gebhart/patrepeval huggingface dataset:
Safety of Targeting ROR1 in Primates with Chimeric Antigen Receptor–Modified T Cells (2014)

Genetic engineering of T cells for adoptive transfer by introducing a tumor-targeting chimeric antigen receptor (CAR) is a new approach to cancer immunotherapy. A challenge for the field is to define cell surface molecules that are both preferentially expressed on tumor cells and can be safely targeted with T cells. The orphan tyrosine kinase receptor ROR1 is a candidate target for T-cell therapy with CAR-modified T cells (CAR-T cells) because it is expressed on the surface of many lymphatic and epithelial malignancies and has a putative role in tumor cell survival. The cell surface isoform of ROR1 is expressed in embryogenesis but absent in adult tissues except for B-cell precursors and low levels of transcripts in adipocytes, pancreas, and lung. ROR1 is highly conserved between humans and macaques and has a similar pattern of tissue expression. To determine if low-level ROR1 expression on normal cells would result in toxicity or adversely affect CAR-T cell survival and/or function, we adoptively transferred autologous ROR1 CAR-T cells into nonhuman primates. ROR1 CAR-T cells did not cause overt toxicity to normal organs and accumulated in bone marrow and lymph node sites, where ROR1-positive B cells were present. The findings support the clinical evaluation of ROR1 CAR-T cells for ROR1(+) malignancies and demonstrate the utility of nonhuman primates for evaluating the safety of immunotherapy with engineered T cells specific for tumor-associated molecules that are homologous between humans and nonhuman primates.
Deiodination of Thyroid Hormone by Human Liver (1988)

Liver is an important site for the peripheral production of T3 by outer ring deiodination (ORD) of T4 as well as for the clearance of plasma rT3, which is produced by inner ring deiodination (IRD) of T4 in other tissues. However, little is known about the underlying enzymatic reactions, and current concepts about thyroid hormone deiodination are largely based on studies in rat tissue. Here we describe the results of detailed studies of the catalytic properties of the iodothyronine deiodinase activity of human liver. The results demonstrated a high degree of similarity with the type I deiodinase of rat liver. The enzyme activity was found in the microsomal fraction. rT3 was the preferred substrate, since its ORD was catalyzed roughly 400 times more efficiently than the ORD or IRD of T4 or the IRD of T3. The deiodination of sulfated substrates was more rapid, as demonstrated by the roughly 30-fold increase in the IRD of T3 sulfate (T3S) compared with T3. The deiodinations exhibited ping-pong-type kinetics with dithiothreitol as the cofactor. Inhibition by propylthiouracil was uncompetitive with substrate and competitive with dithiothreitol, and PTU was an equally effective inhibitor of the ORD of rT3 and the IRD of T3S (Ki, 0.10-0.16 mumol/L). Various compounds with widely different inhibitory potencies had similar effects on ORD (rT3) and IRD (T3S). These results suggest that in human liver microsomes a single enzyme catalyzes the deiodination of the outer as well as the inner ring of iodothyronines by the same catalytic mechanism and with the same substrate specificity as the type I deiodinase of rat liver.
Peroxisome Proliferator-Activated Receptors: From Genes to Physiology (2001)

The peroxisome proliferator-activated receptors (PPARalpha, gamma, delta) are members of the nuclear receptor superfamily of ligand-activated transcription factors that have central roles in the storage and catabolism of fatty acids. Although the three PPAR subtypes are closely related and bind to similar DNA response elements as heterodimers with the 9-cis retinoic acid receptor RXR, each subserves a distinct physiology. PPARalpha (NR1C1) is the receptor for the fibrate drugs, which are widely used to lower triglycerides and raise high-density lipoprotein cholesterol levels in the treatment and prevention of coronary artery disease. In rodents, PPARalpha agonists induce hepatomegaly and stimulate a dramatic proliferation of peroxisomes as part of a coordinated physiological response to lipid overload. PPARgamma (NR1C3) plays a critical role in adipocyte differentiation and serves as the receptor for the glitazone class of insulin-sensitizing drugs used in the treatment of type 2 diabetes. In contrast to PPARalpha and PPARgamma, relatively little is known about the biology of PPARdelta (NR1C2), although recent findings suggest that this subtype also has a role in lipid homeostasis. All three PPARs are activated by naturally occurring fatty acids and fatty acid metabolites, indicating that they function as the body's fatty acid sensors. Three-dimensional crystal structures reveal that the ligand-binding pockets of the PPARs are much larger and more accessible than those of other nuclear receptors, providing a molecular basis for the promiscuous ligand-binding properties of these receptors. Given the fundamental roles that the PPARs play in energy balance, drugs that modulate PPAR activity are likely to be useful for treating a wide range of metabolic disorders, including atherosclerosis, dyslipidemia, obesity, and type 2 diabetes.
Immunophenotypic Features of Acute Myeloid Leukemias Overexpressing the Interleukin 3 Receptor Alpha Chain (2004)

In a previous study we have shown that the interleukin-3 receptor alpha chain (IL-3Ralpha) is over expressed in about 45% of acute myeloid leukemias (AMLs) and this phenomenon was associated with high blast cell counts at diagnosis, high rate of cycling of leukemic blasts and with a worse prognosis. Here we have investigated the immunophenotypic features of 125 AML patients subdivided into three groups (IL-3R(high), IL-3R(middle) and IL-3R(low)) according to the level of IL-3Ralpha expression. AMLs over expressing the IL-3Ralpha represent a subgroup of AMLs with a peculiar immunophenotype mainly consisting in the elevated expression of CD34 and several receptor membrane tyrosine kinases, such as c-kit and flt3, and in a usually low expression of myeloid-associated antigens such as CD11b, CD14 and CD15. These findings suggest that IL-3Ralpha + + + AMLs are blocked at an early stage of differentiation and express at elevated levels several growth factor receptors. It is proposed that these findings may further help to understand the mechanisms involved in the development of high-risk acute leukemias.
Neutralizing Monoclonal Antibodies Against Russian Strain of the West Nile Virus (2005)

We have developed a panel of 16 hybridomas secreting neutralizing monoclonal antibodies (Nt- MAbs) to Russian isolate (LEIV-Vlg99-27889-human) of the West Nile virus (WNV). Most of the Nt-Mabs were either IgG1 or IgG3 subtypes. Nine of the 16 neutralizing MAbs detected WNV protein E in Western blot. According to their Nt-activities, Western blot results and cross-reactivity, the MAbs were divided into four groups. Monoclonal antibodies from group I were able to neutralize WNV strains Vlg99-27889, Vlg00-27924, Hp-94, A-1640, A-72, Tur-2914, and Eg101. The Nt-activity of MAbs from groups II-IV towards these WNV strains was variable. Recombinant fragments E(1-180), E(1-321), and E(260-466) of protein E were used for preliminary mapping of domains recognized by Nt-MAbs. Only five Nt-MAbs were able to react with the recombinant polypeptides. The MAbs 9E2, 7G9, 11G3, and 7E6 from group Ia recognized Nt-epitope(s) between amino acids 321 and 466 of protein E and Nt-MAb 4F11 (group III) reacted with residues 1-180. This demonstrates that two discrete regions of protein E are involved in neutralization of WNV. Our data on immunochemical, biological activities of Nt-MAbs and mapping of Nt-epitopes using recombinant polypeptides suggest at least 13 different Nt-epitopes for WNV.
Synporins--synthetic proteins that emulate the pore structure of biological ionic channels. (1990)

A class of proteins that mimic the fundamental pore structure of authentic ionic channels has been designed, synthesized, and characterized. The design is based on our earlier result that a 23-mer peptide with the sequence of the M2 segment of the Torpedo californica acetylcholine receptor delta subunit--Glu-Lys-Met-Ser-Thr-Ala-Ile-Ser-Val-Leu-Leu-Ala-Gln-Ala-Val-Phe -Leu- Leu-Leu-Thr-Ser-Gln-Arg--forms cation-selective channels in lipid bilayers, presumably by self-assembly of conductive oligomers. Accordingly, a tethered parallel tetramer was synthesized with four M2 delta peptides attached to a carrier template--a 9-amino acid backbone with four attachment sites. As expected, the complete 101-residue protein does form channels in lipid bilayers reproducing several features that are characteristic of authentic acetylcholine receptor channels, such as single-channel conductance, cation selectivity, transitions between closed and open states in the millisecond time range, and sensitivity to local anesthetic channel blockers. An analogue protein, in which the serine residue in position 8 is replaced with alanine in each of the four M2 delta 23-mer peptides ([Ala8]M2 delta), also forms channels that, however, exhibit lower single-channel conductance. By contrast, a similar tethered tetramer with M1 delta peptides does not form channels, in accord with expectations. The general validity of this strategy to other channel sequences and oligomer numbers is anticipated. Thus, synporins--a term coined to identify this class of synthetic pore proteins--enrich our armamentarium directed toward the elucidation of structure-function relationships.
LEVANTAMENTO DA CADEIA PRODUTIVA DO PESCADO DO RESERVATÓRIO DE ITAIPU (1999)

A construcao da maior usina hidreletrica do mundo, a Itaipu Binacional, no rio Parana, na fronteira entre Brasil e Paraguai, implicou a criacao de um reservatorio de 1 350 km2, que inundou aproximadamente 900 km2 de terras do lado brasileiro. A pesca comercial foi estimulada com a possibilidade de escoamento da producao criada pela abertura de novas estradas e pelo ingresso na regiao de intermediarios da comercializacao que levavam o pescado para outras cidades do Parana e tambem para outros estados. A atividade e monitorada pela Itaipu Binacional e reflete a preocupacao da empresa pelo fato de a atividade pesqueira nao ter conseguido consolidar-se economicamente, pois os pescadores sao pouco especializados e, como reflexo, o produto pescado tem pouca difusao nos mercados. Atraves de pesquisa de campo tendo por base a analise de cadeia produtiva, este estudo abordou pescadores, intermediarios na venda do peixe e consumidores para diagnosticar os pontos de estrangulamento que criam obstaculos ao desenvolvimento da atividade. Dentre eles, podem ser destacadas as condicoes da pesca (material, barcos e propulsao), condicoes para manutencao do pescado, condicoes da comercializacao, baixo nivel de organizacao dos pescadores, os quais se refletem na pequena difusao do produto no mercado, segmento este que tem no consumidor um agente com restricoes ao consumo do peixe, pelo preco relativamente alto e pelas condicoes de preparo mais exigentes, embora reconheca as qualidades do produto. Palavras-chave: economia da pesca, cadeia produtiva, economia paranaense.
High-sensitivity determination of birefringence in turbid media with enhanced polarization-sensitive optical coherence tomography (2005)

Polarization-sensitive optical coherence tomography provides high-resolution cross-sectional characterization of birefringence in turbid media. Weakly birefringent biological tissues such as the retinal nerve fiber layer (RNFL) require advanced speckle noise reduction for high-sensitivity measurement of form birefringence. We present a novel method for high-sensitivity birefringence quantification by using enhanced polarization-sensitive optical coherence tomography (EPS-OCT) and introduce the polarimetric signal-to-noise ratio, a mathematical tool for analyzing speckle noise in polarimetry. Multiple incident polarization states and non-linear fitting of normalized Stokes vectors allow determination of retardation with +/-1 degrees uncertainty with invariance to unknown unitary polarization transformations. Results from a weakly birefringent turbid film and in vivo primate RNFL are presented. In addition, we discuss the potential of EPS-OCT for noninvasive quantification of intracellular filamentous nanostructures, such as neurotubules in the RNFL that are lost during the progression of glaucoma.
Noninvasive prenatal diagnosis of aneuploidy using cell‐free nucleic acids in maternal blood: promises and unanswered questions (2007)

The discovery of cell-free fetal (cff) DNA and RNA in the maternal circulation has driven developments in noninvasive prenatal diagnosis (NIPD) for the past decade. Detection of paternally derived alleles in cff DNA is becoming well established. Now much interest is focussing on NIPD of fetal chromosomal abnormalities, such as trisomy 21, which is a considerable challenge because this demands accurate quantitative measurements of the amounts of specific cff DNA or cff RNA sequences in maternal blood samples. Emerging strategies for distinguishing and quantifying the fetal nucleic acids in the maternal circulation promise continued development of the field, and pose a number of unanswered questions.
The Urbanet Revolution: Sensor Power to the People! (2007)

With mobile devices becoming ubiquitous, the time is ripe to bring sensor data out of close-loop networks into the center of daily urban life. The Internet has become a great success because its applications appeal to regular people. This isn't the case with sensor networks, which are generally perceived as "something" remote in the forest or on the battlefield. With few exceptions, first-generation sensor networks address application-specific, static-sensor deployments to accurately monitor the sensed environment in real time.
Impact of VP1-Specific Protein Sequence Motifs on Adeno-Associated Virus Type 2 Intracellular Trafficking and Nuclear Entry (2012)

Adeno-associated virus type 2 (AAV2) has gained much interest as a gene delivery vector. A hallmark of AAV2-mediated gene transfer is an intracellular conformational change of the virus capsid, leading to the exposure of infection-relevant protein domains. These protein domains, which are located on the N-terminal portion of the structural proteins VP1 and VP2, include a catalytic phospholipase A(2) domain and three clusters of basic amino acids. We have identified additional protein sequence motifs located on the VP1/2 N terminus that also proved to be obligatory for virus infectivity. These motifs include signals that are known to be involved in protein interaction, endosomal sorting and signal transduction in eukaryotic cells. Among different AAV serotypes they are highly conserved and mutation of critical amino acids of the respective motifs led to a severe infection-deficient phenotype. In particular, mutation of a YXXQ-sequence motif significantly reduced accumulation of virus capsids around the nucleus in comparison to wild-type AAV2. Interestingly, intracellular trafficking of AAV2 was shown to be independent of PLA(2) activity. Moreover, mutation of three PDZ-binding motifs, which are located consecutively at the very tip of the VP1 N terminus, revealed a nuclear transport-defective phenotype, suggesting a role in nuclear uptake of the virus through an as-yet-unknown mechanism.
"They're supportive, BUT. . .": Female graduate students and their parents' reactions to graduate education (2009)

In 2001, there were approximately 1.9 million graduate students in American universities, and a majority of them were women. Graduate students are under a considerable amount of stress and strain, and parents can be a source of social support for their children; however, little research has been done regarding graduate students and the support they receive from their parents. The purpose of this study was to explore parents’ reactions to their daughters’ choice to pursue a graduate degree. Data were collected through open-ended interviews with 18 female graduate students. Results indicated that parents’ reactions to their daughter going to graduate school could be placed into five categories that varied in level of supportiveness.
[Colorectal polyps and colorectal cancer]. (2005)

与结直肠癌相关的癌前病变包括结直肠腺瘤、非腺瘤性结直肠息肉病和炎症性肠病,认识这些癌前病变对于结直肠癌的预防、结直肠癌的危险性评估以及结直肠癌的诊断均具有重要意义.新的WHO结直肠癌定义的明确阐述提出了许多必须面对的新问题。
Differential accumulation of transcripts for four tomato 1-aminocyclopropane-1-carboxylate synthase homologs under various conditions. (1992)

Degenerate oligonucleotide primers corresponding to conserved regions flanking the active-site domain of 1-aminocyclopropane-1-carboxylate (ACC) synthase (EC 4.4.1.14) were used for the polymerase chain reaction (PCR) to amplify DNA fragments from mRNA isolated from tomato fruit and tomato suspension cell culture. Antibodies raised against two conserved peptide sequences (TNPSNPLGTT and SLSKDLGLPGFRVG) were used to screen for positive colonies, after the PCR products were cloned into a Bluescript plasmid and expressed in Escherichia coli. Four distinct cDNA fragments encoding ACC synthase homologs were isolated. While pBTAS1 and pBTAS4 were obtained from fruit mRNA, cell culture mRNA yielded three sequences, pBTAS1, pBTAS2, and pBTAS3. Sequencing of these gene fragments revealed that pBTAS1 and pBTAS4 were identical to those full-length sequences previously reported by Van Der Straeten et al. [Van Der Straeten, D., Van Wiemeersch, L., Goodman, H. & Van Montague, M. (1990) Proc. Natl. Acad. Sci. USA 87, 4859-4863] and Olson et al. [Olson, D. C., White, J. A., Edelman, J., Harkin, R. N. & Kende, H. (1991) Proc. Natl. Acad. Sci. USA 88, 5340-5344] from tomato fruit, whereas pBTAS2 and pBTAS3 represent new sequences. Ribonuclease protection assays were used to examine the expression of these transcripts under three different conditions of enhanced ethylene production--namely, during fruit ripening, in response to mechanical wounding in fruit tissue, and auxin stimulation in vegetative tissue. Transcripts of pBTAS1 accumulated massively during ripening and wounding but only slightly in response to auxin treatment. Although pBTAS4 was associated with fruit ripening, it was unresponsive to auxin treatment in vegetative tissue. In contrast, the expression of pBTAS2 and pBTAS3 was greatly promoted in auxin-treated vegetative tissue but was absent from fruit tissue. While the expression of pBTAS2 was moderately dependent on wounding, pBTAS3 was unresponsive to wounding. These data support the view that ACC synthase is encoded by a multigene family and that the members are differentially expressed in response to developmental, environmental, and hormonal factors.
In Vivo Gene Therapy in Young and Adult RPE65-/- Dogs Produces Long-Term Visual Improvement (2003)

Defects in the RPE65 gene, which is selectively expressed in the retinal pigment epithelium (RPE), result in blindness and gradual photoreceptor cell degeneration. Experiments were conducted to assess the efficacy of gene replacement therapy in restoring retinal function in RPE65-/- dogs. Long-term effects of RPE65 gene therapy were assessed using visual behavioral testing and electroretinographic (ERG) recordings at 10-12 weeks and 6-9 months after surgery in five affected dogs. Subretinal injections of similar dosages of two constructs were performed in affected dogs at the ages of 4-30 months: rAAV.RPE65 into one eye and, in four of five dogs, rAAV.GFP contralaterally. Before surgery all RPE65-/- dogs were behaviorally blind with either no or very low-amplitude ERG responses to light stimuli. Marked improvements in visual behavior and ERG responses were observed as early as 4 weeks after surgery in affected animals. Except for light-adapted 50 Hz ERG flicker responses, all ERG parameters tested increased significantly in the eyes treated with the rAAV.RPE65 construct at the early follow-up. Gradual progressive improvements in ERG responses were observed in the RPE65-treated eyes over time. An unexpected finding was that on long-term follow-up, marked improvement of photopic ERG responses were also observed in the contralateral control eye in both young and older dogs. These results are promising for future clinical trials of human patients with retinal degenerative diseases, such as Leber congenital amaurosis, that result from RPE65 gene defects.
HDL-cholesterol and physical performance: results from the ageing and longevity study in the sirente geographic area ( ilSIRENTE Study) (2007)

The present study suggests that among very old subjects living in the community the higher levels of HDL-cholesterol are associated with better functional performance.
Modelling of silver modules incorporating a lambertian rear reflector (2004)

Modules incorporating cells which are bifacial and narrow can make use of rear reflectors to capture most of the incident sunlight while covering only a fraction of the module area with cells. Sliver® cells, invented and developed at the ANU, meet these criteria. In this paper we analyse the performance limits of such modules for the case where a diffuse (lambertian) reflector is used. The analysis is carried out for various cell thicknesses, cell spacings and reflectivities of the lambertian reflector. The results show that excellent performance can be realised despite the simplicity of the structure. A module with a 50% coverage with 70µm thick cells can capture up to 84% of the light entering the module. Importantly, the performance of this kind of module is insensitive to module orientation. The results of the analytical model are compared with ray tracing studies and measurements and are shown to be in good agreement. It is concluded that significant module cost reductions can be achieved for only modest reductions in performance by covering half or less of the module surface with cells.
A pathway to earlier discharge following TAVI: Assessment of safety and resource utilization (2015)

Same/next day discharge can be performed safely in appropriately selected patients. Although this will be achieved in a minority of patients (21.7% in this study using an early discharge pathway) it has potential for resource and cost savings. © 2015 Wiley Periodicals, Inc.
The effect of a novel C5 inhibitor (K-76 COONa) on tumor cell chemotaxis. (1983)

Walker carcinosarcoma cells were cultured as an ascitic tumor in the rat. These cells were studied for their response to human chemotactic factors derived from complement. Complement activation for tumor chemotaxis was performed by reaction of serum with a tumor extract. An anticomplementary agent, K-76 sodium monocarboxylic acid (K-76 COONa), was tested in these systems. It was found to be effective in blocking the formation of a chemotactic factor for tumor cells from human complement at a concentration of 300 micrograms/ml. Addition of K-76 COONa after complement activation had no effect. No effect on random migration of tumor cells was found at concentrations of 500 micrograms/ml. No effect on tumor cell viability was found up to 500 micrograms/ml. At 1000 micrograms/ml there was a 15% decrease in viability (p less than 0.05). Since chemotactic mechanisms (probably from activated complement) may play a role in the movement of tumor cells, this apparently low toxic anticomplementary agent (K-76 COONa) may be of value in the prevention of tumor metastases.
Measurement of diffuse ventricular fibrosis with myocardial T1 in patients with atrial fibrillation (2015)

AF at the time of CMRI was associated with lower post-contrast ventricular T1 compared with sinus rhythm. This effect was at least partly due to elevated heart rate. T1 was not associated with the recurrence of AF after ablation.