gebhart/patrepeval huggingface dataset:
Activation of STAT3 in thymic epithelial tumours correlates with tumour type and clinical behaviour (2006)

The STAT3 (signal transducers and activators of transcription 3) signalling pathway plays a pivotal role in oncogenesis and appears essential for postnatal maintenance of thymic architecture and thymocyte survival. The association of STAT3 activation with thymic epithelial tumours (TETs) and myasthenia gravis (MG) has not been elucidated. In this study, 118 cases of TET and 25 non-neoplastic thymic tissue samples were evaluated for STAT3 and phospho-STAT3 (pSTAT3) expression immunohistochemically. In addition, 44 normal thymuses of different ages were included for comparison. It was found that STAT3 activation in thymic epithelial cells (TECs), as evidenced by pSTAT3 expression and/or nuclear STAT3, was present in the majority of non-neoplastic thymuses (88%, 22/25), including those from young children, but not in fetal thymus. In thymoma (n = 73), activated STAT3 was noted at a significantly higher frequency in the cases of lymphocyte-rich thymoma (ie types AB, B1, and B2, 46%, 23/50) in comparison with lymphocyte-depleted thymoma (types A and B3, 1/23) (p = 0.009). Thymoma with activated STAT3 tended to present at an earlier stage, show complete resectability and less aggressive behaviour, and have a higher correlation with MG than the STAT3-negative/inactive group (p < 0.05). In contrast, thymic carcinoma with activated STAT3 (14/45, 31%) had significantly higher rates of unresectability, vascular invasion, and regional lymph node metastasis (p < 0.05). These data provide the first evidence that constitutive STAT3 activation is seen in both benign and neoplastic thymic tissue and is associated with the persistence of thymic tissue and the presence of MG. It is likely to be induced by different factors in thymoma and thymic carcinoma.
CC-Chemokine Ligand 20/Macrophage Inflammatory Protein-3α and CC-Chemokine Receptor 6 Are Overexpressed in Myeloma Microenvironment Related to Osteolytic Bone Lesions (2008)

The expression of the chemokine CC-chemokine ligand 20 (CCL20)/macrophage inflammatory protein (MIP)-3alpha and its receptor CC-chemokine receptor 6 (CCR6) by multiple myeloma (MM) and microenvironment cells and their potential relationship with osteoclast (OC) formation and osteolytic bone lesions in MM patients was investigated in this study. First, we found that MM cells rarely produce CCL20/MIP-3alpha but up-regulate its production by bone marrow (BM) osteoprogenitor cells and osteoblasts in coculture with the involvement of soluble factors as interleukin-1beta and tumor necrosis factor alpha. MM cells also stimulate both CCL20/MIP-3alpha and CCR6 expression by OCs in coculture. Thereafter, we showed that CCL20/MIP-3alpha significantly increases both the number of multinucleated tartrate-resistant acid phosphatase-positive OCs and receptor activator of nuclear factor-kappaB-positive OC progenitor cells similar to CCL3/MIP-1alpha. Finally, we found that blocking anti-CCL20/MIP-3alpha and anti-CCR6 antibodies significantly inhibits MM-induced OC formation. In vitro data were further expanded in vivo analyzing a total number of 64 MM patients. Significantly higher CCL20/MIP-3alpha levels were detected in MM patients versus monoclonal gammopathy of uncertain significance (MGUS) subjects and in MM osteolytic patients versus nonosteolytic ones. Moreover, a significant increase of CCL20/MIP-3alpha-positive osteoblasts in osteolytic MM patients compared with nonosteolytic ones was observed. Interestingly, no significant difference in BM CCL20/MIP-3alpha expression and level was observed between MGUS and nonosteolytic MM patients. Our data indicate that CCL20/MIP-3alpha and its receptor CCR6 are up-regulated in the bone microenvironment by MM cells and contribute to OC formation and osteolytic bone lesions in MM patients.
Vascular responses to 17β‐oestradiol in postmenopausal women (1995)

The vascular responses to 17 beta-oestradiol were examined in 23 postmenopausal women (59 +/- 7 years [mean +/- SD]) using a placebo-controlled double-blind crossover design. All women received 1 mg 17 beta-oestradiol or placebo (P) sublingually on consecutive days in random order. Axial diameters and blood flow rates of the left common femoral arteries were determined before and 60-80 min after application of verum or placebo as well as 10-30 min after 10 mg isosorbide dinitrate (ISDN) with a quantitative duplex ultrasound technique. Oestradiol induced a vasodilation of femoral arteries (+6.4 +/- 4.1% of basal, P < 0.001 vs. basal and P), the vessel diameter was unchanged with placebo (+0.7 +/- 2.1%). The blood flow rate increased significantly after oestradiol application (+30 +/- 28%, P < 0.05 vs. basal and P), but not after placebo (+11 +/- 21%). Mean blood pressure and heart rate remained constant with both drugs. Despite its vasodilatory effect, ISDN significantly reduced the arterial blood flow after pretreatment with oestradiol and placebo, probably through cardiac preload reduction. In conclusion, 17 beta-oestradiol alters the vascular tone of systemic arteries resulting in a vasodilation and increase of blood flow. We suggest that these direct vascular actions may contribute to the preventive properties of oestrogens on cardiovascular diseases in postmenopausal women.
Watson–Crick base pairing, electronic and photophysical properties of triazole modified adenine analogues: a computational study (2015)

Triazole adenine nucleobase analogues show fluorescence in the UV-Vis region and form Watson–Crick base pairing with thymine nucleobases.
Testosterone suppresses anti‐DNA antibody production in peripheral blood mononuclear cells from patients with systemic lupus erythematosus (1997)

These results suggest that testosterone may directly suppress anti-DNA antibody production in PBMC from SLE patients by inhibiting B cell hyperactivity and, indirectly, by down-regulating IL-6 production in monocytes. These results support the therapeutic effects of testosterone on SLE.
AAV-Mediated gene transfer slows photoreceptor loss in the RCS rat model of retinitis pigmentosa (2003)

In the Royal College of Surgeons (RCS) rat, the retinal pigment epithelium (RPE) cannot phagocytose the outer segment discs that are continually shed from photoreceptors. The resulting accumulation of debris in the subretinal space leads to a progressive loss of photoreceptors. The defect results from a mutation in the Mertk gene, which is normally expressed in the RPE. Mertk is a receptor tyrosine kinase, involved in the binding of photoreceptor debris. Mutations in MERTK have also been described in patients with retinitis pigmentosa (RP). Here we demonstrate that subretinal injection of recombinant adeno-associated virus (AAV) expressing the murine Mertk gene can significantly prolong photoreceptor cell survival in the RCS rat. Electroretinographic analysis of treated eyes showed that functional photoreceptors were still present at 9 weeks, when there is virtually no activity in untreated control eyes. Histological analysis of treated eyes revealed a decrease in the amount of debris in the subretinal space, suggesting that RPE function was restored. Moreover, 9 weeks after treatment the number of photoreceptors was 2.5-fold higher in treated than in control eyes. This study provides strong support for the development of AAV-mediated gene therapy for RP caused by mutations in the MERTK gene.
Short-Term Indicators (1996)

Short-term economic indicators play an important role in the assessment of current cyclical situations and in the establishment of forecasts. Broadly, two types of short-term indicators can be distinguished: qualitative indicators, reflecting businessmen’s subjective assessment of the cyclical situation (e.g., production prospects or judgements on orderbooks), and quantitative indicators, reflecting past developments of production or employment. The usefulness of qualitative indicators rests on their reliability to approximate the possible evolution of the quantitative ones.The present document shows the results of a pilot study for six industrial sectors in seven Member countries whereby short-term qualitative indicators are used to nowcast a quantitative indicator, the production index. The objective is to enhance the timeliness of short-term industrial statistics through estimation of data points for the most recent periods for which they are not yet available.From the current ...
Serial dilution microchip for cytotoxicity test (2004)

Today's pharmaceutical industry is facing challenges resulting from the vast increases in sample numbers produced by high-throughput screening (HTS). In addition, the bottlenecks created by increased demand for cytotoxicity testing (required to assess compound safety) are becoming a serious problem. We have developed a polymer PDMS (polydimethylsiloxane) based microfluidic device that can perform a cytotoxicity test in a rapid and reproducible manner. The concept that the device includes is well adjustable to automated robots in huge HTS systems, so we can think of it as a potential dilution and delivery module. Cytotoxicity testing is all about the dilution and dispensing of a drug sample. Previously, we made a PDMS based microfluidic device which automatically and precisely diluted drugs with a buffer solution with serially increasing concentrations. This time, the serially diluted drug solution was directly delivered to 96 well plates for cytotoxicity testing. Cytotoxic paclitaxel solution with 2% RPMI 1640 has been used while carrying out cancerous cell based cytotoxicity tests. We believe that this rapid and robust use of the PDMS microchip will overcome the growing problem in cytotoxicity testing for HTS.
Selection of Streptavidin Binders from a DNA-Encoded Chemical Library (2006)

DNA-encoded libraries of small organic molecules facilitate the construction of large, encoded self-assembling chemical libraries for the identification of high-affinity binders to protein targets. We have constructed a library of 477 chemical compounds, coupled to 48mer-oligonucleotides, each containing a unique six-base sequence serving as “bar-code” for the identification of the chemical moiety. The functionality of the library was confirmed by selection and amplification of both high- and low-affinity binding molecules specific to streptavidin.
Chemical cross‐linking and mass spectrometry to map three‐dimensional protein structures and protein–protein interactions (2006)

Closely related to studying the function of a protein is the analysis of its three-dimensional structure and the identification of interaction sites with its binding partners. An alternative approach to the high-resolution methods for three-dimensional protein structure analysis, such as X-ray crystallography and NMR spectroscopy, consists of covalently connecting two functional groups of the protein(s) under investigation. The location of the created cross-links imposes a distance constraint on the location of the respective side chains and allows one to draw conclusions on the three-dimensional structure of the protein or a protein complex. Recently, chemical cross-linking of proteins has been combined with a mass spectrometric analysis of the created cross-linked products. This review article describes the most popular cross-linking reagents for protein structure analysis and gives an overview of the different available strategies that employ chemical cross-linking and different mass spectrometric techniques. The challenges for mass spectrometry caused by the enormous complexity of the cross-linking reaction mixtures are emphasized. The various approaches described in the literature to facilitate the mass spectrometric detection of cross-linked products as well as computer software for data analyses are reviewed.
Reactions of quinones and quinoid molecules with the Cp*Ru+ fragment. Electron redistribution and transposition reactions (1992)

International audience
Purification to homogeneity and partial characterization of interleukin 2 from a human T-cell leukemia. (1984)

A method utilizing reversed-phase high-performance liquid chromatography has been developed for the purification to homogeneity of interleukin 2 (IL-2) isolated from a human T-cell leukemia. A final purification of 500,000-fold was obtained with a specific activity of pure IL-2 of 10(9) units/mg. The amino acid analysis of natural IL-2 is strikingly similar to the composition deduced from sequence analysis of a cDNA coding for human IL-2. Protein sequence analysis of CNBr-derived peptides yields data consistent with the sequence proposed from cloned cDNA. The availability of homogeneous IL-2 will allow accurate biological studies of its activity free from the contamination of the numerous lymphokine species that are known to be co-produced with IL-2 during the induction procedure.
Testicular Adrenal Rest Tumors and Leydig and Sertoli Cell Function in Boys with Classical Congenital Adrenal Hyperplasia (2007)

TART in prepubertal males with classic CAH could be found during childhood. We also report differences in markers of gonadal function in a subgroup of patients, especially in those with inadequate control.
Enhanced Antitumor Activity of Cetuximab in Combination with the Jak Inhibitor CYT387 against Non-Small-Cell Lung Cancer with Various Genotypes (2015)

Cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, is effective in the treatment of non-small-cell lung cancers (NSCLCs). However, resistance to EGFR inhibitors limits its effectiveness. In this study, we investigated the effectiveness of Jak-2 inhibitor, CYT387, in combination with cetuximab. Xenograft animal models were administered with cetuximab or CYT387 or their combination. It was observed that NSCLC cells exhibited enormous differences in responses to cetuximab; cell lines were more intrinsically resistant to cetuximab. In resistant cell lines (H1975 and H1650), the efficacy of cetuximab was increased when combined with CYT387, whereas CYT387 alone in low doses exhibited little effect on NSCLC cell proliferation. In addition, the antitumor activity of cetuximab was increased in H1975 resistant model in spite of low efficacy of cetuximab treatment alone in. Jak/STAT signaling was suppressed effectively by the combination of cetuximab and CYT387. In summary, our findings indicated that CYT387 has a potent indirect antitumor activity, and it is also synergistic in its activity in combination with cetuximab against NSCLC tumors, especially with cetuximab intrinsic-resistance tumors. These indications were mediated via Janus kinase (Jak)-signal transducer and transcription (STAT) pathway activator. Our results strongly and consistently supported the potential synergism of CYT387 as Jak inhibitor for anti-NSCLC therapy with EGFR-targeting agents.
DEEP BRAIN STIMULATION (2006)

Deep brain stimulation (DBS) has provided remarkable benefits for people with a variety of neurologic conditions. Stimulation of the ventral intermediate nucleus of the thalamus can dramatically relieve tremor associated with essential tremor or Parkinson disease (PD). Similarly, stimulation of the subthalamic nucleus or the internal segment of the globus pallidus can substantially reduce bradykinesia, rigidity, tremor, and gait difficulties in people with PD. Multiple groups are attempting to extend this mode of treatment to other conditions. Yet, the precise mechanism of action of DBS remains uncertain. Such studies have importance that extends beyond clinical therapeutics. Investigations of the mechanisms of action of DBS have the potential to clarify fundamental issues such as the functional anatomy of selected brain circuits and the relationship between activity in those circuits and behavior. Although we review relevant clinical issues, we emphasize the importance of current and future investigations on these topics.
T-cell-directed cancer vaccines: the melanoma model (2001)

Significant advances in the understanding of the molecular basis for tumour/host interactions in humans have occurred in the last decade through studying patients with metastatic melanoma. This disease is characterised by its tendency to be modulated by immunologic factors. Furthermore, immunologic manipulation of the host with various systemic agents, in particular IL-2, frequently affects this natural phenomenon and can lead to complete rejection of cancer. By studying the cellular immunology occurring in patients undergoing immunotherapy, several tumour antigens (TA) and their epitopes recognised by human leukocyte antigen (HLA) class I-restricted cytotoxic T-lymphocytes (CTL) have been identified. Most of these TA are non-mutated molecules expressed by the majority of melanoma in vivo and most melanoma cell lines. In addition, unique minimal epitopic sequences play an immunodominant role in the context of specific HLA class I alleles. Since melanoma lesions from different patients often share expression of the same TA, and a minimal peptide sequence from a TA can cause immunologic changes in multiple patients, interest has grown in the development of TA-specific vaccines suitable for broad patient populations. Repeated in vitro stimulation of peripheral blood mononuclear cells (PBMC) with TA-derived epitopes can induce a high frequency of TA-reactive T-cells in melanoma patients. The same epitopes can also enhance TA-specific T-cell reactivity in vivo when administered subcutaneously in combination with Incomplete Freund's Adjuvant (IFA). Epitope-based vaccinations, however, have not shown strong clinical efficacy unless combined with IL-2 administration. Attempts to increase the efficacy of these vaccines have combined specialised antigen-presenting cells or the administration of whole TA through DNA- or RNA-based vaccines with the intention of increasing antigen presentation and processing. Save for scattered reports, however, the success of these approaches has been limited and T-cell-directed vaccination against cancer remains at a paradoxical standstill whereby anticancer immunisation can be induced but it is not sufficient, in most cases, to induce tumour regression. Using melanoma as the standard model for immunotherapy, we will review various methods of T-cell-directed vaccination, the monitoring and analysis of the resulting immune response, and several clinical trials in which cancer vaccines have successfully induced immunisation.
Transcription of Virulence Factors in Staphylococcus aureus Small-Colony Variants Isolated from Cystic Fibrosis Patients Is Influenced by SigB (2005)

Staphylococcus aureus small-colony variants (SCVs) are believed to account in part for the persistence of S. aureus during chronic infections. Little is understood about the gene expression profile that may explain the phenotype and distinguish SCVs from prototype S. aureus strains. In this study, DNA array transcriptional profiles of clinical SCVs isolated from the airways of cystic fibrosis patients were obtained and compared to those obtained from a laboratory-derived SCV strain (i.e., a respiratory-deficient hemB mutant) and prototype S. aureus strains. The genes commonly up-regulated in both hemB and clinical SCVs were found to be implicated in fermentation and glycolysis pathways. The well-known virulence regulator agr was not activated in SCVs, and such strains had low levels of alpha-toxin (hla) gene expression. Clinical SCVs also had a transcriptional signature of their own. Of striking interest is that many genes, most of them under the positive control of the alternate sigma factor SigB, were specifically up-regulated and differed in that way from that seen in prototype S. aureus and the hemB mutant. Since SigB influences up-regulation of adhesin type genes while indirectly down-regulating exoproteins and toxins, we evaluated the internalization and persistence of SCVs in mammalian cells. Results showed that clinical SCVs persisted much more efficiently in cells than the hemB and prototype strains and that a sigB mutant was a poor persister. Thus, it appears that the agr locus plays a minor role in the regulation of the virulon of SCVs, unlike SigB, which may have a key role in intracellular persistence.
Resonance Raman and surface- and tip-enhanced Raman spectroscopy methods to study solid catalysts and heterogeneous catalytic reactions (2010)

Resonance Raman (RR) spectroscopy has several advantages over the normal Raman spectroscopy (RS) widely used for in situ characterization of solid catalysts and catalytic reactions. Compared with RS, RR can provide much higher sensitivity and selectivity in detecting catalytically-significant surface metal oxides. RR can potentially give useful information on the nature of excited states relevant to photocatalysis and on the anharmonic potential of the ground state. In this critical review a detailed discussion is presented on several types of RR experimental systems, three distinct sources of so-called Raman (fluorescence) background, detection limits for RR compared to other techniques (EXAFS, PM-IRAS, SFG), and three well-known methods to assign UV-vis absorption bands and a band-specific unified method that is derived mainly from RR results. In addition, the virtues and challenges of surface-enhanced Raman spectroscopy (SERS) are discussed for detecting molecular adsorbates at catalytically relevant interfaces. Tip-enhanced Raman spectroscopy (TERS), which is a combination of SERS and near-field scanning probe microscopy and has the capability of probing molecular adsorbates at specific catalytic sites with an enormous surface sensitivity and nanometre spatial resolution, is also reviewed (300 references).
Pancreatic Adenocarcinoma (2014)

Cancer of the pancreas is predominantly adenocarcinoma and involves activating KRAS mutations in the large majority of cases. Surgical resection can be effective in localized disease; combination chemotherapy offers some palliation in advanced disease.
Edge-Lighting Light Guide Plate Based on Micro-Prism for Liquid Crystal Display (2009)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> We designed an edge-lighting light guide plate (LGP) based on a micro-prism structure for liquid crystal display. Its top and bottom surfaces have micro-prisms, and a layer of high reflection film is coated on the bottom surface. The principle of the LGP was analyzed. The optical simulation tool ASAP was used to calculate the apex angle and height of the micro-prism on the top of the LGP, the apex angle of the micro-prism on the bottom of the LGP and the emitting angle dependent luminous flux of the LGP. By adjusting the width of micro-prisms on the bottom, the LGP achieved uniform luminance. A 12-in LGP based on a micro-prism structure as an example was designed. The results proved that the LGP based on a micro-prism structure is thin and simple with uniform luminance and high efficiency. </para>
Infrared spectra and resonance interaction of amide‐I vibration of the antiparallel‐chain pleated sheet (1976)

Abstract Theoretical treatment of resonance interaction of amide‐I vibration has been done in a dipole–dipole approximation on the basis of perturbation theory. A single infinite antiparallel‐chain pleated sheet as well as different kinds of its finite fragments have been considered. A good agreement has been obtained between calculated spectral parameters of amide I of the infinite sheet and observed ones in infrared and Raman spectra of synthetic polypeptides and fibrous proteins. A theoretical dependence of the resonance frequency shift of the main component and frequency splitting of two components active in the infrared spectra on the number of polypeptide chains in the finite sheet has been found.