gebhart/patrepeval huggingface dataset:
Distinction between gamma c detection and function in YT lymphoid cells and in the granulocyte-macrophage colony-stimulating factor-responsive human myeloid cell line, Tf-1 (1995)

Peripheral blood monocytes respond to interleukin-2 (lL-2) and express the gamma common (gamma c) subunit of the lL-2 receptor (lL-2R) complex. However, the role of lL-2 in myeloid development has recently become of interest for several reasons, including the effect gamma c mutations may or may not have on myeloid development in patients with XSCID. Many studies of lL-2 function in the myeloid cell lineage have been performed on a murine background. To study gamma c expression and function in human myeloid precursors, we introduced the human myelomonocytic cell line, Tf-1, with a retroviral vector containing the human lL-2R beta subunit to create functional human intermediate lL-2R consisting of beta gamma c dimers. We have characterized this transfected variant of Tf-1 (Tf-1 beta) with regard to its response to lL-2. Unlike the parental Tf-1 cell line that is deficient in both lL-2R alpha and lL-2R beta expression, the Tf-1 beta transfectant binds and responds to lL-2 through intermediate-affinity lL-2Rs. Scatchard analyses indicate the number of intermediate-affinity receptors on Tf-1 beta is similar to the number found on the well-characterized YT cell line. However, detection of gamma c on Tf-1 beta cells is dramatically less than on YT cells by Western blot analysis and is undetectable by flow cytometric studies and surface iodinations. The gamma c component on YT cells is readily detected by all three methods. We conclude from these studies that the intermediate-affinity lL-2Rs on the Tf-1 cell line behave differently than those on YT cells with respect to gamma c detection. Either the gamma c molecule itself is different, or the cellular environment in which it functions is altered. Elucidation of gamma c function on this cell line will allow for its use as a model in which other cytokines using gamma c (including lL-2, lL-4, and lL-15) can be studied on the same cellular background.
β‐catenin signaling marks the prospective site of primitive streak formation in the mouse embryo (2004)

Beta-catenin signaling has been shown to be involved in triggering axis formation in several organisms, including Xenopus and zebrafish. Genetic analysis has demonstrated that the Wnt/beta-catenin signaling pathway is also involved in axis formation in the mouse, since a targeted deletion of beta-catenin results in embryos that have a block in anterior-posterior axis formation, fail to initiate gastrulation, and do not form mesoderm. However, because beta-catenin is ubiquitously expressed, the precise time and cell types in which this signaling pathway is active during early embryonic development remain unknown. Thus, to better understand the role of the Wnt/beta-catenin signaling pathway in axis formation and mesoderm specification, we have examined both the distribution and signaling activity of beta-catenin during early embryonic development in the mouse. We show that the N-terminally nonphosphorylated form of beta-catenin as well as beta-catenin signaling is first detectable in the extraembryonic visceral endoderm in day 5.5 embryos. Before the initiation of gastrulation at day 6.0, beta-catenin signaling is asymmetrically distributed within the epiblast and is localized to a small group of cells adjacent to the embryonic--extraembryonic junction. At day 6.5 and onward, beta-catenin signaling was detected in the primitive streak and mature node. Thus, beta-catenin signaling precedes primitive streak formation and is present in epiblast cells that will go on to form the primitive streak. These results support a critical role for the Wnt/beta-catenin pathway in specifying cells to form the primitive streak and node in the mammalian embryo as well as identify a novel domain of Wnt/beta-catenin signaling activity during early embryogenesis.
Upregulated Expression of Chemokines in Herniated Nucleus Pulposus Resorption (1996)

Inflammatory cells and their positivity for chemokines, such as monocyte chemotactic protein-1 and macrophage inflammatory protein-1 alpha, are associated with blood vessels. Chemokines, such as monocyte chemotactic protein-1 and macrophage inflammatory protein-1 alpha, were overexpressed in macrophages, fibroblasts, and endothelial cells, suggesting that these chemokines contribute to activation and recruitment of macrophages in a paracrine or autocrine fashion.
The Status of Ultrasound and Color Doppler Imaging for the Early Detection of Ovarian Carcinoma (1997)

Noninvasive imaging techniques such as ultrasound and color doppler imaging have been evaluated during the last decade for their ability to detect organ-confined curable ovarian cancer. While sensitivities approaching 100% can be achieved by these techniques, their specificities and the frequent invasive procedures required to confirm the abnormal sonographic findings have led to caution regarding the widespread use of ultrasound screening for ovarian cancer. These data are reviewed, as well as the NIH Consensus Panel on ovarian cancer's recommendation that routine screening for ovarian carcinoma should not be carried out at this time. Hereditary ovarian cancer syndromes account for approximately 5-10% of the cases. Many of the genes responsible for these syndromes have recently been elucidated. Due to the significant increase in the risk of ovarian cancer in these families, many screening studies have focused on this patient population. Findings from these trials, as well as studies on the psychological impact of screening are presented.
Trends in Glycosylation, Glycoanalysis and Glycoengineering of Therapeutic Antibodies and Fc-Fusion Proteins (2008)

Monoclonal antibodies (MAbs) are the fastest growing class of human pharmaceuticals. More than 20 MAbs have been approved and several hundreds are in clinical trials in various therapeutic indications including oncology, inflammatory diseases, organ transplantation, cardiology, viral infection, allergy, and tissue growth and repair. Most of the current therapeutic antibodies are humanized or human Immunoglobulins (IgGs) and are produced as recombinant glycoproteins in eukaryotic cells. Many alternative production systems and improved constructs are also being actively investigated. IgGs glycans represent only an average of around 3% of the total mass of the molecule. Despite this low percentage, particular glycoforms are involved in essential immune effector functions. On the other hand, glycoforms that are not commonly biosynthesized in human may be allergenic, immunogenic and accelerate the plasmatic clearance of the linked antibody. These glyco-variants have to be identified, controlled and limited for therapeutic uses. Glycosylation depends on multiple factors like production system, selected clonal population, manufacturing process and may be genetically or chemically engineered. The present account reviews the glycosylation patterns observed for the current approved therapeutic antibodies produced in mammalian cell lines, details classical and state-of-the-art analytical methods used for the characterization of glycoforms and discusses the expected benefits of manipulating the carbohydrate components of antibodies by bio- or chemical engineering as well as the expected advantages of alternative biotechnological production systems developed for new generation of therapeutic antibodies and Fc-fusion proteins.
Real-time self-localization from panoramic images on mobile devices (2011)

Self-localization in large environments is a vital task for accurately registered information visualization in outdoor Augmented Reality (AR) applications. In this work, we present a system for self-localization on mobile phones using a GPS prior and an online-generated panoramic view of the user's environment. The approach is suitable for executing entirely on current generation mobile devices, such as smartphones. Parallel execution of online incremental panorama generation and accurate 6DOF pose estimation using 3D point reconstructions allows for real-time self-localization and registration in large-scale environments. The power of our approach is demonstrated in several experimental evaluations.
The revolution in advanced wound-care converting. (2005)

In the advanced wound-care sector, there is an accelerating trend away from serial batch production towards transformational, continuous and integrated process lines. This is creating new standards and challenges in converting processes, which run faster, produce less waste and require fewer operators to run them. This article identifies those challenges and highlights the increasing importance of the relationship between wound-care manufacturer, materials science and the design of the converting process.
Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver function (2012)

A critical regulator of autophagy is the Class III PI3K Vps34 (also called PIK3C3). Although Vps34 is known to play an essential role in autophagy in yeast, its role in mammals remains elusive. To elucidate the physiological function of Vps34 and to determine its precise role in autophagy, we have generated Vps34(f/f) mice, in which expression of Cre recombinase results in a deletion of exon 4 of Vps34 and a frame shift causing a deletion of 755 of the 887 amino acids of Vps34. Acute ablation of Vps34 in MEFs upon adenoviral Cre infection results in a diminishment of localized generation of phosphatidylinositol 3-phosphate and blockade of both endocytic and autophagic degradation. Starvation-induced autophagosome formation is blocked in both Vps34-null MEFs and liver. Liver-specific Albumin-Cre;Vps34(f/f) mice developed hepatomegaly and hepatic steatosis, and impaired protein turnover. Ablation of Vps34 in the heart of muscle creatine kinase-Cre;Vps34(f/f) mice led to cardiomegaly and decreased contractility. In addition, while amino acid-stimulated mTOR activation was suppressed in the absence of Vps34, the steady-state level of mTOR signaling was not affected in Vps34-null MEFs, liver, or cardiomyocytes. Taken together, our results indicate that Vps34 plays an essential role in regulating functional autophagy and is indispensable for normal liver and heart function.
Use of Arsenic Trioxide as an Antivascular and Thermosensitizing Agent in Solid Tumors (2000)

Arsenic trioxide, As2O3 (ATO), has been found to be an effective chemotherapeutic for acute promyelocytic leukemia but its effect on solid tumors has not been fully explored. In the present report, we describe our observation that ATO is a potent antivascular agent and that it markedly enhances the effect of hyperthermia on tumors. The tumor blood perfusion in SCK tumors of A/J mice and FSaII tumors of C3H mice was significantly suppressed for up to 24 hours after an i.p. injection of 8 mg/kg ATO. ATO was also found to be able to increase the thermosensitivity of tumor cells in vitro. As a probable consequence of these effects, ATO treatment markedly increased the tumor growth delay caused by hyperthermia at 41.5 to 42.5 degrees C. Immunohistochemical staining of tumor tissue revealed that the expression levels of several adhesion molecules and TNFalpha are noticeably increased in tumors 2 to 6 hours after systemic ATO treatment. It is concluded that ATO is potentially useful to enhance the effect of hyperthermia on tumors at a clinically relevant temperature.
Adenocaine and Mg2+ reduce fluid requirement to maintain hypotensive resuscitation and improve cardiac and renal function in a porcine model of severe hemorrhagic shock* (2012)

Resuscitation with 7.5% NaCl ALM increases cardiac function and reduces fluid requirements during hypotensive resuscitation, whereas a second AL infusion during blood resuscitation transiently reduces whole body oxygen consumption and improves cardiac and renal function.
Actinobacillus actinomycetemcomitans fimbriae (1988)

Freshly isolated Actinobacillus actinomycetemcomitans strains were found to possess fimbriae. These appendages appeared to be irreversibly lost after 30 to 40 subcultures in the laboratory. The fimbriated strains were associated with a specific type of colonial morphology designated SP (Star Positive); the non‐fimbriated variant colony was designated SN (Star Negative). The fimbriae were approximately 5 nm wide and could be several μm in length. The fimbriated cells tended to aggregate readily whereas the non‐fimbriated cells formed uniform suspensions. Three stains of fimbriated A. actinomycetemcomitans isolated from different patients were compared to their non‐fimbriated variants for attachment to hydroxyapatite (HA) and saliva coated hydroxyapatite (SHA). Two of the fimbriated variants exhibited a 3‐ to 4‐fold enhancement of attachment to HA and SHA over their non‐fimbriated variant. However, there did not appear to be any specificity for SHA over HA. One strain (Pag) showed no major differences in attachment of the fimbriated or non‐fimbriated variant, albeit the fimbriae were indistinguishable from those of the other A. actinomycetemcomitans strains. Thus, there may be molecular differences among fimbriae of various A. actinomycetemcomitans strains which determine both their tissue specificity and their affinity for particular substrates.
Modified DFT filter banks with perfect reconstruction (1999)

In this paper, essential features of the recently introduced modified discrete Fourier transform DFT (MDFT) filter bank are presented. First, it is shown that all analysis and synthesis filters-obtained by appropriate complex modulation of a low-pass prototype filter-are linear phase. This is important for subband image coding applications. Another important property is the structure-inherent alias cancellation: all odd alias spectra are automatically compensated in the synthesis filter bank. Further, the MDFT filter bank provides perfect reconstruction for the same prototypes as for cosine-modulated filter banks. Thus, the same design methods can be used. Finally, different mappings of the input signal into the subbands are discussed and a comparison to the well-known cosine-modulated filter banks is given.
Colour As a Signal for Entraining the Mammalian Circadian Clock (2015)

Twilight is characterised by changes in both quantity ("irradiance") and quality ("colour") of light. Animals use the variation in irradiance to adjust their internal circadian clocks, aligning their behaviour and physiology with the solar cycle. However, it is currently unknown whether changes in colour also contribute to this entrainment process. Using environmental measurements, we show here that mammalian blue-yellow colour discrimination provides a more reliable method of tracking twilight progression than simply measuring irradiance. We next use electrophysiological recordings to demonstrate that neurons in the mouse suprachiasmatic circadian clock display the cone-dependent spectral opponency required to make use of this information. Thus, our data show that some clock neurons are highly sensitive to changes in spectral composition occurring over twilight and that this input dictates their response to changes in irradiance. Finally, using mice housed under photoperiods with simulated dawn/dusk transitions, we confirm that spectral changes occurring during twilight are required for appropriate circadian alignment under natural conditions. Together, these data reveal a new sensory mechanism for telling time of day that would be available to any mammalian species capable of chromatic vision.
NEURODEGENERATIVE DISEASES: New Concepts of Pathogenesis and Their Therapeutic Implications (2006)

Abstract Neurodegenerative diseases as diverse as Alzheimer's, Parkinson's, and Creutzfeldt-Jakob disease share a common pathogenetic mechanism involving aggregation and deposition of misfolded proteins, which leads to progressive central nervous system disease. Although the type of aggregated protein and the regional and cellular distribution of deposition vary from disease to disease, these disorders may all be linked by similar pathways of protein aggregation with fibril formation and amyloid deposition. This perspective on pathogenesis suggests that a wide variety of neurodegenerative diseases can be grouped mechanistically as brain amyloidoses, an outlook that yields novel insights into potential therapeutic approaches that may be applicable across the broad spectrum of neurodegenerative disease.
Targeting CD38 Suppresses Induction and Function of T Regulatory Cells to Mitigate Immunosuppression in Multiple Myeloma (2017)

<b>Purpose:</b> We study CD38 levels in immunosuppressive CD4<sup>+</sup>CD25<sup>high</sup>Foxp3<sup>+</sup> regulatory T cells (Treg) and further define immunomodulating effects of a therapeutic CD38 mAb isatuximab/SAR650984 in multiple myeloma.<b>Experimental Design:</b> We evaluated percentages of CD38-expressing subsets in Tregs from normal donors and multiple myeloma patients. Peripheral blood mononuclear cells (PBMC) were then treated with isatuximab with or without lenalidomide or pomalidomide to identify their impact on the percentage and immunosuppressive activity of Tregs on CD4<sup>+</sup>CD25<sup>-</sup> T cells (Tcons). We investigated the mechanism of increased Tregs in multiple myeloma patients in <i>ex vivo</i> cocultures of multiple myeloma cells with PBMCs or Tcons.<b>Results:</b> CD38 expression is higher on Tregs than Tcons from multiple myeloma patients versus normal donors. CD38 levels and the percentages of CD38<sup>high</sup> Tregs are increased by lenalidomide and pomalidomide. Isatuximab preferentially decreases Treg and increases Tcon frequencies, which is enhanced by pomalidomide/lenalidomide. Isatuximab reduces Foxp3 and IL10 in Tregs and restores proliferation and function of Tcons. It augments multiple myeloma cell lysis by CD8<sup>+</sup> T and natural killer cells. Coculture of multiple myeloma cells with Tcons significantly induces Tregs (iTregs), which express even higher CD38, CD25, and FoxP3 than natural Tregs. This is associated with elevated circulating CD38<sup>+</sup> Tregs in multiple myeloma patients versus normal donors. Conversely, isatuximab decreases multiple myeloma cell- and bone marrow stromal cell-induced iTreg by inhibiting both cell-cell contact and TGFβ/IL10. Finally, CD38 levels correlate with differential inhibition by isatuximab of Tregs from multiple myeloma versus normal donors.<b>Conclusions:</b> Targeting CD38 by isatuximab can preferentially block immunosuppressive Tregs and thereby restore immune effector function against multiple myeloma. <i>Clin Cancer Res; 23(15); 4290-300. ©2017 AACR</i>.
Problems monitoring response in multiple myeloma (2005)

There has been a revolution in the treatment of multiple myeloma over the past decade. This article seeks to correlate advances in imaging with advances in treatment and to highlight how proper understanding of both is necessary for optimum management.
Characterization of lineage-negative blast subpopulations derived from normal and chronic myelogenous leukemia bone marrows and determination of their responsiveness to human c-kit ligand. (1993)

Lineage-negative (lin-) normal and chronic myelogenous leukemia (CML) marrow blast populations were obtained by negative selection and subsequently separated on the basis of size by velocity sedimentation. The three subpopulations of lin- blasts obtained were enriched for F8 (the more primitive small blasts), F11 (blasts intermediate in size), and F13 (the more mature large blasts). We examined the morphological and phenotypic characteristics and cell cycle status of the subpopulations and determined the responsiveness of granulocyte-monocyte progenitors (colony-forming units/granulocyte-macrophage) derived from each subpopulation to mast cell growth factor in combination with granulocyte (G-CSF) or granulocyte-macrophage (GM-CSF) colony-stimulating factors alone and in combination. Morphological assessment revealed that an increased proportion of CML lin- blasts exhibited early cytoplasmic maturation as evidenced by the appearance of azurophilic (nonspecific) granules in the cytoplasm. Although the percentages of CML and normal small blasts expressing CD34 were similar, the proportion of CML lin- blasts expressing CD34 declined in the intermediate and more mature large lin- blast subpopulations by about 50%, whereas the percentage of CD34+ normal blasts remained essentially the same, indicating an earlier loss of CD34 expression by CML lin- blasts. In addition, the percentages of CML small blasts expressing CD33 were higher than normal (26-61% versus 0-16%, respectively), indicating that a higher proportion of CML small lin- blasts had a more mature phenotype. Mast cell growth factor addition to cultures stimulated by G-CSF, GM-CSF, or G-CSF plus GM-CSF, exerted the greatest synergistic effect (increased colony number and size) in the normal small and intermediate lin- blast cultures, but mast cell growth factor had considerably less effect, or no effect, in cultures of comparable CML subpopulations, indicating that CML lin- progenitors had a somewhat lower requirement for multiple growth factors. The findings suggest that the differences observed between normal and CML marrow subpopulations are proportional differences and that a greater proportion of CML lin- blast subpopulations exhibit characteristics associated with a more advanced stage of maturation than comparable normal lin- blast subpopulations.
Impact of Cognitive Impairment on Wandering Behavior (2001)

The purpose of this study was to explore cognitive impairment as a predictor of wandering rhythm and pattern in a sample of 25 demented residents from two long-term care settings. Parameters of rhythm indicating cycle frequency and structure were examined for wandering patterns (random, lapping, and pacing) and for nonwandering (direct) ambulation. All measures of cognitive impairment (Mini-Mental State Exam, Mattis Dementia Rating Scale, and a neuropsychologist's clinical rating) were significant predictors of parameters signifying frequency of wandering for random and lapping patterns but not for the pacing pattern. In addition, for nonwandering ambulation, cognitive impairment predicted some parameters of cycle structure (mean locomoting and nonlocomoting phase durations) but not those denoting frequency of ambulation. Results indicate that cognitive impairment plays an important role in determining the frequency of wandering cycles, but other factors may better explain parameters that characterize its cycle structure.
Utility of Survival Motor Neuron ELISA for Spinal Muscular Atrophy Clinical and Preclinical Analyses (2011)

This SMN ELISA assay enables the reliable, quantitative and rapid measurement of SMN in healthy human and SMA patient PBMCs, muscle and fibroblasts. SMN was also detected in several tissues in a mouse model of SMA, as well as in wildtype mouse tissues. This SMN ELISA has general translational applicability to both preclinical and clinical research efforts.