gebhart/patrepeval huggingface dataset:
Mcl-1 Mediates Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Resistance in Human Cholangiocarcinoma Cells (2004)

Cholangiocarcinomas are usually fatal neoplasms originating from bile duct epithelia. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for cancer therapy, including cholangiocarcinoma. However, many cholangiocarcinoma cells are resistant to TRAIL-mediated apoptosis. Thus, our aim was to examine the intracellular mechanisms responsible for TRAIL resistance in human cholangiocarcinoma cell lines. Three TRAIL-resistant human cholangiocarcinoma cell lines were identified. All of the cell lines expressed TRAIL receptor 1/death receptor 4 (TRAIL-R1/DR4) and TRAIL-R2/DR5. Expression of TRAIL decoy receptors and the antiapoptotic cellular FLICE-inhibitory protein (cFLIP) was inconsistent across the cell lines. Of the antiapoptotic Bcl-2 family of proteins profiled (Bcl-2, Bcl-x(L), and Mcl-1), Mcl-1 was uniquely overexpressed by the cell lines. When small-interfering-RNA (siRNA) technology was used to knock down expression of Bcl-2, Bcl-x(L), and Mcl-1, only the Mcl-1-siRNA sensitized the cells to TRAIL-mediated apoptosis. In a cell line stably transfected with Mcl-1-small-hairpin-RNA (Mcl-1-shRNA), Mcl-1 depletion sensitized cells to TRAIL-mediated apoptosis despite Bcl-2 expression. TRAIL-mediated apoptosis in the stably transfected cells was associated with mitochondrial depolarization, Bax activation, cytochrome c release from mitochondria, and caspase activation. Finally, flavopiridol, an anticancer drug that rapidly down-regulates Mcl-1, also sensitized cells to TRAIL cytotoxicity. In conclusion, these studies not only demonstrate that Mcl-1 mediates TRAIL resistance in cholangiocarcinoma cells by blocking the mitochondrial pathway of cell death but also identify two strategies for circumventing this resistance.
Clinical and biological implications of driver mutations in myelodysplastic syndromes (2013)

Myelodysplastic syndromes (MDS) are a heterogeneous group of chronic hematological malignancies characterized by dysplasia, ineffective hematopoiesis and a variable risk of progression to acute myeloid leukemia. Sequencing of MDS genomes has identified mutations in genes implicated in RNA splicing, DNA modification, chromatin regulation, and cell signaling. We sequenced 111 genes across 738 patients with MDS or closely related neoplasms (including chronic myelomonocytic leukemia and MDS-myeloproliferative neoplasms) to explore the role of acquired mutations in MDS biology and clinical phenotype. Seventy-eight percent of patients had 1 or more oncogenic mutations. We identify complex patterns of pairwise association between genes, indicative of epistatic interactions involving components of the spliceosome machinery and epigenetic modifiers. Coupled with inferences on subclonal mutations, these data suggest a hypothesis of genetic "predestination," in which early driver mutations, typically affecting genes involved in RNA splicing, dictate future trajectories of disease evolution with distinct clinical phenotypes. Driver mutations had equivalent prognostic significance, whether clonal or subclonal, and leukemia-free survival deteriorated steadily as numbers of driver mutations increased. Thus, analysis of oncogenic mutations in large, well-characterized cohorts of patients illustrates the interconnections between the cancer genome and disease biology, with considerable potential for clinical application.
The vacuolar ATPase is required for physiological as well as pathological activation of the Notch receptor (2010)

Evidence indicates that endosomal entry promotes signaling by the Notch receptor, but the mechanisms involved are not clear. In a search for factors that regulate Notch activation in endosomes, we isolated mutants in Drosophila genes that encode subunits of the vacuolar ATPase (V-ATPase) proton pump. Cells lacking V-ATPase function display impaired acidification of the endosomal compartment and a correlated failure to degrade endocytic cargoes. V-ATPase mutant cells internalize Notch and accumulate it in the lysosome, but surprisingly also show a substantial loss of both physiological and ectopic Notch activation in endosomes. V-ATPase activity is required in signal-receiving cells for Notch signaling downstream of ligand activation but upstream of gamma-secretase-dependent S3 cleavage. These data indicate that V-ATPase, probably via acidification of early endosomes, promotes not only the degradation of Notch in the lysosome but also the activation of Notch signaling in endosomes. The results also suggest that the ionic properties of the endosomal lumen might regulate Notch cleavage, providing a rationale for physiological as well as pathological endocytic control of Notch activity.
Mammalian Protein Geranylgeranyltransferase-I: Substrate Specificity, Kinetic Mechanism, Metal Requirements, and Affinity Labeling (1995)

Protein geranylgeranyltransferase-I (PGGT-I) catalyzes the transfer of the 20-carbon prenyl group from geranylgeranyl pyrophosphate to the cysteine residue near the C-termini of a variety of eukaryotic proteins. Kinetic analysis of homogenous PGGT-I from bovine brain reveals that the reaction follows a sequential pathway in which either prenyl donor or acceptor can bind first to the enzyme and that the reaction operates at steady-state rather than at rapid equilibrium. Substrate inhibition by prenyl acceptor but not by prenyl donor suggests that geranylgeranyl pyrophosphate binding first to free enzyme is the kinetically preferred pathway. This is supported by isotope trapping experiments which show that the ternary complex goes on to products faster than the release of geranylgeranyl pyrophosphate from the complex. The KM for the interaction of geranylgeranyl pyrophosphate with PGGT-I is markedly affected by the structure of the prenyl acceptor bound to the enzyme. A detailed analysis of the substrate specificity of PGGT-I reveals that peptides which contain a C-terminal leucine are preferred (kcat/KM = 1-5 x 10(5) M-1 s-1) to those that end in serine (kcat/KM = 2-4 x 10(3) M-1 s-1) or phenylalanine (kcat/KM = 0.5 x 10(3) M-1 s-1). PGGT-I also catalyzes the farnesylation of peptides that have a C-terminal leucine; kcat for farnesylation and KM for farnesyl pyrophosphate are similar to those for geranylgeranylation, but the KM for the peptide is 30-fold higher. Geranyl pyrophosphate is utilized by PGGT-I but is a poor substrate. Optimal activity of PGGT-I is obtained in the presence of micromolar amounts of Zn2+ and mM amounts of Mg2+. Mn2+ or Cd2+ but not Co2+ can substitute for Zn2+ and for Mg2+. Metals are not required for tight-binding of geranylgeranyl pyrophosphate to PGGT-I, and the measured dissociation equilibrium constant for this binary complex is 16 nM. Photoaffinity analogues of geranylgeranyl pyrophosphate and farnesyl pyrophosphate were prepared and shown to exclusively label the beta-subunit. The implication of the results for the substrate specificity of protein prenylation in cells is briefly discussed.
Brain Injury Causes Loss of Cardiovascular Response to Hemorrhagic Shock (1993)

The combined cardiovascular effects of hemorrhagic shock and mechanical brain injury were modeled in five groups of pigs. Standard and hypertonic saline resuscitation of hypotension were evaluated. Changes in mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), intracranial pressure (ICP), and brain water were measured. Brain injury (BI) was produced with a fluid percussion device that generated an extradural pressure of 3.5 x 10(5) N/m2 for 400 msec. Shock was caused by bleeding to a MAP of 60 mm Hg for 60 minutes and then resuscitated with shed blood only or shed blood plus 0.9% or 1.8% saline. Brain-injured only and shocked-only pigs served as controls. We found that brain injury alone caused refractory hypotension. Less shed blood was required to produce shock in brain injured animals (p < .05). Shock accompanied by brain injury was not reversed with crystalloid solutions. Volumes of saline required to restore blood pressure were large (> 6 L in 3 hours). 1.8% saline produced less rise in ICP than 0.9% saline but was less effective in restoring blood pressure. Brain edema was not decreased with 1.8% saline. Brain injury altered vascular compensation to hemorrhage and made accepted resuscitative measures ineffective.
Proteomic-based identification of injury-specific patterns of biomarkers in rotational and penetrating TBI (2010)

Background: Traumatic Brain Injury (TBI) biomarkers would be highly valuable in the diagnosis of various forms of TBI and also in evaluation and treatment of TBI patients and may even provide prediction of outcome of the future impairments of the patients. Here we use proteomics to investigate the temporal changes of chosen proteins in serum and brain in 2 different animal TBI models. Methods: The first model is a controlled penetration of 2 mm thick needle shaped object, which is accelerated with a bullet from air gun or a pendulum, pen-TBI. In the second model where we produce diffuse axonal injury, the animal is subjected to high-speed sagittal rotation acceleration, rot-TBI. The rats were sacrificed 1 day, 3 days and 14 days post injury. We used 30rats, 15rats in each model, 5 rats for each timepoint where 2 of these where sham, these results were compared with values from normal rats. The FC (FC) and HC (HC) were extracted in addition to serum samples. The tissue extractions were analyzed with reverse capture antibody based proteomics for N-cadherin, S-100B, Tau, NSE, NF200, TNF-a, MBP, BDNF, C3, C9, C5b9,Results: In brain significant changes could be seen in N-cadherin in HC in pen-TBI on day 1, BDNF showed a peak in rot-TBI on day 1 while in pen-TBI the peak was after 14 days. C3 increased significantly in the HC of rot-TBI at day 1. C9 increased significantly in rot-TBI both in FC and HC on day 3 and day1 and 3 respectively. C5b9 had its peak in HC in rot-TBI on day 1 but in pen-TBI at day14. N-cadherin in serum of rot-TBI showed a significant increase in day 1 and 14 with a nadir at day3. The pattern was different in pen-TBI where there was an increase at all timepoint with increase overtime. Tau in serum was significantly increased uniformly at all time points in both models. TNF-a was also increased at all timepoints but in rot-TBI it decreased by day 14. S-100B showed no significant change in rot-TBI while in pen-TBI it was significantly increased at all timepoints. NSE in rot-TBI had a peak at day 1 and declined but in pen-TBI there was a nadir at day 3 and the peak was reached by day14. Similar pattern was seen in NF200. MBP was increased at all timepoints with a peak at day 3 in both models. C3 was increased at all timepoints but in pen-TBI it had a peak in day 3. C9 in rot-TBI increased significantly at day 3 and 14 while in pen-TBI it increased from day1 till day 14. C5b9 was significantly increased at all timepoints in both models however in rot-TBI it increased overtime while in pen-TBI it had a peak on day 14.Conclusion: To the best of our knowledge these are the first results showing TBI – type specific changes in different proteins that can be considered as future biomarkers.
Simultaneous measurement of strain and temperature using the first- and second-order diffraction wavelengths of Bragg gratings (1997)

A method of discriminating between temperature and strain effects in fibre sensing using a conventionally written, in-fibre Bragg grating is presented. The technique uses wavelength information from the first and second diffraction orders of the grating element to determine the wavelength dependent strain and temperature coefficients, from which independent temperature and strain measurements can be made. The authors present results that validate this matrix inversion technique and quantify the strain and temperature errors which can arise for a given uncertainty in the measurement of the reflected wavelength.
1,5-Diphosphabicyclo[3.3.1]nonane 1,5-disulfide (1988)

Cristallisation dans P2 1 /c avec affinement jusqu'a 0,030. La molecule a une conformation chaise-chaise. L'atome P a une coordination tetraedrique legerement deformee
Characterization of Intrinsic Properties of Promoters (2015)

Accurate characterization of promoter behavior is essential for the rational design of functional synthetic transcription networks such as logic gates and oscillators. However, transcription rates observed from promoters can vary significantly depending on the growth rate of host cells and the experimental and genetic contexts of the measurement. Furthermore, in vivo measurement methods must accommodate variation in translation, protein folding, and maturation rates of reporter proteins, as well as metabolic load. The external factors affecting transcription activity may be considered to be extrinsic, and the goal of characterization should be to obtain quantitative measures of the intrinsic characteristics of promoters. We have developed a promoter characterization method that is based on a mathematical model for cell growth and reporter gene expression and exploits multiple in vivo measurements to compensate for variation due to extrinsic factors. First, we used optical density and fluorescent reporter gene measurements to account for the effect of differing cell growth rates. Second, we compared the output of reporter genes to that of a control promoter using concurrent dual-channel fluorescence measurements. This allowed us to derive a quantitative promoter characteristic (ρ) that provides a robust measure of the intrinsic properties of a promoter, relative to the control. We imposed different extrinsic factors on growing cells, altering carbon source and adding bacteriostatic agents, and demonstrated that the use of ρ values reduced the fraction of variance due to extrinsic factors from 78% to less than 4%. This is a simple and reliable method to quantitatively describe promoter properties.
Beyond Trending Topics: Real-World Event Identification on Twitter (2011)

User-contributed messages on social media sites such as Twitter have emerged as powerful, real-time means of information sharing on the Web. These short messages tend to reflect a variety of events in real time, earlier than other social media sites such as Flickr or YouTube, making Twitter particularly well suited as a source of real-time event content. In this paper, we explore approaches for analyzing the stream of Twitter messages to distinguish between messages about real-world events and non-event messages. Our approach relies on a rich family of aggregate statistics of topically similar message clusters, including temporal, social, topical, and Twitter-centric features. Our large-scale experiments over millions of Twitter messages show the effectiveness of our approach for surfacing real-world event content on Twitter.
Fiber optic sensor for dual measurement of temperature and strain using a combined fluorescence lifetime decay and fiber Bragg grating technique (2001)

A fiber optic sensor device has been developed incorporating a short length of erbium doped fiber fused in close proximity to a single-fiber Bragg grating, to measure both the fluorescent lifetime decay and the wavelength shift in these respective elements, for temperature and strain determination. Calibration results obtained from this simple, low cost, intrinsic sensor scheme show standard deviation errors of 20.4 με and 1.2 °C over strain and temperature ranges of 22–1860 με and 25–120 °C, respectively.
A Phase II, Double-Blind, Randomized, Placebo-Controlled Clinical Trial of tgAAVCF Using Maxillary Sinus Delivery in Patients with Cystic Fibrosis with Antrostomies (2002)

tgAAVCF, an adeno-associated cystic fibrosis transmembrane conductance regulator (CFTR) viral vector/gene construct, was administered to 23 patients in a Phase II, double-blind, randomized, placebo-controlled clinical trial. For each patient, a dose of 100,000 replication units of tgAAVCF was administered to one maxillary sinus, while the contralateral maxillary sinus received a placebo treatment, thereby establishing an inpatient control. Neither the primary efficacy endpoint, defined as the rate of relapse of clinically defined, endoscopically diagnosed recurrent sinusitis, nor several secondary endpoints (sinus transepithelial potential difference [TEPD], histopathology, sinus fluid interleukin [IL]-8 measurements) achieved statistical significance when comparing treated to control sinuses within patients. One secondary endpoint, measurements of the anti-inflammatory cytokine IL-10 in sinus fluid, was significantly (p < 0.03) increased in the tgAAVCF-treated sinus relative to the placebo-treated sinus at day 90 after vector instillation. The tgAAVCF administration was well tolerated, without adverse respiratory events, and there was no evidence of enhanced inflammation in sinus histopathology or alterations in serum-neutralizing antibody titer to adeno-associated virus (AAV) capsid protein after vector administration. In summary, this Phase II trial confirms the safety of tgAAVCF but provides little support of its efficacy in the within-patient controlled sinus study. Various potentially confounding factors are discussed.
Targeted Adenovirus Vectors (2004)

Recombinant adenovirus (Ad) vectors continue to be the preferred vectors for gene therapy and the study of gene function because they are relatively easy to construct, can be produced at high titer, and have high transduction efficiency. However, in some applications gene transfer with Ad vectors is less efficient because the target cells lack expression of the primary receptor, coxsackievirus and adenovirus receptor (CAR). Another problem is the wide biodistribution of vector in tissue following in vivo gene transfer because of the relatively broad tissue expression of CAR. To overcome these limitations, various approaches have been developed to modify Ad tropism. In one approach, the capsid proteins of Ad are modified, such as with the addition of foreign ligands or the substitution of the fiber with other types of Ad fiber, in combination with the ablation of native tropism. In other approaches, Ad vectors are conjugated with adaptor molecules, such as antibody and fusion protein containing an anti-Ad single-chain antibody (scFv) or the extracellular domain of CAR with the targeting ligands, or chemically modified with polymers containing the targeting ligands. In this paper, we review advances in the development of targeted Ad vectors.
Distinct Olfactory Signaling Mechanisms in the Malaria Vector Mosquito Anopheles gambiae (2010)

Anopheles gambiae is the principal Afrotropical vector for human malaria, in which olfaction mediates a wide range of both adult and larval behaviors. Indeed, mosquitoes depend on the ability to respond to chemical cues for feeding, host preference, and mate location/selection. Building upon previous work that has characterized a large family of An. gambiae odorant receptors (AgORs), we now use behavioral analyses and gene silencing to examine directly the role of AgORs, as well as a newly identified family of candidate chemosensory genes, the An. gambiae variant ionotropic receptors (AgIRs), in the larval olfactory system. Our results validate previous studies that directly implicate specific AgORs in behavioral responses to DEET as well as other odorants and reveal the existence of at least two distinct olfactory signaling pathways that are active in An. gambiae. One system depends directly on AgORs; the other is AgOR-independent and requires the expression and activity of AgIRs. In addition to clarifying the mechanistic basis for olfaction in this system, these advances may ultimately enhance the development of vector control strategies, targeting olfactory pathways in mosquitoes to reduce the catastrophic effects of malaria and other mosquito-borne diseases.
Growth of Breath Figures (1986)

Measurements are reported of the growth of breath figures, the patterns that form when a vapor is condensed onto a cold surface. The pattern for water on glass was studied by direct observation and light scattering as a function of the contact angle $\ensuremath{\theta}$, flux $F$, degree of supersaturation $\ensuremath{\Delta}T$, and time $t$. When $\ensuremath{\theta}=0\ifmmode^\circ\else\textdegree\fi{}$, a uniform layer forms whose thickness grows as $t$ at constant $F$ and $\ensuremath{\Delta}T$. For $\ensuremath{\theta}=90\ifmmode^\circ\else\textdegree\fi{}$ droplets are formed; at constant $F$ and $\ensuremath{\Delta}T$ the radius of an isolated droplet grows as ${t}^{0.23}$, but as a result of coalescences the average droplet radius grows as ${t}^{0.75}$. The growth process is self-similar---coalescences simply rescale the distances and leave the basic droplet pattern unaltered.
Postannealing effects on magnetic properties and microstructure of CoCrPt/Ti perpendicular recording media (2003)

In this work, we investigate the postannealing effects on the magnetic and structural properties of CoCrPt perpendicular films. We observe a coercivity of 5000 Oe in the films with a 2 nm CrMn overlayer, which is about two times larger than the coercivity of similar films without a CrMn overlayer. This increment is attributed to the decoupling of grains by diffusion of CrMn from the top layer through the grain boundaries. An increase in the negative nucleation field and a decrease in intergranular exchange coupling with annealing temperatures was observed for the films with a CrMn overlayer. On the other hand, the films without a CrMn overlayer show the opposite trends except at high annealing temperature (450 °C). We observe a coercivity of ∼7600 Oe and a negative nucleation field of ∼2400 Oe for a film with a CrMn overlayer annealed at 450 °C for 5 min.
Solid‐state droplet laser made from an organic blend with a conjugated polymer emitter (1997)

Lasers based on organic materials have been produced with a wide range of resonator design and in a variety of geometries. A new strategy is presented for fabricating permanently near‐spherical whispering gallery mode (WGM) lasers from a blend of PPV7 and PBD (see Figure) by a melting and resolidification process. The thresholds and quality factors of these resonators are estimated and discussed. magnified image