gebhart/patrepeval huggingface dataset:
Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses (2005)

Molecular characterization of the severe acute respiratory syndrome coronavirus has revealed genetic diversity among isolates. The spike (S) glycoprotein, the major target for vaccine and immune therapy, shows up to 17 substitutions in its 1,255-aa sequence; however, the biologic significance of these changes is unknown. Here, the functional effects of S mutations have been determined by analyzing their affinity for a viral receptor, human angiotensin-converting enzyme 2 (hACE-2), and their sensitivity to Ab neutralization with viral pseudotypes. Although minor differences among eight strains transmitted during human outbreaks in early 2003 were found, substantial functional changes were detected in S derived from a case in late 2003 from Guangdong province [S(GD03T0013)] and from two palm civets, S(SZ3) and S(SZ16). S(GD03T0013) depended less on the hACE-2 receptor and was markedly resistant to Ab inhibition. Unexpectedly, Abs that neutralized most human S glycoproteins enhanced entry mediated by the civet virus S glycoproteins. The mechanism of enhancement involved the interaction of Abs with conformational epitopes in the hACE-2-binding domain. Finally, improved immunogens and mAbs that minimize this complication have been defined. These data show that the entry of severe acute respiratory syndrome coronaviruses can be enhanced by Abs, and they underscore the need to address the evolving diversity of this newly emerged virus for vaccines and immune therapies.
Synthesis and Anti‐Algal Effect of Zinc Ferrite Nanoparticles (2016)

Summary This study aims at the effect of Zinc ferrite nanoparticles of particle size (14 ± 2) nm prepared by sol‐gel technique on chlorella pyrenoidosa at two different concentrations (1.0 µM and 2.0 µM). The structural characterizations of the prepared sample (ZnFe 2 O 4 ) were carried out by XRD, TEM, and XRF. XRD analysis revealed single phased cubic spinel structure having space group Fd3m. XRF analysis confirmed the purity of the sample. The negative effect of ZnFe 2 O 4 on chlorella pyrenoidosa was manifested by the progressive depletion of cell count. It was found that the algal growth was inhibited by 47% even at a low concentration of 2 µM indicating that zinc ferrite nanoparticles are promising agent for the control of unwanted algal growth. To the best of our knowledge, the effect of ferrite nanoparticles on algae has not been reported elsewhere.
The role of the prostaglandin E2 receptors in vulnerability of oligodendrocyte precursor cells to death (2015)

Therefore, inhibitors of the EP3 receptor appear to enhance survival of OPCs following toxic challenge and may help facilitate remyelination.
Clinical and molecular approaches to well differentiated and dedifferentiated liposarcoma (2011)

Although complete surgical resection is currently the most effective treatment for WDLS and DDLS, the majority of patients with retroperitoneal liposarcoma will eventually have recurrence and die of disease. It is hoped that a multimodality approach, which incorporates targeted therapies and complete surgical resection, will significantly improve patient outcomes.
PARSHL: An analysis/synthesis program for non-harmonic sounds based on a sinusoidal representation (1987)

This paper describes a peak-tracking spectrum analyzer, called Parshl, which is useful for extracting additive synthesis parameters from inharmonic sounds such as the piano. Parshl is based on the Short-Time Fourier Transform (STFT), adding features for tracking the amplitude, frequency, and phase trajectories of spectral lines from one FFT to the next. Parshl can be thought of as an “inharmonic phase vocoder ” which uses tracking vocoder analysis channels instead of a fixed harmonic filter bank as used in previous FFT-based vocoders. This is the original full version from which the Technical Report (CCRMA STAN-M-43) and conference paper (ICMC-87) were prepared. Additionally, minor corrections are included, and a few pointers to more recent work have
Current Progress in CAR-T Cell Therapy for Solid Tumors (2019)

Cancer immunotherapy by chimeric antigen receptor-modified T (CAR-T) cells has shown exhilarative clinical efficacy for hematological malignancies. Recently two CAR-T cell based therapeutics, Kymriah (Tisagenlecleucel) and Yescarta (Axicabtagene ciloleucel) approved by US FDA (US Food and Drug Administration) are now used for treatment of B cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL) respectively in the US. Despite the progresses made in treating hematological malignancies, challenges still remain for use of CAR-T cell therapy to treat solid tumors. In this landscape, most studies have primarily focused on improving CAR-T cells and overcoming the unfavorable effects of tumor microenvironment on solid tumors. To further understand the current status and trend for developing CAR-T cell based therapies for various solid tumors, this review emphasizes on CAR-T techniques, current obstacles, and strategies for application, as well as necessary companion diagnostics for treatment of solid tumors with CAR-T cells.
Alzheimer paired helical filaments, untreated and pronase digested, studied by vertical platinum-carbon replication and high resolution transmission electron microscopy (1995)

Untreated paired helical filaments (PHF) and pronase treated PHF filaments have been stereoscopically imaged with a freeze-drying vertical platinum-carbon replication preparation method for TEM. The untreated PHF have an average wide region, W = 22.8 +/- 2.4 nm, a narrow region width, T = 10.6 +/- 1.7 nm, and a helical turn period, L = 78.6 +/- 13.4. The widths of the pronase treated PHF were significantly reduced and had average measurements of W = 14.8 +/- 1.2 nm, T = 5.7 +/- 1.0 nm, with the helical period unchanged, L = 75.4 +/- 17 nm. The surfaces of the untreated PHF contained approximately 1.0 and approximately 0.4 nm strands, the size of normal and denatured tau monomer. The pronase treated PHF contained approximately 1.0 and approximately 0.4 nm strands as well as approximately 2.0 nm strands. The stereoscopic images of the untreated and the pronase digested PHF do not support a double helical morphology for the PHF. The PHF appear to be long helical ribbons. The approximately 1.0 and approximately 2 nm substructure has been organized both parallel and orthogonal to the PHF-core axis for distances less than 80 nm. The most frequent structural appearance is of a disorganized PHF core. The surfaces of the untreated PHF also have a similar disorganized appearance.
BE-23372M, a novel protein tyrosine kinase inhibitor. III. Synthesis. (1994)

In a preceding paper, the physico-chemical properties and structural elucidation of BE-23372M, a potent novel protein tyrosine kinase inhibitor, were described. In this paper, we report the synthesis of BE-23372M from 3-(3, 4-dimethoxybenzoyl)propionic acid and veratraldehyde or 3, 4-diacetoxy-benzaldehyde. The structure of BE-23372M was confirmed to be (E)-3-(3, 4-dihydroxybenzylidene)-5-(3, 4-dihydroxyphenyl)-2(3H)-furanone.
Somatic gene therapy for phenylketonuria and other hepatic deficiencies (1996)

Gene therapy is the delivery of genetic material to specific cell types of an organism to alter its physiology or function. This technology is being explored as a means of treating diseases caused by deficiencies of hepatic gene products. The two diseases being used as models for hepatic gene therapy are classical phenylketonuria (PKU) and haemophilia B. Vectors derived from adenoviruses can be used to completely correct these diseases in animal models. The phenotypic correction generated in these studies is transient, and cannot be duplicated by vector readministration. The transient nature of transgene expression results from the destruction of the virally-transduced cells by a cellular immune response directed against the late viral gene products that are also expressed in the target cells. The inability to repeatedly administer virus is caused by a humoral immune response directed against viral proteins present at the time of infusion. If the host immune response is suppressed, transgene expression can persist for 6 months or more. These findings suggest that host immunomodulation in combination with further modification of the adenoviral vector to reduce or eliminate late viral gene expression may permit long-term expression of potentially therapeutic gene products in mammalian liver.
Subcutaneous administration of anticancer agents. (2014)

In recent years, much has been discussed on the development of oral anticancer treatment in terms of practical aspects and convenience for the patient. Less has been devoted to the potential of subcutaneous administration as a parenteral alternative. However, recent approvals (bortezomib, omacetaxine, trastuzumab) seem to show a renewed interest in this route of administration. All anticancer agents given subcutaneously display a very high bioavailability (>80%) and are rapidly absorbed (except the monoclonal antibodies trastuzumab and alemtuzumab). Subcutaneous delivery does not impact on the rate of elimination when compared to the intravenous route (azacitidine, cladribine, bortezomib, trastuzumab). Some formulations may be self-administered in educated patients (methotrexate, cladribine) but others require hospitalization (omacetaxine). When available, comparative studies with intravenous administration showed comparable clinical issues with an advantage for subcutaneous bortezomib with regard to the occurrence of peripheral neurotoxicity. Subcutaneous formulations of trastuzumab and, in the future rituximab, may allow for ambulatory treatment and self-administration. From an economic point of view, subcutaneous formulations of monoclonal antibodies may lead to lower healthcare costs but will have to face the arrival of less expensive intravenous biologically similar agents ('biosimilars') that will reduce the cost of hospitalization.
Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes (2004)

One mechanism contributing to immunologic unresponsiveness toward tumors may be presentation of tumor antigens by tolerogenic host APCs. We show that mouse tumor-draining LNs (TDLNs) contained a subset of plasmacytoid DCs (pDCs) that constitutively expressed immunosuppressive levels of the enzyme indoleamine 2,3-dioxygenase (IDO). Despite comprising only 0.5% of LN cells, these pDCs in vitro potently suppressed T cell responses to antigens presented by the pDCs themselves and also, in a dominant fashion, suppressed T cell responses to third-party antigens presented by nonsuppressive APCs. Adoptive transfer of DCs from TDLNs into naive hosts created profound local T cell anergy, specifically toward antigens expressed by the transferred DCs. Anergy was prevented by targeted disruption of the IDO gene in the DCs or by administration of the IDO inhibitor drug 1-methyl-D-tryptophan to recipient mice. Within the population of pDCs, the majority of the functional IDO-mediated suppressor activity segregated with a novel subset of pDCs coexpressing the B-lineage marker CD19. We hypothesize that IDO-mediated suppression by pDCs in TDLNs creates a local microenvironment that is potently suppressive of host antitumor T cell responses.
c-Abl-mediated Phosphorylation of WAVE3 Is Required for Lamellipodia Formation and Cell Migration (2007)

The activity of the Wiskott-Aldrich syndrome-related WAVE3 protein is critical for the regulation of the Arp2/3-dependent cytoskeleton organization downstream of Rac-GTPase. The Ableson (Abl) non-receptor tyrosine kinase is also involved in the remolding of actin cytoskeleton in response to extracellular stimuli. Here we show that platelet-derived growth factor stimulation of cultured cells results in WAVE3-Abl interaction and localization to the cell periphery. WAVE3-Abl interaction promotes the tyrosine phosphorylation of WAVE3 by Abl, and STI-571, a specific inhibitor of Abl kinase activity, abrogates the Abl-mediated phosphorylation of WAVE3. We have also shown that Abl targets and phosphorylates four tyrosine residues in WAVE3 and that the Abl-dependent phosphorylation of WAVE3 is critical for the stimulation of lamellipodia formation and cell migration. Our results show that the activation of WAVE3 to promote actin remodeling is enhanced by the c-Abl-mediated tyrosine phosphorylation of WAVE3.
An Investigation of the Differential Expression of Her2/neu Gene Expression in Normal Oral Mucosa, Epithelial Dysplasia, and Oral Squamous Cell Carcinoma in Taiwan (2008)

These findings suggested a dynamic change in Her2/neu expression during the development of OSCC. The overexpression of Her2/neu can be used as a marker in distinguishing NOM/ED from OSCC.
A sequence-specific conformational epitope on U1 RNA is recognized by a unique autoantibody. (1988)

An autoantibody from a patient with lupus-overlap syndrome was found to bind a specific region of U1 RNA. By using RNA sequence analysis, immunoprecipitation, and competition experiments with in vitro synthesized fragments of U1 RNA, a region of 40 nucleotides representing a stem-loop secondary structure was found to be an immunoreactive domain. This antibody recognized a conformational epitope because neither the RNA stem nor the RNA loop alone was immunoprecipitable. Antisense U1 RNA, U1 DNA, and other small RNAs were not reactive with the antibody. While the origins of nucleic acid-binding antibodies are unknown, this RNA-specific autoantibody probably originated by direct presentation to the immune system or as an anti-idiotype against a more common U1 small nuclear ribonucleoprotein-specific autoantibody. Thus, these findings have implications for the mechanisms of autoimmune recognition and provide an immunological approach to probing RNA structure and protein-RNA interactions.
Artificial hybrid protein containing a toxic protein fragment and a cell membrane receptor-binding moiety in a disulfide conjugate. II. Biochemical and biologic properties of diphtheria toxin fragment A-S-S-human placental lactogen. (1977)

The biochemical and biologic properties of a purified disulfide conjugate of diphtheria toxin fragment A and human placental lactogen (toxin A-hPL) have been studied by (a) assaying the ADP-ribosyltransferase activity of the intact conjugate, (b) assaying the binding of the intact conjugate to mammary gland plasma membrane lactogenic receptors, and (c) assaying the effect of the conjugate on the rate of protein synthesis in rabbit mammary gland explants maintained in organ culture. The toxin A-hPL conjugate retains one-third of the NAD+:EF-2 ADP-ribosyltransferase activity of toxin A, and 26% of the hPL-binding activity to lactogenic receptors. Binding activity was demonstrated by radioreceptor assay and by assaying toxin A activity bound to membranes which was competitively displaced by excess hPL. Since the toxin A-hPL conjugate retained activities of its separate subunits, it could be regarded as a structural analogue of nicked diphtheria toxin with replacement of the original membrane-binding chain by another binding chain that is specific for lactogenic receptor. However, the conjugate failed to inhibit protein synthesis in organ-cultured mammary gland explants, although these were sensitive to native diphtheria toxin and could bind hPL. It is concluded from these results that the toxin A-hPL conjugate does not act as a functional analogue of diphtheria toxin with altered receptor specificity, and that the hPL receptor cannot mediate the entry of toxin A or toxin A-hPL from membrane-bound conjugate into the cytosol site of action of toxin A.
Doxycycline-regulated gene expression in the opportunistic fungal pathogen Aspergillus fumigatus (2005)

The vectors described in this report provide a new set of options to experimentally manipulate the level of specific gene products in A. fumigatus.
Solar Radiation Is Shown to Select for Pigmented Bacteria in the Ambient Outdoor Atmosphere (1997)

Abstract— The percentage of pigmented to total bacteria in the outdoor atmospheric population was studied in the field and in controlled laboratory experiments to evaluate the effects of solar radiation (SR) on bacterial survival. The field experiments showed that the percentage of pigmented bacteria positively correlated with SR activity during clear summer days. The percentage was lowest during darkness before dawn and around midnight ( ca 33%) and as the SR increased during the day, gradually increased to a maximum of ca 50–60% at noontime to early afternoon and decreased thereafter. In the laboratory the ambient outdoor atmospheric bacteria impacted on culture plates were exposed to simulated SR and a germicidal light. With increased exposure, more nonpig‐mented bacteria were killed and the percentage of pigmented bacteria gradually increased. These observations suggest an inverse relationship between the atmospheric bacterial survival and the percentage of pigmented bacteria contained therein, thus supporting the notion that pigmentation might provide protection for outdoor atmospheric bacteria from sunlight damage. As a consequence, viable pigmented bacteria (and other UV‐resistant forms) in the atmosphere could be enriched under areas of stratospheric ozone depletion.
Human blood contains two subsets of dendritic cells, one immunologically mature and the other immature. (1994)

Two subsets of dendritic cells, differing in T-cell stimulatory function, have been purified directly from human blood. Both subsets are positive for major histocompatibility complex (MHC) class II expression and negative for lineage-specific antigens (e.g. CD3, CD14, CD16, CD19 negative), but are separated by exploiting differences in expression of the beta 2-integrin, CD11c. The CD11c-negative subset is functionally immature, requiring monocyte-derived cytokines to develop into typical dendritic cells. The CD11c-positive subset has potent T-cell stimulating activity and expresses the activation antigen CD45RO, unlike its immature counterpart. However, these mature cells only develop typical dendritic morphology and high levels of MHC proteins and adhesins after a period of culture independent of exogenous cytokines. Although the freshly isolated mature dendritic cells resemble monocytes in cytospin preparations, the former lack CD14 and have a much stronger primary T-cell stimulatory capacity. We hypothesize that the CD11c-negative immature cells are marrow-derived precursors to tissue dendritic cells, such as epidermal Langerhans' cells, while the CD11c-positive cells are derived from tissues where they have been activated by antigen, and are en route to the spleen or lymph nodes to stimulate T-cell responses there.
CTL Fail to Accumulate at Sites of HIV-1 Replication in Lymphoid Tissue (2007)

The inability of HIV-1-specific CTL to fully suppress virus replication as well as the failure of administration of exogenous CTL to lower viral loads are not understood. To evaluate the hypothesis that these phenomena are due to a failure of CTL to localize at sites of HIV-1 replication, we assessed the distribution of HIV-1 RNA and HIV-1-specific CTL identified by HIV-1 peptide/HLA class I tetrameric complexes (tetramers) within lymph nodes of 14 HIV-1-infected individuals who were not receiving antiretroviral therapy. A median of 0.04% of follicular compared with 0.001% of extrafollicular CD4(+) cells were estimated to be producing HIV-1 RNA, a 40-fold difference (p = 0.0001). Tetramer-stained cells were detected by flow cytometry in disaggregated lymph node cells from 11 subjects and constituted a significantly higher fraction of CD8(+) cells in lymph node (mean, 2.15%) than in PBMC (mean, 1.52%; p = 0.02). In situ tetramer staining in three subjects' lymph nodes, in which high frequencies of tetramer-stained cells were detected, revealed that tetramer-stained cells were primarily concentrated in extrafollicular regions of lymph node and were largely absent within lymphoid follicles. These data confirm that HIV-1-specific CTL are abundant within lymphoid tissues, but fail to accumulate within lymphoid follicles where HIV-1 replication is concentrated, suggesting that lymphoid follicles may be immune-privileged sites. Mechanisms underlying the exclusion of CTL from lymphoid follicles as well as the role of lymphoid follicles in perpetuating other chronic pathogens merit further investigation.
Early detection of chemoresistance in vivo through the use of a radiolabeled antisense oligonucleotide. (2003)

In our study, resistant cell lines and tumor showed greater retention of the specific probe than the sensitive ones. This constitutes a further advance towards non invasive imaging of resistant genes involved in chemoresistance. These results are encouraging: the current trend in innovative cancer therapy is moving towards targeting the genes of interest.
Topical transplantation of mesenchymal stem cells accelerates gastric ulcer healing in rats (2008)

Mesenchymal stem cells (MSCs), a subpopulation of adult somatic stem cells, are an attractive stem cell source in regenerative medicine because of their multipotentiality. We examined the effects of MSC transplantation on gastric ulcer healing. Putative MSCs, isolated from bone marrow aspirates of male rats by dish adherence and expanded in culture, were characterized by flow cytometry and reverse transcription-polymerase chain reaction. Gastric ulcers were induced by serosal application of acetic acid on the anterior wall of the stomach in female rats. Either MSCs (labeled with PKH67; 1x10(7) cells) or vehicle was injected into the gastric wall surrounding the ulcer. The healing process of the ulcer and the influence of anti-vascular endothelial growth factor (VEGF) antibody were examined. CD29-positive, CD90-positive, CD34-negative, and CD45-negative MSCs expressed mRNAs for VEGF and hepatocyte growth factor (HGF). The MSCs were transplantable to the gastric tissue surrounding the ulcer, where a majority of the engrafted cells were positive for vimentin. The transplantation significantly accelerated gastric ulcer healing compared with controls. The engrafted MSCs also expressed VEGF and HGF. Administration of anti-VEGF neutralizing antibody dose dependently reduced the MSC-induced promotion of ulcer healing. In conclusion, MSC transplantation accelerated gastric ulcer healing, possibly through the induction of angiogenesis in the gastric mucosa via the secretion of VEGF. The beneficial effects of MSCs might be mediated not only by their differentiation into gastric interstitial cells, but also by their ability to supply angiogenic factors.
Obesity genes and insulin resistance (2010)

Deeper understanding of the functional links between genes that control inflammatory responses to diet-induced obesity is crucial to the development of therapies for obese, insulin-resistant patients.
Formation of synthetic analogues of double metal-hydroxy carbonate minerals under controlled pH conditions: I. The synthesis of pyroaurite and reevesite (1990)

Abstract Two-layered Fe(III)-M(II) hydroxy carbonates (M(II) = Ni or Mg) have been synthesized by induced hydrolysis using controlled air oxidation of an aqueous Fe(II)-M(II) mixture (M(II)/Fe(II) ratio &gt;3) at a pH below which the hydroxide of the M(II) cation precipitates. The crystalline, homogeneous product can be a single phase consisting of very thin circular to hexagonal plates (0·2–0·8 µm diam.). For synthetic reevesite (Ni(II)-Fe(III) hydroxy carbonate), stable spherular aggregates are formed. The well crystallized products have an M(II)/Fe(III) ratio of about two. However, by varying the pH, the initial M(II)-Fe(III) ratio and the oxidation rate, the M(II)/Fe(III) ratio in the product and its crystallinity can be varied. The derived formulae are in reasonable agreement with the known composition of pyroaurite-type compounds. Possible synthesis pathways are discussed. The ability to control some physical and morphological features of the products indicates that the synthesis technique could prove advantageous in the preparation of certain catalyst precursors.