gebhart/patrepeval huggingface dataset:
Porcine reproductive and respiratory syndrome virus replicates in testicular germ cells, alters spermatogenesis, and induces germ cell death by apoptosis (1997)

Like other arteriviruses, porcine reproductive and respiratory syndrome virus (PRRSV) is shed in semen, a feature that is critical for the venereal transmission of this group of viruses. In spite of its epidemiological importance, little is known of the association of PRRSV or other arteriviruses with gonadal tissues. We experimentally infected a group of boars with PRRSV 12068-96, a virulent field strain. By combined use of in situ hybridization and immunohistochemistry, we detected infection by PRRSV in the testes of these boars. The PRRSV testicular replication in testis centers on two types of cells: (i) epithelial germ cells of the seminiferous tubules, primarily spermatids and spermatocytes, and (ii) macrophages, which are located in the interstitium of the testis. Histopathologically, hypospermatogenesis, formation of multinucleated giant cells (MGCs), and abundant germ cell depletion and death were observed. We obtained evidence that such germ cell death occurs by apoptosis, as determined by a characteristic histologic pattern and evidence of massive DNA fragmentation detected in situ (TUNEL [terminal deoxynucleotidyltransferase-mediated digoxigenin-UTP nick end labeling] assay). Simultaneously with these testicular alterations, we observed that there is a significant increase in the number of immature sperm cells (mainly MGCs, spermatids, and spermatocytes) in the ejaculates of the PRRSV-inoculated boars and that these cells are infected with PRRSV. Our results indicate that PRRSV may infect target cells other than macrophages, that these infected cells can be primarily responsible for the excretion of infectious PRRSV in semen, and that PRRSV induces apoptosis in these germ cells in vivo.
Developmental and pathological changes at the node and paranode in human sural nerves (1996)

The nodes and paranodes of peripheral nerve fibers are complex structures that are especially prone to artificial and pathological changes which have to be distinguished from normal developmental changes. Alterations during normal development are mainly caused by an increase in axonal diameter and myelin sheath thickness. The nodal, and paranodal axon diameters in human sural nerves reach their adult values at 3–5 years of age, simultaneously to the internodal diameter. The ratio between internodal and paranodal axon diameters remain relatively constant, with an average value of 1.8 to 2.0 (range: 1.6 to 2.5). Despite a considerable increase of the number of myelin lamellae, the length of the paranodal myelin sheath attachment zone at the axon does not increase correspondingly, because of (1) attenuation of the terminal myelin loops, (2) separation of some of these from the axolemma, and their piling up in the paranode. Separation of variable numbers of terminal myelin loops from the underlying axolemma results in the formation of the spines on the “double bracelet épineux” of Nageotte, while the transverse bands of these loops disappear. The adaptation of the paranodal myelin sheath to axonal expansion during development probably occurs by uneven gliding of the paranodal myelin loops simultaneously with internodal slippage of myelin lamellae. Artificial changes are caused by insufficient fixation or mechanical stress during excision and further handling (cutting, dedydrating, embedding) of nerves whereas pathological changes may be induced by a multitude of causes. An attempt to classify these changes is presented in Table 2. © 1996 Wiley-Liss, Inc.
Isolation of dominant negative mutants and inhibitory antisense RNA sequences by expression selection of random DNA fragments (1992)

Selective inhibition of specific genes can be accomplished using genetic suppressor elements (GSEs) that encode antisense RNA, dominant negative mutant proteins, or other regulatory products. GSEs may correspond to partial sequences of target genes, usually identified by trial and error. We have used bacteriophage lambda as a model system to test a concept that biologically active GSEs may be generated by random DNA fragmentation and identified by expression selection. Fragments from eleven different regions of lambda genome, encoding specific peptides or antisense RNA sequences, rendered E. coli resistant to the phage. Analysis of these GSEs revealed some previously unknown functions of phage lambda, including suppression of the cellular lambda receptor by an 'accessory' gene of the phage. The random fragment selection strategy provides a general approach to the generation of efficient GSEs and elucidation of novel gene functions.
Epithelial Cell Differentiation of Human Mesenchymal Stromal Cells in Decellularized Lung Scaffolds (2014)

Identification of appropriate donor cell types is important for lung cell therapy and for lung regeneration. Previous studies have indicated that mesenchymal stromal cells derived from human bone marrow (hBM-MSCs) and from human adipose tissue (hAT-MSCs) may have the ability to trans-differentiate into lung epithelial cells. However, these data remain controversial. Herein, the ability of hBM-MSCs and hAT-MSCs to repopulate acellular rodent lung tissue was evaluated. hBM-MSCs and hAT-MSCs were isolated from bone marrow aspirate and lipoaspirate, respectively. Rat lungs were decellularized with CHAPS detergent, followed by seeding the matrix with hBM-MSCs and hAT-MSCs. Under appropriate culture conditions, both human MSC populations attached to and proliferated within the lung tissue scaffold. In addition, cells were capable of type 2 pneumocyte differentiation, as assessed by marker expression of surfactant protein C (pro-SPC) at the protein and the RNA level, and by the presence of lamellar bodies by transmission electron microscopy. Additionally, hAT-MSCs contributed to Clara-like cells that lined the airways in the lung scaffolds, whereas the hBM-MSCs did not. We also tested the differentiation potential of MSCs on different extracellular matrix components in vitro, and found that protein substrate influences MSC epithelial differentiation. Together our data show the capacity for human MSCs to differentiate toward lung epithelial phenotypes, and the possibility of using these cells for lung cell therapies and tissue engineering.
Phase II Trial of a Toll-Like Receptor 9–Activating Oligonucleotide in Patients With Metastatic Melanoma (2006)

These results indicate that TLR9-targeted therapy can stimulate innate immune responses in cancer patients, identify biomarkers that may be associated with TLR9-induced tumor regression, and encourage the design of follow-up studies to evaluate the ability of this therapeutic approach to target human cancer.
Protein variability in male and female Wistar rat liver proteins (1995)

In the emerging field of mechanistic toxicology, growing attention is being paid to the interpretation of sex-related toxic responses. The Wistar rat outbred stock is a frequently used rodent for toxicity testing. Outbred strains, which display a relatively high degree of genetic variability between the individual animals are often used in risk assessment, as they are considered to best approximate the variability present in a human population. In this study two-dimensional (2-D) protein gel electrophoresis was applied to investigate the liver protein patterns of male and female Wistar rats and to search for (i) sex-related and (ii) interindividual qualitative and quantitative differences in protein expression. Among the sexes, six proteins were detected that were shown to be exclusively present in male rats and one that was present only in females. A male-specific protein was tentatively assigned to alpha 2u globulin. Seven protein spots showed statistically significant abundance changes (p < 0.001) between males and females, one was tentatively assigned to heme oxygenase 1 and another to the 23 kDa morphin-binding protein. Four sets of protein spots were detected that showed positional shifts in the individual patterns and are likely to represent polymorphic proteins inherent in the Wistar rat. These results form a valuable basis for future investigations of drug-induced changes in the male and female Wistar rat liver pattern.
An Efficient Procedure for the Synthesis of Crystalline Aryldiazonium Trifluoroacetates – Synthetic Applications (1999)

We have developed a very mild procedure for the synthesis of crystalline aryldiazonium trifluoroacetate salts in high yields under anhydrous conditions. Over thirty mono- or polyfunctional aniline derivatives have been diazotized by this method, including water- and acid-sensitive substrates. The o- and p-hydroxyaryldiazonium salts, derived from the corresponding anilines, could be deprotonated by treatment with K2CO3 to yield pure diazoquinones. NMR and UV/Vis spectra have been recorded for all the synthesized salts; the data are in good agreement with the rather limited published data and constitute a first extensive report of 13C-NMR chemical shifts in diazonium salts. An excellent linear relationship emerged between Brown's substituent constants s+p and the 13Cipso chemical shifts. The diazonium salts obtained proved to be much more soluble in organic solvents than their tetrafluoroborate counterparts. They were tested in Pd-mediated coupling reactions of various Carbon-Carbon double bonds, and were found to give good yields within short reaction times under very mild conditions. We believe that diazonium trifluoroacetates represent a very attractive alternative to diazonium tetrafluoroborates.
Retinoids are important cofactors in T cell activation. (1992)

Murine thymic T cells depleted of antigen-presenting cells proliferate poorly in response to crosslinking anti-CD3 monoclonal antibodies or concanavalin A when cultured in conventional fetal calf serum-containing serum. However, in a serum-free medium formulated to contain, in addition to basic ingredients, insulin, transferrin, albumin, linoleic acid (ITLB), and retinol, proliferation is vigorous. The presence of retinol is critical, because when omitted, cells do not become activated. The subsets of T cells proliferating with the assistance of retinol cofactor are both CD4+ and CD8+ thymic T cells, and CD4+ peripheral T cells. Mature CD8+ T cells of lymph nodes can also be activated in ITLB medium plus retinol, provided that interleukin 2 (IL-2) is added. Retinol needs to be present at the time when T cell receptor triggering is initiated, suggesting that early activation events (G0 to G1 transition) are dependent on retinol. It is currently less clear whether or not subsequent events associated with G1 to S phase transition also require the presence of retinol. 14-hydroxy-retroretinol (14HRR) is a metabolic product of retinol in lymphocytes, and this retinoid effectively supports T cell activation in conjunction with a mitogen in lieu of retinol. Thus, while retinol and its intracellular product, 14HRR, are unable to activate T cells on their own, they are important cofactors. The requirement for retinol in CD3-mediated T cell activation cannot be satisfied by retinoic acid or ILs-1, 2, 4, and 6, and tumor necrosis factor-alpha whereas interferon gamma can substitute for retinol. Our experiments are compatible with the idea that retinol, in the course of cellular activation, is converted to 14HRR, which is needed as intracellular messenger. If substantiated by molecular studies now underway, our data should lead to the description of a new signal pathway distinct from the retinoic acid signal pathway observed in nonlymphoid cells, but perhaps functioning by a similar mechanism, i.e., ligand-assisted transcriptional regulation.
Zinc binding, circular dichroism, and equilibrium sedimentation studies on insulin (bovine) and several of its derivatives (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTZinc binding, circular dichroism, and equilibrium sedimentation studies on insulin (bovine) and several of its derivativesJose Goldman and Frederick H. CarpenterCite this: Biochemistry 1974, 13, 22, 4566–4574Publication Date (Print):October 1, 1974Publication History Published online1 May 2002Published inissue 1 October 1974https://pubs.acs.org/doi/10.1021/bi00719a015https://doi.org/10.1021/bi00719a015research-articleACS PublicationsRequest reuse permissionsArticle Views808Altmetric-Citations147LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The timing of chromosome elimination in hexaploid wheat × maize crosses (1989)

Early seed development in crosses between the hexaploid wheat genotype 'Chinese Spring' and the maize genotype 'Seneca 60' was studied to determine the timing of elimination of the maize chromosomes. Elimination of one or more maize chromosomes occurred in about 70% of zygotic mitoses. Metaphase nuclei from two-celled embryos had 5 to 10 maize chromosomes, most of which were lost during the second cell division. About half the metaphase nuclei from four-celled embryos had no maize chromosomes, and the remainder had one to five. Anaphase or telophase nuclei from four-celled embryos showed no maize chromosomes in about half the cells and one or more pairs of lagging maize daughter chromosomes in the remainder. No maize chromosomes were seen in metaphase preparations from embryos with eight or more cells. These data strongly suggest that all maize chromosomes were lost during the first three cell-division cycles in most embryos. All embryos with four or more cells had micronuclei, showing that embryo development was dependent on fertilization. The only primary endosperm metaphase obtained in the experiment had 42 wheat and 10 maize chromosomes and the presence of micronuclei in most developing endosperms showed that at least 85% were of hybrid origin. Few endosperm nuclei were formed in comparison with self-pollinated 'Chinese Spring' caryopses, and many were abnormal. The implications of the results for wheat haploid production and gene transfer from maize to wheat are discussed.Key words: wheat, maize, wide hibridization, chromosome elimination.
Differential Activation of the Sympathetic Innervation of Adipose Tissues by Melanocortin Receptor Stimulation (2007)

Melanocortins are implicated in the control of energy intake/expenditure. Centrally administered melanotan II (MTII), a synthetic melanocortin 3/4-receptor agonist, decreases adiposity beyond that accountable by food intake decreases. Melanocortin-4 receptor (MC4-R) mRNA is expressed on sympathetic nervous system (SNS) outflow neurons to white adipose tissue (WAT) in Siberian hamsters, suggesting a role in lipid mobilization. Therefore, we tested whether third ventricular injections of MTII increased sympathetic drive to WAT and interscapular brown adipose tissue (IBAT) using norepinephrine turnover (NETO) as a measure of sympathetic drive. We also tested for MTII-induced changes in lipolysis-related WAT gene expression (beta3-adrenoceptors, hormone sensitive lipase) and IBAT thermogenesis (beta3-adrenoceptor, uncoupling protein-1). Finally, we tested whether third ventricularly injected MTII, a highly selective MC4-R agonist (cyclo[beta-Ala-His-D-Phe-Arg-Trp-Glu]NH2) increased or agouti-related protein decreased IBAT temperature in hamsters implanted with sc IBAT temperature transponders. Centrally administered MTII provoked differential sympathetic drives to WAT and IBAT (increased inguinal WAT, dorsosubcutaneous WAT and IBAT NETO, but not epididymal WAT and retroperitoneal WAT NETO). MTII also increased circulating concentrations of the lipolytic products free fatty acids and glycerol but not plasma catecholamines, suggesting lipid mobilization via WAT SNS innervation and not via adrenal medullary catecholamines. WAT or IBAT gene expression was largely unaffected by acute MTII treatment, but IBAT temperature was increased by MTII and the MC4-R agonist and decreased by agouti-related protein. Collectively, this is the first demonstration of central melanocortin agonist stimulation of WAT lipolysis through the SNS and confirms melanocortin-induced changes in BAT thermogenesis.
The Effect of Dexmedetomidine on Agitation during Weaning of Mechanical Ventilation in Critically ill Patients (2010)

Ventilated patients receiving opioids and/or benzodiazepines are at high risk of developing agitation, particularly upon weaning towards extubation. This is often associated with an increased intubation time and length of stay in the intensive care unit and may cause long-term morbidity. Anxiety, fear and agitation are amongst the most common non-pulmonary causes of failure to liberate from mechanical ventilation. This prospective, open-label observational study examined 28 ventilated adult patients in the intensive care unit (30 episodes) requiring opioids and/or sedatives for >24 hours, who developed agitation and/or delirium upon weaning from sedation and failed to achieve successful extubation with conventional management. Patients were ventilated for a median (interquartile range) of 115 [87 to 263] hours prior to enrolment. Dexmedetomidine infusion was commenced at 0.4 microg/kg/hour for two hours, after which concurrent sedative therapy was preferentially weaned and titrated to obtain target Motor Activity Assessment Score score of 2 to 4. The median (range) maximum dose and infusion time of dexmedetomidine was 0.7 microg/kg/hour (0.4 to 1.0) and 62 hours (24 to 252) respectively. The number of episodes at target Motor Activity Assessment Score score at zero, six and 12 hours after commencement of dexmedetomidine were 7/30 (23.3%), 28/30 (93.3%) and 26/30 (86.7%), respectively (P < 0.001 for 6 and 12 vs. 0 hours). Excluding unrelated clinical deterioration, 22 episodes (73.3%) achieved successful weaning from ventilation with a median (interquartile range) ventilation time of 70 (28 to 96) hours after dexmedetomidine infusion. Dexmedetomidine achieved rapid resolution of agitation and facilitated ventilatory weaning after failure of conventional therapy. Its role as first-line therapy in ventilated, agitated patients warrants further investigation.
Multiphonon Orbit-Lattice Relaxation of Excited States of Rare-Earth Ions in Crystals (1968)

A systematic study has been made of multiphonon orbit-lattice relaxation of excited states of rare-earth ions in crystals. By measuring both excited-state fluorescence lifetimes and multiphonon relaxation quantum efficiencies, pure multiphonon transition rates were determined for the following set of crystals: (1) La${\mathrm{Br}}_{3}$: ${\mathrm{Nd}}^{3+}$, La${\mathrm{Br}}_{3}$: ${\mathrm{Dy}}^{3+}$, and La${\mathrm{Br}}_{3}$: ${\mathrm{Ho}}^{3+}$; (2) La${\mathrm{F}}_{3}$: ${\mathrm{Er}}^{3+}$ and La${\mathrm{F}}_{3}$: ${\mathrm{Ho}}^{3+}$; (3) Sr${\mathrm{F}}_{2}$: ${\mathrm{Ho}}^{3+}$ and Sr${\mathrm{F}}_{2}$: ${\mathrm{Er}}^{3+}$; and (4) ${\mathrm{Y}}_{2}$${\mathrm{O}}_{3}$: ${\mathrm{Er}}^{3+}$ and ${\mathrm{Y}}_{2}$${\mathrm{O}}_{3}$: ${\mathrm{Ho}}^{3+}$. Lifetimes were measured both in the near infrared using the fluorescence phase-shift technique, and in the visible region using pulse-excitation techniques. Measurements were performed at 4.2\ifmmode^\circ\else\textdegree\fi{}K to determine spontaneous multiphonon transition rates, as well as at higher temperatures. The temperature dependences were fitted with a theoretical model involving the stimulated emission of phonons due to the thermally populated phonon modes. These results indicate that the decay involves the emission of high-energy optical phonons and occurs in approximately the lowest order permitted by energy conservation and cutoff in the phonon spectrum. The spontaneous transiton rate was found to have a systematic exponential dependence on the transition energy to the terminal level, that is, on the energy gap. This behavior is interpreted as being due to the simple convergence of the orbit-lattice perturbation expansion. With the precise features of the interacting phonon modes and atomic levels averaged out for these high-order processes, the only critical parameter within a given lattice is the energy gap, i.e., the order of the process. The dependence on the order has been extracted by normalizing the energy gap by the optical-phonon cutoff energy. The rate for a given order and the swiftness of the convergence reflect the strength of the orbit-lattice interaction. The relative behavior for a given host can be explained through its known crystalline properties, in particular the phonon frequency distribution function and the static crystal field. The observed order dependence in ${\mathrm{Y}}_{2}$${\mathrm{O}}_{3}$ indicates a relative weakness in the orbit-lattice interaction for crystals with strong covalency.
Immunohistochemical Analysis of Human Uterine Estrogen and Progesterone Receptors Throughout the Menstrual Cycle* (1988)

Estrogen receptors (ER) and progesterone receptors (PgR) were studied immunohistochemically using specific antireceptor monoclonal antibodies in uterine tissue samples from 33 women in various stages of the menstrual cycle. Immunohistochemical localization was quantified as to intensity of staining and tissue distribution in glandular epithelium, stroma, and myometrium, and the results were compared with those of standard ligand binding assays. In all samples ER and PgR localized within the nuclei of target cells. The maximal concentrations of ER and PgR occurred in the mid- to late proliferative phase of the menstrual cycle. ER content declined throughout the secretory phase. In contrast, PgR content underwent unexpectedly complex and dyssynchronous fluctuations during the secretory phase of the menstrual cycle. Specifically, the glandular epithelium had diminished PgR content, while the stroma and myometrium maintained a significant PgR content. PgR and perhaps ER are not concordant in different cell types within the uterus. Segregation of function through alteration of receptor content may be an important mechanism in steroid-dependent growth and differentiation of target tissues.
Multiwavelength reconfigurable WDM/ATM/SONET network testbed (1996)

This paper describes the multiwavelength reconfigurable all-optical network testbed designed and constructed as a part of the optical networks technology consortium (ONTC) phase I program with a group of working members consisting of Bellcore, Columbia University, Hughes Research Laboratories, Northern Telecom, Rockwell Science Center, Case Western Reserve University, United Technology Research Center, Uniphase Telecommunications Product, and Lawrence Livermore National Laboratories. The architecture of the testbed and its nodes is presented together with a description of the key component technologies. Network control and management is discussed along with applications and services.