and sodium azide in micellar media (1998)

Abstract An effective method for the preparation of 5‐substituted tetrazoles from the corresponding nitriles in micellar media is described. It was demonstrated that almost quantitative yields of tetrazoles can be obtained if the amount of water‐surfactant is optimized. The advantages of the methods presented over many others currently used are the simplicity, facility of isolation of tetrazole products and elimination of using relatively expensive solvents and reagents.
Syp (SH-PTP2) is a positive mediator of growth factor-stimulated mitogenic signal transduction. (1994)

Syp (SH-PTP2) was recently identified as a phosphotyrosine phosphatase containing two SH2 domains within its primary structure. In response to appropriate growth factor stimulation, Syp becomes phosphorylated on tyrosine residues and associates with insulin receptor substrate 1 (IRS-1) and/or the corresponding growth factor receptor via its SH2 domains, leading to increased Syp activity. To assess the importance of Syp in mitogenic signaling, we microinjected mammalian fibroblasts with several reagents designed to interfere with Syp SH2/phosphotyrosine interaction in vivo. Insulin-, insulin-like growth factor-1-, and epidermal growth factor-stimulated DNA synthesis, indicated by bromodeoxyuridine (BrdUrd) incorporation, was dramatically decreased following microinjection of a Syp antibody (Ab) (65-85%) or a Syp GST-SH2 fusion protein (approximately 90%) in comparison with cells microinjected with control IgG or glutathione S-transferase (GST), respectively. In addition, microinjection of an IRS-1-derived phosphonopeptide, which inhibits in vitro binding of Syp-SH2 to IRS-1 with an ED50 value of approximately 23 microM, also decreased BrdUrd incorporation in vivo by approximately 50-75%. Microinjection of the Syp Ab, Syp GST-SH2 fusion protein, or the phosphonopeptide had no effect on serum-stimulated BrdUrd incorporation. In conclusion, disruption of Syp function in living cells inhibited cell cycle progression in response to growth factor stimulation, indicating that Syp is a critical positive regulator of mitogenic signal transduction.
Gene therapy for ADA‐SCID, the first marketing approval of an ex vivo gene therapy in Europe: paving the road for the next generation of advanced therapy medicinal products (2017)

Gene and cell therapy research recently reached a fundamental milestone toward the goal to deliver new medicines for orphan diseases. In 2016, the European Commission granted market approval to GlaxoSmithKline ( GSK ) for ex vivo hematopoietic stem cell ( HSC ) gene therapy for the treatment of adenosine deaminase ( ADA )‐deficient severe combined immunodeficiency ( SCID ), a very rare congenital disorder of the immune system. The new medicine, named Strimvelis™, is an advanced therapy medicinal product ( ATMP ) (Salmikangas et al , ) originally developed by the San Raffaele Telethon Institute for Gene Therapy ( SR ‐Tiget), a joint venture between Telethon Foundation and San Raffaele Scientific Institute. This ATMP is the first ex vivo stem cell gene therapy to receive regulatory approval anywhere in the world. Strimvelis™ consists of a single infusion of autologous gene‐corrected HSC and is prepared from the patient's own bone marrow ( BM ) HSC s, which are genetically modified using a gamma‐retroviral vector to insert a functional copy of the ADA gene.
Transactivation Domain 2 (TA2) of p65 NF-κB (1995)

The p65 subunit of the inducible transcription factor NF-kappa B contains at least two strong transactivation domains (TADs) within its C terminus. The first domain, TA1, is contained within the last 30 amino acids of p65, whereas TA2 comprises the adjacent 90 amino acids. In this study, squelching experiments revealed that both TADs of p65, as well as the related subunit c-Rel, compete for the same cofactor(s) mediating transactivation. Both TADs of p65 share a common sequence motif, which is evolutionarily conserved and displays a remarkable degree of spatial organization when aligned on an alpha-helical surface. The functional importance of the common sequence motif was confirmed by deletion analysis of TA2. Within the conserved sequence motif, a 7-amino-acid repeat was noted. Idealized heptad repeats fused to the DNA binding domain of Gal4 were transcriptionally active, but only as multimers. Phosphorylation and transcriptional activity of a defined region within the TA2 domain was found to be stimulated by phorbol ester treatment of cells. In contrast, TA1 was constitutively phosphorylated, and its activity did not significantly respond to phorbol ester stimulation. The stimulatory effect of phorbol ester on transcription of the TA2 domain was completely blocked by the protein kinase C inhibitor. These data suggest that protein kinase C has a dual effect on NF-kappa B activity. It not only causes removal of I kappa B-alpha from cytoplasmic NF-kappa B but also augments the transactivation potential of activated nuclear NF-kappa B.
Estimation of the utilities of the NAL units in H.264/AVC scalable video bitstreams (2011)

In our previous work [1,2], we proposed a framework to provide optimized unequal error protection (UEP) with Reed-Solomon codes to the H.264/AVC scalable video bitstreams to get robust video streaming for uni-/multicast applications.In that framework, we need to measure the real utilities of the network abstraction layer (NAL) units in a separate process before the transmission of the bitstream.This process requires, however, multiple decoding processes of the whole bitstream, which makes the framework not directly applicable to a live streaming system, where the video content is captured and must be transmitted within a constrained delay.In this work, we present a simple but very effective algorithm to estimate the utilities of the NAL units on the enhancement layer.With the estimation algorithm, we don't need additional decoding processes, except those with the complete base layer and enhancement layer, which are integrated in the encoder.We performed intensive tests with the estimation algorithm for different sequences in the UEP framework.Our simulation results show that good UEP performance can be achieved with the estimated utilities.The loss of performance using the estimated utilities against the real utilities is very low, if the estimation period is appropriately selected.
Differentiation Between Intracerebral Hemorrhage and Ischemic Stroke by Transcranial Color-Coded Duplex-Sonography (1998)

In comparison to the "gold standard" of CT, TCCS identified stroke complications and differentiated between intracerebral hemorrhage and ischemic stroke with reasonable sensitivity. Thus, if CT is not readily available, TCCS may complement clinical examination in patients with acute stroke. In addition, it may also be useful in detecting stroke complications in the follow-up of stroke patients.
Using AutoCAD 2000 (2000)

From the Publisher:
Special Edition Using AutoCAD 2000 allows you to quickly become acquainted with the AutoCAD software, even if you have no previous AutoCAD experience. The extensive use of case studies throughout the book familiarizes you with the numerous commands, as well as where they are accessed and how they work. There is a strong emphasis on the heads-up design of the interface carried through the book, making you less reliant on the keyboard and more efficient using the software. New features and changes to the software are clearly marked from cover to cover, highlighting exactly what is new in the software.
In vitro reconstitution of pancreatic islets (2014)

The lack of transplantable pancreatic islets is a serious problem that affects the treatment of patients with type 1 diabetes mellitus. Beta cells can be induced from various sources of stem or progenitor cells, including induced pluripotent stem cells in the near future; however, the reconstitution of islets from β cells in culture dishes is challenging. The generation of highly functional islets may require three-dimensional spherical cultures that resemble intact islets. This review discusses recent advances in the reconstitution of islets. Several factors affect the reconstitution of pseudoislets with higher functions, such as architectural similarity, cell-to-cell contact, and the production method. The actual transplantation of naked or encapsulated pseudoislets and islet-like cell clusters from various stem cell sources is also discussed. Advancing our understanding of the methods used to reconstitute pseudoislets should expand the range of potential strategies available for developing de novo islets for therapeutic applications.