gebhart/patrepeval huggingface dataset:
Unexpected Effects of the IL-2 receptor alpha subunit on high affinity IL-2 receptor assembly and function detected with a mutant IL-2 analog (1993)

Binding of IL-2 to the high affinity IL-2R results in the formation of a stable complex consisting of IL-2 and at least three distinct, noncovalently associated receptor subunits: IL-2R alpha (p55), IL-2R beta (p70-75), and IL-2R gamma (p64). Ligand binding also stimulates the rapid endocytosis of this receptor complex. To gain further insight into the function of the various subunits of the multicomponent high affinity IL-2R complex, we have carried out binding, internalization, and proliferation assays using an IL-2 analog designated F42A that contains a single Phe for Ala amino acid substitution at position 42. This mutation markedly reduces the intrinsic affinity of the resultant IL-2 analog for the low affinity IL-2R alpha subunit although having little or no effect on binding to the IL-2R beta (or IL-2R beta/gamma) intermediate affinity receptor. We have confirmed that F42A does not bind to the IL-2R alpha chain when expressed alone on MT-1 cells or in the presence of the large or small excess of IL-2R beta chains present on either YT-1 cells or forskolin-induced YT-1 cells, respectively. However, although F42A does not interact with the large number of low affinity IL-2R alpha chains present on HUT 102B2 cells, this ligand does bind to the small number of IL-2R beta chains present on these cells with at least 10-fold higher than expected affinity. These findings indicate that excess IL-2R alpha chains may exert positive effects on binding perhaps by changing the conformation of IL-2R beta. In F42A-stimulated internalization assays on forskolin-induced YT-1 cells, the IL-2R alpha chain is consistently endocytosed together with the IL-2R beta subunit indicating that IL-2R alpha is stably associated with the F42A-IL-2R beta complex even though the alpha-subunit contributes little if any affinity to the F42A binding reaction. In proliferation assays on mouse IL-3-dependent pro-B BA/F3 cells stably coexpressing transfected human IL-2R alpha and IL-2R beta subunits (but a mouse IL-2R gamma subunit), F42A proved to be a more effective agonist of growth than wild-type IL-2. These results suggest that the interaction between wild-type IL-2 but not F42A and the IL-2R alpha subunit in this mixed species high affinity receptor complex may induce an unfavorable receptor conformation leading to diminished rather than enhanced growth signal transduction.
Microtubules Contribute to the Birefringence of the Retinal Nerve Fiber Layer (2005)

MTs make a significant contribution to RNFL birefringence. The decrease of RNFL birefringence in glaucoma may indicate a loss of MTs.
Cytologic and flow cytometric DNA analysis of multinucleated tumor cells and derived microcells. (1989)

Microcell production by means of Colcemid-induced micronucleation and subsequent enucleation with the density gradient technique was adjusted for use with the murine T-lymphoma line ESb-M. Modification of the standard protocol for a cell type on which no experiments had previously been performed required careful monitoring of the multiple steps in the procedure in order to optimize the final microcell yield. Traditional microscopic verification may sometimes be ambiguous, due to the lack of a clear cutoff point between small whole cells and cell fragments; in these conditions, the level of variability increases, thus impairing quantitative estimations. Flow cytometric (FCM) analysis of DNA content and size of donor cells and microcells was therefore applied in parallel to provide additional quantitative information. The FCM results supplemented the microscopic data in assessing which fraction recovered from the gradient has the lowest percentage of contaminant whole cells; however, FCM analysis may provide more statistically significant data due to the large size of the sample examined. Moreover, FCM is of prospective use in providing the basis for subsequent sorting of either pure microcells or specific subpopulations of defined DNA content and size.
Two enhancer regions in the mouse En-2 locus direct expression to the mid/hindbrain region and mandibular myoblasts (1993)

An En-2/lacZ gene fusion containing 9.5 kb of En-2 genomic DNA was capable of directing lacZ expression in an En-2-specific manner both temporally and spatially during embryogenesis and in the adult. lacZ expression was confined in the embryo to cells within the mid/hindbrain and mandibular arch regions and in the adult to cells of the molecular and granular layers of the cerebellum, and within the pons and colliculi regions. Interestingly, in the adult, transgene expression patterns within the cerebellum in two lines appeared to mark distinct anterior-posterior compartments. Analysis of the expression pattern of this transgene, in fetal and adult mice lacking a functional En-2 protein, provided evidence that the En-2 gene in mouse is not autoregulated. Deletion analysis of the En-2 genomic region and the use of a heterologous promoter identified two enhancer-containing regions of 1.5 and 1.0 kb in length, 5' of the transcribed sequences, which independently directed expression in the embryo to either the mid/hindbrain region or mandibular myoblasts, respectively. The 1.5 kb fragment contains the most anterior neural enhancer and the 1.0 kb fragment, the earliest myogenic enhancer thus far characterized. These En-2-specific regulatory regions can now be used in a biochemical analysis to identify proteins important in anterior-posterior patterning of the vertebrate CNS and in the specification of muscle identity as well as in a mutational analysis to direct expression of other developmentally important genes to these regions.
Dysphagia and aspiration pneumonia in older adults (2010)

Numerous physical, cognitive, or environmental factors have been identified as predictors of aspiration pneumonia. Knowledge of clinical features, treatments, and prevention will help NPs improve outcomes in older adults with aspiration pneumonia; especially those in long-term care.
Targeted human cytolytic fusion proteins at the cutting edge: harnessing the apoptosis-inducing properties of human enzymes for the selective elimination of tumor cells (2019)

Patient-specific targeted therapy represents the holy grail of anti-cancer therapeutics, allowing potent tumor depletion without detrimental off-target toxicities. Disease-specific monoclonal antibodies have been employed to bind to oncogenic cell-surface receptors, representing the earliest form of immunotherapy. Targeted drug delivery was first achieved by means of antibody-drug conjugates, which exploit the differential expression of tumor-associated antigens as a guiding mechanism for the specific delivery of chemically-conjugated chemotherapeutic agents to diseased target cells. Biotechnological advances have expanded the repertoire of immunology-based tumor-targeting strategies, also paving the way for the next intuitive step in targeted drug delivery: the construction of recombinant protein drugs consisting of an antibody-based targeting domain genetically fused with a cytotoxic peptide, known as an immunotoxin. However, the most potent protein toxins have typically been derived from bacterial or plant virulence factors and commonly feature both off-target toxicity and immunogenicity in human patients. Further refinement of immunotoxin technology thus led to the replacement of monoclonal antibodies with humanized antibody derivatives, including the substitution of non-human toxic peptides with human cytolytic proteins. Preclinically tested human cytolytic fusion proteins (hCFPs) have proven promising as non-immunogenic combinatory anti-cancer agents, however they still require further enhancement to achieve convincing candidacy as a single-mode therapeutic. To date, a portfolio of highly potent human toxins has been established; ranging from microtubule-associated protein tau (MAP tau), RNases, granzyme B (GrB) and death-associated protein kinase (DAPk). In this review, we discuss the most recent findings on the use of these apoptosis-inducing hCFPs for the treatment of various cancers.
A Newly Identified Member of the Tumor Necrosis Factor Receptor Superfamily with a Wide Tissue Distribution and Involvement in Lymphocyte Activation (1997)

The tumor necrosis factor receptor (TNFR) superfamily consists of approximately 10 characterized members of human proteins. We have identified a new member of the TNFR superfamily, TR2, from a search of an expressed sequence tag data base. cDNA cloning and Northern blot hybridization demonstrated multiple mRNA species, of which a 1.7-kilobase form was most abundant. However, TR2 is encoded by a single gene which, maps to chromosome 1p36.22-36.3, in the same region as several other members of the TNFR superfamily. The most abundant TR2 open reading frame encodes a 283-amino acid single transmembrane protein with a 36-residue signal sequence, two perfect and two imperfect TNFR-like cysteine-rich domains, and a short cytoplasmic tail with some similarity to 4-1BB and CD40. TR2 mRNA is expressed in multiple human tissues and cell lines and shows a constitutive and relatively high expression in peripheral blood T cells, B cells, and monocytes. A TR2-Fc fusion protein inhibited a mixed lymphocyte reaction-mediated proliferation suggesting that the receptor and/or its ligand play a role in T cell stimulation.
Improved amplitude preservation for prestack depth migration by inverse scattering theory (2001)

A prestack reverse time‐migration image is not properly scaled with increasing depth. The main reason for the image being unscaled is the geometric spreading of the wavefield arising during the back‐propagation of the measured data and the generation of the forward‐modelled wavefields. This unscaled image can be enhanced by multiplying the inverse of the approximate Hessian appearing in the Gauss–Newton optimization technique. However, since the approximate Hessian is usually too expensive to compute for the general geological model, it can be used only for the simple background velocity model.We show that the pseudo‐Hessian matrix can be used as a substitute for the approximate Hessian to enhance the faint images appearing at a later time in the 2D prestack reverse time‐migration sections. We can construct the pseudo‐Hessian matrix using the forward‐modelled wavefields (which are used as virtual sources in the reverse time migration), by exploiting the uncorrelated structure of the forward‐modelled wavefields and the impulse response function for the estimated diagonal of the approximate Hessian. Although it is also impossible to calculate directly the inverse of the pseudo‐Hessian, when using the reciprocal of the pseudo‐Hessian we can easily obtain the inverse of the pseudo‐Hessian. As examples supporting our assertion, we present the results obtained by applying our method to 2D synthetic and real data collected on the Korean continental shelf.
A Synthesis of Racemic Thalidomide (2003)

Abstract A synthesis of racemic thalidomide is described using formal [3+3] cycloaddition strategy as the key step. The total yield of thalidomide was 30% in three steps from ester 2.
The Impact of Optimized Daylight and Views on the Sleep Duration and Cognitive Performance of Office Workers (2020)

A growing awareness has recently emerged on the health benefits of exposure to daylight and views. Daylight exposure is linked to circadian rhythm regulation, which can have significant impacts on sleep quality and cognitive function. Views of nature have also been shown to impact emotional affect and performance. This study explores the impact of optimized daylight and views on the sleep and cognitive performance of office workers. Thirty knowledge workers spent one week working in each of two office environments with identical layouts, furnishings, and orientations; however, one was outfitted with electrochromic glass and the other with traditional blinds, producing lighting conditions of 40.6 and 316 equivalent melanopic lux, respectively. Participants in the optimized daylight and views condition slept 37 min longer as measured by wrist-worn actigraphs and scored 42% higher on cognitive simulations designed to test their higher order decision-making performance. Both sleep and cognitive function were impacted after one day in the space, yet the impacts became more significant over the course of the week. The positive effect of optimized daylight and views on cognitive function was comparable for almost all participants, while increases in sleep duration were significantly greater for those with the lowest baseline sleep duration. This study stresses the significance of designing with daylight in order to optimize the sleep quality and performance of office workers.
EPIDEMIOLOGIC AND SEROLOGIC STUDIES OF E. COLI 04:H5 IN A PREMATURE NURSERY (1968)

A multiple drug-resistant strain of E. coli, serotype 04:H5, was found to be prevalent as a commensal organism among newborns in a premature nursery. Rectal colonization occurred earliest at 2 days of life (average 12 days) and continued up to 6 months. The umbilicus and throat also were often colonized. The organism was not found in the nursery environment; on rectal, vaginal or throat swabs from the mothers; or from rectal and throat cultures of nursery personnel. It was concluded that transmission probably occurred via the nurses' hands. Serological studies using indirect hemagglutination showed that most of the maternal bloods had significant titers, whereas the cord bloods did not. All of 27 colonized babies showed significant titer increases, and 11 non-colonized babies with measurable cord blood titers subsequently showed a decrease. There was no relationship between antibody level and occurrence or termination of colonization. The only disease manifestation of the study strain was that of urinary tract infection in two colonized male babies who had normal genitourinary systems.
Synthesis of micro and nano-sized calcium carbonate particles and their applications (2014)

This paper is an authoritative review of the synthesis of nano and micro-sized calcium carbonate particles and their applications.
Defective zonae pellucidae in Zp2-null mice disrupt folliculogenesis, fertility and development (2001)

All vertebrate eggs are surrounded by an extracellular matrix. This matrix is known as the zona pellucida in mammals and is critically important for the survival of growing oocytes, successful fertilization and the passage of early embryos through the oviduct. The mouse zona pellucida is composed of three glycoproteins (ZP1, ZP2 and ZP3), each encoded by a single copy gene. Using targeted mutagenesis in embryonic stem cells, Zp2-null mouse lines have been established. ZP1 and ZP3 proteins continue to be synthesized and form a thin zona matrix in early follicles that is not sustained in pre-ovulatory follicles. The abnormal zona matrix does not affect initial folliculogenesis, but there is a significant decrease in the number of antral stage follicles in ovaries isolated from mice lacking a zona pellucida. Few eggs are detected in the oviduct after stimulation with gonadotropins, and no two-cell embryos are recovered after mating Zp2-null females with normal male mice. The structural defect is more severe than that observed in Zp1-null mice, which have decreased fecundity, but not quite as severe as that observed in Zp3-null mice, which never form a visible zona pellucida and are sterile. Although zona-free oocytes matured and fertilized in vitro can progress to the blastocyst stage, the developmental potential of blastocysts derived from either Zp2- or Zp3-null eggs appears compromised and, after transfer to foster mothers, live births have not been observed. Thus, in addition to its role in fertilization and protection of early embryos, these data are consistent with the zona pellucida maintaining interactions between granulosa cells and oocytes during folliculogenesis that are critical to maximize developmental competence of oocytes.
Intracellular Delivery of a Cytolytic T-Lymphocyte Epitope Peptide by Pertussis Toxin to Major Histocompatibility Complex Class I without Involvement of the Cytosolic Class I Antigen Processing Pathway (1999)

A CD8(+) cytolytic T-lymphocyte (CTL) response to antigen-presenting cells generally requires intracellular delivery or synthesis of antigens in order to access the major histocompatibility complex (MHC) class I processing and presentation pathway. To test the ability of pertussis toxin (PT) to deliver peptides to the class I pathway for CTL recognition, we constructed fusions of CTL epitope peptides with a genetically detoxified derivative of PT (PT9K/129G). Two sites on the A (S1) subunit of PT9K/129G tolerated the insertion of peptides, allowing efficient assembly and secretion of the holotoxin fusion by Bordetella pertussis. Target cells incubated with these fusion proteins were specifically lysed by CTLs in vitro, and this activity was shown to be MHC class I restricted. The activity was inhibited by brefeldin A, suggesting a dependence on intracellular trafficking events, but was not inhibited by the proteasome inhibitors lactacystin and N-acetyl-L-leucyl-L-leucyl-L-norleucinal (LLnL). Furthermore, the activity was present in mutant antigen-presenting cells lacking the transporter associated with antigen processing, which transports peptides from the cytosol to the endoplasmic reticulum for association with MHC class I molecules. PT may therefore bypass the proteasome-dependent cytosolic pathway for antigen presentation and deliver epitopes to class I molecules via an alternative route.
Cesium Lead Halide Perovskites with Improved Stability for Tandem Solar Cells (2016)

A semiconductor that can be processed on a large scale with a bandgap around 1.8 eV could enable the manufacture of highly efficient low cost double-junction solar cells on crystalline Si. Solution-processable organic-inorganic halide perovskites have recently generated considerable excitement as absorbers in single-junction solar cells, and though it is possible to tune the bandgap of (CH3NH3)Pb(BrxI1-x)3 between 2.3 and 1.6 eV by controlling the halide concentration, optical instability due to photoinduced phase segregation limits the voltage that can be extracted from compositions with appropriate bandgaps for tandem applications. Moreover, these materials have been shown to suffer from thermal degradation at temperatures within the processing and operational window. By replacing the volatile methylammonium cation with cesium, it is possible to synthesize a mixed halide absorber material with improved optical and thermal stability, a stabilized photoconversion efficiency of 6.5%, and a bandgap of 1.9 eV.
Tat protein of human immunodeficiency virus type 1 represses expression of manganese superoxide dismutase in HeLa cells. (1993)

Using a HeLa cell line stably transfected with the tat gene from human immunodeficiency virus type 1, we have found that the expression of the regulatory Tat protein suppresses the expression of cellular Mn-containing superoxide dismutase (Mn-SOD). This enzyme is one of the cell's primary defenses against oxygen-derived free radicals and is vital for maintaining a healthy balance between oxidants and antioxidants. The parental HeLa cells expressed nearly equivalent amounts of Cu,Zn- and Mn-SOD isozymes. Those cells expressing the Tat protein, however, contained 52% less Mn-SOD activity than parental cells, whereas that of the Cu,Zn enzyme was essentially unchanged. The steady-state levels of Mn-SOD-specific RNAs were also lower in the HeLa-tat cell line than in the parental line. No difference was seen in the steady-state levels of Cu,Zn-SOD-specific RNAs. In addition to the decreased Mn-SOD-activity, HeLa-tat cell showed evidence of increased oxidative stress. Carbonyl proteins were markedly higher, and total cellular sulfhydryl content decreased in cell extracts at a faster rate, probably reflecting ongoing lipid peroxidation. HeLa and HeLa-tat extracts were incubated with radiolabeled Mn-SOD transcripts, and the reaction products were subjected to UV crosslinking, digestion with ribonuclease A, and electrophoretic analysis. The results suggest a direct interaction between Tat protein and Mn-SOD gene transcripts.
Regulation of Hemopoiesis by Bone Marrow Stromal Cells and Their Products (1990)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Visual Comparison of Hierarchically Organized Data (2008)

Abstract We provide a novel visualization method for the comparison of hierarchically organized data. Our technique visualizes a pair of hierarchies that are to be compared and simultaneously depicts how these hierarchies are related by explicitly visualizing the relations between matching subhierarchies. Elements that are unique to each hierarchy are shown, as well as the way in which hierarchy elements are relocated, split or joined. The relations between hierarchy elements are visualized using Hierarchical Edge Bundles (HEBs). HEBs reduce visual clutter, they visually emphasize the aforementioned splits, joins, and relocations of subhierarchies, and they provide an intuitive way in which users can interact with the relations. The focus throughout this paper is on the comparison of different versions of hierarchically organized software systems, but the technique is applicable to other kinds of hierarchical data as well. Various data sets of actual software systems are used to show how our technique can be employed to easily spot splits, joins, and relocations of elements, how sorting both hierarchies with respect to each other facilitates comparison tasks, and how user interaction is supported.
Towards Bright and Fast Lu3Al5O12:Ce,Mg Optical Ceramics Scintillators (2016)

The recent advent of Lu 3 Al 5 O 12 :Ce optical ceramics marks a turning point in scintillator material technology. Because of their lower preparation temperature, brightness, and robustness such materials can now compete with single crystals. Their further scintillation efficiency optimization includes the thorough control of the defects responsible for optical and scintillation losses. The choice of sintering agent appears critical to achieve both high optical transparency and scintillation performance. In this work, the optical investigations coupled with X‐ray absorption near‐edge spectroscopy evidence the beneficial role of MgO sintering agent. Mg 2+ co‐dopants in ceramics drive the partial conversion of Ce 3+ to Ce 4+ . The Ce 4+ center, however, does not impair the scintillation performance due to its capability to positively influence the scintillation process. The importance of simultaneous application of such co‐doping and annealing treatment is also demonstrated. With 0.3 at% Mg, our ceramics display a light yield of ≈25000 photons/MeV with short 1 μs shaping time, a relative fast component intensity as high as 60%, and very low afterglow. Such performances are better than those of the isostructural single crystals ever reported. We discuss the role of co‐doping and annealing in the scintillation mechanism that make such combined treatments a positive strategy for material engineering.
The raven's progressive matrices:Its usefulness for identifying gifted/talented students (1993)

(1993). The raven's progressive matrices: Its usefulness for identifying gifted/talented students. Roeper Review: Vol. 15, Longitudinal Studies in Gifted Education, pp. 183-186.