gebhart/patrepeval huggingface dataset:
Transplanted retinal pigment epithelium modifies the retinal degeneration in the RCS rat. (1989)

Transplantation of dissociated retinal epithelial cells obtained from the retinas of normal, congenic pigmented strain of rats to Bruch's membrane and the subretinal space of dystrophic rats from the Royal College of Surgeon (RCS) strain can prevent photoreceptor cell degeneration in this retina for at least 4 months after transplantation. Host and transplant cells form close apposition with one another but can be distinguished by the presence of both phagosomes and melanin granules in the transplant and the absence of these inclusions in the host retinal epithelium. Transplanted cells show excessive amounts of phagosomal material within 48 hr after transplantation, implying that restoration of phagocytosis is responsible for the photoreceptor survival.
Prevention of vincristine-induced peripheral neuropathy by genetic deletion of SARM1 in mice (2016)

Peripheral polyneuropathy is a common and dose-limiting side effect of many important chemotherapeutic agents. Most such neuropathies are characterized by early axonal degeneration, yet therapies that inhibit this axonal destruction process do not currently exist. Recently, we and others discovered that genetic deletion of SARM1 (sterile alpha and TIR motif containing protein 1) dramatically protects axons from degeneration after axotomy in mice. This finding fuels hope that inhibition of SARM1 or its downstream components can be used therapeutically in patients threatened by axonal loss. However, axon loss in most neuropathies, including chemotherapy-induced peripheral neuropathy, is the result of subacute/chronic processes that may be regulated differently than the acute, one time insult of axotomy. Here we evaluate if genetic deletion of SARM1 decreases axonal degeneration in a mouse model of neuropathy induced by the chemotherapeutic agent vincristine. In wild-type mice, 4 weeks of twice-weekly intraperitoneal injections of 1.5 mg/kg vincristine cause pronounced mechanical and heat hyperalgesia, a significant decrease in tail compound nerve action potential amplitude, loss of intraepidermal nerve fibres and significant degeneration of myelinated axons in both the distal sural nerve and nerves of the toe. Neither the proximal sural nerve nor the motor tibial nerve exhibit axon loss. These findings are consistent with the development of a distal, sensory predominant axonal polyneuropathy that mimics vincristine-induced peripheral polyneuropathy in humans. Using the same regimen of vincristine treatment in SARM1 knockout mice, the development of mechanical and heat hyperalgesia is blocked and the loss in tail compound nerve action potential amplitude is prevented. Moreover, SARM1 knockout mice do not lose unmyelinated fibres in the skin or myelinated axons in the sural nerve and toe after vincristine. Hence, genetic deletion of SARM1 blocks the development of vincristine-induced peripheral polyneuropathy in mice. Our results reveal that subacute/chronic axon loss induced by vincristine occurs via a SARM1 mediated axonal destruction pathway, and that blocking this pathway prevents the development of vincristine-induced peripheral polyneuropathy. These findings, in conjunction with previous studies with axotomy and traumatic brain injury, establish SARM1 as the central determinant of a fundamental axonal degeneration pathway that is activated by diverse insults. We suggest that targeting SARM1 or its downstream effectors may be a viable therapeutic option to prevent vincristine-induced peripheral polyneuropathy and possibly other peripheral polyneuropathies.
Nanocomposite Si/C/N Powder Production by Laser–Aerosol Interaction (1994)

Ultrafine preceramic Si/C/N powders were obtained via ultrasonic injection of aerosol particles into a highpower CO 2 laser beam, using hexamethyldisilazane, which strongly absorbs the CO 2 laser radiation at 10.6 μm, as the precursor. Introduction of aerosol droplets via a flowing argon or argon–NH 3 mixture into the laser beam yielded nanosized (30 to 60 nm), amorphous powders. Yield and particle composition were controlled by varying the synthesis conditions. Powder changes, such as crystallization during heat treatment under nitrogen or argon, were studied.
The chaplins: a family of hydrophobic cell-surface proteins involved in aerial mycelium formation in Streptomyces coelicolor (2003)

The filamentous bacterium Streptomyces coelicolor differentiates by forming specialized, spore-bearing aerial hyphae that grow into the air. Using microarrays, we identified genes that are down-regulated in a mutant unable to erect aerial hyphae. Through this route, we identified a previously unknown layer of aerial mycelium surface proteins (the "chaplins"). The chaplins share a hydrophobic domain of approximately 40 residues (the "chaplin domain"), and all have a secretion signal. The five short chaplins (ChpD,E,F,G,H) have one chaplin domain, whereas the three long chaplins (ChpA,B,C) have two chaplin domains and a C-terminal "sorting signal" that targets them for covalent attachment to the cell wall by sortase enzyme. Expression of the two chaplin genes examined (chpE, chpH) depended on aerial hyphae formation but not sporulation, and egfp fusions showed their expression localized to aerial structures. Mass spectrometry of cell wall extracts confirmed that the short chaplins localized to the cell surface. Deletion of chaplin genes caused severe delays in aerial hyphae formation, a phenotype rescued by exogenous application of chaplin proteins. These observations implicate the chaplins in aerial mycelium formation, and suggest that coating of the envelope by the chaplins is required for aerial hyphae to grow out of the aqueous environment of the substrate mycelium into the air.
CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells. (1996)

While interactions between CD28 and members of the B7 family costimulate and enhance T cell responses, recent evidence indicates that the CD28 homologue CTLA-4 plays a downregulatory role. The mechanism by which this occurs is not clear, but it has been suggested that CTLA-4 terminates ongoing responses of activated T cells, perhaps by induction of apoptosis. Here we demonstrate that CTLA-4 engagement by antibody cross-linking or binding to B7 inhibits proliferation and accumulation of the primary T cell growth factor, IL-2, by cells stimulated with anti-CD3 and anti-CD28. This inhibition is not a result of enhanced cell death. Rather it appears to result from restriction of transition from the G1 to the S phase of the cell cycle. Our observation that upregulation of both the IL-2R alpha chain and the CD69 activation antigen are inhibited by CTLA-4 engagement supplies further evidence that CTLA-4 restricts the progression of T cells to an activated state. Together this data demonstrates that CTLA-4 can regulate T cell activation in the absence of induction of apoptotic cell death.
Expression and characterization of recombinant rat α3(IV)NC1 and its use in induction of experimental autoimmune glomerulonephritis (2001)

This purified recombinant rat alpha 3(IV)NC1, which is both antigenic and nephritogenic, will be of value in analysing autoimmune responses in experimental anti-GBM disease.
Replicator Neural Networks for Universal Optimal Source Coding (1995)

Replicator neural networks self-organize by using their inputs as desired outputs; they internally form a compressed representation for the input data. A theorem shows that a class of replicator networks can, through the minimization of mean squared reconstruction error (for instance, by training on raw data examples), carry out optimal data compression for arbitrary data vector sources. Data manifolds, a new general model of data sources, are then introduced and a second theorem shows that, in a practically important limiting case, optimal-compression replicator networks operate by creating an essentially unique natural coordinate system for the manifold.
OC05.01: MoM‐based approach to non‐invasive prenatal testing using exponentially weighted moving average chart and chromosomal fingerprint (2015)

The aim of this study was to develop a new method of screening for fetal aneuploidies based on the detection of deviation in the distribution of cell-free fetal DNA (cfDNA) in maternal plasma. We combined three innovative approaches: the number of reads expressed in multiples of median (MoM), chromosomal fingerprint and exponentially weighted moving average chart (EWMA). In singleton pregnancies cfDNA was isolated from maternal plasma using QIAamp Circulating Nucleic Acid Kit (Qiagen) and the whole-genome sequencing using Ion Proton (Life Technologies) was performed. The numbers of reads in 60 kb bins were expressed in MoMs. Revealing that all fragments are not replicated and sequenced identically, we constructed “chromosomal fingerprints”, a kind of chromosomal map, where every bin is characterised by the average and standard deviation of the number of reads in MoMs. When testing an unknown sample, the deviation in the distribution of MoMs in every bin from the expected values of the fingerprint is expressed as Z-score. To assess the distribution of Z-scores along the chromosome the EWMA chart is used, where the deviation of the curve above the upper limit indicates a high risk of Trisomy. The approach was assessed using 179 prenatal samples. Fingerprints for chromosomes 13, 18 and 21 were constructed using 93 samples from euploid pregnancies. 179 samples with known fetal karyotype (145 euploid, 3 with T13, 9 with T18 and 22 with T21) were sequenced and EWMA charts produced. More than 15% of EWMA curve was above the limit in all 34 samples from trisomic pregnancies (100% detection rate for T13, T18 and T21). In 145 euploid samples there were only 2 cases in which chromosome 21 showed more than 15% of EWMA above the limit. The new MoM-based approach using chromosomal fingerprint and EWMA has a high performance in noninvasive aneuploidy screening with high sensitivity and low false positivity. The further information will be available from the currently ongoing clinical phase.
A Role for STAT5 in the Pathogenesis of IL-2-Induced Glucocorticoid Resistance (2002)

Abstract Glucocorticoids (GC) are highly effective in the control of diseases associated with T cell activation. However, a subset of individuals is GC insensitive. Previous studies have demonstrated that IL-2 can induce steroid resistance in mouse T cells. However, the mechanism for this phenomenon is unknown. In the current study we found that the murine cell line (HT-2) is steroid resistant when incubated with IL-2, but steroid sensitive when grown in IL-4. Furthermore, when HT-2 cells are treated with IL-2, the glucocorticoid receptor (GCR) does not translocate to the cell nucleus after dexamethasone treatment. In contrast, the GCR in IL-4-stimulated HT-2 cells does translocate into the cell nucleus after dexamethasone treatment. IL-2-induced steroid insensitivity in HT-2 cells appears to be a signaling event as the effects of IL-2 on nuclear translocation of the GCR occurred within 30 min even in the presence of cycloheximide. Indeed, preincubation of HT-2 cells with a Janus-associated kinase 3 inhibitor restored nuclear translocation of the GCR even in the presence of IL-2. Immunoprecipitation experiments revealed that phosphorylated STAT5 and GCR formed immune complexes. This association may lead to retardation of GCR nuclear translocation because IL-2 was not able to induce steroid insensitivity in splenocytes from STAT5 knockout mice. This study demonstrates a novel role for STAT5 in IL-2-induced steroid insensitivity.
Regulation of cyclooxygenase-2 expression by the Wnt and ras pathways. (2003)

Mutations in the adenomatous polyposis coli (APC) gene and K-ras occur in the majority of human colorectal cancers. Loss of functional APC protein activates the Wnt signal transduction pathway, allowing the nuclear accumulation of beta-catenin, which then binds to T-cell factor-4 (Tcf-4), causing increased transcriptional activation of downstream target genes. We investigated the hypothesis that the activation of the WNT pathway regulates cyclooxygenase-2 (COX-2). COX-2 was down-regulated after the induction of full-length APC in the HT29-APC cell line. We identified a Tcf-4-binding element (TBE) in the COX-2 promoter that specifically bound to Tcf-4 in an electrophoretic mobility shift assay. COX-2 promoter luciferase activity is down-regulated by APC in a promoter reporter construct containing the, TBE but not with mutant TBE. Mutant beta-catenin expression up-regulated the COX-2 promoter activity and the endogenous COX-2 mRNA expression in HuH7, hepatocellular carcinoma cell line, which is partially abrogated by cotransfection with a dominant-negative Tcf-4 expression vector. Although beta-catenin alone did not increase COX-2 protein to detectable levels in HuH7 cells, coexpression of both mutant beta-catenin and mutant K-ras increased COX-2 protein expression, which is consistent with the previous reports that K-ras can stabilize COX-2 mRNA. Taken together, our data support the hypothesis that COX-2 is down-regulated by APC and up-regulated by nuclear beta-catenin accumulation, and additionally implicate the Wnt signal transduction pathway in colon and liver carcinogenesis.
Expression Cloning of a Human cDNA Restoring Sphingomyelin Synthesis and Cell Growth in Sphingomyelin Synthase-defective Lymphoid Cells (2004)

Sphingomyelin (SM) synthase has been assumed to be involved in both cell death and survival by regulating pro-apoptotic mediator ceramide and pro-survival mediator diacylglycerol. However, its precise functions are ambiguous due to the lack of molecular cloning of SM synthase gene(s). We isolated WR19L/Fas-SM(-) mouse lymphoid cells, which show a defect of SM at the plasma membrane due to the lack of SM synthase activity and resistance to cell death induced by an SM-directed cytolytic protein lysenin. WR19L/Fas-SM(-) cells were also highly susceptible to methyl-beta-cyclodextrin (MbetaCD) as compared with the WR19L/Fas-SM(+) cells, which are capable of SM synthesis. By expression cloning method using WR19L/Fas-SM(-) cells and MbetaCD-based selection, we have succeeded in cloning of a human cDNA responsible for SM synthase activity. The cDNA encodes a peptide of 413 amino acids named SMS1 (putative molecular mass, 48.6 kDa), which contains a sterile alpha motif domain near the N-terminal region and four predicted transmembrane domains. WR19L/Fas-SM(-) cells expressing SMS1 cDNA (WR19L/Fas-SMS1) restored the resistance against MbetaCD, the accumulation of SM at the plasma membrane, and SM synthesis by transferring phosphocholine from phosphatidylcholine to ceramide. Furthermore, WR19L/Fas-SMS1 cells, as well as WR19L/Fas-SM(-) cells supplemented with exogenous SM, restored cell growth ability in serum-free conditions, where the growth of WR19L/Fas-SM(-) cells was severely inhibited. The results suggest that SMS1 is responsible for SM synthase activity in mammalian cells and plays a critical role in cell growth of mouse lymphoid cells.
Multiple effects of CD40&ndash;CD40L axis in immunity against infection and cancer (2018)

CD8<sup>+</sup> cytotoxic T lymphocyte (CTL) protects against infection and cancer cells. Understanding the mechanisms involved in generation and maintenance of effective CTL responses is essential for improving disease therapy and vaccine protocols. During CTL responses, immune cells encounter several tightly regulated signaling pathways; therefore, in such a dynamic process, proper integration of critical signals is necessary to orchestrate an effective immune response. In this review, we have focused on CD40-CD40L interactions (a key signal) in the regulation of dendritic cell (DC)-T cell (CD4<sup>+</sup> T and CD8<sup>+</sup> T) cross-talk, rescuing CTL exhaustion, and converting DC tolerization. We have also highlighted the knowledge gap and future directions to design immunotherapies.
ENZYMATIC RESOLUTION AND BASE PAIRING PROPERTIES OF D- AND L-CYCLOHEXENYL NUCLEIC ACIDS (CeNA) (2005)

An enzymatic transesterification reaction afforded large scale resolution of the cyclohexenol precursor needed for preparation of both series of CeNA building blocks. CeNA oligos of "D-like" chirality display a strong and selective interaction with RNA, while preserving RNase H activity, and therefore have potential as antisense constructs. CeNAs of opposite chirality form a self-pairing system on their own.
SPINK 2 deficiency causes infertility by inducing sperm defects in heterozygotes and azoospermia in homozygotes (2017)

Azoospermia, characterized by the absence of spermatozoa in the ejaculate, is a common cause of male infertility with a poorly characterized etiology. Exome sequencing analysis of two azoospermic brothers allowed the identification of a homozygous splice mutation in <i>SPINK2,</i> encoding a serine protease inhibitor believed to target acrosin, the main sperm acrosomal protease. In accord with these findings, we observed that homozygous <i>Spink2</i> KO male mice had azoospermia. Moreover, despite normal fertility, heterozygous male mice had a high rate of morphologically abnormal spermatozoa and a reduced sperm motility. Further analysis demonstrated that in the absence of Spink2, protease-induced stress initiates Golgi fragmentation and prevents acrosome biogenesis leading to spermatid differentiation arrest. We also observed a deleterious effect of acrosin overexpression in HEK cells, effect that was alleviated by SPINK2 coexpression confirming its role as acrosin inhibitor. These results demonstrate that SPINK2 is necessary to neutralize proteases during their cellular transit toward the acrosome and that its deficiency induces a pathological continuum ranging from oligoasthenoteratozoospermia in heterozygotes to azoospermia in homozygotes.
شناخت تکنولوژی پوشش دادن بذر(Coating) وتهیه اولین بذر پوششیافته چغندرقند ایرانی (2016)

شناخت تکنولوژی پوشش دادن بذر(‭Coating‬) وتهیه اولین بذر پوشش‌یافته چغندرقند ایرانی , شناخت تکنولوژی پوشش دادن بذر(‭Coating‬) وتهیه اولین بذر پوشش‌یافته چغندرقند ایرانی , فهرستگان یکپارچه پژوهشی و آموزشی کشاورزی
Phase I-II Study of Paclitaxel, Cisplatin, and Gemcitabine in Advanced Transitional-Cell Carcinoma of the Urothelium (2000)

This combination of paclitaxel, cisplatin, and gemcitabine is feasible and highly active in patients with advanced TCC of the urothelium. Further evaluation of this regimen in patients with TCC is warranted.
Il catalogo e le risorse elettroniche in biblioteca: un’integrazione possibile (2003)

The continuous development of electronic resources and their increasing importance as a part of library collections make their exclusion from the catalogue more and more unjustifiable. However, a decision to catalogue electronic resources brings with it two major problems. On the one hand we see a partial change in the nature of the catalogue itself, as it moves from providing information about the documents that the library stores physically to providing information about the documents whose accessibility is assured by the library; and on the other we experience the emergence of new dilemmas, such as the choice of the electronic resources to be catalogued, how to catalogue them, and the relation between the catalogue and other tools that provide access to these publications. As regards the choice of the electronic resources to be catalogued, criteria can change according to the sort of resource. Different problems result from local access electronic resources, free remote access electronic resources and fee-paying remote access electronic resources, and it is in any case difficult to delineate sharp boundaries in respect of both the local/remote and the free/fixed-fee dichotomy. The problems concerning how the electronic resources are to be catalogued go beyond the choice of cataloguing rules and standards and concern other matters such as: the exact specification of the documents to be catalogued and of their hierarchical level; the multiple versions problem, that is, the choice between creating an autonomous bibliographic record for every document to be catalogued or creating only one record for all of them; the need to create bibliographic records that inform the users about the permitted and prohibited uses of the electronic resources, about their accessibility and about their location. Lastly, even if the library decides to catalogue electronic resources, it would be better to utilize other tools in addition, in particular web pages, as a starting point for the access to these kinds of resources. The electronic environment, where catalogue, web pages and electronic resources live together, allows the integration of all these elements and easy navigation from one to another.
Clinical utility of circulating cell-free Epstein-Barr virus DNA in patients with gastric cancer (2017)

Recent comprehensive molecular subtyping of gastric cancer (GC) identified Epstein-Barr virus (EBV)-positive tumors as a subtype with distinct salient molecular and clinical features. In this study, we aimed to determine the potential utility of circulating cell-free EBV DNA as a biomarker for the detection and/or monitoring of therapeutic response in patients with EBV-associated gastric carcinoma (EBVaGC). The EBV genes-to-ribonuclease P RNA component H1 ratios (EBV ratios) in the GC tumors and plasma samples were determined by quantitative real-time polymerase chain reaction in 153 patients with GC, including 14 patients with EBVaGC diagnosed by the conventional method. Circulating cell-free EBV DNA was detected in 14 patients with GC: the sensitivity and specificity of detection were 71.4% (10/14) and 97.1% (135/139), respectively. Plasma EBV ratios were significantly correlated with the size of EBVaGC tumors, and the plasma EBV DNA detected before surgery in EBVaGC cases disappeared after surgery. Patients with EBVaGC may have a better prognosis, but circulating cell-free EBV DNA had no or little impact on prognosis. In addition, repeated assessment of the plasma EBV ratio in EBVaGC showed a decrease and increase in plasma EBV DNA after treatment and during tumor progression/recurrence, respectively. These results suggest the potential utility of circulating cell-free DNA to reveal EBV DNA for the identification of the EBVaGC subtype and/or for real-time monitoring of tumor progression as well as treatment response in patients with EBVaGC.
The Michigan State University Superconducting Cyclotron Program (1979)

Status of the superconducting cyclotron program is reviewed as of September 1978. A number of design details have changed since the previous conference. Novel features have been checked in a variety of prototype test facilities.