gebhart/patrepeval huggingface dataset:
Preclinical Development Handbook (2007)

Preclinical development handbook , Preclinical development handbook , کتابخانه مرکزی دانشگاه علوم پزشکی تهران
The function of interleukin 17 in the pathogenesis of rheumatoid arthritis (2007)

Interleukin (IL)-17 is a 30- to 35-kDa homodimeric polypeptide cytokine cloned in 1993 and originally named cytotoxic T lymphocyte-associated antigen-8 (CTLA-8). Sequencing the human genome resulted in the discovery of an additional five members of the IL-17 family that were consecutively named IL-17B to IL-17F. IL-17A is exclusively produced by a newly identified CD4+ T-helper subset that was recently named Th17. Differentiation of these cells from naive CD4+ T cells requires both TGF-beta and IL-6. IL-15 and, especially, IL-23 are required for these cells' survival and efficient IL-17 production. IL-17 binding to an IL-17 receptor expressed on epithelial, endothelial, and fibroblastic stromal cells triggers the activation of transcription factor NF-kappaB and mitogen-activated protein kinase (p-38), which in turn results in the secretion of IL-1, TNF-alpha, IL-6, IL-8, or prostaglandin E2. The IL-17 family plays a key role in the regulation of immune and inflammatory response, in the homeostasis of several tissues, and the progression of autoimmune diseases. In addition, IL-17 exerts synergistic effects with TNF-alpha and IL-1 in the induction of joint inflammation and cartilage and joint destruction. Given these properties, it is not surprising that in certain pathological conditions, for example rheumatoid arthritis, Th17 cells emerge as a new pathological cell type that, by IL-17 production and release, contributes to their pathogeneses.
Nutrient and hormonal regulation of pyruvate kinase gene expression (1998)

Mammalian pyruvate kinase (PK), a key glycolytic enzyme, has two genes named PKL and PKM, which produce the L- and R-type isoenzymes by means of alternative promoters, and the M1-and M2-types by mutually exclusive alternative splicing respectively. The expression of these genes is tissue-specific and under developmental, dietary and hormonal control. The L-type isoenzyme (L-PK) gene contains multiple regulatory elements necessary for regulation in the 5' flanking region, up to position -170. Both L-II and L-III elements are required for stimulation of L-PK gene transcription by carbohydrates such as glucose and fructose, although the L-III element is itself responsive to carbohydrates. The L-II element is also responsible for the gene regulation by polyunsaturated fatty acids. Nuclear factor-1 proteins and hepatocyte nuclear factor 4, which bind to the L-II element, may also be involved in carbohydrate and polyunsaturated fatty acid regulation of the L-PK gene respectively. However, the L-III-element-binding protein that is involved in carbohydrate regulation remains to be clarified, although involvement by an upstream stimulating factor has been proposed. Available evidence suggests that the carbohydrate signalling pathway to the L-PK gene includes a glucose metabolite, possibly glucose 6-phosphate or xylulose 5-phosphate, as well as phosphorylation and dephosphorylation mechanisms. In addition, at least five regulatory elements have been identified in the 5' flanking region of the PKM gene up to position -279. Sp1-family proteins bind to two proximal elements, but the binding of proteins to other elements have not yet been clarified. Glucose may stimulate the transcription of the PKM gene via hexosamine derivatives. Sp1 may be involved in this regulation via its dephosphorylation, although the carbohydrate response element has not been determined precisely in the PKM gene. Thus glucose stimulates transcription of the PKM gene by the mechanism which is probably different from the L-PK gene.
Vertex cutsets of undirected graphs (1995)

This paper deals with the enumeration of all minimal s-t vertex cutsets separating two vertices (source and terminal) in an undirected graph. The problem is handled by direct-enumeration based on a necessary and sufficient condition for a set of vertices to be a minimal vertex cutset. The algorithm thus does not enumerate paths or basic paths as a first step. This approach has yielded an algorithm which generates minimal vertex cutsets at: O(e/spl middot/n) {where e,n=number of (edges, vertices) in the graph} computational effort per vertex cutset. Formal proofs of the algorithm and its complexity are presented. Results of some computational experience show that, (a) this algorithm is appreciably faster than previous algorithms, and (b) can handle much larger graphs due to less memory requirements. The number of vertex cutsets does not exceed (/sub gilb( 1/2 (n-2))//sup n-2/)+2.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cationic Nanoliposomes Meet mRNA: Efficient Delivery of Modified mRNA Using Hemocompatible and Stable Vectors for Therapeutic Applications (2017)

Synthetically modified mRNA is a unique bioactive agent, ideal for use in therapeutic applications, such as cancer vaccination or treatment of single-gene disorders. In order to facilitate mRNA transfections for future therapeutic applications, there is a need for the delivery system to achieve optimal transfection efficacy, perform with durable stability, and provide drug safety. The objective of our study was to comprehensively analyze the use of 3β-[N-(N',N'-dimethylaminoethane) carbamoyl](DC-Cholesterol)/dioleoylphosphatidylethanolamine (DOPE) liposomes as a potential transfection agent for modified mRNAs. Our cationic liposomes facilitated a high degree of mRNA encapsulation and successful cell transfection efficiencies. More importantly, no negative effects on cell viability or immune reactions were detected posttransfection. Notably, the liposomes had a long-acting transfection effect on cells, resulting in a prolonged protein production of alpha-1-antitrypsin (AAT). In addition, the stability of these mRNA-loaded liposomes allowed storage for 80 days, without the loss of transfection efficacy. Finally, comprehensive analysis showed that these liposomes are fully hemocompatible with fresh human whole blood. In summary, we present an extensive analysis on the use of DC-cholesterol/DOPE liposomes as mRNA delivery vehicles. This approach provides the basis of a safe and efficient therapeutic strategy in the development of successful mRNA-based drugs.
Titration of Antibodies to Salmonella O Antigens by Enzyme-Linked Immunosorbent Assay (1972)

A new type of immunoassay (enzyme-linked immunosorbent assay, ELISA) has been used for the detection of antibodies against Salmonella O antigens. The results show that ELISA is specific and highly sensitive. When compared with the Widal reaction, passive hemagglutination, and quantitative precipitation, ELISA was shown to be more sensitive. In addition, immunoglobulin G and immunoglobulin M antibodies were both detected approximately as efficiently with ELISA.
In vitrotranscription and translational efficiency of chimeric SP6 messenger RNAs devoid of 5′ vector nucleotides (1988)

A plasmid containing the bacteriophage SP6 promoter, designated pHSTO, permits in vitro transcription of RNAs devoid of vector-derived nucleotides. This vector has been characterized for relative transcriptional activity using constructs which alter the conserved nucleotides extending beyond the SP6 transcriptional initiation site. SP6 polymerase efficiently transcribes cDNA inserts which contain a guanosine (G) nucleotide at position +1 relative to the SP6 promoter; however, inserts with an adenosine (A) or pyrimidine at position +1 are not transcribed. Several cellular and viral cDNAs have been transcribed into translatable messenger RNA using this vector; however, SP6 polymerase will not transcribe the A-T rich untranslated leader from alfalfa mosaic virus RNA 4 efficiently unless the viral mRNA cap site is separated from the transcriptional initiation site by twelve base pairs of vector DNA. Chimeric messenger RNAs were created by linking the untranslated leader sequence of several viral mRNAs to the coding region of barley alpha-amylase, and the resultant mRNAs were translated in a wheat germ extract to determine relative translational efficiencies. The untranslated leader sequences of turnip yellow mosaic virus coat protein mRNA and black beetle virus RNA 2 did not increase translational efficiency, while the tobacco mosaic virus leader stimulated translation significantly. The results indicate that substitution of a cognate untranslated leader sequence with a leader derived from a highly efficient mRNA does not necessarily predict enhanced translational efficiency of the chimeric mRNA.
Roles of chemokines in renal ischemia/reperfusion injury (2008)

Ischemia-reperfusion injury (IR) is a common and an important clinical cause of renal disease, such as renal transplantation, renal artery stenosis and following shock from any cause. Inflammatory reaction after IR is regulated by various kinds of mediators. Chemokines are major mediators of the inflammation, and regulate pro-inflammatory cytokine and adhesion molecule expression, and leukocyte infiltration and activation. Chemokines are the key players of inflammation, angiogenesis and fibrosis. These inflammatory processes mediated by chemokines were observed in not only experimental animal models, but also in human renal diseases with ischemic injury. A number of challenges of chemokine targeted therapy is trying to prevent the ischemic injury, and will give some beneficial effect on the injury.
Concise and Diversity-Oriented Synthesis of Ligand Arm-Functionalized Azoamides (2008)

Azoamides, previously established as bioactive intracellular GSH-depleting agents, were decorated with a terminal alkyne moiety to 4 and then were transformed, by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), into different ligand-arm functionalized azoamides 6. Azides 5 having ligand-arms amenable for binding to platinum(II) were selected for this study. Because, for the fragile azoamides 4, the typically employed reaction conditions for CuAAC failed, several alternative solvents and copper catalysts were tested. Excellent results were obtained with copper(II) sulfate pentahydrate/metallic copper and especially with heterogeneous catalysts, such as copper-in-charcoal, cupric oxide, and cuprous oxide. The heterogeneous catalysts were employed to obtain the desired products in almost quantitative yields by a simple three-step "stir-filter-evaporate" protocol with no or negligible contamination with copper impurities. This is of particular importance because compounds 6 have been designed for coordination.
Murine erythropoietin gene: cloning, expression, and human gene homology. (1986)

The gene for murine erythropoietin (EPO) was isolated from a mouse genomic library with a human EPO cDNA probe. Nucleotide sequence analysis permitted the identification of the murine EPO coding sequence and the prediction of the encoded amino acid sequence based on sequence conservation between the mouse and human EPO genes. Both the coding DNA and the amino acid sequences were 80% conserved between the two species. Transformation of COS-1 cells with a mammalian cell expression vector containing the murine EPO coding region resulted in secretion of murine EPO with biological activity on both murine and human erythroid progenitor cells. The transcription start site for the murine EPO gene in kidneys was determined. This permitted tentative identification of the transcription control region. The region included 140 base pairs upstream of the cap site which was over 90% conserved between the murine and human genes. Surprisingly, the first intron and much of the 5'- and 3'-untranslated sequences were also substantially conserved between the genes of the two species.
Thin Film Transistor of ZnO Fabricated by Chemical Solution Deposition (2001)

A ZnO thin film was deposited on a Si wafer having an oxidized SiO 2 layer using a chemical solution deposition process and was applied to a bottom-gate type thin film transistor (TFT). The films prepared by combined heating at 600° and 900°C exhibited typical enhancement-type TFT characteristics with electrons as carriers. The low heating temperature around 600°C degraded the insulating properties of the SiO 2 layer but high temperature annealing recovered that.
Melan-A/MART-151–73represents an immunogenic HLA-DR4-restricted epitope recognized by melanoma-reactive CD4+T cells (2000)

The human Melan-A/MART-1 gene encodes an HLA-A2-restricted peptide epitope recognized by melanoma-reactive CD8(+) cytotoxic T lymphocytes. Here we report that this gene also encodes at least one HLA-DR4-presented peptide recognized by CD4(+) T cells. The Melan-A/MART-1(51-73) peptide was able to induce the in vitro expansion of specific CD4(+) T cells derived from normal DR4(+) donors or from DR4(+) patients with melanoma when pulsed onto autologous dendritic cells. CD4(+) responder T cells specifically produced IFN-gamma in response to, and also lysed, T2.DR4 cells pulsed with the Melan-A/MART-1(51-73) peptide and DR4(+) melanoma target cells naturally expressing the Melan-A/MART-1 gene product. Interestingly, CD4(+) T cell immunoreactivity against the Melan-A/MART-1(51-73) peptide typically coexisted with a high frequency of anti-Melan-A/MART-1(27-35) reactive CD8(+) T cells in freshly isolated blood harvested from HLA-A2(+)/DR4(+) patients with melanoma. Taken together, these data support the use of this Melan-A/MART-1 DR4-restricted melanoma epitope in future immunotherapeutic trials designed to generate, augment, and quantitate specific CD4(+) T cell responses against melanoma in vivo.
Opportunities and challenges in long-read sequencing data analysis (2020)

Long-read technologies are overcoming early limitations in accuracy and throughput, broadening their application domains in genomics. Dedicated analysis tools that take into account the characteristics of long-read data are thus required, but the fast pace of development of such tools can be overwhelming. To assist in the design and analysis of long-read sequencing projects, we review the current landscape of available tools and present an online interactive database, long-read-tools.org, to facilitate their browsing. We further focus on the principles of error correction, base modification detection, and long-read transcriptomics analysis and highlight the challenges that remain.
Trial Watch: (2014)

Oncolytic viruses are natural or genetically modified viral species that selectively infect and kill neoplastic cells. Such an innate or exogenously conferred specificity has generated considerable interest around the possibility to employ oncolytic viruses as highly targeted agents that would mediate cancer cell-autonomous anticancer effects. Accumulating evidence, however, suggests that the therapeutic potential of oncolytic virotherapy is not a simple consequence of the cytopathic effect, but strongly relies on the induction of an endogenous immune response against transformed cells. In line with this notion, superior anticancer effects are being observed when oncolytic viruses are engineered to express (or co-administered with) immunostimulatory molecules. Although multiple studies have shown that oncolytic viruses are well tolerated by cancer patients, the full-blown therapeutic potential of oncolytic virotherapy, especially when implemented in the absence of immunostimulatory interventions, remains unclear. Here, we cover the latest advances in this active area of translational investigation, summarizing high-impact studies that have been published during the last 12 months and discussing clinical trials that have been initiated in the same period to assess the therapeutic potential of oncolytic virotherapy in oncological indications.
Structure−Activity Relationship Studies on Benzofuran Analogs of Propafenone-Type Modulators of Tumor Cell Multidrug Resistance (1996)

A series of benzofurylethanolamine analogs of propafenone (1a) have been prepared and evaluated for multidrug resistance-reversing activity in two in vitro assay systems. As for propafenones, an excellent correlation of biological data with calculated lipophilicity values was found for benzofurans, whereby the latter generally had lower activity/lipophilicity ratios. Almost identical slopes of the regression lines were obtained for both propafenones and benzofurans. Multiple linear regression analysis of the complete data set yielded an equation with excellent predictive power (r2 cross-valid = 0.968). Interaction measurements with artificial membranes indicated that the differences in activity between these two series of compounds are not due to differences in the interaction pattern with biological membranes.
The Regulation of Hemostasis: The Protein C System (1986)

We speak very frequently of the normal clotting time. In a glass tube?... Glass tubes have held the center of the stage for quite a long time but the process of clotting is now observed in plastic vessels and a considerably longer period of time is required than when glass is used.... If the same blood were kept outside the body in a test tube made from a vein or artery it would take a very long time to clot.— Charles H. Best, 19481 EXTENSIVE investigation into the mechanisms of blood clotting has yielded substantial insights into the process . . .
Tensile strained Ge p-i-n photodetectors on Si platform for C and L band telecommunications (2005)

We demonstrate a 0.25% tensile strained Ge p-i-n photodetector on Si platform that effectively covers both C and L bands in telecommunications. The direct band edge of the Ge film has been pushed from 1550 to 1623 nm with 0.25% tensile strain, enabling effective photon detection in the whole L band. The responsivities of the device at 1310, 1550, and 1620 nm are 600, 520, and 100mA∕W under 0 V bias, which can be further improved to 980, 810, and 150mA∕W with antireflection coating based on calculations. Therefore, the device covers the whole wavelength range used in telecommunications. The responsivities at 1310 and 1550 nm are comparable to InGaAs photodetectors currently used in telecommunications. In the spectrum range of 1300–1650 nm, maximum responsivity was already achieved at 0 V bias because carrier transit time is much shorter than carrier recombination life time, leading to ∼100% collection efficiency even at 0 V bias. This is a desirable feature for low voltage operation. The absorption coefficients of 0.25% tensile strained Ge in the L band have been derived to be nearly an order of magnitude higher than bulk Ge. The presented device is compatible with conventional Si processing, which enables monolithic integration with Si circuitry.
Fetuin-A is a HIF target that safeguards tissue integrity during hypoxic stress (2021)

Intrauterine growth restriction (IUGR) is associated with reduced kidney size at birth, accelerated renal function decline, and increased risk for chronic kidney and cardiovascular diseases in adults. Precise mechanisms underlying fetal programming of adult diseases remain largely elusive and warrant extensive investigation. Setting up a mouse model of hypoxia-induced IUGR, fetal adaptations at mRNA, protein and cellular levels, and their long-term functional consequences are characterized, using the kidney as a readout. Here, we identify fetuin-A as an evolutionary conserved HIF target gene, and further investigate its role using fetuin-A KO animals and an adult model of ischemia-reperfusion injury. Beyond its role as systemic calcification inhibitor, fetuin-A emerges as a multifaceted protective factor that locally counteracts calcification, modulates macrophage polarization, and attenuates inflammation and fibrosis, thus preserving kidney function. Our study paves the way to therapeutic approaches mitigating mineral stress-induced inflammation and damage, principally applicable to all soft tissues.
Electron Crystallography Reveals Atomic Structures of Metal–Organic Nanoplates with M12(μ3-O)8(μ3-OH)8(μ2-OH)6 (M = Zr, Hf) Secondary Building Units (2017)

Nanoscale metal-organic frameworks (nMOFs) have shown tremendous potential in cancer therapy and biomedical imaging. However, their small dimensions present a significant challenge in structure determination by single-crystal X-ray crystallography. We report here the structural determination of nMOFs by rotation electron diffraction (RED). Two isostructural Zr- and Hf-based nMOFs with linear biphenyldicarboxylate (BPDC) or bipyridinedicarboxylate (BPYDC) linkers are stable under intense electron beams to allow the collection of high-quality RED data, which reveal a MOF structure with M<sub>12</sub>(μ<sub>3</sub>-O)<sub>8</sub>(μ<sub>3</sub>-OH)<sub>8</sub>(μ<sub>2</sub>-OH)<sub>6</sub> (M = Zr, Hf) secondary building units (SBUs). The nMOF structures differ significantly from their UiO bulk counterparts with M<sub>6</sub>(μ<sub>3</sub>-O)<sub>4</sub>(μ<sub>3</sub>-OH)<sub>4</sub> SBUs and provide the foundation for clarifying the structures of a series of previously reported nMOFs with significant potential in cancer therapy and biological imaging. Our work clearly demonstrates the power of RED in determining nMOF structures and elucidating the formation mechanism of distinct nMOF morphologies.
Human embryonal carcinoma cells and their differentiation in culture (1987)

Based on the study of two clonal cell lines, 2102Ep and TERA-2, isolated from human germ cell tumours, we have identified several properties that are commonly expressed by human embryonal carcinoma (EC) cells, the stem cells of teratocarcinomas. These properties include the expression of surface antigens SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81, and the presence of cytokeratin in the cytoplasm. However, some human EC cells lack expression of SSEA-3 and -4, although glycolipids containing these epitopes can be extracted from such variant cells. Analysis of the glycolipid composition of TERA-2 cells suggests that the switching of oligosaccharide core structure synthesis from globo-series to lacto- and ganglio-series is a key event during the differentiation of these cells. Variant, SSEA-3 and -4-negative EC cells may have already initiated these changes while retaining other features of the EC phenotype. Other studies have indicated that human EC cells variably express class I MHC antigens. We have shown that interferon induces expression of these surface molecules in EC cells without inhibiting their growth or inducing their differentiation or resistance to viral infection.
Simultaneous full‐waveform inversion for source wavelet and earth model (2009)

The theory of full‐waveform inversion developed by Tarantola (1988) included inversion for the source wavelet. Source‐wavelet inversion has been performed in the time domain by Zhou et al. (1997) and in the frequency domain by Pratt (1999). Minkoff and Symes (1997) performed simultaneous inversion for reflectivity and source based on primary reflections in a layered earth. Since we believe a synthetic study of the stability and accuracy of source inversion to be important to both seismic acquisition and inversion communities, we performed a simultaneous full‐waveform inversion for the source wavelet and model parameters (P‐wave velocity in this test). Our approach is distinguished from the previous research by taking into account all of the observed data including multiples and by its easy extension to a higher‐dimensional earth model. Our synthetic test shows very robust and accurate convergence of source‐wavelet inversion even with an inaccurate starting earth model. A good initial guess for the wavelet is not necessary for our inversion to work. In fact, we used an initial guess of zero for all of the results presented here. Due to inaccuracies in the earth model estimate, some artifacts could appear in the source inversion and would cause slower convergence. Our solution to this problem is to optimize the source wavelet with constraints on its spectrum and time duration.