gebhart/patrepeval huggingface dataset:
Randomized trial of ibrutinib vs ibrutinib plus rituximab in patients with chronic lymphocytic leukemia (2018)

Ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase, is an effective therapy for patients with chronic lymphocytic leukemia (CLL). To determine whether rituximab provides added benefit to ibrutinib, we conducted a randomized single-center trial of ibrutinib vs ibrutinib plus rituximab. Patients with CLL requiring therapy were randomized to receive 28-day cycles of once-daily ibrutinib 420 mg, either as a single agent (n = 104), or together with rituximab (375 mg/m<sup>2</sup>; n = 104), given weekly during cycle 1, then once per cycle until cycle 6. The primary end point was progression-free survival (PFS) in the intention-to-treat population. We enrolled 208 patients with CLL, 181 with relapsed CLL and 27 treatment-naive patients with high-risk disease (17p deletion or <i>TP53</i> mutation). After a median follow-up of 36 months, the Kaplan-Meier estimates of PFS were 86% (95% confidence interval [CI], 76.6-91.9) for patients receiving ibrutinib, and 86.9% (95% CI, 77.3-92.6) for patients receiving ibrutinib plus rituximab. Similarly, response rates were the same in both arms (overall response rate, 92%). However, time to normalization of peripheral blood lymphocyte counts and time to complete remission were shorter, and residual disease levels in the bone marrow were lower, in patients receiving ibrutinib plus rituximab. We conclude that the addition of rituximab to ibrutinib in relapsed and treatment-naive high-risk patients with CLL failed to show improvement in PFS. However, patients treated with ibrutinib plus rituximab reached their remissions faster and achieved significantly lower residual disease levels. Given these results, ibrutinib as single-agent therapy remains current standard-of-care treatment in CLL. This trial was registered at www.clinicaltrials.gov as #NCT02007044.
Complementary actions of VEGF and Angiopoietin‐1 on blood vessel growth and leakage* (2002)

Vascular endothelial growth factor (VEGF) and Angiopoietins are families of vascular-specific growth factors that regulate blood vessel growth, maturation and function. To learn more about the effects of these factors in vivo, we have overexpressed VEGF-A or Angiopoietin-1 (Ang1) in two systems in mice, and examined the effects on blood vessel growth and function. In one set of studies, VEGF, Ang1, or both factors, were transgenically overexpressed in the skin under the keratin-14 (K14) promoter. The skin of mice overexpressing VEGF (K14-VEGF) had numerous tortuous, capillary-sized vessels which were leaky to the plasma tracer Evans blue under baseline conditions. In contrast, the skin of mice overexpressing Ang1 (K14-Ang1) had enlarged dermal vessels without a significant increase in vessel number. These enlarged vessels were less leaky than those of wild-type mice in response to inflammatory stimuli. In double transgenic mice overexpressing VEGF and Ang1, the size and number of skin vessels were both increased; however, the vessels were not leaky. In a second set of studies, VEGF or Ang1 was systemically delivered using an adenoviral approach. Intravenous injection of adenovirus encoding VEGF (Adeno-VEGF) resulted in widespread tissue oedema within 1-2 days after administration, whereas injection of Adeno-Ang1 resulted in the skin vessels becoming less leaky in response to topical inflammatory stimuli or local injection of VEGF. The decreased leakage was not accompanied by morphological changes. Thus, overexpressing VEGF appears to promote growth of new vessels accompanied by plasma leakage, whereas overexpressing Ang1 promotes the enlargement of existing vessels and a resistance to leakage. Further understanding of the interrelationship of these factors during normal development could lead to their application in the treatment of ischaemic diseases.
Wavelength mutations and posttranslational autoxidation of green fluorescent protein. (1994)

The green fluorescent protein (GFP) of the jellyfish Aequorea victoria is an unusual protein with strong visible absorbance and fluorescence from a p-hydroxybenzylidene-imidazolidinone chromophore, which is generated by cyclization and oxidation of the protein's own Ser-Tyr-Gly sequence at positions 65-67. Cloning of the cDNA and heterologous expression of fluorescent protein in a wide variety of organisms indicate that this unique posttranslational modification must be either spontaneous or dependent only on ubiquitous enzymes and reactants. We report that formation of the final fluorophore requires molecular oxygen and proceeds with a time constant (approximately 4 hr at 22 degrees C and atmospheric pO2) independent of dilution, implying that the oxidation does not require enzymes or cofactors. GFP was mutagenized and screened for variants with altered spectra. The most striking mutant fluoresced blue and contained histidine in place of Tyr-66. The availability of two visibly distinct colors should significantly extend the usefulness of GFP in molecular and cell biology by enabling in vivo visualization of differential gene expression and protein localization and measurement of protein association by fluorescence resonance energy transfer.
Delayed Morbidity and Mortality of Albumin/SV40 T-Antigen Transgenic Mice after Insertion of an α-Fetoprotein/Herpes Virus Thymidine Kinase Transgene and Treatment with Ganciclovir (1994)

The alpha-fetoprotein (AFP) gene is normally expressed in fetal liver and transcriptionally silent in adult tissues, but can be abnormally reactivated in hepatocellular carcinoma (HCC). We linked 7.6 kb of 5'-flanking DNA from the mouse AFP gene to the herpes simplex virus (HSV) thymidine kinase gene (tk), and a line of transgenic mice was produced that expressed TK in a pattern similar to endogenous AFP. When these AFP/tk transgenic mice were crossed to another transgenic line that develops multifocal HCC due to expression of a SV40 large T-antigen transgene under regulation of the albumin promoter/enhancer complex, a significant delay of tumor progression could be achieved by administration of ganciclovir (GCV), a cytotoxic compound that is a substrate for phosphorylation by viral, but not mammalian, TK. Control animals carrying only the tk gene were unaffected by GCV treatment. These results illustrate the feasibility of prophylactic gene therapy for ablation of cancer, utilizing a strategy in which the tk gene is regulated by a promoter expected to be active only in tumor cells.
Data Visualization Using Augmented Reality (2018)

Data visualization in computer science has been limited to computer screens and paper printouts. Often information can be displayed to the user, but it lacks context. Augmented reality technologies enable us to add context to the information. The goal was to experiment with embedding data representations into the physical world using augmented reality. The Unity™ game development platform was chosen to develop the models. C# was used to develop software to retrieve and direct data to user facing objects. It is also used to manipulate graph objects to display new graph data. Unity™ also offers plugins that allow for developers to use the recently released Apple ARKit® APIs for augmented reality development. Several user interactions were developed to allow the user to select and place graphs. To date most of the experiences with augmented reality have been associated with the gaming industry. However, the technology has the possibility to impact a much broader audience. Augmented reality provides a unique way to synthesize data and the physical world in a way rarely seen in computer science. It can provide context to data representing physical objects by visualizing the data in the physical world. The project demonstrates that data can be visualized using augmented reality. One of the most exciting observations is that this method can help contextualize data. Limitations in the augmented reality make some interactions less natural. Placing graphs require a horizontal surface, or extreme model drift is observed. However, the APIs are relatively new, and updates are available that might facilitate better user interactions.
Engineering cysteine mutants to obtain crystallographic phases with a cutinase from Fusarium solani pisi (1993)

Cutinases are extracellular enzymes involved in the disruption of cutine, an insoluble polyester which covers the surface of plants. They belong to a class of serine esterases that are able to hydrolyse fatty acid esters and emulsified triglycerides as efficiently as lipases, but without displaying interfacial activation. Classical crystallographic methods for obtaining heavy-atom derivatives failed, so the cutinase structure has been solved exclusively by the multiple isomorphous replacement method using four Hg derivatives obtained from mutants S4C, S92C, S120C and S129C. Two of these derivatives behaved as expected: (i) the cys mutant of the catalytic Ser S120C, located at the surface of the active site pocket, leads to a good derivative; and (ii) the Hg atom of the derivative obtained with the S92C mutant is completely accessible to the solvent and occupies two alternative positions--consequently a poor derivative results. In contrast, two mutants show an unexpected behaviour: (i) the Hg atom in the S129C mutant was completely buried 10 A below the protein surface and yielded the best derivative; and (ii) a poor quality derivative was obtained with the S4C mutant. Cys 4 belongs to the disordered propeptide 1-16. The Cys 4 bound Hg atom is located in front of the Asp58 side chain, but neither Cys4 nor parts of the propeptide are clearly visible in the electron density maps of the derivative structure.
Biopolymers and biodegradable smart implants for tissue regeneration after spinal cord injury (2003)

Purpose of review This article reviews recent experimental advances in the development of biosynthetic implants for repair of spinal cord injury. Recent findings Various important advances in the development of biosynthetic conduits for spinal cord repair have recently been reported. It was found that implantation of freeze dried alginate sponge into completely transected spinal cord supports axonal regeneration across the lesion site. A poly(lactic-co-glycolic acid) scaffold seeded with neural stem cells has been developed that promotes axonal regeneration across the gap. It was found that polyethylene glycol can reseal damaged spinal cord axons and restore impulse conduction. Findings have been reported that poly-β-hydroxybutyrate conduits in combination with alginate and fibronectin provide neuroprotection for axotomized descending neurones. It has been reported that conduits made of fibronectin mats or fibrin in combination with neurotrophic growth factors promote axonal growth into the grafts. Finally, magnetic resonance imaging after experimental spinal cord injury has been used to monitor regeneration in biosynthetic conduits in vivo over time. Summary Biosynthetic conduits carrying extracellular matrix molecules and different cell lines, and supplemented with neurotrophic growth factors have yielded encouraging results in the treatment of experimental spinal cord injury. These findings provide a basis for further development of techniques aimed at spinal cord repair in humans.
UV ozonation of paraquat (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTUV ozonation of paraquatPhilip C. Kearney, John M. Ruth, Qiang Zeng, and Paul MazzocchiCite this: J. Agric. Food Chem. 1985, 33, 5, 953–957Publication Date (Print):September 1, 1985Publication History Published online1 May 2002Published inissue 1 September 1985https://pubs.acs.org/doi/10.1021/jf00065a044https://doi.org/10.1021/jf00065a044research-articleACS PublicationsRequest reuse permissionsArticle Views189Altmetric-Citations22LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Inactivation of Campylobacter jejuni by chlorine and monochloramine (1986)

Campylobacter jejuni and closely related organisms are important bacterial causes of acute diarrheal illness in the United States. Both endemic and epidemic infections have been associated with consuming untreated or improperly treated surface water. We compared susceptibility of three C. jejuni strains and Escherichia coli ATCC 11229 with standard procedures used to disinfect water. Inactivation of bacterial preparations with 0.1 mg of chlorine and 1.0 mg of monochloramine per liter was determined at pH 6 and 8 and at 4 and 25 degrees C. Under virtually every condition tested, each of the three C. jejuni strains was more susceptible than the E. coli control strain, with greater than 99% inactivation after 15 min of contact with 1.0 mg of monochloramine per liter or 5 min of contact with 0.1 mg of free chlorine per liter. Results of experiments in which an antibiotic-containing medium was used suggest that a high proportion of the remaining cells were injured. An animal-passaged C. jejuni strain was as susceptible to chlorine disinfection as were laboratory-passaged strains. These results suggest that disinfection procedures commonly used for treatment of drinking water to remove coliform bacteria are adequate to eliminate C. jejuni and further correlate with the absence of outbreaks associated with properly treated water.
Radiosensitization of Human Fibroblasts by 3-Aminobenzamide: An Inhibitor of Poly(ADP-Ribosylation) (1985)

The poly(ADP-ribose) synthetase inhibitor 3-aminobenzamide (3AB) increases the radiosensitivity of normal human fibroblasts in tissue culture in a dose-dependent manner at noncytotoxic concentrations. 3AB was also found to inhibit the repair of potentially lethal damage as well as the recovery occurring when radiation was delivered as fractionated vs single exposures. However, repair as measured by an increased survival when radiation is delivered at low dose rate compared to high dose rate was not effected by 3AB administration.
Harnessing Protease Activity to Improve Cancer Care (2017)

Proteolysis plays critical roles in normal and pathologic physiology; these enzymes are intricately involved in cancer progression and spread. Our understanding of protease function has advanced from nonspecific degrading enzymes to a modern appreciation of their diverse roles in posttranslational modification and signaling in a complex microenvironment. This new understanding has led to next-generation diagnostics and therapeutics that exploit protease activity in cancer. For diagnostics, protease activity may be measured as a biomarker of cancer, with wide-ranging utility from early detection to monitoring therapeutic response. Therapeutically, while broad inhibition of protease activity proved disappointing, new approaches that more specifically modulate proteases in concert with secondary targets might enable potent combination therapies. In addition, clinical evaluation is underway for tools that leverage protease activity to activate therapeutics, ranging from imaging agents that monitor surgical margins to immunotherapies with improved specificity. Technologies that interact with, measure, or modulate proteases are poised to improve cancer management on diagnostic and therapeutic fronts to realize the promise of precision medicine.
Interleukin-12 Overcomes Paclitaxel-Mediated Suppression of T-Cell Proliferation (1998)

The antineoplastic agent paclitaxel (TAXOL) is a potent inhibitor of tumor cell division and a useful chemotherapeutic for the treatment of refractory ovarian and breast carcinoma. Multiple immune system actions have been ascribed to paclitaxel, including the capacity to induce macrophage antitumor cytotoxic molecule production. However, T-cells are susceptible to paclitaxel's cytostatic functions, and no studies have investigated the effects of direct paclitaxel administration on lymphocyte function in the tumor-bearing host (TBH). Because paclitaxel is currently used as an antitumor chemotherapeutic agent and tumor growth alters leukocyte functions, we assessed T-cell function following chemotherapeutic-type paclitaxel treatment. Paclitaxel administration significantly compromised the proliferative capacity of both normal host and TBH lymphocytes in vitro. Although tumor growth impaired T-cell interferon-gamma (IFN-gamma) production, paclitaxel treatment did not alter IFN-gamma. We speculate that the immunostimulatory cytokine interleukin-12 (IL-12), which promoted T-cell activation and proliferation, was capable of reversing paclitaxel-mediated immunosuppression. Exogenous IL-12 fully reconstituted proliferative reactivity and enhanced IFN-gamma production by both normal host and TBH lymphocytes in vitro. Collectively, these data suggest that chemotherapeutic paclitaxel regimens impart significant but reversible inhibition of lymphocyte populations, and IL-12 may be a useful ancillary immunotherapeutic to overcome paclitaxel-induced modulation of lymphocyte activities.
Tunable coupling regimes of silicon microdisk resonators using MEMS actuators (2006)

Tunable coupling regimes of a silicon microdisk resonator controlled by MEMS (microelectromechanical system) actuation are demonstrated for the first time. By varying the gap spacing between the waveguide and the disk, this microresonator can dynamically operate in either under-, ciritcal or over-coupling regime. The waveguide transmittance is suppressed by 30 dB in critical coupling, and the quality factor of the microdisk is measured to be as high as 10(5). Additionally, the microdisk presents tunable group delay from 27 ps to 65 ps, and tunable group velocity dispersion from 185 ps/nm to 1200 ps/nm. Waveguides, microdisks and actuators are all integrated on a silicon-on-insulator (SOI) substrate. This compact device exhibits the promise to construct resonator-based reconfigurable photonic integrated circuits.
Photodynamic therapy with low-strength ALA, repeated applications and short contact periods (40-60 minutes) in acne, photoaging and vitiligo. (2009)

Topical aminolevulinic acid (ALA) photodynamic therapy (PDT) is currently being used for the treatment of actinic keratosis of the face and scalp. This study reports the results obtained after three to four treatments with ALA-PDT in patients with acne (n=12), photoaging (n=8) and vitiligo (n=6). ALA was applied on large areas (e.g., full face) and at very low strengths (1-2%). Side effects were minimal and self-limited.
El laboratorio en la vigilancia, el control y la investigación de la rabia en España. La experiencia del Centro Nacional de Microbiología (2021)

España presenta una situación peculiar Europa, ya que nunca se vio afectada por la epizootia europea de rabia vulpina, pero mantiene un tráfico intenso de bienes y personas con territorios altamente endémicos del norte de África, e incluso fronteras terrestres en Ceuta y Melilla, lo que nos coloca en una situación vulnerable en cuanto a importación de casos. Por otra parte, sabemos de la presencia de dos de los lisavirus de murciélago europeos en nuestro territorio. El laboratorio es un elemento esencial en la vigilancia que se hace imprescindible ante esta situación. El Centro Nacional de Microbiología lleva más de treinta años actuando de laboratorio nacional de referencia en apoyo de los laboratorios autonómicos existentes y haciendo diagnóstico para el resto del territorio, además de representar a España en la red europea de laboratorios RABNET. Así, en el CNM se han diagnosticado y caracterizado la gran mayoría de los casos declarados en España en este período, tanto de rabia de murciélagos, como de rabia importada animal y humana. De manera complementaria a esta actividad de vigilancia, se realizan investigaciones tanto sobre rabia canina como de murciélagos, que, desde hace años, se han ampliado a otros agentes víricos asociados a murciélagos.
Increased Circulating HLA‐DR+CD4+ T Cells in Systemic Lupus Erythematosus: Alterations Associated with Prednisolone Therapy (1990)

Patients with active systemic lupus erythematosus (SLE) in the circulation have a selective increase of a subset of the CD4+ helper/inducer T cells bearing HLA-DR+, major histocompatibility complex class II antigens. We studied prednisolone-induced alterations of HLA-DR+, CD4+, and CD8+ T-cell subsets in three patients with active SLE. Prednisolone therapy was accompanied by a drastic reduction in circulating HLA-DR+, CD4+ T-cell subsets, serum anti-DNA titre, normalization of the serum immunoglobulin profile, and CD4+ T-cell responses to phytohaemagglutinin and concanavalin A. These changes in immune functions were associated with eventual improvement in the clinical condition of active SLE. A low percentage of HLA-DR+, CD8+ T-cell subsets was present in the circulation, which was not changed by prednisolone therapy. These results suggest that HLA-DR+, CD4+ T-cell subsets play a major role in the pathogenesis of active SLE, and that prednisolone-induced immunosuppression in this disease is mediated by changes in the HLA-DR+, CD4+ T-cell subsets in circulating blood.
Pentapeptide nuclear localization signal in adenovirus E1a. (1987)

The adenovirus E1a gene products are nuclear proteins important in transcriptional control of viral functions during infection. By producing normal E1a proteins and derivatives of E1a in bacteria and microinjecting these proteins into cultured cells, we were able to examine their ability to localize to the nucleus. We showed that a short peptide sequence at the carboxyl terminus of E1a is necessary for the rapid (30-min) nuclear localization of that protein. Additionally, we showed that just the last five amino acids of E1a are sufficient to direct nuclear accumulation of a heterologous protein, Escherichia coli galactokinase, with the same kinetics as native E1a. The mechanism by which this pentamer mediates rapid nuclear localization was examined by testing the ability of a galactokinase derivative which has no signal pentamer to exit the nucleus, as well as to enter it. Because neither free entry nor exit was detected, the effect of the signal is unlikely to be through increased nuclear retention of freely diffusible proteins but rather by enhancement of entry into the nucleus.
Multiple input/multiple output (MIMO) equalization for space-time block coding (2003)

In this paper, we propose to combine space-time block codes (ST-BC) with multiple input multiple output equalizer (MIMO-EQ) for achieving transmit diversity in a frequency selective Rayleigh fading channel. In the proposed system, MIMO-EQ equalizes the channel into a temporal intersymbol interference (ISI)-free channel, and then a simple linear processing is used to perform the maximum likelihood (ML) decoding for ST-BC. Our simulation results show that the proposed system can achieve the full spatial diversity gain.