gebhart/patrepeval huggingface dataset:
Differentiation between ulcerative colitis and Crohn’s disease by a quantitative immunohistochemical evaluation of T lymphocytes, neutrophils, histiocytes and mast cells (2002)

Mucosal biopsy criteria has limited validity in terms of discrimination between ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to set up quantitative immunohistochemical criteria, with a special focus on inflammatory cell distribution within individual specimens and throughout the large bowel. Quantitative evaluation was performed for the density of CD8+, CD45RO+, neutrophil elastase+, CD68+ and mast cell tryptase+ cells in affected and unaffected mucosa taken from 41 patients with UC and 61 patients with CD. Each slide was examined at the highest and lowest density fields, which were further divided into the upper and deeper half of mucosa. Multiple logistic regression analysis using 51 features as independent variables constructed a predictive equation finding the probability of UC (PUC), and the diagnostic categories were subsequently defined based on a receiver-operating characteristic curve. The analysis disclosed five significant features suggesting UC; these implied intense infiltration of CD8+ and mast cell tryptase+ cells, diffuse infiltration of neutrophil elastase+ and CD68+ cells, and continuous infiltration of CD45RO+ cells. The criteria consisted of three diagnostic categories, 'suggestive of UC (PUC > or = 0.7)', 'indeterminate (0.3 < PUC < 0.7)', and 'suggestive of CD (PUC < or = 0.3)'; the criteria had values for sensitivity and specificity exceeding 95%. The immunohistochemical criteria distinguishing UC from CD may help to confirm the diagnosis in patients with ambiguous endoscopic and histological diagnosis.
Multiple Sclerosis: An Immune or Neurodegenerative Disorder? (2008)

Multiple sclerosis (MS) is an inflammatory-mediated demyelinating disease of the human central nervous system. The clinical disease course is variable, usually starts with reversible episodes of neurological disability in the third or fourth decade of life, and transforms into a disease of continuous and irreversible neurological decline by the sixth or seventh decade. We review data that support neurodegeneration as the major cause of irreversible neurological disability in MS patients. We question whether inflammatory demyelination is primary or secondary in the disease process and discuss the challenges of elucidating the cause of MS and developing therapies that will delay or prevent the irreversible and progressive neurological decline that most MS patients endure.
Recognition of diverse sequences by class I zinc fingers: asymmetries and indirect effects on specificity in the interaction between CF2II and A+T-rich elements. (1996)

The Drosophila CF2II protein, which contains zinc fingers of the Cys2His2 type and recognizes an A+T-rich sequence, behaves in cell culture as an activator of a reporter chloramphenicol acetyltransferase gene. This activity depends on C-terminal but not N-terminal zinc fingers, as does in vitro DNA binding. By site-specific mutagenesis and binding site selection, we define the critical amino acid-base interactions. Mutations of single amino acid residues at the leading edge of the recognition helix are rarely neutral: many result in a slight change in affinity for the ideal DNA target site; some cause major loss of affinity; and others change specificity for as many as two bases in the target site. Compared to zinc fingers that recognize G+C-rich DNA, CF2II fingers appear to bind to A+T-rich DNA in a generally similar manner, but with additional flexibility and amino acid-base interactions. The results illustrate how zinc fingers may be evolving to recognize an unusually diverse set of DNA sequences.
Multicolor imaging and contrast enhancement in cancer-tumor localization using laser-induced fluorescence in hematoporphyrin-derivative-bearing tissue (1985)

Simultaneous imaging of laser-induced fluorescence in three selected wavelength bands from hematoporphyrin-derivative-bearing tissue has been performed, permitting considerable contrast enhancement for cancer-tumor localization.
Chirality transfer in nematic liquid crystals doped with (S)-naproxen-functionalized gold nanoclusters: an induced circular dichroism study (2007)

In a recent study, we found that nematic liquid crystals (N-LCs) doped with chiral (S)-naproxen-functionalized dodecane thiolate protected gold nanoclusters (Au2, Au3) or non-chiral alkyl thiolate protected Au clusters (Au1) produce thin film textures with characteristic uniform stripe patterns separated by areas of homeotropic alignment. While these textures closely resemble textures commonly observed for chiral nematic (N*-)phases with large helical pitch, so-called cholesteric finger textures, they originate from local concentration differences of the nanoclusters in the N-LC solvent. While areas with higher particle content form linear particle aggregates (stripe domains) due to the surface anchoring of the N-LC molecules to the cluster surface, areas of lower particle concentration give homeotropic alignment as a result of particles residing at the glass–N-LC interfaces. To elucidate and confirm a chirality transfer from the chirally modified gold clusters to the non-chiral N-LC, despite the complex thin film textures, we here present detailed induced circular dichroism (ICD) studies of thin films of 5CB doped with the three different Au clusters. These experiments revealed that the chiral Au nanoclusters (Au2, Au3) successfully transfer chirality to the N-LC host producing a chiral nematic phase (N*) with the opposite helical sense in comparison to the pure, organic chiral dopant dispersed in the same N-LC host. Thus, these results provide the first experimental proof for the usefulness of gold nanoclusters as chiral dopants for N-LCs. In contrast, for the non-chiral Au cluster, at a macroscopic level, no relationship between the cholesteric finger-like textures and chirality was found.
Inhibition of phosphotyrosine phosphatases reveals candidate substrates of the PDGF receptor kinase. (1989)

In normal fibroblasts stimulated by platelet derived growth factor (PDGF), PDGF receptors are transiently phosphorylated on tyrosine and represent the major phosphotyrosine containing protein. The phosphate of the phosphotyrosine groups turns over rapidly, and extensive evidence indicates a dynamic balance between phosphorylation and dephosphorylation reactions. Thus, the effect of an inhibitor of phosphatases, orthovanadate, on the pattern of the tyrosine phosphorylations induced by PDGF in Swiss 3T3 fibroblasts was investigated. Western blot analysis with antibodies against phosphotyrosine indicated that whereas in unstimulated cells no phosphotyrosine containing proteins were detected, treatment of cells with orthovanadate alone elicited the slow phosphorylation of several proteins including a 170 kDa component that was recognized to be the phosphorylated PDGF receptor. Addition of PDGF to cells shortly pretreated with vanadate highly increased the intensity of the 170 kDa band corresponding to the phosphorylated receptor and caused its stabilization during time. In addition, the phosphorylation on tyrosine of other proteins (molecular mass 116, 80, 73, 60, 50 and 39 kDa) was also induced. Both the receptor and the other tyrosine phosphorylated proteins appeared to be associated with the detergent insoluble matrix.
Patterning of self-assembled monolayers with lateral dimensions of 0.15 μm using advanced lithography (1999)

The use of advanced lithography to pattern self-assembled monolayers (SAMs) was investigated as a means to create surfaces with regions of different chemical functionality with dimensions of order 0.10 μm. SAMs were prepared by the chemisorption of octadecyltrichlorosilane on silicon wafers, and exposed to synchrotron x-ray (0.814 nm) radiation or extreme ultraviolet (EUV, 13.4 nm) radiation. Exposure to x rays in the presence of oxygen resulted in the incorporation of hydroxy (C–OH) and aldehyde (CH=O) functional groups on the SAM surfaces. The extent of chemical modification was a function of exposure dose and air pressure. Patterned SAMs with various shapes at scales from 50 μm to 0.15 μm were obtained by exposing SAMs to x rays through a mask, or with interferometric EUV lithography. The SAM patterns were imaged directly by condensation figures and lateral force microscopy, and were imaged indirectly using atomic force microscopy and the topography of thin films of diblock copolymers. The contrast in the indirect method resulted from a difference in film thickness due to different wetting behavior of thin films of diblock copolymers on the patterned surfaces.
Demonstration and immunochemical characterization of natural, autologous anti-idiotypic antibodies throughout the course of experimental syphilis (1990)

Immunoglobulin Gs (IgGs) from serial bleeds obtained 1 week to 5 months after infection of rabbits with Treponema pallidum were examined for autologous anti-idiotypic (auto-anti-Id) antibodies. The capacities of IgGs to bind 125I-IgG F(ab')2 anti-T. pallidum prepared from earlier bleeds were determined by using radioimmunoassays. Results obtained in these assays suggested that auto-anti-Id IgGs were demonstrable between 60 and 180 days postinfection. Following reinfection, 90 days after the initial infection, auto-anti-Id IgGs peaked 6 to 8 weeks later, even though they were first noted as early as 2 weeks postreinfection. In the reinfection model the auto-anti-Id continued to persist throughout the remaining 3 months of the study. As auto-anti-Id antibodies to anti-fibronectin antibodies were demonstrable also in reinfected animals, our findings raise questions concerning the possible role of the anti-Id in modulating the Id expression of both T. pallidum-specific and autoimmune humoral responses.
New (alternative) temozolomide regimens for the treatment of glioma (2008)

One barrier to successful treatment of malignant glioma is resistance to alkylating agents such as temozolomide. The cytotoxic activity of temozolomide and other alkylating agents is believed to manifest largely by the formation of O(6)-methylguanine DNA adducts. Consequently, the primary mechanism of resistance to temozolomide is a function of the activity of the DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT). Fortuitously, MGMT is inactivated after each reaction (i.e., suicide enzyme). Therefore, if the rate of DNA alkylation were to outpace the rate of MGMT protein synthesis, the enzyme could, in theory, be depleted. Several studies have shown that prolonged exposure to temozolomide can deplete MGMT activity in blood cells, a process that could potentially increase the antitumor activity of the drug. To date, however, there are limited data demonstrating the depletion of MGMT activity in tumor tissue exposed to temozolomide. A variety of dosing schedules that increase the duration of exposure and the cumulative dose of temozolomide are currently being investigated for the treatment of glioma, with the goal of improving antitumor activity and overcoming resistance. These alternative dosing regimens have been shown to deplete MGMT activity in peripheral blood mononuclear cells, but the regimen that provides the best balance between enhanced antitumor activity and acceptable hematologic toxicity has yet to be determined.
Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine (2020)

The outbreak of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health, calling for the development of safe and effective prophylactics and therapeutics against infection of its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV). The CoV spike (S) protein plays the most important roles in viral attachment, fusion and entry, and serves as a target for development of antibodies, entry inhibitors and vaccines. Here, we identified the receptor-binding domain (RBD) in SARS-CoV-2 S protein and found that the RBD protein bound strongly to human and bat angiotensin-converting enzyme 2 (ACE2) receptors. SARS-CoV-2 RBD exhibited significantly higher binding affinity to ACE2 receptor than SARS-CoV RBD and could block the binding and, hence, attachment of SARS-CoV-2 RBD and SARS-CoV RBD to ACE2-expressing cells, thus inhibiting their infection to host cells. SARS-CoV RBD-specific antibodies could cross-react with SARS-CoV-2 RBD protein, and SARS-CoV RBD-induced antisera could cross-neutralize SARS-CoV-2, suggesting the potential to develop SARS-CoV RBD-based vaccines for prevention of SARS-CoV-2 and SARS-CoV infection.
Diphenyl cyancarbonimidate and dichlorodiphenoxymethane as synthons for the construction of heterocyclic systems of medicinal interest (1987)

Abstract Simple high yield methods for the preparation of heterocyclic N ‐cyanoguanidines (including the anti‐ulcer drug cimetidine), substituted triazoles, benzimidazoles and oxadiazoles with anti‐histaminic (H2) activity from the title compounds are described.
Cooccupancy of the Outer Vestibule of Voltage-Gated Sodium Channels by μ-Conotoxin KIIIA and Saxitoxin or Tetrodotoxin (2010)

The guanidinium alkaloids tetrodotoxin (TTX) and saxitoxin (STX) are classic ligands of voltage-gated sodium channels (VGSCs). Like TTX and STX, micro-conotoxin peptides are pore blockers but with greater VGSC subtype selectivity. micro-Conotoxin KIIIA blocks the neuronal subtype Na(V)1.2 with nanomolar affinity and we recently discovered that KIIIA and its mutant with one fewer positive charge, KIIIA[K7A], could act synergistically with TTX in a ternary peptide x TTX x Na(V) complex. In the complex, the peptide appeared to trap TTX in its normal binding site such that TTX could not readily dissociate from the channel until the peptide had done so; in turn, the presence of TTX accelerated the rate at which peptide dissociated from the channel. In the present study we examined the inhibition of Na(V)1.2, exogenously expressed in Xenopus oocytes, by STX (a divalent cation) and its sulfated congener GTX2/3 (with a net +1 charge). Each could form a ternary complex with KIIIA and Na(V)1.2, as previously found with TTX (a monovalent cation), but only when STX or GTX2/3 was added before KIIIA. The KIIIA x alkaloid x Na(V) complex was considerably less stable with STX than with either GTX2/3 or TTX. In contrast, ternary KIIIA[K7A] x alkaloid x Na(V) complexes could be formed with either order of ligand addition and were about equally stable with STX, GTX2/3, or TTX. The most parsimonious interpretation of the overall results is that the alkaloid and peptide are closely apposed in the ternary complex. The demonstration that two interacting ligands ("syntoxins") occupy adjacent sites raises the possibility of evolving a much more sophisticated neuropharmacology of VGSCs.
Synthesis and Characterization of Enzymatically Degradable PEG‐Based Peptide‐Containing Hydrogels (2010)

Biodegradable hydrogels were synthesized by the click reaction of 4-arm azido-terminated PEG differing in molecular weight (2,100 and 8,800) and two alkyne-terminated peptides: [alkyne]-GFLGK-[alkyne] and ([alkyne]-GFLG)(2)K. The physical properties of in situ formed hydrogels were examined. The hydrogels were highly elastic as determined by rheological and microrheological studies. Swelling degree and enzymatic degradation by papain were dependent on the molecular weight of the PEG, but not the peptide. For PEG8800-based hydrogels, time-course analysis of degradation showed that the molecular weight of the soluble fraction quickly reached the PEG precursor value. These findings may guide future design of hydrogels with controllable mechanical properties and enzymatic degradability.
Susceptibility of mononuclear phagocytes to influenza A virus infection and possible role in the antiviral response (1997)

Among leukocytes, only monocytes and macrophages were found to be highly susceptible to an infection by influenza A virus. After infection, de novo viral protein synthesis was initiated but then interrupted after 4-6 h. Most macrophages died by apoptosis within 25-30 h. Before cell death, however, macrophages responded to influenza A virus with a high cytokine gene transcription and subsequent release of tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, interferon (IFN)-alpha/beta, and CC-chemokines. The basic mechanisms of virus-induced cytokine expression are still unknown and appear to involve transcription factors such as nuclear factor-kappaB and AP-1 which, however, were only activated for 2 h and declined below control values thereafter. After influenza A virus infection, only the mononuclear cell attracting CC-chemokines macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and RANTES were produced while the prototype neutrophil CXC-chemoattractants IL-8 and GRO-alpha were entirely suppressed. This selective induction of CC-chemokines may explain the preferential influx of mononuclear leukocytes into virus-infected tissue. Our data show that monocytes and macrophages represent a primary target for an influenza A virus infection. Thus, the mononuclear phagocyte response leads to a rapid proinflammatory reaction and an enhanced immigration of mononuclear leukocytes, which may condition the infected host for the subsequent virus antigen-specific defense.
Gaucher disease: new molecular approaches to diagnosis and treatment (1992)

Gaucher disease is characterized by the accumulation of glucocerebroside, leading to enlargement of the liver and spleen and lesions in the bones. It is caused by an inherited deficiency of the enzyme glucocerebrosidase. Many mutations exist, but four of these account for over 97% of the mutations in Ashkenazi Jews, the population group in which Gaucher disease is the most common. Although there is a strong relation between the mutations and disease manifestations, genetic counseling is made difficult by the fact that within each genotype there is considerable variability in the severity of the disease. Intravenous infusion of glucocerebrosidase is an effective treatment, but the availability of enzyme replacement therapy is limited by its high cost. Marrow transplantation is also effective in treating the disease, but is rarely performed because of the risks involved. In the future gene transfer may become the treatment of choice.
Pharmacologic properties of P2Z/P2X7receptor characterized in murine dendritic cells: role on the induction of apoptosis (2000)

Abstract In the immune system, extracellular adenosine 5′-triphosphate (ATP) mediates a variety of effects mainly through activation of a particular receptor subtype, the pore-forming P2Z/P2X7 purinoceptor. This purinergic receptor has been described chiefly in cells of hemopoietic origin such as T cells, thymocytes, monocytes, macrophages, and phagocytic cells of thymic reticulum. In this study, we characterized the P2Z/P2X7 purinoceptor and the ATP-mediated apoptosis in murine spleen–derived dendritic cells (DCs). Dye uptake and apoptosis were evaluated by flow cytometry. ATP-treated DCs were permeable to different low-molecular-weight fluorescent probes such as ethidium bromide, YO-PRO 1, and lucifer yellow. Such an effect was dose-dependent (EC50: 721 μmol/L); mediated by the fully anionic agonist (ATP4−); and specifically stimulated by ATP, BzATP, and ATPγS. Additionally, an ATP-induced increase in intracellular calcium was detected by microfluorometry. Furthermore, ATP treatment induced a significant increase in apoptotic DCs (64.46% ± 3.8%) when compared with untreated control cells (34% ± 5.8%), as ascertained by the TdT-mediated dUTP nick end labeling technique. Both ATP-induced DC permeabilization and apoptosis were inhibited by oxidized ATP, a P2Z/P2X7-specific antagonist. In conclusion, we characterized the expression of the P2Z/P2X7purinoceptor in murine spleen–derived DCs and described its role on the induction of apoptosis.
Cloning and sequencing of a bile acid-inducible operon from Eubacterium sp. strain VPI 12708 (1990)

Two bile acid-inducible polypeptides from Eubacterium sp. strain VPI 12708 with molecular weights of 27,000 and approximately 45,000 have previously been shown to be encoded by genes residing on a 2.9-kb EcoRI fragment. We now report the cloning and sequencing of three additional overlapping DNA fragments upstream from this EcoRI fragment. Together, these four fragments contain a large segment of a bile acid-inducible operon which encodes the 27,000- and 45,000-Mr (now shown to be 47,500-Mr) polypeptides and open reading frames potentially coding for four additional polypeptides with molecular weights of 59,500, 58,000, 19,500, and 9,000 to 11,500. A bile acid-inducible polypeptide with an apparent Mr of 23,500, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was purified to homogeneity, and the N-terminal amino acid sequence that was obtained matched the sequence deduced from the open reading frame coding for the 19,500-Mr polypeptide. A short DNA segment containing the 3' downstream end of the gene coding for the 47,500-Mr polypeptide was not successfully cloned but was directly sequenced from DNA fragments synthesized by polymerase chain reaction. The mRNA initiation site for the bile acid-inducible operon was shown by primer extension to be immediately upstream from the gene encoding the 58,000-Mr polypeptide. A potential promoter region upstream from the mRNA initiation site displayed significant homology with the promoter regions of previously identified bile acid-inducible genes from Eubacterium sp. strain VPI 12708. We hypothesize that this bile acid-inducible operon codes for most of the enzymes involved in the bile acid 7 alpha-dehydroxylation pathway in this bacterium.
New approach to the high quality epitaxial growth of lattice-mismatched materials (1986)

We have reconsidered the problem of the critical layer thickness hc for growth of strained heterolayers on lattice-mismatched substrates, using a new approach which allows us to determine the spatial distribution of stresses in a bi-material assembly and include the effects of a finite size of the sample. The possibility of dislocation-free growth of lattice-mismatched materials on porous silicon substrates is discussed as an example of a more general problem of heteroepitaxial growth on small seed pads of lateral dimension l, having a uniform crystal orientation over the entire substrate wafer. It turns out that for a given mismatch f, the critical film thickness hlc strongly depends on l, rising sharply when the latter is sufficiently small, l≲lmin. The characteristic size lmin( f ) below which, effectively, hlc( f )→∞, is determined in terms of the experimentally known (or calculated for growth on a monolithic substrate) function h∞c( f )≡hc( f ). When l≲lmin, then the entire elastic stress in the epitaxial film will be accommodated without dislocations.