Miracle-dz/UniFAR-FTUs huggingface dataset:
Model of Autochthonous Prostate Cancer Self/Tumor-Specific CD8 T Cells in a Murine Delays but Does Not Prevent Dysfunction of Signaling b Cell-Intrinsic Abrogation of TGF-Ratliff,

Adoptive T cell therapy (ACT) for the treatment of established cancers is actively being pursued in clinical trials. However, poor in vivo persistence and maintenance of antitumor activity of transferred T cells remain major problems. TGF- b is a potent immunosuppressive cytokine that is often expressed at high levels within the tumor microenvironment, potentially limiting T cell-mediated antitumor activity. In this study, we used a model of autochthonous murine prostate cancer to evaluate the effect of cell-intrinsic abrogation of TGF- b signaling in self/tumor-speciﬁc CD8 T cells used in ACT to target the tumor in situ. We found that persistence and antitumor activity of adoptively transferred effector T cells deﬁcient in TGF- b signaling were signiﬁcantly improved in the cancerous prostate. However, over time, despite persistence in peripheral lymphoid organs, the numbers of transferred cells in the prostate decreased and the residual prostate-inﬁltrating T cells were no longer functional. These ﬁndings reveal that TGF- b negatively regulates the accumulation and effector function of transferred self/tumor-speciﬁc CD8 T cells and highlight that, when targeting a tumor Ag that is also expressed as a self-protein, additional substantive obstacles are operative within the tumor microenvironment, potentially hampering the success of ACT for solid tumors. The Journal of Immunology , 2012, 189: 000–000.
Role of electrostatic interactions in amyloid β -protein (A β ) oligomer formation: A discrete molecular dynamics study

Pathological folding and oligomer formation of the amyloid β -protein (A β ) are widely per-ceived as central to Alzheimer’s disease (AD). Experimental approaches to study A β self-assembly provide limited information because most relevant aggregates are quasi-stable and inhomogeneous. We apply a discrete molecular dynamics (DMD) approach combined with a four-bead protein model to study oligomer formation of A β . We address the diﬀerences between the two most common A β alloforms, A β 40 and A β 42, which oligomerize diﬀer-ently in vitro . Our previous study showed that, despite simpliﬁcations, our DMD approach accounts for the experimentally observed diﬀerences between A β 40 and A β 42 and yields structural predictions amenable to in vitro testing. Here we study how the presence of electrostatic interactions (EIs) between pairs of charged amino acids aﬀects A β 40 and A β 42 oligomer formation. Our results indicate that EIs promote formation of larger oligomers in both A β 40 and A β 42. Both A β 40 and A β 42 display a peak at trimers/tetramers, but A β 42 displays additional peaks at nonamers and tetradecamers. EIs thus shift the oligomer size distributions to larger oligomers. Nonetheless, the A β 40 size distribution remains unimodal, whereas the A β 42 distribution is trimodal, as observed experimentally. We show that structural diﬀerences between A β 40 and A β 42 that already appear in the monomer folding, are not aﬀected by EIs. A β 42 folded structure is characterized by a turn in the C-terminus that is not present in A β 40. We show that the same C-terminal region is also responsible for the strongest intermolecular contacts in A β 42 pentamers and larger oligomers. Our results suggest that this C-terminal region plays a key role in the formation of A β 42 oligomers and the relative importance of this region increases in the presence of EIs. These results suggest that inhibitors targeting the C-terminal region of A β 42 oligomers may be able to prevent oligomer formation or structurally modify the assemblies to reduce their toxicity. Our results indicate that in A β 40 pentamers and larger oligomers, EIs weaken intramolecular interactions. In A β 42, in contrast, the intramolecular contacts in the turn region D23-K28 are enhanced. Surprisingly, in both A β 40 and A β 42 oligomers, the intermolecular contacts involving the CHC are signiﬁcantly weaker in the presence of EIs. In addition, in A β 42 oligomers, the contacts involving the CTR and MHR get stronger. These results, combined with the fact that EIs promote larger oligomers, imply that the intermolecular interactions between pairs of CHCs in an indirect way oppose the formation of larger oligomers, while the interactions between pairs of CTRs, and to a smaller extent also pairs of MHRs, promote formation of larger oligomers. Thus, therapeutic strategies using inhibitors that target the CTR and MHR may prove successful in either inhibiting formation of toxic A β 42 oligomers or inducing structural modiﬁcations neutralizing their toxicity.
Mechanism-Based Inactivation of Cytochrome P450 3A4 by Mibefradil through Heme Destruction □ S

: Mibefradil (Posicor) was developed as a calcium channel blocker for the treatment of chronic hypertension. The compound was withdrawn from the market in 1998 because of the potential for rhabdomyolysis, renal failure, or bradycardia when it was coadministered with other drugs. Mibefradil has previously been shown to be a potent reversible (IC 50 (cid:1) 0.3–2 (cid:2) M) and mechanism-based ( K i (cid:1) 2.3 (cid:2) M; k inact (cid:1) 0.4 min (cid:3) 1 ) inhibitor of CYP3A4-catalyzed statin metabolism. At present, the mechanism of CYP3A4 inactivation by mibefradil is not known. Mechanism-based inactivation experiments and spectral studies were used to examine the mechanism of CYP3A4 inactivation by mibefradil and its major metabolite, des-methoxyacetyl mibefradil (Ro 40-5966), in vitro. Both mibefradil and Ro 40-5966 were shown to exhibit type I binding characteristics ( K s (cid:1) 0.69 (cid:4) 0.06 and 1.39 (cid:4) 0.04 (cid:2) M, respectively) toward CYP3A4. Complete K i / k inact experiments were performed, revealing a rapid and irreversible decrease in CYP3A4-catalyzed 1 (cid:2) -hydroxymidazolam formation. Approximately 70% of CYP3A4 activity was lost in the first minute of incubation with mibefradil, and inactivation was nonlinear after 2 min. Ro 40-5966 also resulted in time-dependent inhibition of CYP3A4, albeit to a lesser extent than mibefradil. The decrease in CYP3A4 activity in the presence of mibefradil and NADPH was subsequently shown to have a good correlation with the time-dependent loss of CO binding, which, coupled with the lack of stable heme and/or apoprotein adducts, suggests heme destruction as the mechanism of inactivation of CYP3A4 by mibefradil. to determine the Secondary (final concentration) on the inactivation of CYP3A4 by mibefradil assessed using a similar protocol for mibefradil time-dependent inactivation experiments Spectral Studies. Binding affinity studies using purified CYP3A4 together with metabolite-intermediate complex formation and carbon monoxide binding experiments in Baculosomes were conducted in an attempt to further elucidate the mechanism of inactivation. Binding spectra of mibefradil and Ro 40-5966 CYP3A4 obtained using difference at To further confirm binding mibefradil, complex verapamil For CO binding Baculosomes, Slide-A-Lyzer
EVALUATION OF SOME RICE VARIETIES FOR THEIR ABILITIES TO IMMATURE EMBRYO CULTURE UNDER SALINITY STRESS

This study was carried out to evaluate some rice varieties for their ability to immature embryo culture under salt stress condition. Therefore, three varieties were used as the donor plants for immature embryo culture in order to assessment their abilities for response under salinity stress. The recorded data on the embryo response percentage, shoot bud percentage and plantlet percentage were subjected for statistical analyses. The test of significance of the mean squares of genotypes at the three levels of NaCl except for embryo response percentage at control level, indicated the presence of significant differences among these genotypes for all in vitro traits. This finding indicated that these genotypes were varied in their response to immature embryo culture. Furthermore, levels and genotype × levels interaction mean squares were highly significant in plantlet percentage trait. This result indicated that these genotypes gave different response for different NaCl levels. At level 2000 ppm, although the greatest mean values for shoot bud percentage was recorded in Giza 177 with the mean of 69.98% which was not significantly differed than Giza 182 (64.00%). Also, the greatest mean values for plantlet percentage was recorded in Giza 182 with the mean of 58.79%. On the other hand, the lowest shoot bud percentage was observed in Giza 178 with the mean of 44.80% as well as, Giza 177 which recorded the lowest values for plantlet percentage with the mean of 34.58%. Regarding the third level of NaCl 4000 ppm, the best variety with the highest mean values for shoot bud and plantlet percentages was Giza182. This finding indicated that Giza 182 was highly tolerant to NaCl concentration at in vitro levels and may produce somaclones with NaCl tolerance
Targeted Inactivation of the IL-4 Receptor (cid:2) Chain I4R Motif Promotes Allergic Airway Inﬂammation

The insulin/interleukin-4 (IL-4) receptor (I4R) motif mediates the association of insulin receptor substrate (IRS)-2 with the interleukin-4 (IL-4)R (cid:2) chain and transduces mitogenic signals in response to IL-4. Its physiological functions were analyzed in mice with a germline point mutation that changed the motif’s effector tyrosine residue into phenylalanine (Y500F). The Y500F mutation abrogated IRS-2 phosphorylation and impaired IL-4–induced CD4 (cid:3) T lymphocyte proliferation but left unperturbed Stat6 activation, up-regulation of IL-4-responsive gene products, and Th cell differentiation under Th2 polarizing conditions. However, in vivo the Y500F mutation was associated with increased allergen-induced IgE production, airway responsiveness, tissue eosinophilia, and mucus production. These results define an important role for the I4R motif in regulating allergic inflammation.
Automatic Alignment System in Simple Planes for Projection Mapping

Projection of computer graphics images on walls or architecture, known as projection mapping, has been used widely and applied in many fields. In projection mapping, the relative alignment between the projected images and the target is important because the efficiency of projection mapping may be reduced due to misregistration. However, the process of alignment is manual and time-consuming. To solve this problem, we propose an automatic alignment method th at uses depth information and geometrical characteristics of a plane. This meth od enables the correction of a distorted image proj ected from an arbitrary angle. As a result, distortion is reduced by applying our proposed method, which is evaluated by the error rate defined. Performing additional experiments and evalua ting the effect of our method will be a part of our future works.
motifs in the promoters of AP2/ERF gene clusters in other

biosynthesis of diverse specialized metabolites, steroidal glycoalkaloids in ), and pharmaceutically valuable terpenoid indole alkaloids (TIAs) in Madagascar periwinkle 45 ( Catharanthus ). However, the regulatory relationships between individual AP2/ERF genes within the cluster remain unexplored. We uncovered intra-cluster regulation of the C. roseus AP2/ERF regulatory circuit, which consists of ORCA3 , ORCA4 , and ORCA5 . ORCA3 and ORCA5 activate ORCA4 by directly binding to a GC-rich motif in the ORCA4 promoter. ORCA5 regulates its own expression through a positive auto-regulatory loop, and indirectly activates ORCA3 . In determining the functional conservation of AP2/ERF clusters in other plant species, we found that GC-rich motifs are present in the promoters of analogous AP2/ERF clusters in tobacco, tomato, and potato. Intra-cluster regulation is evident within the tobacco NICOTINE2 ( NIC2 ) ERF cluster. Moreover, overexpression of ORCA5 in tobacco and of NIC2 ERF189 in C. roseus hairy nicotine and TIA pathway genes, respectively, suggesting that the AP2/ERFs are This study demonstrates intra-cluster and mutual gene a regulatory biosynthesis of of plant metabolites 6,7-Epoxidases Initiate Lochnericine-Derived Alkaloid Biosynthesis
An Analytic Recursive Method for Optimal Multiple Stopping: Canadization and Phase-Type Fitting

We study an optimal multiple stopping problem for call-type payoff driven by a spectrally negative Levy process. The stopping times are separated by constant refraction times, and the discount rate can be positive or negative. The computation involves a distribution of the Levy process at a constant horizon and hence the solutions in general cannot be attained analytically. Motivated by the maturity randomization (Canadization) technique by Carr (1998), we approximate the refraction times by independent, identically distributed Erlang random variables. In addition, fitting random jumps to phase-type distributions, our method involves repeated integrations with respect to the resolvent measure written in terms of the scale function of the underlying Levy process. We derive a recursive algorithm to compute the value function in closed form, and sequentially determine the optimal exercise thresholds. A series of numerical examples are provided to compare our analytic formula to results from Monte Carlo simulation.
Estimating diurnal temperature variation at the stratopause from horizon radiance measurements

Rocket measurements of diurnal temperature variations in the stratopause region are much larger than predicted by tidal theory or direct radiative control and have different phases. Three models of temperature variation (measured, tidal, and radiative control) were superposed on a mean temperature profile; 15-μ horizon radiance profiles were then calculated and harmonically analyzed to give amplitude and phase as functions of height. The measured temperature variation leads to an horizon radiance variation three times as large as predicted by the tidal model at 45-km tangent height, and the phases differ by three hours. The difference in diurnal range between measured and tidal models is eight times resolution at that height for a satellite at 400-km altitude. This means that horizon radiance measurements could discriminate among the models and could indicate whether the temperature disagreement is due to the rocket measurements or to the theory.
Morita equivalence for partially ordered monoids and po-Γ-semigroups with unities

We prove that operator pomonoids of a po-Γ-semigroup with unities are Morita equivalent pomonoids. Conversely, we show that if L and R are Morita equivalent pomonoids then a po-Γ-semigroup A with unities can be constructed such that left and right operator pomonoids of A are Pos -isomorphic to L and R respectively. Using this nice connection between po-Γ-semigroups and Morita equivalence for pomonoids we, in one hand, obtain some Morita invariants of pomonoids using the results of po-Γ-semigroups and on the other hand, some recent results of Morita theory of pomonoids are used to obtain some results of po-Γ-semigroups.
Li+ ion source development for the Neutralized Drift Compression Experiment (NDCX)

We report results on lithium alumino-silicate ion source development in preparation for warm-dense-matter heating experiments on the new Neutralized Drift Compression Experiment (NDCX-II). The practical limit to the current density for a lithium alumino-silicate source is determined by the maximum operating temperature that the ion source can withstand before running into problems of heat transfer, melting of the alumino-silicate material, and emission lifetime. Using small prototype emitters, at a temperature of ≈ 1275 0 C, a space-charge-limited Li + beam current density of J ≈ 1 mA/cm 2 was obtained. The lifetime of the ion source was ≈ 50 hours while pulsing at a rate of 0.033 Hz with a pulse duration of 5-6 μ s.
A Fast Fractal Image Compression Coding Method

Fast algorithms for reducing encoding complexity of fractal image coding have recently been an important research topic. Search of the best matched domain block is the most computation intensive part of the fractal encoding process. In this paper, a fast fractal approximation coding scheme implemented on a personal computer based on matching in range block's neighbours is presented. Experimental results show that the proposed algorithm is very simple in implementation, fast in encoding time and high in compression ratio while PSNR is almost the same as compared with Barnsley's fractal block coding .
Cytotoxic and Antimigration Effects of Different Parts of Oroxylum Indicum Extract on Human Breast Cancer MCF-7 Cells

The objective of this research was to investigate the effects of Oroxylum indicum extracts on breast cancer MCF-7 cell proliferation and migration. Four parts of O. indicum , including leaf, bark, pod, and seed, were used. The total phenolic and flavonoid contents were determined to be at high concentrations in the four parts of O. indicum with the seed extract showing the highest levels. For MCF-7 cell death and proliferation, all O. indicum extracts caused stimulating cancer cell death and inhibiting cancer cell proliferation in dose- and time-dependent manners, surprisingly; the seed extract had the highest effects to inhibit cell proliferation. The IC 50 values of cell viability of O. indicum extracts were demonstrated as 161.2±8.63, 286.73±33.01, 149.03±8.81, and 107.06±5.66  g/mL for leaf, pod, bark, and seed, respectively. Cell counts by crystal violet staining showed that the seed extract stimulated cell death at the lowest concentration. Moreover, all of the O . indicum extracts decreased MCF-7 cell colony formation. Finally, we found that O . indicum extracts could inhibit cancer cell migration in a dose-dependent manner. In conclusion, our results showed that the seed extract of O . indicum showed the highest cytotoxic and anti-migratory activity, which was more than in the leaf, pod, and bark, on breast MCF-7 cell cancer and O . indicum can be an anticancer agent for breast cancer patients.
MYOCARDIAL ISCHEMIA Clinical Implications of Silent Versus Symptomatic Exercise-Induced Myocardial Ischemia in Patients With Stable Coronary Disease

Objectives. This study was undertaken to better understand the functional and prognostic signiﬁcance of silent relative to symptomatic ischemia. Background. Previous studies have reached conﬂicting conclusions as to whether painless ischemia identiﬁed during noninvasive cardiac testing is related to a lesser extent of myocardial ischemia or a different prognosis than ischemia accompanied by angina, or both. Methods. Nine hundred thirty-six clinically stable patients 1 to 6 months after an acute coronary event, either myocardial infarction or unstable angina, underwent ambulatory monitoring, exercise treadmill testing and stress thallium-201 scintigraphy. They were then followed up prospectively for a mean of 23 months for recurrent cardiac events (cardiac death, nonfatal myocardial infarction or unstable angina). Results. Compared with patients with symptomatic ischemia during testing (n (cid:53) 125), those with silent ischemia (n (cid:53) 378) demonstrated less severe and extensive reversible defects on stress thallium scintigraphy (p (cid:53) 0.0008), less functional impair-ment during treadmill testing manifested by longer exercise duration (640 (cid:54) vs. s, p and longer time to ST segment depression (530 frequent ST segment depression during ambulatory
The right dorsolateral prefrontal cortex prevents post-error slowing

-2-ABSTRACT Adjusting behavior following the detection of inappropriate actions allows flexible adaptation to task demands and environmental contingencies during goal-directed behaviors. Post-error behavioral adjustments typically consist in adopting more cautious response mode, which manifests as a slowing down of response speed. Although converging evidence involves the dorsolateral prefrontal cortex (DLPFC) in post-error behavioral adjustment, whether and when the left or right DLPFC is critical for post-error slowing (PES), as well as the underlying brain mechanisms, remain highly debated. To resolve these issues, we used single-pulse transcranial magnetic stimulation in healthy human adults to disrupt the left or right DLPFC selectively at various delays within the 30-180ms interval following false alarms commission, while participants preformed a standard visual Go/NoGo task. PES significantly increased after TMS disruption of the right, but not the left DLPFC at 150ms post-FA response. We discuss these results in terms of an involvement of the right DLPFC in reducing the detrimental effects of error detection on subsequent behavioral performance, as opposed to implementing adaptative error-induced slowing down of response speed.
FDR Control in the Presence of an Unknown Correlation Structure

The false discovery rate (FDR, Benjamini and Hochberg 1995) is a powerful approach to multiple testing. However, the original approach developed by Benjamini and Hochberg (1995) applies only to independent tests. Yekutieli (2008) showed that a modification of the Benjamini-Hochberg (BH) approach can be used in the presence of dependent tests and labelled his procedure as separate subsets BH (ssBH). However, Yekutieli (2008) left the practical specification of the subsets of p values largely unresolved. In this paper we propose a modification of the ssBH procedure based on a selection of the subsets that guarantees that the dependence properties needed to control the FDR are satisfied. We label this new procedure as the separate pairs BH (spBH). An extensive Monte Carlo analysis is presented that compares the properties of the BH and spBH procedures.
Phytochemical investigation and evaluation of anti-oxidant potential of Berberis lycium roots from Himachal Pradesh

Berberis lycium , a thorny evergreen shrub, commonly known as kashmal, found in subtropical and temperate regions of the world and mentioned in Indian traditional system of medicine. The present study deals with the preliminary phytochemical evaluation of different extracts of roots of B. lycium , isolation and identification of bioactive constituents from root extracts, its fractions and evaluation of their antioxidant potential by using hydrogen peroxide radical scavenging assay and reducing power assay. Extracts were fractionated and screened for their phytochemicals which resulted in isolation and identification of Stigmasterol (steroid), berberine, palmatine and jatrorrhizine (alkaloids), 4-methyl-7-hydroxycoumarin (coumarin) and 4,4-dimethylhexadeca-3-ol, responsible for the good anti-oxidant potential of the roots of B. lycium .