gebhart/patrepeval huggingface dataset:
Stable Transduction with Lentiviral Vectors and Amplification of Immature Hematopoietic Progenitors from Cord Blood of Preterm Human Fetuses (2001)

Umbilical cord blood (CB) from the early gestational human fetus is recognized as a rich source of hematopoietic stem cells. To examine the value of fetal CB for gene therapy of inborn immunohematopoietic disorders, we tested the feasibility of genetic modification of CD34+ cells from CB at weeks 24 to 34 of pregnancy, using lentiviral vector-mediated transfer of the green fluorescent protein (GFP) gene. The transduction rate of CD34+ cells was 42 ± 9%, resulting in GFP expression in 23 ± 4% of colonies derived from colony-forming units (CFUs) and 11 ± 1% from primitive long-term culture-initiating cells (LTC-ICs). Cell cycle analysis demonstrated transduction and GFP expression in cells in the G0 phase, which contains immature hematopoietic progenitors. Transduced fetal CD34+ cells could be expanded 1000-fold in long-term cultures supplemented with megakaryocyte growth and development factor along with Flt-3 ligand. At week 10, expression of GFP was observed in 40.5 ± 11.7% of CFU-derived colonies. While prestimulation of CD34+ cells with cytokines prior to transduction increased the efficiency of GFP transfer 2- to 3-fold, long-term maintenance of GFP-expressing CFUs occurred only in the absence of prestimulation. The GFP gene was found integrated into the genomic DNA of 35% of LTC-IC-derived colonies initiated at week 10, but GFP expression was not detectable, suggesting downregulation of transgene activity during the extended culture period. These results indicate that human fetal CB progenitors are amenable to genetic modification by lentiviral vectors and may serve as a target for gene therapy of hematopoietic disorders by prenatal autologous transplantation.
Cell envelope of Neisseria gonorrhoeae: penicillin enhancement of peptidoglycan hydrolysis (1977)

The addition of 10 microgram of penicillin G per ml to log-phase cultures of Neisseria gonorrhoeae JW-31 (minimum inhibitory concentration for penicillin G, less than 0.007 microgram/ml) resulted in cellular lysis after a lag of 30 min. Penicillin markedly decreased the rate of peptidoglycan synthesis and enhanced the rate of hydrolysis of existing peptidoglycan. Hydrolysis was initiated immediately after addition of penicillin; cellular lysis did not occur until a considerable percentage of the peptidoglycan had been degraded. Cellular lysis was not due to penicillin per se but resulted from inhibition of cell wall synthesis. When cells were grown in media buffered with N-2-hydroxyethyl piperazine-N'-2-ethanesulfonic acid at pH 6, penicillin did not cause lysis; however, at this pH, peptidoglycan hydrolysis occurred and cells lost viability at the same rate as in the control (pH 7.2). We suggest that the stability of gonococci grown at pH 6 is related to increased stability of the outer membrane. The penicillin-enhanced rate of peptidoglycan hydrolysis decreased approximately 50% at pH 6.0. Penicillin-enhanced lysis, peptidoglycan hydrolysis, and loss of viability were also markedly reduced in cells grown at 28 degrees C.
Spinal Glia and Proinflammatory Cytokines Mediate Mirror-Image Neuropathic Pain in Rats (2003)

Mirror-image allodynia is a mysterious phenomenon that occurs in association with many clinical pain syndromes. Allodynia refers to pain in response to light touch/pressure stimuli, which normally are perceived as innocuous. Mirror-image allodynia arises from the healthy body region contralateral to the actual site of trauma/inflammation. Virtually nothing is known about the mechanisms underlying such pain. A recently developed animal model of inflammatory neuropathy reliably produces mirror-image allodynia, thus allowing this pain phenomenon to be analyzed. In this sciatic inflammatory neuropathy (SIN) model, decreased response threshold to tactile stimuli (mechanical allodynia) develops in rats after microinjection of immune activators around one healthy sciatic nerve at mid-thigh level. Low level immune activation produces unilateral allodynia ipsilateral to the site of sciatic inflammation; more intense immune activation produces bilateral (ipsilateral + mirror image) allodynia. The present studies demonstrate that both ipsilateral and mirror-image SIN-induced allodynias are (1) reversed by intrathecal (peri-spinal) delivery of fluorocitrate, a glial metabolic inhibitor; (2) prevented and reversed by intrathecal CNI-1493, an inhibitor of p38 mitogen-activated kinases implicated in proinflammatory cytokine production and signaling; and (3) prevented or reversed by intrathecal proinflammatory cytokine antagonists specific for interleukin-1, tumor necrosis factor, or interleukin-6. Reversal of ipsilateral and mirror-image allodynias was rapid and complete even when SIN was maintained constantly for 2 weeks before proinflammatory cytokine antagonist administration. These results provide the first evidence that ipsilateral and mirror-image inflammatory neuropathy pain are created both acutely and chronically through glial and proinflammatory cytokine actions.
Image Compression Using Block Truncation Coding (1979)

A new technique for image compression called Block Truncation Coding (BTC) is presented and compared with transform and other techniques. The BTC algorithm uses a two-level (one-bit) nonparametric quantizer that adapts to local properties of the image. The quantizer that shows great promise is one which preserves the local sample moments. This quantizer produces good quality images that appear to be enhanced at data rates of 1.5 bits/picture element. No large data storage is required, and the computation is small. The quantizer is compared with standard (minimum mean-square error and mean absolute error) one-bit quantizers. Modifications of the basic BTC algorithm are discussed along with the performance of BTC in the presence of channel errors.
A Crosstalk Between Myeloma Cells and Marrow Stromal Cells Stimulates Production of DKK1 and Interleukin-6: A Potential Role in the Development of Lytic Bone Disease and Tumor Progression in Multiple Myeloma (2005)

Multiple myeloma (MM) is a malignancy of antibody-secreting plasma cells. B-cell plasmacytomas stimulate bone resorption and angiogenesis, resulting in osteolytic lesions in the skeleton which persist upon successful treatment of the malignancy with chemotherapy. We found that an interaction between MM cells and mesenchymal stem cells (MSCs) from bone marrow stroma results in the formation and persistence of osteolytic bone lesions. It is known that MM cells activate osteoclast activity and secrete high levels of the Wnt inhibitor, Dickkopf-1, which prevents MSCs from differentiating into osteoblasts. We show that the Wnt signaling activator 6-bromoindirubin-3'-monoxime (BIO) releases MSCs from the osteoinhibitory effects of Dickkopf-1, whereas LiCl treatment does not. Additionally, we show that the >5-kDa fraction of MSC-conditioned medium promotes the proliferation of Dickkopf-1-secreting MM cells and that an interleukin-6 (IL-6)-neutralizing antibody blocks this effect. IL-6 expression levels were higher in undifferentiated MSCs than in MSCs treated with osteogenic medium, remained high in the presence of Dkk1, and were reduced by BIO treatment. Therefore, BIO treatment reduces the MSC-stimulated proliferation of MM cells and may enable MSCs to repair existing osteolytic lesions.
Movement-produced stimulation in the development of visually guided behavior. (1963)

Full and exact adaptation to sensory rearrangement in adult human Ss requires movement-produced sensory feedback. Riesen's work suggested that this factor also operates in the development of higher mammals but he proposed that sensory-sensory associations are the prerequisite. To test these alternatives, visual stimulation o f the active member (A) o f each of 10 pairs of neonatal kittens was allowed to vary with its locomotor movements while equivalent stimulation o f the second member (P) resulted from passive motion. Subsequent tests of visually guided paw placement, discrimination on a visual cliff, and the blink response were normal for A but failing in P. When other alternative explanations are excluded, this result extends the conclusions of studies of adult rearrangement to neonatal development. Hebb's writing (1949) has stirred interest
Single Cell T Cell Receptor Sequencing: Techniques and Future Challenges (2018)

The peculiarity of T cell is their ability to recognize an infinite range of self and foreign antigens. This ability is achieved during thymic development through a complex molecular mechanism based on somatic recombination that leads to the expression of a very heterogeneous population of surface antigen receptors, the T Cell Receptors (TCRs). TCRs are cell specific and represent a sort of "molecular tag" of T cells and have been widely studied to monitor the dynamics of T cells in terms of clonality and diversity in several contexts including lymphoid malignancies, infectious diseases, autoimmune diseases, and tumor immunology. In this review, we provide an overview of the strategies used to investigate the TCR repertoire from the pioneering techniques based on the V segments identification to the revolution introduced by Next-Generation Sequencing that allows for high-throughput sequencing of alpha and beta chains. Single cell based approaches brought the analysis to a higher level of complexity and now provide the opportunity to sequence paired alpha and beta chains. We also discuss novel approaches that through the integration of TCR tracking and mRNA single cell sequencing offer a valuable tool to associate antigen specificity to transcriptional dynamics and to understand the molecular mechanisms of T cell plasticity.
La mediación penal como método de resolución de conflictos: posibilidades de aplicación a los delitos de violencia de género y doméstica (2014)

In this work, we demonstrate ultra-low-threshold, optically pumped, room-temperature lasing in GaN microdisk and micro-ring cavities containing InGaN quantum dots and fragmented quantum wells, with the lowest measured threshold at a record low of 6.2 μJ/cm<sup>2</sup>. When pump volume decreases, we observe a systematic decrease in the lasing threshold of micro-rings. The photon loss rate, γ, increases with increasing inner ring diameter, leading to a systematic decrease in the post-threshold slope efficiency, while the quality factor of the lasing mode remains largely unchanged. A careful analysis using finite-difference time-domain simulations attributes the increased γ to the loss of photons from lower-quality higher-order modes during amplified spontaneous emission.
Atrophin-1, the DRPLA Gene Product, Interacts with Two Families of WW Domain-Containing Proteins (1998)

Atrophin-1 contains a polyglutamine repeat, expansion of which is responsible for dentatorubral and pallidoluysian atrophy (DRPLA). The normal function of atrophin-1 is unknown. We have identified five atrophin-1 interacting proteins (AIPs) which bind to atrophin-1 in the vicinity of the polyglutamine tract using the yeast two-hybrid system. Four of the interactions were confirmed using in vitro binding assays. All five interactors contained multiple WW domains. Two are novel. The AIPs can be divided into two distinct classes. AIP1 and AIP3/WWP3 are MAGUK-like multidomain proteins containing a number of protein-protein interaction modules, namely a guanylate kinase-like region, two WW domains, and multiple PDZ domains. AIP2/WWP2, AIP4, and AIP5/WWP1 are highly homologous, each having four WW domains and a HECT domain characteristic of ubiquitin ligases. These interactors are similar to recently isolated huntingtin-interacting proteins, suggesting possible commonality of function between two proteins responsible for very similar diseases.
Insulin-like growth factor (IGF)-II binding to IGF-binding proteins and IGF receptors is modified by deletion of the N-terminal hexapeptide or substitution of arginine for glutamate-6 in IGF-II (1993)

Recombinant insulin-like growth factor-II (IGF-II) and two structural analogues, des(1-6)IGF-II and [Arg6]-IGF-II, were produced to investigate the role of N-terminal residues in binding to IGF-binding proteins (IGFBPs) and hence the biological properties of the modified peptides. The growth factors were modelled on two previously characterized variants of IGF-I, des(1-3)IGF-I and [Arg3]-IGF-I, which both show substantially decreased binding to IGFBPs and were expressed as fusion proteins in Escherichia coli. The biological activities of the corresponding analogues of IGF-I and IGF-II were compared in rat L6 myoblasts and H35B hepatoma cells. In the L6-myoblast protein-synthesis assay, the IGF-II analogues, des(1-6)IGF-II and [Arg6]-IGF-II, were slightly more potent than IGF-II but about 10-fold less potent than IGF-I and 100-fold less potent than the respective IGF-I analogues, des(1-3)IGF-I and [Arg3]IGF-I. In H35 hepatoma cells the anabolic response measured was the inhibition of protein breakdown, and the potency order was insulin >>> [Arg3]-IGF-I > des(1-3)IGF-I > [Arg6]-IGF-II > des(1-6)IGF-II > IGF-I > IGF-II. Binding of the IGFs and their analogues to the type 1 IGF receptor in L6 myoblasts and to the insulin receptor in H35 hepatoma cells did not fully explain the observed anabolic potency differences. Moreover, binding of all four analogues to the IGFBPs secreted by L6 myoblasts and H35B hepatoma cells was greatly decreased compared with the parent IGF. We conclude that the observed anabolic response to each IGF was determined by their relative binding to the competing cell receptor and IGFBP binding sites present.
Hydrogel Containing Nanoparticle-Stabilized Liposomes for Topical Antimicrobial Delivery (2014)

Adsorbing small charged nanoparticles onto the outer surfaces of liposomes has become an effective strategy to stabilize liposomes against fusion prior to "seeing" target bacteria, yet allow them to fuse with the bacteria upon arrival at the infection sites. As a result, nanoparticle-stabilized liposomes have become an emerging drug delivery platform for treatment of various bacterial infections. To facilitate the translation of this platform for clinical tests and uses, herein we integrate nanoparticle-stabilized liposomes with hydrogel technology for more effective and sustained topical drug delivery. The hydrogel formulation not only preserves the structural integrity of the nanoparticle-stabilized liposomes, but also allows for controllable viscoeleasticity and tunable liposome release rate. Using Staphylococcus aureus bacteria as a model pathogen, we demonstrate that the hydrogel formulation can effectively release nanoparticle-stabilized liposomes to the bacterial culture, which subsequently fuse with bacterial membrane in a pH-dependent manner. When topically applied onto mouse skin, the hydrogel formulation does not generate any observable skin toxicity within a 7-day treatment. Collectively, the hydrogel containing nanoparticle-stabilized liposomes hold great promise for topical applications against various microbial infections.
Evolution of Poly(ADP-ribose) Polymerase-1 (PARP-1) Inhibitors. From Concept to Clinic (2010)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTEvolution of Poly(ADP-ribose) Polymerase-1 (PARP-1) Inhibitors. From Concept to ClinicDana V. Ferraris*View Author Information Johns Hopkins University Brain Science Institute, 855 N. Wolfe Street, Baltimore, Maryland 21205*Contact information. Phone: (410) 614-1107. Fax: (410) 614-0659. E-mail: [email protected]Cite this: J. Med. Chem. 2010, 53, 12, 4561–4584Publication Date (Web):April 5, 2010Publication History Received6 January 2010Published online5 April 2010Published inissue 24 June 2010https://doi.org/10.1021/jm100012mCopyright © 2010 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views7888Altmetric-Citations275LEARN 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 InReddit Read OnlinePDF (5 MB) Get e-AlertscloseSUBJECTS:Amides,Cancer,Cells,Genetics,Inhibitors Get e-Alerts
Tumor-associated macrophages in breast cancer as potential biomarkers for new treatments and diagnostics (2010)

While several inflammatory cell types participate in cancer development, macrophages specifically play a key role in breast cancer, where they appear to be part of the pathogenesis of high-grade tumors. Tumor-associated macrophages (TAMs) produce factors that promote angiogenesis, remodel tissue and dampen the immune response to tumors. Specific macrophage types contribute to increased metastases in animal models, while human studies show an association between TAMs and tumors with poor prognostic features. Macrophages display a spectrum of phenotypic states, with the tumor microenvironment skewing TAMs towards a 'nonclassical' activation state, known as the M2, or wound healing/regulatory state. These TAMs are found in high-risk breast cancers, making them an important therapeutic target to explore. Improved techniques for identifying TAMs should translate into clinical applications for prognosis and treatment.
Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid dose-dependently reduce fasting serum triglycerides (2010)

The objectives of this review were to determine whether the long-chain omega-3 fatty acids eicosapentaenoic acid and/or docosahexaenoic acid dose-dependently reduce fasting serum triglycerides (TG) and, if so, to create a mathematical model that may be used to predict potential percent reductions in fasting serum TG levels at the recommended intakes of 200-500 mg/day. The assessment included 15 randomized controlled trials that met pre-defined inclusion and exclusion criteria. Across these 15 studies, the dose-response was modeled using a first-order elimination curve. The response variable was defined as percent change from baseline in fasting serum TG, adjusted for the placebo effect. A weighting factor equal to the product of each study's sample size and quality score was used. Using the equation of the dose-response curve, predicted reductions in fasting serum TG levels at the recommended long-chain omega-3 fatty acid intakes of 200-500 mg/day are 3.1 to 7.2%.
Metabolic regulator Fnip1 is crucial for iNKT lymphocyte development (2014)

Folliculin-interacting protein 1 (Fnip1) is an adaptor protein that physically interacts with AMPK, an energy-sensing kinase that stimulates mitochondrial biogenesis and autophagy in response to low ATP, while turning off energy consumption mediated by mammalian target of rapamycin. Previous studies with Fnip1-null mice revealed that Fnip1 is essential for pre-B-cell development. Here we report a critical role of Fnip1 in invariant natural killer T (iNKT) cell development. Thymic iNKT development in Fnip1(-/-) mice was arrested at stage 2 (NK1.1(-)CD44(+)) but development of CD4, CD8, γδ T-cell, and NK cell lineages proceeded normally. Enforced expression of a Vα14Jα18 iNKT TCR transgene or loss of the proapoptotic protein Bim did not rescue iNKT cell maturation in Fnip1(-/-) mice. Whereas most known essential transcription factors for iNKT cell development were represented normally, Fnip1(-/-) iNKT cells failed to down-regulate Promyelocytic leukemia zinc finger compared with their WT counterparts. Moreover, Fnip1(-/-) iNKT cells contained hyperactive mTOR and reduced mitochondrial number despite lower ATP levels, resulting in increased sensitivity to apoptosis. These results indicate that Fnip1 is vital for iNKT cell development by maintaining metabolic homeostasis in response to metabolic stress.
Differentiation of canine bone marrow cells with hemopoietic characteristics from an adherent stromal cell precursor. (1995)

Stromal cell lines were established from canine long-term marrow cultures, cloned by limiting dilution, and maintained in stromal cell-conditioned medium. These cells grew adherent, maintained stable growth rate and morphology under standard conditions (in 20-30% conditioned medium; confluency, 70-90%), and supported hemopoiesis in long-term marrow cultures. In the presence of exogenous recombinant canine stem cell factor (rcSCF), round cells developed from the adherent layer, detached, and remained in culture as viable floating cells. Round floating cells also appeared when cultures were grown to > 90% confluency without rcSCF. Round cells were smaller than adherent cells, expressed CD34, showed basophilic plasma, and stained positive for c-kit, MHC-class II markers, and myeloid markers. In standard assays for colony formation, the detached cells produced granulocyte-macrophage colony-forming units (CFU-GM), fibroblast colony-forming units (CFU-F), and less well-defined colony-forming units. In addition, on allogeneic feeder cells in long-term cultures, these cells generated hemopoietic colonies. Strikingly, the differentiation was reversible: when nonadherent cells were resuspended at lower density in serum-containing medium, they reattached and grew to confluence when, once again, round cells detached. Detached cells from this secondary cycle produced mainly CFU-F and few CFU-GM when placed in clonal assays. These results suggest that some fibroblast-like stromal cells have the potential to differentiate into cells with hemopoietic characteristics. These observations provide evidence for the existence of a quiescent precursor of hemopoietic progenitors in the bone marrow stroma of the adult dog.
Alterations of Global Gastrointestinal Motility After Sleeve Gastrectomy (2012)

SG accelerates gastric emptying and small bowel transit of semisolids. In addition, it delays the initiation of cecal filling and T ICVt. This early and prolonged contact of food with the distal small bowel mucosa may explain the metabolic effects of SG occurring before substantial weight loss.
Free Radical Studies of Ellagic Acid, a Natural Phenolic Antioxidant (2002)

Ellagic acid, a plant-derived polyphenol, inhibits gamma-radiation (hydroxyl radical) induced lipid peroxidation in rat liver microsomes in a dose- and concentration-dependent manner. Its antioxidant capacity has been estimated using the 1,1-diphenyl-2-picrylhydrazyl radical assay. To understand the actual mechanisms involved in antioxidant activity and the free radical scavenging ability,a nanosecond pulse radiolysis technique has been employed. The rate constants for the reactions of several reactive oxygen species and reactive nitrogen species such as hydroxyl, peroxyl, and nitrogen dioxide radicals have been found to be in the range of 10(6)-10(9) M(-1) s(-1). The ellagic acid radicals have been characterized by the absorption spectra and decay kinetics. Studies on the reactions of ellagic acid with the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) radical and the radicals of ellagic acid with ascorbate have been used to estimate its one-electron reduction potential. Ellagic acid has also been found to be a good scavenger of peroxynitrite. Using stopped-flow reaction analyzer with absorption detection, the rate constant for this reaction has been determined to be 3.7 x 10(3) M(-1) s (-1). The electron spin resonance spectra of the oxidized ellagic acid radicals have been recorded by horseradish peroxidase and hydrogen peroxide method.