gebhart/patrepeval huggingface dataset:
Stem-like Tumor-Initiating Cells Isolated from IL13Rα2 Expressing Gliomas Are Targeted and Killed by IL13-Zetakine–Redirected T Cells (2012)

Abstract Purpose: To evaluate IL13Rα2 as an immunotherapeutic target for eliminating glioma stem–like cancer initiating cells (GSC) of high-grade gliomas, with particular focus on the potential of genetically engineered IL13Rα2-specific primary human CD8+ CTLs (IL13-zetakine+ CTL) to target this therapeutically resistant glioma subpopulation. Experimental Design: A panel of low-passage GSC tumor sphere (TS) and serum-differentiated glioma lines were expanded from patient glioblastoma specimens. These glioblastoma lines were evaluated for expression of IL13Rα2 and for susceptibility to IL13-zetakine+ CTL-mediated killing in vitro and in vivo. Results: We observed that although glioma IL13Rα2 expression varies between patients, for IL13Rα2pos cases this antigen was detected on both GSCs and more differentiated tumor cell populations. IL13-zetakine+ CTL were capable of efficient recognition and killing of both IL13Rα2pos GSCs and IL13Rα2pos differentiated cells in vitro, as well as eliminating glioma-initiating activity in an orthotopic mouse tumor model. Furthermore, intracranial administration of IL13-zetakine+ CTL displayed robust antitumor activity against established IL13Rα2pos GSC TS-initiated orthotopic tumors in mice. Conclusions: Within IL13Rα2 expressing high-grade gliomas, this receptor is expressed by GSCs and differentiated tumor populations, rendering both targetable by IL13-zetakine+ CTLs. Thus, our results support the potential usefullness of IL13Rα2-directed immunotherapeutic approaches for eradicating therapeutically resistant GSC populations. Clin Cancer Res; 18(8); 2199–209. ©2012 AACR.
Effects of hypothalamic lesions on the body temperature rhythm of the golden hamster (1995)

The effects of electrolytic and neurotoxic lesions of the suprachiasmatic nucleus (SCN) and preoptic area (POA) of the anterior hypothalamus were studied by temperature telemetry in the golden hamster (Mesocricetus auratus) examined under two ambient temperature conditions: 24 degrees C and 6 degrees C. Although attempted lesions with microinjections of ibotenic acid proved unsuccessful, electrolytic lesions of the SCN eliminated the circadian rhythm of body temperature (CRT), indicating an active role of this nucleus in the establishment of the CRT. Electrolytic lesions of the POA, but not of the SCN, resulted in an increased amplitude of the CRT at both 24 degrees C and 6 degrees C, with the lower ambient temperature enhancing this amplitude change to a greater extent. These results suggest that the POA and the SCN are independently responsible for the homeostatic and circadian regulation of body temperature, respectively. The increased amplitude of the CRT after POA lesions raises the possibility that the thermoregulatory system may oppose rather than defend the circadian control of body temperature in normal animals, which is consistent with several recent behavioral findings.
Substrate Phage: Selection of Protease Substrates by Monovalent Phage Display (1993)

A method is described here for identifying good protease substrates among approximately 10(7) possible sequences. A library of fusion proteins was constructed containing an amino-terminal domain used to bind to an affinity support, followed by a randomized protease substrate sequence and the carboxyl-terminal domain of M13 gene III. Each fusion protein was displayed as a single copy on filamentous phagemid particles (substrate phage). Phage were then bound to an affinity support and treated with the protease of interest. Phage with good protease substrates were released, whereas phage with substrates that resisted proteolysis remained bound. After several rounds of binding, proteolysis, and phagemid propagation, sensitive and resistant substrate sequences were identified for two different proteases, a variant of subtilisin and factor Xa. The technique may also be useful for studying the sequence specificity of a variety of posttranslational modifications.
Evaluation of Waterflooding Performance in Heavy Oil Reservoirs Applying Capacitance-Resistive Model (2011)

Abstract Rapid evaluation of waterflooding performance, especially in the case of lack of exact reservoir description, has crucial importance in first stages of reservoir studies. The authors studied the recent introduced techniques of quantifying communication between vertical wells in a reservoir based on fluctuation in production rates of producers and injection rates of injectors. The considered waterflooding evaluation techniques in this study were multilinear regression model (MLR), a MLR model utilized by diffusivity filters, and a capacitance-resistive model (CRM). The capacitance-resistive model has been derived to make an analogy between fluid flow through porous media and electrical flow in the circuit. The authors used a more complicated model including capacitance (compressibility) as well as resistance (transmissibility) effects to provide information about preferential transmissibility trends and the presence of permeability barriers. The authors conclude that CRMs can provide a better insight into interwell connectivities than MLR models due to reservoir compressibility.
Innate lymphoid cells regulate intestinal epithelial cell glycosylation (2014)

Fucosylation of intestinal epithelial cells, catalyzed by fucosyltransferase 2 (Fut2), is a major glycosylation mechanism of host-microbiota symbiosis. Commensal bacteria induce epithelial fucosylation, and epithelial fucose is used as a dietary carbohydrate by many of these bacteria. However, the molecular and cellular mechanisms that regulate the induction of epithelial fucosylation are unknown. Here, we show that type 3 innate lymphoid cells (ILC3) induced intestinal epithelial Fut2 expression and fucosylation in mice. This induction required the cytokines interleukin-22 and lymphotoxin in a commensal bacteria-dependent and -independent manner, respectively. Disruption of intestinal fucosylation led to increased susceptibility to infection by Salmonella typhimurium. Our data reveal a role for ILC3 in shaping the gut microenvironment through the regulation of epithelial glycosylation.
Ultra-thin film fully-depleted SOI CMOS with raised G/S/D device architecture for sub-100 nm applications (2002)

Fully-Depleted (FD) Silicon-on-Insulator (SOI) has become very attractive for deep submicron CMOS applications because of its quasi-ideal properties. Scaling FD SOI involves, amongst many other technology parameters, reducing the thickness of the silicon film. However, thinning the SOI film down to 50 nm or below may result in high series resistance or even full consumption of the silicon during the salicidation process. Therefore, a dedicated device architecture is needed like for example the raised gate/source/drain (G/S/D) device architecture. The authors have fabricated FD SOI transistors on top of an ultra-thin silicon film of 30 nm with gate lengths down to 0.1 /spl mu/m. After a short description of the device fabrication, the electrical results on DC and HF performance are presented and discussed.
Beta-Glucuronidase-Mediated Drug Release (2002)

The selective activation of a relatively non-toxic prodrug by an enzyme present only in the tumour should enhance the drug concentration at the tumour site and result in a better anti-tumour effect and a reduction in systemic toxicity as compared to conventional chemotherapy. beta-Glucuronidase is such an enzyme. It is normally expressed in the lysosomes of cells. In larger tumours, however, high levels of the enzyme are present in necrotic areas. Several glucuronide prodrugs have been synthesised that can be activated by beta-glucuronidase. They are relatively non-toxic due to their hydrophilic nature, which prevents them from entering cells and thus from contact with lysosomal beta-glucuronidase. The main problem of glucuronide prodrugs for clinical use is their fast renal clearance. Special attention should be paid to the development of new less hydrophilic prodrugs with slower clearance, as this would result in a prolonged exposure to beta-glucuronidase at the site of the tumour and a reduction of the amount of prodrug needed. A number of interesting anthracyclin-based glucuronide prodrugs have been synthesised and have shown favourable therapeutic effects compared to treatment with the parent drug. The tumoural levels of beta-glucuronidase can even be enhanced by two-step approaches, in which exogenous enzyme is targeted to the tumour by an antibody (ADEPT) or by the gene encoding the enzyme in transduced tumour cells (GDEPT). The ADEPT and GDEPT approaches in combination with glucuronide prodrugs have shown enhanced efficacy in experimental tumour models. Further improvement of ADEPT and GDEPT is warranted to optimise the tumour uptake and retention of antibody-enzyme fusion proteins and the efficiency and safety of current gene delivery methods. In conclusion, it is clear that glucuronide prodrugs hold promise for future use in the treatment of cancer in patients as monotherapy. Enhancement of the therapeutic effects of glucuronide prodrugs, also in patients with small tumour lesions, may possibly be achieved by techniques that target beta-glucuronidase specifically to the site of the tumour.
Metabolic imaging of tissues by infrared fiber-optic spectroscopy: an efficient tool for medical diagnosis (2004)

Infrared fingerprints of molecules in biology contain much information on cells metabolism allowing one to distinguish between healthy and altered tissues. Here, to collect infrared signatures, we used evanescent wave spectroscopy based on an original infrared transmitting tapered glass fiber. A strict control of the fiber diameter in the tapered sensing zone allows high sensitivity and wide spectral range exploration from 800 to 3000 cm(-1). Then, merely in depositing the mouse liver biopsies on the fiber, this device has enable us to differentiate between tumorous and healthy tissues.
The binding of human lgG subclasses to human monocytes (1972)

Abstract The direct binding of human IgG subclasses to human monocytes has been measured by autoradiography using radiolabeled myeloma proteins. Only IgGl and IgG3 were found to bind strongly to the monocyte surface. This binding could be inhibited both by fresh human serum and by soluble immune complexes.
Deep mutational scanning of S. pyogenes Cas9 reveals important functional domains (2017)

RNA-guided endonucleases (RGENs) have invigorated the field of site-specific nucleases. The success of Streptococcus pyogenes Cas9 (SpCas9) has led to the discovery of several other CRISPR-associated RGENs. As more RGENs become available, it will be necessary to refine their activity before they can be translated into the clinic. With this in mind, we sought to demonstrate how deep mutational scanning (DMS) could provide details about important functional regions in SpCas9 and speed engineering efforts. Consequently, we developed a nuclease screening platform which could distinguish active Cas9 mutants. We screened a library of 1.9 × 10<sup>7</sup> with over 8500 possible non-synonymous mutations and inferred the effects of each mutation using DMS. We demonstrate that the RuvC and HNH domains are the least tolerant regions to mutation. In contrast, the Rec2 and PI domains tolerate mutation better than other regions. The mutation information defined in this work provides a foundation for further SpCas9 engineering. Together, our results demonstrate how DMS can be a powerful tool to uncover features important to RGEN function. Application of this approach to emerging RGENs should enhance their engineering and optimization for therapeutic and other applications.
Androgen therapy in women (2005)

Androgens in women either derive from direct ovarian production or from peripheral conversion of the adrenal sex steroid precursor, dehydroepiandrosterone, towards active androgens. Therefore, loss of adrenal or ovarian function, caused by Addison's disease or consequent to bilateral oophorectomy, results in severe androgen deficiency, clinically often associated with a loss of libido and energy. Importantly, physiological menopause does not necessarily lead to androgen deficiency, as androgen synthesis in the ovaries may persist despite the decline in estrogen production. However, the definition of female androgen deficiency, as recently provided by the Princeton consensus statement, is not precise enough and may lead to over-diagnosis due to the high prevalence of its diagnostic criteria: androgen levels below or within the lower quartile of the normal range and concurrent sexual dysfunction. Importantly, physiological menopause is not necessarily associated with androgen deficiency and therefore does not routinely require androgen therapy. Current replacement options include transdermal testosterone administration or dehydroepiandrosterone treatment, both of which have been shown to result in significant improvements, in particular in libido and mood, while effects on body composition and muscular function are not well documented. It is important to keep in mind that the number of randomized controlled trials is still limited and that currently none of the available preparations is officially approved for use in women. Currently, androgen replacement should be reserved for women with severe androgen deficiency due to an established cause and matching clinical signs and symptoms.
Spontaneous somatic mutations. Structural studies on mutant immunoglobulins. (1978)

The precise alterations in the protein amino acid sequences of the immunoglobulin heavy chains of spontaneously arisen MOPC 21 mutant clones IF2 and IF1 have been determined. All the cyanogen bromide fra-ments of both heavy chains have been isolated and compared to the wild type CNBr fragments. For IF2, there is an internal deletion, from the wild type sequence, of 96 amino acids, from residues 121 to 215 inclusive. Moreover, in IF2, there are no disulfide bonds formed between heavy and light chains, presumably because of the deletion of the CH1 pseudosubunit. There are no other alterations in its covalent structure. For IF1, there is a deletion of the COOH-terminal 83 amino acids (residues 358 to 440, inclusive). Although IF1 heavy chain behaves on dodecyl sulfate-polyacryl-amide gels as if it were only 10 to 15 residues shorter than wild type, no other amino acid sequence differences from wild type are found. IF1 arose most likely by a nonsense mutation of a serine codon. For IF2, whose deletion is like that seen in some human heavy chain disease proteins, the most likely explanation is an error of recombination. The structure of IF2 suggests that the heavy chain variable region ends at a position homologous to residue 120 of the MOPC 21 heavy chain.
Structure-Based Design, Synthesis, and Biological Evaluation of Potent and Selective Macrocyclic Checkpoint Kinase 1 Inhibitors (2007)

Based on the crystallographic analysis of a urea-checkpoint kinase 1 (Chk1) complex and molecular modeling, a class of macrocyclic Chk1 inhibitors were designed and their biological activities were evaluated. An efficient synthetic methodology for macrocyclic ureas was developed with Grubbs metathesis macrocyclization as the key step. The structure-activity relationship studies demonstrated that the macrocyclization retains full Chk1 inhibition activity and that the 4-position of the phenyl ring can tolerate a wide variety of substituents. These novel Chk1 inhibitors exhibit excellent selectivity over a panel of more than 70 kinases. Compounds 5b, 5c, 5f, 15, 16d, 17g, 17h, 17k, 18d, and 22 were identified as ideal Chk1 inhibitors, which showed little or no single-agent activity but significantly potentiate the cytotoxicities of the DNA-damaging antitumor agents doxorubicin and camptothecin. These novel Chk1 inhibitors abrogate the doxorubicin-induced G2 and camptothecin-induced S checkpoint arrests, confirming that their potent biological activities are mechanism-based through Chk1 inhibition.
Synchronization and storage models for multimedia objects (1990)

A technique is presented for the formal specification and modeling of multimedia composition with respect to intermedia timing. The proposed model is based on the logic of temporal intervals and timed Petri nets. A strategy is evinced for constructing a database schema to facilitate data storage and retrieval of media elements based on the temporal relationship established by the proposed modeling tool. An algorithm which allows the retrieval of media elements from the constructed database in a manner which preserves the temporal requirements of the initial specification is presented. Using the proposed model, the synchronization requirements of complex structures of temporally related objects can be easily specified.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A 4.8 kbps multi-band excitation speech coder (2003)

A speech model, referred to as the multiband excitation (MBE) speech model, has been shown to be capable of synthesizing speech without the artifacts common to model-based speech systems and has been used to develop a 4.8 kb/s speech coder. This system was developed using several new approaches to quantize the MBE model parameters. These techniques were designed to utilize additional redundancy amongst these parameters, thereby permitting more efficient quantization. The result of information listening tests indicate that this system can achieve high quality for both clean and noisy speech as the MBE speech is extremely robust to the presence of background noise in speech.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Chromatin structure of the telomeric region and 3'-nontranscribed spacer of Tetrahymena ribosomal RNA genes. (1986)

The chromatin structure of the 3'-nontranscribed spacer of the linear rRNA gene molecules of Tetrahymena thermophila was examined. This region includes the transcription termination site, two sets of recently identified conserved spacer repeats (Type IV and V repeats (Challoner, P. B., Amin, A. A., Pearlman, R. E., and Blackburn, E. H. (1985) Nucleic Acids Res. 13, 2661-2680], and the terminus of the molecule. Using sensitivity to nucleases as a probe, a unique chromatin structure was found in this rDNA region. Proceeding from the end of the rDNA molecule, the telomeric repeated sequence, (CCCCAA)n, was packaged in a non-nucleosomal complex adjacent to three phased nucleosomes. This nucleosomal structure was disrupted at the Type V repeat region, which, compared with the neighboring nucleosomal region, was more accessible to nucleases and, from both micrococcal nuclease and DNase I digestion results, was packaged in chromatin differently from the sequences flanking it on both sides. The region between the Type V repeats and adjacent to the transcription termination site was in yet another distinguishable chromatin structure as judged by its sensitivity to nucleases. It includes sites protected in chromatin and sites which were cleaved in chromatin but not detectably digested in DNA controls, suggesting that specific proteins are also associated with this region.
Gangliosides activate microglia via protein kinase C and NADPH oxidase (2004)

Microglia, the major immune effector cells in the central nervous system, are activated when the brain suffers injury. A number of studies indicate that gangliosides activate microglia. However, the signaling mechanisms involved in microglial activation are not yet to be elucidated. Our results show that gangliosides induce the expression of interleukin (IL)-1beta, tumor necrosis factor-alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) in rat brain microglia and BV2 murine microglia via protein kinase C (PKC) and NADPH oxidase. Expression of IL-1beta, TNF-alpha, and iNOS in ganglioside-treated cells was significantly reduced in the presence of inhibitors of PKC (GF109203X, Go6976, Ro31-8220, and rottlerin) and NADPH oxidase (diphenyleneiodonium chloride [DPI]). In response to gangliosides, PKC-alpha, betaII, and delta and NADPH oxidase p67(phox) translocated from the cytosol to the membrane. ROS generation was also activated within 5 min of ganglioside treatment. Ganglioside-induced ROS generation was blocked by PKC inhibitors. Furthermore, ganglioside-induced activation of NF-kappaB, an essential transcription factor that mediates the expression of IL-1beta, TNF-alpha, and iNOS, was reduced in the presence of GF109203X and DPI. Our results collectively suggest that gangliosides activate microglia via PKC and NADPH oxidase, which regulate activation of NF-kappaB.
Measurement of plasminogen activator system components in plasma and tumor tissue extracts obtained from patients with breast cancer: an EORTC Receptor and Biomarker Group collaboration. (2005)

The plasminogen activator (PA) system comprises the 2 serine proteases, urokinase PA (uPA) and tissue PA (tPA), the 2 serpin inhibitors, PAI-1 and PAI-2 and the uPA receptor (uPAR; CD87). High levels of uPA, PAI-1, uPA-PAI-1 complex and uPAR in breast cancer tissue are associated with poor prognosis, while high levels of tPA or PAI-2 correlate with good prognosis. In this study, pre-operative plasma levels of uPA, PAI-1, uPAR, tPA, uPA-PAI-1 complex, and tPA-PAI-1 complex were measured in patients with benign (n=103) and malignant breast disease (n=113) by immunoenzymatic assays (ELISA). While plasma antigen levels of uPA, PAI-1, uPA-PAI-1 complex and uPAR were not significantly different in the 2 groups, antigen levels of tPA and tPA-PAI-1 complex were significantly higher in patients with breast carcinoma compared to the control group. In plasma from the breast cancer patients, uPA levels correlated weakly but significantly with those of tPA (r=0.20, p=0.035) and uPAR (r=0.208, p=0.028). tPA levels correlated strongly with tPA-PAI-1 complex (r=0.972, p=0.0001) while uPA-PAI-1 levels were significantly associated with PAI-1 levels (r=0.534, p<0.0001), tPA levels (r=0.348, p=0.0003) and tPA-PAI-1 levels (r=0.356, p=0.002). However, no significant correlation was found between plasma and tumor tissue levels of uPA, PAI-1, uPA-PAI-1 complex, tPA or tPA-PAI-1. Our findings indicate that determination of these factors in plasma do not reflect their concentration in tumor tissue. Therefore, measurement of PA components in blood cannot be recommended for assessing prognosis in breast cancer.
Ipriflavone in the Treatment of Postmenopausal Osteoporosis<SUBTITLE>A Randomized Controlled Trial</SUBTITLE> (2001)

Our data indicate that ipriflavone does not prevent bone loss or affect biochemical markers of bone metabolism. Additionally, ipriflavone induces lymphocytopenia in a significant number of women.
A Shortened Insulin with Full in vitro Potency (1985)

Des[(B26-30)-pentapeptide]insulin-B25-amide was prepared from protected des-[(B23-30)-octapeptide]insulin (pig) and H-Gly-Phe-Phe-NH2 by trypsin-mediated semisynthesis in a yield of 9% (based on insulin). The analogue was characterized with respect to chemistry, biological function and CD spectroscopy. While des[(B26-30)-pentapeptide]insulin with free carboxylate group exhibited a typical insulin activity of only 25% in vitro, des[(B26-30)-pentapeptide]insulinamide was fully active. Therefore des[(B26-30)-pentapeptide]insulin meets all structural and dynamic requirements for recognition and binding of the receptor as well as exertion of the biological effect, provided that the negative charge in the hydrophobic environment of PheB25 is neutralized.