gebhart/patrepeval huggingface dataset:
Degrading Ci: who is Cul-pable? (2002)

Proper cell fate specification and pattern formation rely on a cell’s ability to sense and interpret graded spatial information. One class of spatial signals widely used in animal development is the Hedgehog (Hh) family. Hh family members govern numerous developmental processes in both vertebrates and invertebrates, and in many instances act as morphogens that specify distinct developmental outcomes as a function of their concentrations (for review, see Ingham and McMahon 2001). How different thresholds of Hh are perceived and transmitted by signal-receiving cells to elicit distinct responses remains largely unknown; however, recent studies on the Drosophila Hh signaling effector, Cubitus interruptus (Ci), provide important insights. Ci exists in two distinct forms: a full-length form (Ci155) and a C-terminally truncated form (Ci75) that is derived from Ci155 by partial degradation (Fig. 1B; AzaBlanc et al. 1997). These two forms of Ci play distinct roles in Drosophila appendage development. In developing wings, for example, Ci155 is processed to generate Ci75 in anterior (A) compartment cells distant from the anteroposterior (A/P) compartment boundary, where Ci75 acts as a transcriptional repressor to block the expression of a subset of Hh-responsive genes including decapentaplegic (dpp; Methot and Basler 1999). In A-compartment cells near the A/P boundary, Hh inhibits Ci processing and thus the generation of its repressor form. In addition, Hh stimulates the activity and nuclear translocation of the accumulated Ci155, which acts as a transcriptional activator to turn on other Hh-responsive genes including patched (ptc) and engrailed (en; Alexandre et al. 1996; Methot and Basler 1999). The regulation of Ci processing and activity has been subject to numerous studies in the past several years, ranging from early genetic identification of Hh pathway components to more recent biochemical characterization of large signaling complexes (Ingham and McMahon 2001). Strikingly, almost all the intracellular Hh signaling components identified so far are involved in Ci processing, forecasting the complexity of this process. Here, I briefly review several recent findings that provide new insights into how Ci processing is accomplished, including a paper in this issue of Genes & Development (Ou et al. 2002) that uncovers a novel regulatory pathway of Ci degradation. Ci processing: a tale of three kinases
The use of interleukin 12-secreting neural stem cells for the treatment of intracranial glioma. (2002)

Neural stem cells (NSCs) are capable of tracking migrating glioma cells. To exploit this tropism to generate an antitumor T-cell response, particularly against disseminating tumor pockets, we inoculated intracranial glioma-bearing mice with interleukin 12 (IL-12) producing NSCs. Intratumoral therapy with IL-12-secreting NSCs prolonged survival compared to treatment with nonsecretory NSCs or saline. NSCs demonstrated strong tropism for disseminating glioma, and IL-12-secreting NSC therapy was associated with enhanced T-cell infiltration in tumor microsatellites and long-term antitumor immunity. These results indicate that the use of tumor tracking NSCs represents a potent new therapeutic modality for glioma.
Attributing users based on web browser history (2017)

Investigating network and computer related crime requires the combination of heterogeneous sources of reliable evidential weight. Information such as name, surname, email address, login details, social network account and banking details may provide insight on the identity of the device, however, it does not guarantee the identity of the entity using the device. Several sources of potential evidence have been adapted for digital investigation processes. As a probable complementary source of evidence, this study proposed the integration of the semantic properties of web-browser history into digital forensics. To achieve this aim, the study developed a web-browser analysis tool which is independent of the type of browser. Experimental process was carried using nine users. Cosine and Jaccard similarity functions and motifs similarity measures were used to explore the probability of attributing a user based on web-browser history data. The result substantiates the theoretical assertion of the reliability of the semantic characteristics of web-browser information. Using the developed tool and the semantic properties of web-browser data, a forensic investigator can complement the evidential weight of potential digital evidence used in a forensic investigation. This result can also be used as a complementary metrics for strengthening security and digital forensic auditing process.
Environmental law enforcement: The importance of global networks and collaborative practices (2011)

This paper provides a brief commentary on the importance of global networking and collaborative practices if environmental law enforcement is to improve simultaneously as the need for it expands. In other words, the effectiveness of environmental law enforcement, particularly in the light of restricted budgets and under-resourced units, will very much depend upon how well partnerships are formed and strategies implemented, and the flexibility of interventions in the context of rapid social and ecological change.
Enzymatic synthesis of 2,3-O-isopropylidene-sn-glycerol, a chiral building block for platelet-activating factor. (1986)

An enzymatic synthesis of 2, 3-O-isopropylidene-sn-glycerol (10), the synthetic key intermediate for platelet-activating factor, was achieved. Several 1, 3-di-O-acyl-2-benzylglycerols (5a-d) were synthesized from dihydroxyacetone dimer (2), and subjected to enzyme-catalyzed asymmetric hydrolysis. The optical purities of the mono-hydrolyzed products (6) were determined from the 400 MHz proton nuclear magnetic resonance spectra after conversion of 6 to the esters of (-)α-methoxy-α-trifluoromethylphenylacetic acid. Upon hydrogenolysis of the benzyl ether, followed by protection of diol and hydrolysis of the acetate, (-)-6a afforded 10.
Ovine interferon-tau inhibits estrogen receptor up-regulation and estrogen-induced luteolysis in cyclic ewes. (1995)

This study determined whether intrauterine injection of interferon-tau (IFN tau) could block luteolysis in cyclic ewes treated with a luteolytic dose of 17 beta-estradiol benzoate (E) on day 12 of the estrous cycle. Thirty-two ewes were fitted with uterine catheters on day 5 of the estrous cycle and treated with recombinant ovine IFN tau (2 x 10(7) antiviral units/ewe/day) or control proteins (6 mg/day) by intrauterine injection from day 10 until hysterectomy. At 1900 h on day 12, all ewes received 750 micrograms E, im, and were hysterectomized 12, 24, 36, or 48 h post-E administration. Plasma concentrations of progesterone declined in control animals but increased in IFN tau-treated ewes after E injection (P < 0.01, treatment x day interaction). Likewise, total corpus luteum weight decreased in control but not IFN tau-treated ewes after E administration (P < 0.02, treatment x time interaction). In control ewes, endometrial estrogen receptor (ER) messenger RNA (mRNA; P < 0.03) and progesterone receptor (PR) mRNA (P < 0.10) increased after 12 h, whereas concentrations of ER protein (P < 0.02) and PR protein (P < 0.04) increased after 24 h. In situ hybridization and immunohistochemical analyses indicated that ER gene expression increased first in the epithelium at 12 h and then in the stroma by 48 h, whereas PR gene expression first increased in the stroma and then in the epithelium. In control ewes, endometrial oxytocin receptor (OTR) density increased (P < 0.10) after 12 h, with the largest increase occurring between 36-48 h. In IFN tau-treated ewes, endometrial ER mRNA and protein and OTR density did not increase after E administration. Levels of PR mRNA increased (P < 0.01) between 12-36 h, but decreased after 36 h. PR mRNA abundance increased between 12-36 h in the stroma, but not in the epithelium. Concentrations of PR protein were low and did not change in IFN tau-treated ewes. Immunoreactive PR protein was present at low levels in the stroma of all IFN tau-treated ewes. The results indicate that induction of luteolysis by E in control ewes involved sequential increases in endometrial ER mRNA and ER protein in the epithelium that preceded maximal increases in OTR density. Intrauterine injection of recombinant ovine IFN tau prevented luteolysis by inhibiting estrogen-induced increases in endometrial ER and OTR gene expression.
The activation and maintenance ofPax2expression at the mid-hindbrain boundary is controlled by separate enhancers (2002)

Pax2 is the earliest known gene to be expressed throughout the mid-hindbrain region in late gastrula embryos of the mouse and is essential for the formation of an organizing center at the midbrain-hindbrain boundary (MHB), which controls midbrain and cerebellum development. We have used transgenic analysis to identify three MHB-specific enhancers in the upstream region of the mouse Pax2 gene. A 120 bp enhancer (at -3.7 kb) in cooperation with the endogenous promoter was sufficient to induce transgene expression in the anterior neural plate of late gastrula embryos, while it was already inactivated again at the MHB during somitogenesis. The activity of this early enhancer was severely reduced by mutation of three homeodomain-binding sites, two of which are part of a recognition sequence for POU homeodomain proteins. Oct3/4 (Pou5f1), the mouse ortholog of zebrafish Pou2, efficiently bound to this sequence, suggesting its involvement in the regulation of the early Pax2 enhancer. Starting at the four-somite stage, Pax2 is expressed at the MHB under the control of two enhancers located at -4.1 kb and -2.8 kb. The distal late enhancer contains a 102 bp sequence that is not only highly conserved between the mouse and pufferfish Pax2 genes, but also contributes to the enhancer activity of both genes in transgenic mice. The proximal 410 bp enhancer, which overlaps with a kidney-specific regulatory element, contains a functional Pax2/5/8-binding site and thus maintains Pax2 expression at the MHB under auto- and cross-regulatory control by Pax2/5/8 proteins. Importantly, the early and proximal late enhancers are not only sufficient but also necessary for expression at the MHB in the genomic context of the Pax2 locus, as their specific deletion interfered with correct temporal expression of a large Pax2 BAC transgene. Hence, separate enhancers under the control of distinct transcription factors activate and maintain Pax2 expression at the MHB.
Inhalation of dry-powder mannitol increases mucociliary clearance (1997)

Inhalation of hypertonic saline stimulates mucociliary clearance (MCC) in healthy subjects and those with obstructive lung disease. We investigated the effect of inhaling the osmotic agent mannitol on MCC. We used a dry-powder preparation of mannitol British Pharmacopea (BP) which was encapsulated and delivered using a Dinkihaler. MCC was measured for 75 min in six asthmatic and six healthy subjects on two occasions before and after the mannitol inhalation or its control, using 99mTc-sulphur colloid and a gamma camera. The inhaled dose of mannitol was 267+/-171 mg (mean+/-SD) and 400 mg and the percentage fall in forced expiratory volume in one second (FEV1) was 22+/-3 and 4+/-2% in the asthmatic and healthy subjects, respectively. The total clearance in the whole right lung for the 60 min from the start of inhalation of mannitol was greater by 263+/-11.9% in the asthmatic and 18.1+/-4.9% in the healthy subjects compared to the control. The total clearance over 75 min was 54.7+/-9.6% and 33.6+/-9.4% on the mannitol and control day (p<0.002), respectively, in the asthmatic subjects and 40.5+/-7.1% and 24.8+/-7.8% (p<0.002) in the healthy subjects. In conclusion, inhalation of dry-powder mannitol increases mucociliary clearance in asthmatic and healthy subjects and may benefit patients with abnormal mucociliary clearance.
Rapid and Sensitive Identification of Major Histocompatibility Complex Class I-associated Tumor Peptides by Nano-LC MALDI MS/MS (2005)

Identification of major histocompatibility complex (MHC)-associated peptides recognized by T-lymphocytes is a crucial prerequisite for the detection and manipulation of specific immune responses in cancer, viral infections, and autoimmune diseases. Unfortunately immunogenic peptides are less abundant species present in highly complex mixtures of MHC-extracted material. Most peptide identification strategies use microcapillary LC coupled to nano-ESI MS/MS in a challenging on-line approach. Alternatively MALDI PSD analysis has been applied for this purpose. We report here on the first off-line combination of nanoscale (nano) LC and MALDI TOF/TOF MS/MS for the identification of naturally processed MHC peptide ligands. These peptides were acid-eluted from human leukocyte antigen (HLA)-A2, HLA-A3, and HLA-B/-C complexes separately isolated from a renal cell carcinoma cell lysate using HLA allele-specific antibodies. After reversed-phase HPLC, peptides were further fractionated via nano-LC. This additional separation step provided a substantial increase in the number of detectable candidate species within the complex peptide pools. MALDI MS/MS analysis on nano-LC-separated material was then sufficiently sensitive to rapidly identify more than 30 novel HLA-presented peptide ligands. Peptide sequences contained perfect anchor amino acid residues described previously for HLA-A2, HLA-A3, and HLA-B7. The most promising candidate for a T-cell epitope is an HLA-B7-binding nonamer peptide derived from the tumor-associated gene NY-BR-16. To demonstrate the sensitivity of our approach we characterized peptides binding to HLA-C molecules that are usually expressed at the cell surface at approximately only 10% the levels of HLA-A or HLA-B. In fact, multiple renal cell carcinoma peptides were identified that contained anchor amino acid residues of HLA-Cw5 and HLA-Cw7. We conclude that the nano-LC MALDI MS/MS approach is a sensitive tool for the rapid and automated identification of MHC-associated tumor peptides.
Streptococcal M protein: molecular design and biological behavior (1989)

M protein is a major virulence determinant for the group A streptococcus by virtue of its ability to allow the organism to resist phagocytosis. Common in eucaryotes, the fibrillar coiled-coil design for the M molecule may prove to be a common motif for surface proteins in gram-positive organisms. This type of structure offers the organism several distinct advantages, ranging from antigenic variation to multiple functional domains. The close resemblance of this molecular design to that of certain mammalian proteins could help explain on a molecular level the formation of epitopes responsible for serological cross-reactions between microbial and mammalian proteins. Many of the approaches described in the elucidation of the M-protein structure may be applied for characterizing similar molecules in other microbial systems.
The binding of factor IXa to cultured bovine aortic endothelial cells. Induction of a specific site in the presence of factors VIII and X. (1985)

Previous studies have demonstrated a Factor IX and IXa binding site on the endothelial cell surface for which both the zymogen and enzyme compete with equal affinity. In this report, we demonstrate that the affinity of Factor IXa, but not Factor IX, for the cell surface is increased in the presence of both Factors VIII and X. When Factor Xa formation was studied in the presence of saturating concentrations of Factors VIII and X, the half-maximal rate was observed at a Factor IXa concentration of 151 +/- 12 pM. Active site-blocked Factor IXa, 5-dimethylaminonaphthalene-1-sulfonyl-Glu-Gly-Arg-Factor IXa, was a more effective inhibitor of Factor X activation (Ki = 124 pM) than was Factor IX (Ki = 3.0 nM). Radioligand binding studies carried out in the presence of Factors VIII and X confirmed the presence of a selective endothelial cell Factor IXa binding site with Kd = 127 +/- 27 pM. In contrast, when Factor IXa binding was studied in the absence of other coagulation factors, or in the presence of Factor VIII (thrombin-activated or unactivated) alone, this new high affinity site was not observed. Competitive binding studies indicated that Factor IXa was 12 times more effective as an inhibitor of Factor IX-endothelial cell binding in the presence of Factors VIII and X. Consistent with the increased affinity of Factor IXa binding in the presence of factors VIII and X, cell-associated Factor IXa coagulant activity decayed 7 times more slowly in the presence of these coagulation factors. These results demonstrate selective Factor IXa-endothelial cell binding in the presence of Factors VIII and X, suggesting this interaction could be a physiologic occurrence.
An overview of passive RFID (2007)

This article discusses the basics of passive RFID technologies, with an emphasis on tags, for general readers and entry- level practitioners. Following a brief history of RFID, it describes the types of tags and their operation, and regulations and frequency ranges. It then presents representative applications and describes the major technical hurdles still to be overcome before the adoption of RFID can be widespread, and offers a vision of the technology's future.
Conjugate vaccines (2003)

Conjugate vaccines in which the capsular polysaccharide of Haemophilus influenzae type b, common serotypes of Streptococcus pneumoniae and group C Neisseria meningitidis are covalently bound to a protein antigen to convert a T-cell-independent immune response into a T-cell-dependent response have proved highly effective in the prevention of invasive disease in infants and young children. This review looks at what has been learnt from developing these vaccines that could be useful for the clinical development of future conjugate vaccines, in such areas as combination vaccines, dose-ranging, cross-protection of closely related antigens, prevention of noninvasive disease, correlates of protection and use in older age groups. In addition, a wide range of other organisms may be susceptible to conjugate vaccines and new indications and approaches are considered. This will be a highly active area for many years to come.
Phase II Trial of Idiotype Vaccination in Previously Treated Patients With Indolent Non-Hodgkin’s Lymphoma Resulting in Durable Clinical Responses (2006)

This trial demonstrates that Id/KLH alone can induce tumor regression and durable objective responses. Further study of Id/KLH is recommended in other settings where efficacy may be further enhanced as in first-line therapy or after cytoreductive therapy.
Rho-kinase as a Novel Therapeutic Target in Treatment of Cardiovascular Diseases (2002)

Rho-kinase has been identified as one of the effectors of the small GTP-binding protein Rho. Accumulating evidence has demonstrated that the Rho/Rho-kinase-mediated pathway plays an important role in various cellular functions, not only in vascular smooth muscle contraction but also in actin cytoskeleton organization, cell adhesion and motility, cytokinesis, and gene expressions, all of which may be involved in the pathogenesis of arteriosclerosis/atherosclerosis. Indeed, animal experiments have demonstrated that Rho-kinase inhibitors effectively suppress coronary artery spasm and that long-term inhibition of Rho-kinase inhibits the development of coronary arteriosclerotic lesions and even causes regression of coronary vascular lesions in vivo. Recent clinical studies also have demonstrated the inhibitory effect of a Rho-kinase inhibitor on coronary artery spasm in patients with vasospastic angina and on exercise-induced myocardial ischemia in patients with stable effort angina with adequate safety. It is possible that Rho-kinase is also involved in the pathogenesis of other forms of cardiovascular diseases. Thus, Rho-kinase could be regarded as a novel therapeutic target in treatment of cardiovascular diseases.
Oxidative Stress Promotes Ligand-independent and Enhanced Ligand-dependent Tumor Necrosis Factor Receptor Signaling (2008)

Tumor necrosis factor (TNF) receptor 1 (TNFR1, p55) and 2 (TNFR2, p75) are characterized by several cysteine-rich modules in the extracellular domain, raising the possibility that redox-induced modifications of these cysteine residues might alter TNFR function. To test this possibility, we examined fluorescence resonance energy transfer (FRET) in 293T cells transfected with CFP- and YFP-tagged TNFRs exposed to the thiol oxidant diamide. Treatment with high concentrations of diamide (1 mm) resulted in an increase in the FRET signal that was sensitive to inhibition with the reducing agent dithiothreitol, suggesting that oxidative stress resulted in TNFR self-association. Treatment of cells with low concentrations of diamide (1 mum) that was not sufficient to provoke TNFR self-association resulted in increased TNF-induced FRET signals relative to the untreated cells, suggesting that oxidative stress enhanced ligand-dependent TNFR signaling. Similar findings were obtained when the TNFR1- and TNFR2-transfected cells were pretreated with a cell-impermeable oxidase, DsbA, that catalyzes disulfide bond formation between thiol groups on cysteine residues. The changes in TNFR self-association were functionally significant, because pretreating the HeLa cells and 293T cells resulted in increased TNF-induced NF-kappaB activation and TNF-induced expression of IkappaB and syndecan-4 mRNA levels. Although pretreatment with DsbA did not result in an increase in TNF binding to TNFRs, it resulted in increased TNF-induced activation of NF-kappaB, consistent with an allosteric modification of the TNFRs. Taken together, these results suggest that oxidative stress promotes TNFR receptor self-interaction and ligand-independent and enhanced ligand-dependent TNF signaling.
Comparison of Coal Ash Particle Size Distributions from Berner and Dekati Low Pressure Impactors (2007)

This article presents the differential mass size distributions of coal combustion particulate matter (PM) determined with the Berner low-pressure impactor (BLPI, Hauke Model 25-4/0.015) and a newer generation of low pressure impactor, the Dekati low-pressure impactor (DLPI, Dekati Ltd Model 6281). The collection characteristics of the BLPI and DLPI are compared and cutoff diameters are calculated. Samples were collected in the post-combustion zone of a 19 kW vertical downflow combustor from two coal types. Both BLPI and DLPI represent a tri-modal distribution and give statistically similar characterizations of the coal ash particle size distribution. Distributions generated from DLPI data have higher fractions of submicron particles compared to those generated from BLPI data. The DLPI's two additional stages may provide greater resolution in the submicron region than the BLPI.