gebhart/patrepeval huggingface dataset:
Differential Expression of E-Cadherin in Lobular and Ductal Neoplasms of the Breast and Its Biologic and Diagnostic Implications (2001)

We studied the pattern of E-cadherin expression in 183 invasive carcinomas (100 ductal, 42 lobular, 41 with mixed ductal and lobular features) and 198 in situ carcinomas (131 ductal, 53 lobular, 14 in situ with ductal and lobular features) by immunohistochemistry. We found a highly significant correlation of E-cadherin membrane expression with the histologic phenotype of the tumors. While moderate to strong membrane expression of E-cadherin was seen in all invasive and in situ ductal carcinomas, 41 of 42 invasive and 50 of 53 in situ lobular carcinomas showed complete loss of expression. All in situ carcinomas diagnosed histologically as showing mixed ductal and lobular features demonstrated complete loss of staining. Invasive carcinomas with ductal and lobular features showed 3 staining patterns: (1) complete or almost complete lack of membrane staining similar to that seen in lobular carcinomas, (2) uniform membrane expression throughout the tumor similar to ductal carcinomas, and (3) focal loss of E-cadherin staining, which correlated well with the histologic impression of focal lobular features. In tumors with histologically equivocal features, immunohistochemical detection of E-cadherin expression can be a useful diagnostic tool for the differentiation of ductal and lobular carcinomas of the breast.
Thymosin- beta 4 gene. Preliminary characterization and expression in tissues, thymic cells, and lymphocytes. (1989)

A cDNA for rat thymosin-beta 4 was used to investigate the expression of this gene in different tissues, thymic cells, and lymphocytes. Hybridization analysis of total RNA from 13 rat tissues demonstrated the presence of an 800 nucleotides-long mRNA in all the tissues surveyed, with the highest levels in spleen, thymus, and lung. Examination of thymic cells showed that the thymosin-beta 4 gene is predominantly expressed in thymocytes. The thymosin-beta 4 mRNA was also studied in Ig+ and Ig- lymphocytes, being fourfold more abundant in Ig- than Ig+ splenic lymphocytes, whereas similar levels were found in both types of blood cells. The analysis of RNA from T cells at different maturation stages evidenced slight differences in their thymosin-beta 4 mRNA content, indicating that thymosin-beta 4 gene expression is not clearly related to the differentiation process of T cells. All these results do not support the roles for thymosin-beta 4 in cellular immunity and differentiation of lymphoid cells, suggesting a more general function for this peptide. Preliminary characterization of the human beta 4 gene by restriction analysis disclosed a complicated pattern consistent with multiple genes and/or introns. The analysis of genomic DNA from different species ranging from humans to Escherichia coli showed that this gene is only highly conserved in mammals.
IL-15 induces antigen-independent expansion and differentiation of human naive CD8+ T cells in vitro (2003)

Recent studies in mice have shown that although interleukin 15 (IL-15) plays an important role in regulating homeostasis of memory CD8+ T cells, it has no apparent function in controlling homeostatic proliferation of naive T cells. We here assessed the influence of IL-15 on antigen-independent expansion and differentiation of human CD8+ T cells. Both naive and primed human T cells divided in response to IL-15. In this process, naive CD8+ T cells successively down-regulated CD45RA and CD28 but maintained CD27 expression. Concomitant with these phenotypic changes, naive cells acquired the ability to produce interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha), expressed perforin and granzyme B, and acquired cytotoxic properties. Primed CD8+ T cells, from both noncytotoxic (CD45RA-CD27+) and cytotoxic (CD45RA+CD27-) subsets, responded to IL-15 and yielded ample numbers of cytokine-secreting and cytotoxic effector cells. In summary, all human CD8+ T-cell subsets had the ability to respond to IL-15, which suggests a generic influence of this cytokine on CD8+ T-cell homeostasis in man.
Discrete Beta-splines (1987)

Goodman (1985) and Joe (1986) have given explicit formulas for (cubic) Beta-splines on uniform knot sequences with varying s1 and s2 values at the knots, and nonuniform knot sequences with varying s2 values at the knots, respectively. The advantage of the latter formula is that it can also be used for knot sequences with multiple knots. Discrete Beta-splines arise when a Beta-spline curve is subdivided, i.e. the knot sequence is refined so that the curve is expressed in terms of a larger number of control vertices and Beta-splines. We prove that discrete Beta-splines satisfy the same properties as discrete B-splines, and present an algorithm for computing discrete Beta-splines and the new control vertices using the explicit formula of Joe (1986).
An Oral SARS-CoV-2 M pro Inhibitor Clinical Candidate for the Treatment of COVID-19 (2021)

The worldwide outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become an established global pandemic. Alongside vaccines, antiviral therapeutics are an important part of the healthcare response to counter the ongoing threat presented by COVID-19. Here, we report the discovery and characterization of PF-07321332, an orally bioavailable SARS-CoV-2 main protease inhibitor with in vitro pan-human coronavirus antiviral activity, and excellent off-target selectivity and in vivo safety profiles. PF-07321332 has demonstrated oral activity in a mouse-adapted SARS-CoV-2 model and has achieved oral plasma concentrations exceeding the in vitro antiviral cell potency, in a phase I clinical trial in healthy human participants. Clinical Trial Registration ID #: NCT04756531
Analysis of lipopolysaccharide-response genes in B-lineage cells demonstrates that they can have differentiation stage-restricted expression and contain SH2 domains. (1996)

Bacterial lipopolysaccharide (LPS) is a potent stimulator of B-cell activation, proliferation, and differentiation. We examined the genetic response of B-lineage cells to LPS via trapping of expressed genes with a gene-trap retrovirus. This analysis showed that expression of only a small fraction of genes is altered during LPS stimulation of B-lineage cells. Isolation of the cellular portion of the trapped LPS-response genes via 5' RACE (rapid amplification of cDNA ends) cloning identified novel genes for all the cloned loci. These novel LPS-response genes were also found to have differentiation stage-restricted expression within the B-lymphoid lineage. That LPS-response genes in B cells also have differentiation stage-restricted expression suggests that these genes may be involved in the control of B-cell function and differentiation, since the known members of this class of genes have frequently been found to play a role in the function and differentiation of B-lineage cells. The isolation of novel members of this class of genes, including a gene that contains a putative SH2 domain, will further increase our understanding of the molecular events involved in the control of B-cell differentiation and function.
Partition Distribution of Aroma Volatiles from Orange Juice into Selected Polymeric Sealant Films (1990)

ABSTRACT The sorption of organic volatiles from orange juice by polymeric food contact materials was investigated. Three sealant films were evaluated, a commercial low density polyethylene and two developmental films, an ethylene vinyl alcohol copolymer of high ethylene content and a co‐polyester. Samples of the films were immersed in the juice for 24 days at 22°C and the level of sorbed volatiles monitored as a function of time. Three probe compounds (d‐limonene, neral and geranial) were selected as being representative of orange juice flavor components. A gas chromatographic technique was developed to quantify the level of probe compounds in juice and films. Results compared favorably to the more traditional bromide‐bromate titration method. Sorption of organic volatiles by one of the developmental films (co‐polyester) was significantly lower than the others.
Genomic imprinting of experience-dependent cortical plasticity by the ubiquitin ligase gene Ube3a (2010)

A defect in the maternal copy of a ubiqutin ligase gene Ube3a can produce a neurodevelopmental defect in human children known as Angelman syndrome. We investigated the role of the maternally expressed Ube3a gene in experience-dependent development and plasticity of the mouse visual system. As demonstrated by optical imaging, rapid ocular dominance (OD) plasticity after brief monocular deprivation (MD) was severely impaired during the critical period (CP) in the visual cortex (VC) of Ube3a maternal-deficient (m-/p+) mice. Prolonged MD elicited significant plasticity in m-/p+ mice that never matched the level seen in control animals. In older animals after the CP, 7-day MD elicited mild OD shifts in both control and m-/p+ mice; however, the OD shifts in m-/p+ mice lacked the strengthening of visual responses to the two eyes characteristic of normal adult plasticity. Anatomic effects of the maternal deficiency include reduced spine density on basal, but not apical, dendrites of pyramidal neurons in the binocular region of the VC. Imprinting of Ube3a expression was not fully established in the early postnatal period, consistent with the normal development of cortical retinotopy and visual acuity that we observed in m-/p+ mice, but was fully established by the onset of the CP. These results demonstrate that paternal and maternal genomes are not functionally equivalent for cortical plasticity, and that maternally expressed Ube3a is required for normal experience-dependent modification of cortical circuits during and after the CP.
Changing the paradigm for cough: does ’cough hypersensitivity’ aid our understanding? (2014)

Chronic cough is a common reason for patients to seek medication attention. Over the last few decades, we have experienced significant clinical success by applying the paradigm of 'evaluating and treating the causes for chronic cough'. However, we still ask ourselves 'what underlies chronic cough. Indeed in a considerable proportion of patients cough is idiopathic, or unexplained despite vigorous evaluation. Commonly associated conditions such as rhinitis, eosinophilic bronchitis, asthma, or gastroesophageal acidic reflux may not be fundamental to cough, and thus may be triggers rather than causes. The cardinal feature of chronic cough is persistent upregulation the cough reflex, which may be driven by complex interactions between biologic, neurologic, immunologic, genetic, comorbid, and environmental factors. We suggest the new paradigm 'cough hypersensitivity syndrome' should finally bring us further advances in understanding and management of chronic cough.
El museo extremeño e iberoamericano de arte contemporáneo de Badajoz: un proyecto museográfico ejemplar (1996)

En el presente texto se estudia el Museo Extremeo
Lysyl Oxidase Inhibits Ras-Mediated Transformation by Preventing Activation of NF-κB (2003)

Lysyl oxidase (LO), which catalyzes the oxidation of lysine residues, was previously shown to have anti-oncogenic activity on ras-transformed cells. Since oncogenic Ras mediates transformation, in part, through the activation of the transcription factor nuclear factor-kappa B (NF-kappa B), we tested here the effects of LO on NF-kappa B activity. Expression of LO in ras-transformed NIH 3T3 cells led to decreased NF-kappa B binding and activity, as well as the expression of the NF-kappa B target gene c-myc. Importantly, ectopic expression of LO led to a dramatic decrease in colony formation by ras-transformed NIH 3T3 cells, a finding comparable to the expression of the I kappa B alpha dominant-negative mutant, which could be rescued by p65/p50 NF-kappa B subunit expression. LO was unable to directly inhibit the activity of ectopically expressed p65 and c-Rel NF-kappa B subunits, suggesting that LO affected an upstream signaling pathway(s) induced by Ras. Consistent with this hypothesis, LO expression decreased both the rate of I kappa B alpha turnover and the activities of IKK alpha and IKK beta. Moreover, the ectopic expression of a constitutively active version of either kinase reversed the negative effects of LO. Ras can induce NF-kappa B via both the phosphatidylinositol 3-kinase (PI3K)/Akt and Raf/MEK pathways. LO potently downregulated the PI3K and Akt kinases, while partially inhibiting MEK kinase activity. Expression of a constitutively activated, myristylated Akt or PDK1 was able to counteract the effect of LO on NF-kappa B, whereas constitutively activated Raf was only partially effective. Importantly, LO blocked membrane localization of Akt and PDK1 in Ras-transformed cells. Overall, these results strongly argue that the anti-oncogenic effects of LO on ras-mediated transformation are due to its ability to inhibit signaling pathways that lead to activation of NF-kappa B.
A binary vector based on Basta resistance for in planta transformation of Arabidopsis thaliana (1993)

Nous decrivons un nouveau vecteur de transformation de plantes, pGKB5, pour l'etiquetage de genes par l'ADN-T chez Arabidopsis thaliana, a l'aide des techniques de transformation in planta. La region ADN-T contient deux marqueurs selectionnables conferant la resistance a la kanamycine et au Basta. Un gene rapporteur β-glucuronidase sans promoteur est accole a la frontiere droite de l'ADN-T, pour realiser des fusions de gene par insertion dans le genome vegetal. La resistance au Basta permet la selection de transformants en serre a haute densite [...]
Student Perceptions of Peer Assessment in an Action Research Context (2004)

A peer assessment method was implemented as part of an action research project where the primary goal was to create constructivist science classrooms. Student reflective writings, which had been created in the process of action research, were analyzed to examine the perceptions of the students concerning the peer assessment method employed in their earth science classrooms. Five perception categories and thirteen statements were developed from the student writings. These indicated that the students appreciated the positive nature of peer assessment and the effects of it as an alternative method for promoting learning. It was also revealed, however, that some students displayed inappropriate behaviors toward peer assessment which led to negative perceptions of the new assessment method. Implications for future use of peer assessment in science classrooms are discussed. Limitations founded in the present study as well as possible solutions are provided.
An estimation of parameters in an energy function used in a simulated annealing method (2003)

When a combinatorial optimization problem such as the traveling salesman problem is solved by a simulated annealing method, it is common to use an energy function that consists of two kinds of terms: a cost term which should be minimized and a constraint term which expresses constraints imposed on solutions. The author proposes a method for determining appropriate values of weights of constraint terms in the annealing process. If appropriate values of parameters expressing the weights of the constraint terms are not given, only solutions which do not satisfy all constraints, or high-cost solutions, can be found. A method is presented that leads to appropriate values of these parameters and finds an optimal solution in a systematic manner. The method was applied to 10-city traveling salesman problems, and the experiments showed the effectiveness of the method.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Natural killer cell‐based immunotherapy in cancer: current insights and future prospects (2009)

As our understanding of the molecular mechanisms governing natural killer (NK) cell activity increases, their potential in cancer immunotherapy is growing increasingly prominent. This review analyses the currently available preclinical and clinical data regarding NK cell-based immunotherapeutic approaches in cancer starting from a historical background and an overview of molecular mechanisms taking part in NK cell responses. The status of NK cells in cancer patients, currently investigated clinical applications such as in vivo modulation of NK cell activity, ex vivo purification/expansion and adoptive transfer as well as future possibilities such as genetic modifications are discussed in detail.
An IP3-activated Ca2+ channel regulates fungal tip growth (2002)

Hyphal extension in fungi requires a tip-high Ca(2+) gradient, which is generated and maintained internally by inositol (1,4,5)-trisphosphate (IP(3))-induced Ca(2+) release from tip-localized vesicles and subapical Ca(2+) sequestration. Using the planar bilayer method we demonstrated the presence of two types of IP(3)-activated Ca(2+) channels in Neurospora crassa membranes with different conductances: one low (13 picosiemens), the other high (77 picosiemens). On sucrose density gradients the low conductance channel co-localized with endoplasmic reticulum and plasma membrane, and the high conductance channel co-localized with vacuolar membranes. We correlated the effect of inhibitors on channel activity with their effect on hyphal growth and Ca(2+) gradients. The inhibitor of IP(3)-induced Ca(2+) release, 2-aminoethoxidiphenylborate (2-APB), inhibits both channels, while heparin, 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate, hydrochloride (TMB-8) and dantrolene inhibit only the large conductance channel. Because 2-APB inhibits hyphal growth and dissipates the tip-high cytosolic [Ca(2+)] gradient, whereas heparin microinjection, TMB-8 and dantrolene treatments do not affect growth, we suggest that the small conductance channel generates the obligatory tip-high Ca(2+) gradient during hyphal growth. Since IP(3) production must be catalyzed by tip-localized phospholipase C, we show that a number of phospholipase C inhibitors [neomycin, 1-[6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]- 1H-pyrrole-2,5-dione (U-73122) (but not the inactive pyrrolidine U-73343), 3-nitrocoumarin] inhibit hyphal growth and affect, similarly to 2-APB, the location of vesicular Ca(2+) imaged by chlortetracycline staining.
Grouting horizontal drainage holes in coalbeds. Report of investigations 1979 (1979)

This report describes a method developed by the Bureau of Mines for sealing horizontal degasification holes so that they do not create a gas explosion hazard when intercepted by mining. A cement slurry is pumped into the hole through an injection pipe that extends to the back of the hole. Pumping continues until the slurry returns through the annulus to the hole collar. The hole is then shut in and the grout allowed to harden. Application of the procedure to six horizontal degasification holes at Eastern Associated Coal Corp.'s Honey Run shaft is discussed.
Endoscopic endonasal surgery of the midline skull base: anatomical study and clinical considerations (2005)

Object The midline skull base is an anatomical area that extends from the anterior limit of the cranial fossa down to the anterior border of the foramen magnum. Resection of lesions involving this area requires a variety of innovative skull base approaches. These include anterior, anterolateral, and posterolateral routes, performed either alone or in combination, and resection via these routes often requires extensive neurovascular manipulation. The goals in this study were to define the application of the endoscopic endonasal approach and to become more familiar with the views and skills associated with the technique by using cadaveric specimens. Methods To assess the feasibility of the endonasal route for the surgical management of lesions in the midline skull base, five fresh cadaver heads injected with colored latex were dissected using a modified endoscopic endonasal approach. Full access to the skull base and the cisternal space around it is possible with this route. From the crista galli to the spinomedullary junction, with incision of the dura mater, a complete visualization of the carotid and vertebrobasilar arterial systems and of all 12 of the cranial nerves is obtainable. Conclusions The major potential advantage of the endoscopic endonasal approach to the skull base is that it provides a direct anatomical route to the lesion without traversing any major neurovascular structures, obviating brain retraction. Many tumors grow in a medial-to-lateral direction, displacing structures laterally as they expand, creating natural corridors for their resection via an anteromedial approach. Potential disadvantages of this procedure include the relatively restricted working space and the danger of an inadequate dural repair with cerebrospinal fluid (CSF) leakage and potential for meningitis resulting. These approaches often require a large opening of the dura mater over the tuberculum sellae and posterior planum sphenoidale, or retroclival space. In addition, they typically involve large intraoperative CSF leaks, which necessitate precise and effective dural closure.
Plastid Transformation in the Monocotyledonous Cereal Crop, Rice (Oryza sativa) and Transmission of Transgenes to Their Progeny (2006)

The plastid transformation approach offers a number of unique advantages, including high-level transgene expression, multi-gene engineering, transgene containment, and a lack of gene silencing and position effects. The extension of plastid transformation technology to monocotyledonous cereal crops, including rice, bears great promise for the improvement of agronomic traits, and the efficient production of pharmaceutical or nutritional enhancement. Here, we report a promising step towards stable plastid transformation in rice. We produced fertile transplastomic rice plants and demonstrated transmission of the plastid-expressed green fluorescent protein (GFP) and aminoglycoside 3'-adenylyltransferase genes to the progeny of these plants. Transgenic chloroplasts were determined to have stably expressed the GFP, which was confirmed by both confocal microscopy and Western blot analyses. Although the produced rice plastid transformants were found to be heteroplastomic, and the transformation efficiency requires further improvement, this study has established a variety of parameters for the use of plastid transformation technology in cereal crops.
The RightPages image-based electronic library for alerting and browsing (1992)

The RightPages electronic library prototype system, which gives users full online library services, is described. The prototype takes advantage of fast hardware, multimedia workstations, and broadband networks to process scientific and technical journals for users and to offer a service that: alerts them to the arrival of new journal articles matching their interest profiles; lets them immediately examine images of pages in the alerted articles and browse through other articles in the database; and enables them to order paper copies of any articles in the database. The system runs on a local area network that connects one or more scanning stations, a centralized document database server and multiple user stations running X Windows servers. The RightPages interface runs as an X Windows application on Sun workstations or X terminals. The system's image and document processing, including noise reduction, document layout analysis, text processing, and display processing are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Dual Targeting of HER2-Positive Cancer with Trastuzumab Emtansine and Pertuzumab: Critical Role for Neuregulin Blockade in Antitumor Response to Combination Therapy (2013)

Dual targeting of HER2 with the combination of T-DM1 and pertuzumab in cell culture and mouse xenograft models resulted in enhanced antitumor activity. In patients, this combination showed an encouraging safety and tolerability profile with preliminary evidence of efficacy.