gebhart/patrepeval huggingface dataset:
Targeting of CD122 enhances antitumor immunity by altering the tumor immune environment (2017)

Mounting evidence demonstrates that CD8<sup>+</sup>CD122<sup>+</sup> T cells have suppressive properties with the capacity to inhibit T cell responses. Therefore, these cells are rational targets for cancer immunotherapy. Here, we demonstrate that CD122 monoclonal antibody (mAb; aCD122) therapy significantly suppressed tumor growth and improved long-term survival in tumor-bearing mice. This therapeutic effect correlated with enhanced polyfunctional, cytolytic intratumoral CD8<sup>+</sup> T cells and a decrease in granulocytic myeloid-derived suppressor cells (G-MDSCs). In addition, aCD122 treatment synergized with a vaccine to augment vaccine-induced antigen (Ag)-specific CD8<sup>+</sup> T cell responses, reject established tumors and generate memory T cells. Furthermore, aCD122 mAb synergized with an anti-GITR (aGITR) mAb to confer significant control of tumor growth. These results suggest CD122 might be a promising target for cancer immunotherapy, either as a single agent or in combination with other forms of immunotherapy.
Nanomaterials engineering for drug delivery: a hybridization approach (2017)

The last twenty years have witnessed great advances in biology, medicine, and materials science, leading to the development of various nanoparticle (NP)-mediated drug delivery systems. Innovation in materials science has led the generation of biodegradable, biocompatible, stimuli-responsive, and targeted delivery systems. However, currently available nanotherapeutic technologies are not efficient, which has culminated in the failure of their clinical trials. Despite huge efforts devoted to drug delivery nanotherapeutics, only a small amount of the injected material could reach the desired target. One promising strategy to enhance the efficiency of NP drug delivery is to hybridize multiple materials, where each component could play a critical role in an efficient multipurpose delivery system. This review aims to comprehensively cover different techniques, materials, advantages, and drawbacks of various systems to develop hybrid nano-vesicles for drug delivery. Attention is finally given to the hybridization benefits in overcoming the biological barriers for drug delivery. It is believed that the advent of modern nano-formulations for multifunctional hybrid carriers paves the way for future advances to achieve more efficient drug delivery systems.
Antileukemic and immunosuppressive activity of 2-chloro-2'-deoxyadenosine. (1984)

The adenosine deaminase-resistant purine deoxynucleoside 2-chloro-2'-deoxyadenosine (CdA) is markedly toxic in vitro to nondividing and proliferating normal human lymphocytes and to many leukemia cell specimens. The CdA is also effective against mouse L1210 leukemia in vivo. The present investigations have examined the pharmacology, chemotherapeutic activity, and toxicity of CdA in nine patients with advanced hematologic malignancies refractory to conventional therapy. When administered by continuous intravenous infusion, the deoxyadenosine analog was well tolerated. As monitored by radioimmunoassay, plasma CdA levels rose gradually during the infusions. The CdA was not deaminated significantly. In all patients with leukemia, the CdA lowered the blast count by at least 50%. In one patient with a T-cell leukemia-lymphoma, and in another patient with chronic myelogenous leukemia in blast crisis, the CdA infusion eliminated all detectable blasts from the blood and bone marrow. In a patient with a diffuse lymphoma complicated by severe autoimmune hemolytic anemia, CdA treatment quickly terminated the hemolytic process. Bone marrow suppression represented the dose-limiting toxicity, and was related to plasma CdA levels, cumulative drug dosage, and the rapid release of CdA that accompanied tumor cell lysis.
Perception of UV-B by the Arabidopsis UVR8 Protein (2011)

To optimize their growth and survival, plants perceive and respond to ultraviolet-B (UV-B) radiation. However, neither the molecular identity of the UV-B photoreceptor nor the photoperception mechanism is known. Here we show that dimers of the UVR8 protein perceive UV-B, probably by a tryptophan-based mechanism. Absorption of UV-B induces instant monomerization of the photoreceptor and interaction with COP1, the central regulator of light signaling. Thereby this signaling cascade controlled by UVR8 mediates UV-B photomorphogenic responses securing plant acclimation and thus promotes survival in sunlight.
Poliomyelitis Viruses in Tissue Culture. IV. Protein-Free Nutrient Media in Stationary and Roller Tube Cultures. (1952)

Poliomyelitis virus may be propagated in test tube, plasma-clot cultures of monkey testicular tissue in the absence of protein in the fluid phase of the nutrient medium. The tubes may be held stationary with the fragments submerged under a thin layer of medium, or they may be turned in a roller drum. The medium used contained lactalbumin enzymatic hydrolysate, serum ultrafiltrate, and balanced salt solution. With such a medium, fibroblasts grow out within 4 days after the cultures are made, and are then suitable for use in virus titrations and neutralization tests in which the presence of virus is indicated by its cytopathogenic effect on the fibroblasts. Also such cultures continue to produce virus for a period of about four weeks, long after the degeneration of the fibroblasts.
An ELISA for tissue factor using monoclonal antibodies (1992)

Whereas tissue factor, a high-affinity cell-surface receptor and essential cofactor for the serine protease factor VII is constitutively present in certain tissues such as epithelial tissue, brain and placenta, it is not normally expressed by cells within the vasculature. However, the stimulation of monocytes and endothelial cells by a variety of inflammatory and immunological reactions results in the induction of cell surface tissue factor (TF) expression. TF is also expressed on tumour cells, and may play a role in tumour growth and metastasis formation. To examine the role of TF in these processes we developed monoclonal antibodies to human tissue factor apoprotein. The antibodies were characterized by neutralization of the procoagulant activity and by immunoblotting. With two of these monoclonal antibodies a sandwich ELISA was developed for the rapid quantitation of TF. The sensitivity of the assay permits extensive studies involving the modulation of TF expression on small numbers of cells. The results are comparable to the functional clotting assay as evaluated with unpurified TF and with the tumour cell line MCF-7. For certain applications, monitoring of cellular TF expression by ELISA using anti-TF monoclonal antibodies is preferable because it is not influenced by other coagulation factors or by inhibitors of procoagulant activity on the cells.
Characterization of a gene that is inversely correlated with estrogen receptor expression (ICERE‐1) in breast carcinomas (1998)

Differential display was used to compare patterns of gene expression in two estrogen receptor (ER)-positive breast carcinoma cell lines (MCF7 and T-47D) and two ER-negative breast carcinoma cell lines (MDA-MB-231 and HBL-100). A 377-bp fragment was identified that was overexpressed in the ER-negative cell lines. Sequence analysis of this clone and comparison with the GenBank/EMBL databases indicated that it did not match any genes published previously. The expression pattern of this gene was inversely correlated with the expression of ER and has been termed ICERE-1 (inversely correlated with estrogen receptor expression). A longer clone of ICERE-1 was isolated from a MDA-MB-231 cDNA library and sequence analysis indicated that this 2168-bp cDNA contained an ORF encoding a protein of 234 amino acids that bears little similarity with any previously described protein sequence. Northern blot analysis of a panel of breast cancer cell lines demonstrated that an ICERE-1 mRNA of approximately 2.2 kb was abundantly expressed in the ER-negative breast carcinoma cell lines, MDA-MB-231 and HBL-100, and the ER-negative cell lines. HEC-1-B, HeLa, and 293. Expression of ICERE-1 was absent or minimal in the ER-positive breast carcinoma cell lines MCF7, T-47D, MDA-MB-361, ZR-75-1, BT-474 and BT-20. Reverse transcription/PCR was used to examine ICERE-1 expression in 29 primary breast carcinomas, 15 of which had been designated as ER positive and 14 as ER negative by immunohistochemistry. The expression level of ICERE-1 was significantly lower (P < 0.001) in the ER-positive tumors compared with the ER-negative tumors. The pattern of expression of ICERE-1 indicates that this gene may be involved in tumor biology specific to hormonally unresponsive breast cancers.
Benign breast disease and breast cancer: A case‐control study in a cohort in italy (1991)

Sixty-two cases of invasive breast cancer were identified in a large cohort of women previously treated for biopsy-proven benign breast disease (BBD) at the Breast Unit of CSPO, in Florence, along with a group of 315 controls, strictly matched by age and year of diagnosis. A pathologist reviewed and reclassified all the original BBD slides according to recently proposed criteria (no evidence of epithelial proliferation, epithelial proliferation without or with atypia). Information about potential confounding factors was collected during personal interviews. In comparison to the women with "non-proliferative" BBD, women classified as having "proliferative disease without atypia" showed a weak and non-significant increase in risk (OR 1.3; 95% CI: 0.5-3.5). In contrast, women with "atypical hyperplasia" were at very high risk of developing breast cancer (OR 13.0; 95% CI: 4.1-41.7). When planning mammography screening or other large-scale early-diagnosis programmes for breast cancer in the general female population, follow-up of high-risk subgroups of BBD patients should be considered.
Antitumor effects of ZD6474, a small molecule vascular endothelial growth factor receptor tyrosine kinase inhibitor, with additional activity against epidermal growth factor receptor tyrosine kinase. (2003)

This study suggests that in addition to inhibiting endothelial cell proliferation by blocking VEGF-induced signaling, ZD6474 may also be able to inhibit cancer cell growth by blocking EGFR autocrine signaling. These results provide also a rationale for the clinical evaluation of ZD6474 combined with taxanes in cancer patients.
Transgenic mouse models for myotonic dystrophy type 1 (DM1) (2003)

The study of animal models for myotonic dystrophy type 1 (DM1) has helped us to 'de- and reconstruct' our ideas on how the highly variable multisystemic constellation of disease features can be caused by only one type of event, i.e., the expansion of a perfect (CTG)(n) repeat in the DM1 locus on 19q. Evidence is now accumulating that cell type, cell state and species dependent activities of the DNA replication/repair/recombination machinery contribute to the intergenerational and somatic behavior of the (CTG)(n) repeat at the DNA level. At the RNA level, a gain-of-function mechanism, with dominant toxic effects of (CUG)(n) repeat containing transcripts, probably has a central role in DM1 pathology. Parallel study of DM2, a closely related form of myotonic dystrophy, has revealed a similar mechanism, but also made clear that part of the attention should remain focused on a possible role for candidate loss-of-function genes from the DM1 locus itself (like DMWD, DMPK and SIX5) or elsewhere in the genome, to find explanations for clinical aspects that are unique to DM1. This review will focus on new insight regarding structure-function features of candidate genes involved in DM1 pathobiology, and on the mechanisms of expansion and disease pathology that have now partly been disclosed with the help of transgenic animal models.
Catatonia and Autistic Spectrum Disorders (2004)

The phenomenon of catatonic-like states in people with autistic spectrum disorders is discussed in the context of current knowledge about catatonia as it occurs in severe mental illness and, less frequently documented, in conjunction with developmental disorders. The existing literature on catatonic-like states in people with autistic spectrum disorders is summarized, and it is suggested that such states are not directly comparable with the existing concepts of catatonia. A concept of 'autistic catatonia' is outlined in terms of both its phenomenology and its possible aetiological and maintaining factors. A case study is presented that examines this phenomenon from a cognitive neuropsychological perspective, together with implications for everyday management. The implications of this work for both research and clinical practice are discussed.
Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity. (2001)

Tumor-infiltrating lymphocytes, particularly CD8(+) T cells, could be a manifestation of antitumor immunity. We clinicopathologically analyzed the biological significance of tumor-infiltrating lymphocytes in 221 patients with renal cell carcinoma without preoperative treatments. More abundant infiltration of tumor tissue not only by CD8(+) but also CD4(+) T cells was associated with shorter survival of the patients, because of the positive correlation between the number of lymphocytes and representative tumor grade factors. This suggests that immune cell reactions are more pronounced as the tumor grade/biological malignancy progresses, probably because of increased antigenicity of tumor cells. We next analyzed the proliferative activity of CD8(+) T cells that infiltrated in tumor cell nests, which could also reflect antitumor immunity. Higher labeling index of Ki-67, a proliferation-associated antigen, among CD8(+) T cells in contact to tumor cells was associated with a longer survival by both uni- and multivariate analyses. Our data in human renal cell carcinoma suggest that infiltration of tumor tissue by T cells itself does not denote the efficacy of antitumor immunity because of its dependence on the biological malignancy of tumor cells, but infiltration of tumor tissue by CD8(+) T cells bearing more pronounced proliferative activity could reflect effective antitumor immunity. This concept would be important for future immunotherapy of human cancer.
Screening of Fungi Capable of Degrading Lignocellulose from Plantation Forests (2009)

In an effort to prevent forest fires after the clear cutting of plantation forests, fungi capable of degrading lignocelluloses were isolated to make a fertilizer from the logging waste. Seventy five fungal species were isolated from fruiting bodies and mycelia in plantation forests of South and North Sumatera, Indonesia. Sixty three of the fungi were identified based on the appearance and morphological characteristics of their fruiting bodies and mycelia, as Pycnoporus sanguineus, Dacryopinax spathularia, Schizophyllum commune, Polyporus sp. and Trametes sp. Twenty fungi were categorized as white-rot fungi and 12 as brown-rot fungi. Moreover, isolates 371, 368, 265, 346, 345 and 338 were selected using indicators and tested for the ability to degrade lignin and holo-cellulose in mangium wood meal over 1 to 4 weeks. Results showed that the 6 fungi could degrade lignin and holo-cellulose in wood meal. An increase in incubation time tended to decrease the amounts of lignin and holo-cellulose. Isolate 371 was found to be best at degrading lignin and holo-cellulose in mangium wood meal.
Pre-clinical evaluation of technetium-99m platelet receptor-binding peptide. (1997)

The combination of high in vitro receptor-binding affinity, high thrombus uptake and definitive in vivo images of both femoral vein and pulmonary thrombi show that 99mTc-P748 has considerable potential as a clinical imaging agent for the detection of venous thromboembolism.
Fatigue and depression predict physician visits and work disability in women with primary Sjogren's syndrome: results from a cohort study (2011)

In pSS, lack of stamina and/or depression cause a higher level of individual and societal burden than dry eyes and mouth. Fatigue and depression deserve more recognition as treatment targets in pSS.
The addition of five minor tobacco alkaloids increases nicotine-induced hyperactivity, sensitization and intravenous self-administration in rats (2009)

Several minor tobacco alkaloids have been found to exhibit properties pharmacologically relevant to the addictive profile of tobacco; however, little is known of their effects on a behavioural model of drug addiction. In this study we compared the locomotor and reinforcing effects of intravenous nicotine (30 microg/kg per infusion) vs. a cocktail of nicotine plus five minor alkaloids found in tobacco smoke (anabasine, nornicotine, anatabine, cotinine and myosmine). Rats were initially tested for their locomotor response to nicotine or nicotine plus the minor alkaloids with six intravenous injections over 1 h. We then assessed the spontaneous acquisition of intravenous self-administration with nicotine or nicotine plus the minor alkaloids, under a fixed-ratio 1 schedule followed by responding on a fixed-ratio 5 schedule, progressive-ratio schedule and a single within-session ascending dose-response test. The activity test was repeated following the progressive-ratio phase to assess locomotor sensitization. A second group of rats were then tested on the locomotor procedure to better clarify the role of each individual minor alkaloid in nicotine-induced locomotor activity. Compared to nicotine alone, addition of the minor tobacco alkaloids increased locomotor activity and increased locomotor sensitization following self-administration. During fixed-ratio 5, progressive ratio and the dose-response test, rats receiving nicotine plus the minor alkaloids responded significantly more than those receiving nicotine alone. Testing of each minor alkaloid in the second experiment indicated that anatabine, cotinine and myosmine individually increased nicotine-induced locomotor activity. These results suggest that the minor tobacco alkaloids, particularly anatabine, cotinine and myosmine, may increase the motivation for nicotine and thus facilitate smoking behaviour.
A Novel Time-Frequency Analysis Method for Mechanical Failure Detection (2006)

This research will attempt to analyze the effectiveness of the Empirical Mode Decomposition (EMD) in diagnostics of gearboxes operating under non-stationary rotational speed. For this, a simple software program for signal processing and extraction of mechanical failure detection was developed and tested. The primary aim is to reveal the nonlinear behavior of the system by using time frequency methods as an alternative to Fourier analysis methodology. Both simulated and experimental response data are analyzed by applying EMD and time-frequency analysis. The following examples demonstrate the improvements in the detection of gear faults.
State of the art: diagnostic tools and innovative therapies for treatment of advanced thymoma and thymic carcinoma (2015)

In this review article, state-of-the-art diagnostic tools and innovative treatments of thymoma and thymic carcinoma (TC) are described with special respect to advanced tumour stages. Complete surgical resection (R0) remains the standard therapeutic approach for almost all a priori resectable mediastinal tumours as defined by preoperative standard computed tomography (CT). If lymphoma or germ-cell tumours are differential diagnostic considerations, biopsy may be indicated. Resection status is the most important prognostic factor in thymoma and TC, followed by tumour stage. Advanced (Masaoka-Koga stage III and IVa) tumours require interdisciplinary therapy decisions based on distinctive findings of preoperative CT scan and ancillary investigations [magnetic resonance imaging (MRI)] to select cases for primary surgery or neoadjuvant strategies with optional secondary resection. In neoadjuvant settings, octreotide scans and histological evaluation of pretherapeutic needle biopsies may help to choose between somatostatin agonist/prednisolone regimens and neoadjuvant chemotherapy as first-line treatment. Finally, a multimodality treatment regime is recommended for advanced and unresectable thymic tumours. In conclusion, advanced stage thymoma and TC should preferably be treated in experienced centres in order to provide all modern diagnostic tools (imaging, histology) and innovative therapy techniques. Systemic and local (hyperthermic intrathoracic chemotherapy) medical treatments together with extended surgical resections have increased the therapeutic options in patients with advanced or recurrent thymoma and TC.
Bubble Dynamics During Boiling in Enhanced Surface Microchannels (2006)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> An experimental investigation is presented on flow boiling of deionized water in 227-&lt;formula formulatype="inline"&gt;&lt;tex&gt;$\mu$&lt;/tex&gt;&lt;/formula&gt;m hydraulic diameter microchannels with reentrant type cavities. Key features of nucleate boiling are discussed. Active nucleation site density, bubble frequency and departure diameter, and flow patterns over mass velocities ranging from 41 kg/m&lt;formula formulatype="inline"&gt;&lt;tex&gt;$^{2}$&lt;/tex&gt;&lt;/formula&gt;-s to 302 kg/m&lt;formula formulatype="inline"&gt;&lt;tex&gt;$^{2}$&lt;/tex&gt;&lt;/formula&gt;-s and heat fluxes ranging from 28 to 445 W/cm&lt;formula formulatype="inline"&gt;&lt;tex&gt;$^{2}$&lt;/tex&gt;&lt;/formula&gt; are studied. Similarities and differences with results obtained on large-scale systems and unenhanced microchannels are discussed.&lt;papernumber&gt;1536&lt;/papernumber&gt; </para>
Range of susceptibility within and between diploid and tetraploid strains of Chloris gayana (Rhodes grass) to Meloidogyne javanica (1990)

SUMMARY Host statu of 22 accessions of Chloris gayana (Rhodes grass) to Meloidogyne javanica (root-hot nematode) was assessed. Eleven diploid and eleven tetraploid types were screened. Tetraploids showed a wider range of susceptibility and were generally more susceptible than diploids. The maximum egg-masses recorded on a diploid plant was 213 and on a tetraploid 412. Not al1 diploids were sufficiently resistant to suppress nematode population increase. Number of egg-masses was a reliable discriminant to identify susceptible plants and select for resistance. Host status is reported with reference to a breeding programme to produce an improved root-hot resistant Rhodes grass to control M. javanica in tobacco rotations. Results are discussed in relation to source and history of material and the nature of resistance.
Activation of GRP78 on Endothelial Cell Membranes by an ADAM15-Derived Peptide Induces Angiogenesis (2010)

Impaired angiogenesis is one of the features of ischemic diseases. We have previously identified, by screening a phage display peptide library, a peptide that induces angiogenesis in endothelial cells under hypoxic conditions by binding the cell's membrane heat shock protein GRP78. Protein data base search identified 4 amino acids (HWRR) of that synthetic peptide present on the ADAM15 metalloprotease domain, a protein considered to be involved in neovascularization. Three peptides were synthesized according to the ADAM15 sequence placing HWRR at different positions. Peptide ADoPep1 exhibited significant angiogenic properties under hypoxic conditions as determined by cell proliferation, migration and tube formation. In a mouse hind limb ischemia model, a single injection of the peptide restored blood perfusion. The identified peptide was found to activate GRP78 on endothelial cell membrane and siRNA directed against the GRP78 mRNA interfered with induction of angiogenesis by the peptide. The peptide binding induced a decrease in heat shock protein GRP78 that is overexpressed under hypoxic conditions. The mechanism of peptide-induced angiogenic activity involves inhibition of apoptosis as well as increased Akt phosphorylation and ERK 1/2 activation. The peptide did not induce VEGF receptor-2 protein synthesis and phosphorylation, suggesting a VEGF-independent mechanism of angiogenesis.