gebhart/patrepeval huggingface dataset:
Treatment-Dependent Androgen Receptor Mutations in Prostate Cancer Exploit Multiple Mechanisms to Evade Therapy (2009)

Mutations in the androgen receptor (AR) that enable activation by antiandrogens occur in hormone-refractory prostate cancer, suggesting that mutant ARs are selected by treatment. To validate this hypothesis, we compared AR variants in metastases obtained by rapid autopsy of patients treated with flutamide or bicalutamide, or by excision of lymph node metastases from hormone-naïve patients. AR mutations occurred at low levels in all specimens, reflecting genetic heterogeneity of prostate cancer. Base changes recurring in multiple samples or multiple times per sample were considered putative selected mutations. Of 26 recurring missense mutations, most in the NH(2)-terminal domain (NTD) occurred in multiple tumors, whereas those in the ligand binding domain (LBD) were case specific. Hormone-naïve tumors had few recurring mutations and none in the LBD. Several AR variants were assessed for mechanisms that might underlie treatment resistance. Selection was evident for the promiscuous receptor AR-V716M, which dominated three metastases from one flutamide-treated patient. For the inactive cytoplasmically restricted splice variant AR23, coexpression with AR enhanced ligand response, supporting a decoy function. A novel NTD mutation, W435L, in a motif involved in intramolecular interaction influenced promoter-selective, cell-dependent transactivation. AR-E255K, mutated in a domain that interacts with an E3 ubiquitin ligase, led to increased protein stability and nuclear localization in the absence of ligand. Thus, treatment with antiandrogens selects for gain-of-function AR mutations with altered stability, promoter preference, or ligand specificity. These processes reveal multiple targets for effective therapies regardless of AR mutation.
Supplementary Info from Cancer-Specific Production of N-Acetylaspartate via NAT8L Overexpression in Non–Small Cell Lung Cancer and Its Potential as a Circulating Biomarker (2023)

&lt;p&gt;Chemical identification of MMG-L as N-acetylaspartate (NAA). Supplementary Methods Supplementary Figure Legends&lt;/p&gt;
Singlet excitation in the intermediate magnetic equivalence regime and field-dependent study of singlet–triplet leakage (2019)

The examination and optimized preparation of nuclear spin singlet order has enabled the development of new types of applications that rely on potentially long-term polarization storage. Lifetimes several orders of magnitude longer than T1 have been observed. The efficient creation of such states relies on special pulse sequences. The extreme cases of very large and very small magnetic equivalence received primary attention, while relatively little effort has been directed towards studying singlet relaxation in the intermediate regime. The intermediate case is of interest as it is relevant for many spin systems, and would also apply to heteronuclear systems in very low magnetic fields. Experimental evidence for singlet-triplet leakage in the intermediate regime is sparse. Here we describe a pulse sequence for efficiently creating singlets in the intermediate regime in a broad-band fashion. Singlet lifetimes are studied with a specially synthesized molecule over a wide range of magnetic fields using a home-built sample-lift apparatus. The experimental results are supplemented with spin simulations using parameters obtained from ab initio calculations. This work indicates that the chemical shift anisotropy (CSA) mechanism is relatively weak compared to singlet-triplet leakage for the proton system observed over a large magnetic field range. These experiments provide a mechanism for expanding the scope of singlet NMR to a larger class of molecules, and provide new insights into singlet lifetime limiting factors.
Design, synthesis and evaluation of human telomerase inhibitors based upon a tetracyclic structural motif. (1999)

There is currently significant interest in the development of inhibitors of human telomerase for the treatment of cancer. We describe here the design and synthesis of a new class of mono-substituted small-molecule inhibitors of human telomerase based upon a tetracyclic structural motif. In contrast to the structurally related molecule 9-hydroxyellipticine, recently shown to inhibit telomerase activity in cell cultures but found to be inactive in a cell-free system, we demonstrate direct inhibition of the telomerase enzyme by the tetracyclic compounds in a modified cell-free TRAP assay. The most potent compounds exhibit activity in the low micromolar range and are thus comparable with some of the more active small-molecule telomerase inhibitors based on planar aromatic chromophores, previously described by ourselves and others. These compounds may represent useful leads for the development of more potent inhibitors of human telomerase.
Pressure, temperature, and electric field dependence of phase transformations in niobium modified 95/5 lead zirconate titanate (2015)

Ceramic niobium modified 95/5 lead zirconate-lead titanate (PZT) undergoes a pressure induced ferroelectric to antiferroelectric phase transformation accompanied by an elimination of polarization and a volume reduction. Electric field and temperature drive the reverse transformation from the antiferroelectric to ferroelectric phase. The phase transformation was monitored under pressure, temperature, and electric field loading. Pressures and temperatures were varied in discrete steps from 0 MPa to 500 MPa and 25 °C to 125 °C, respectively. Cyclic bipolar electric fields were applied with peak amplitudes of up to 6 MV m−1 at each pressure and temperature combination. The resulting electric displacement–electric field hysteresis loops were open “D” shaped at low pressure, characteristic of soft ferroelectric PZT. Just below the phase transformation pressure, the hysteresis loops took on an “S” shape, which split into a double hysteresis loop just above the phase transformation pressure. Far above the phase transformation pressure, when the applied electric field is insufficient to drive an antiferroelectric to ferroelectric phase transformation, the hysteresis loops collapse to linear dielectric behavior. Phase stability maps were generated from the experimental data at each of the temperature steps and used to form a three dimensional pressure–temperature–electric field phase diagram.
Approximated Planes in Parallel Coordinates (2000)

For the visualization of multivariate problems, a multidimensional system of Parallel coordinates is used which provides a one-to-one mapping between subsets of N-space and subsets of 2-space. A rigorous methodology for doing and seeing N-dimensional geometry emerges as well as several applications. Here an application to Error Tolerancing involving the visualization and characterization of 'approximate coplanarity' is presented. The exact description of the neighborhood of an N-dimensional hyperplane in a parallel coordinate system is given.
Statistical critical path analysis considering correlations (2005)

Critical path analysis is always an important task in timing verification. For todays nanometer IC technologies, process variations have a significant impact on circuit performance. The variability can change the criticality of long paths (Gattiker et al., 2002). Therefore, statistical approaches should be incorporated in critical path analysis. In this paper, we present two novel techniques that can efficiently evaluate path criticality under statistical non-linear delay models. They are integrated into a block-based statistical timing tool with the capability of handling arbitrary correlations from manufacturing process dependence and also path sharing. Experiments on ISCAS85 benchmarks as well as industrial circuits prove both accuracy and efficiency of these techniques.
Design of photonic-crystal surface-emitting lasers with circularly-polarized beam (2017)

We propose new structure of photonic-crystal surface-emitting lasers with oblique-triangular-prism-shaped air holes for direct emission of circularly polarized beam. We show appropriate height and tilt angle of oblique-triangular-prism-shaped air holes to achieve high degree of polarization. Secondly, we investigate the influence of cavity length. High degree of polarization can be obtained by appropriate air-hole shape and cavity length. We also show that right-handed or left-handed circular polarization can be chosen by changing tilt direction of air holes.
Surrogate-free machine learning-based organ dose reconstruction for pediatric abdominal radiotherapy (2020)

To study radiotherapy-related adverse effects, detailed dose information (3D distribution) is needed for accurate dose-effect modeling. For childhood cancer survivors who underwent radiotherapy in the pre-CT era, only 2D radiographs were acquired, thus 3D dose distributions must be reconstructed from limited information. State-of-the-art methods achieve this by using 3D surrogate anatomies. These can however lack personalization and lead to coarse reconstructions. We present and validate a surrogate-free dose reconstruction method based on Machine Learning (ML). Abdominal planning CTs (n = 142) of recently-treated childhood cancer patients were gathered, their organs at risk were segmented, and 300 artificial Wilms' tumor plans were sampled automatically. Each artificial plan was automatically emulated on the 142 CTs, resulting in 42,600 3D dose distributions from which dose-volume metrics were derived. Anatomical features were extracted from digitally reconstructed radiographs simulated from the CTs to resemble historical radiographs. Further, patient and radiotherapy plan features typically available from historical treatment records were collected. An evolutionary ML algorithm was then used to link features to dose-volume metrics. Besides 5-fold cross validation, a further evaluation was done on an independent dataset of five CTs each associated with two clinical plans. Cross-validation resulted in mean absolute errors ≤ 0.6 Gy for organs completely inside or outside the field. For organs positioned at the edge of the field, mean absolute errors ≤ 1.7 Gy for [Formula: see text], ≤ 2.9 Gy for [Formula: see text], and ≤ 13% for [Formula: see text] and [Formula: see text], were obtained, without systematic bias. Similar results were found for the independent dataset. To conclude, we proposed a novel organ dose reconstruction method that uses ML models to predict dose-volume metric values given patient and plan features. Our approach is not only accurate, but also efficient, as the setup of a surrogate is no longer needed.
Molecular Interactions between an Enzyme and Its Inhibitor for Selective Detection of Limonene (2022)

Researchers widely apply enzyme inhibition to chemicals such as pesticides, nerve gases, and anti-Alzheimer's drugs. However, application of enzyme inhibition to odorant sensors is less common because the corresponding reaction mechanisms have not yet been clarified in detail. In this study, we propose a new strategy for highly selective detection of odorant molecules by using an inhibitor-specific enzyme. As an example, we analyzed the selective interactions between acetylcholinesterase (AChE) and limonene─the major odorant of citrus and an AChE inhibitor─using molecular dynamics simulations. In these simulations, limonene was found to be captured at specific binding sites of AChE by modifying the binding site of acetylcholine (ACh), which induced inhibition of the catalytic activity of AChE toward ACh hydrolysis. We confirmed the simulation results by experiments using an ion-sensitive field-effect transistor, and the degree of inhibition of ACh hydrolysis depended on the limonene concentration. Accordingly, we quantitatively detected limonene at a detection limit of 5.7 μM. We furthermore distinguished the response signals to limonene from those to other odorants, such as pinene and perillic acid. Researchers will use our proposed odorant detection method for other odorant-enzyme combinations and applications of miniaturized odorant-sensing systems based on rapid testing.
A net with complex weights (2001)

In this article a new neural-network architecture suitable for learning and generalization is discussed and developed. Although similar to the radial basis function (RBF) net, our computational model called the net with complex weights (CWN) has demonstrated a considerable gain in performance and efficiency in number of applications compared to RBF net. Its better performance in classification tasks is explained by the cross-product terms in internal representation of its basis function introduced parsimoniously. Implementation of CWN by the ensemble approach is described. A number of examples, solved using CWN and other networks, are used to illustrate the desirable characteristics of CWN.
A1Adenosine Receptor Activation Promotes Angiogenesis and Release of VEGF From Monocytes (2007)

Adenosine is a proangiogenic purine nucleoside released from ischemic and hypoxic tissues. Of the 4 adenosine receptor (AR) subtypes (A1, A2A, A2B, and A3), the A2 and A3 have been previously linked to the modulation of angiogenesis. We used the chicken chorioallantoic membrane (CAM) model to determine whether A1 AR activation affects angiogenesis. We cloned and pharmacologically characterized chicken AR subtypes to evaluate the selectivity of various agonists and antagonists. Application of the A1 AR-selective agonist N6-cyclopentyladenosine (CPA; 100 nmol/L) to the CAM resulted in a 40% increase in blood vessel number (P<0.01), which was blocked by the A1 AR-selective antagonist C8-(N-methylisopropyl)-amino-N6-(5'-endohydroxy)-endonorbornan-2-yl-9-methyladenine (WRC-0571; 1 micromol/L). Selective A2A AR agonists did not stimulate angiogenesis in the CAM. In an ex vivo rat aortic ring model of angiogenesis that includes cocultured endothelial cells, fibroblasts, and smooth muscle cells, 50 nmol/L CPA did not directly stimulate capillary formation; however, medium from human mononuclear cells pretreated with CPA, but not vehicle, increased capillary formation by 48% (P<0.05). This effect was blocked by WRC-0571 (1.5 micromol/L) or anti-VEGF antibody (1 microg/mL). CPA (5 nmol/L) stimulated a 1.7-fold increase in VEGF release from the mononuclear cells. This is the first study to show that A1 AR activation induces angiogenesis. Stimulation of A2 ARs on endothelial cells results in proliferation and tube formation, and A2 and A3 ARs on inflammatory cells modulate release of angiogenic factors. We conclude that adenosine promotes a coordinated angiogenic response through its interactions with multiple receptors on multiple cell types.
Search forBs0→μ+μ−andB0→μ+μ−Decays inppCollisions ats=7  TeV (2011)

A search for the rare decays B(s)(0) → μ+ μ- and B(0) → μ+ μ- is performed in pp collisions at sqrt[s] = 7 TeV, with a data sample corresponding to an integrated luminosity of 1.14 fb(-1), collected by the CMS experiment at the LHC. In both cases, the number of events observed after all selection requirements is consistent with expectations from background and standard-model signal predictions. The resulting upper limits on the branching fractions are B(B(s)(0) → μ+ μ-) < 1.9 × 10(-8) and B(B(0) → μ+ μ-)<4.6 × 10(-9), at 95% confidence level.
Silicon Photonics Core-, Wavelength-, and Polarization-Diversity Receiver (2011)

A seven-core optical fiber, each core carrying two wavelength channels, is coupled to a novel silicon photonic integrated circuit (PIC). The silicon PIC uses grating couplers, Mach-Zehnder interferometers, and photodiodes to demultiplex and receive all 14 signals. We demonstrate reception of polarization-scrambled 5-Gb/s on-off keyed signals.
Gα(q/11)‐coupled P2Y 2 nucleotide receptor inhibits human keratinocyte spreading and migration (2007)

Reepithelialization is a critical step in wound healing. It is initiated by keratinocyte migration at the wound edges. After wounding, extracellular nucleotides are released by keratinocytes and other skin cells. Here, we report that activation of P2Y2 nucleotide receptor by ATP/UTP inhibits keratinocyte cell spreading and induces lamellipodium withdrawal. Kymography analysis demonstrates that these effects correlate with a durable decrease of lamellipodium dynamics. P2Y2 receptor activation also induces a dramatic dismantling of the actin network, the loss of alpha3 integrin expression at the cell periphery, and the dissolution of focal contacts as indicated by the alteration of alpha(v) integrins and focal contact protein distribution. In addition, activation of P2Y2R prevents growth factor-induced phosphorylation of Erk(1,2) and Akt/PkB. The use of a specific pharmacological inhibitor (YM-254890), the depletion of G alpha(q/11) by siRNA, or the expression of a constitutively active G alpha(q/11) mutant (Q209L) show that activation of G alpha(q/11) is responsible for these ATP/UTP-induced effects. Finally, we report that ATP delays growth factor-induced wound healing of keratinocyte monolayers. Collectively, these findings provide evidence for a unique and important role for extracellular nucleotides as efficient autocrine/paracrine regulators of keratinocyte shape and migration during wound healing.
The aluminium-[18F]fluoride revolution: simple radiochemistry with a big impact for radiolabelled biomolecules (2021)

The aluminium-[<sup>18</sup>F]fluoride ([<sup>18</sup>F]AlF) radiolabelling method combines the favourable decay characteristics of fluorine-18 with the convenience and familiarity of metal-based radiochemistry and has been used to parallel gallium-68 radiopharmaceutical developments. As such, the [<sup>18</sup>F]AlF method is popular and widely implemented in the development of radiopharmaceuticals for the clinic. In this review, we capture the current status of [<sup>18</sup>F]AlF-based technology and reflect upon its impact on nuclear medicine, as well as offering our perspective on what the future holds for this unique radiolabelling method.
Fuel-Optimal Maneuvers for Constrained Relative Satellite Orbits (2009)

This research investigates strategies to enable a deputy satellite to hover within a defined volume fixed in the vicinity of a chief satellite in a circular orbit for an extended period of time. Previous research developed initial methodologies for maintaining restricted teardrop hover orbits that exist in a plane fixed within the chief's local reference frame. These methods use the natural drift of the deputy satellite in the relative frame and impulsive thrust to keep the deputy in a bounded volume relative to the chief, but do not address fuel optimality. This research extends and enhances that work by finding the optimal trajectories produced with discrete thrusts that minimize fuel spent per unit time and stay within the user-defined volume, thus providing a practical hover capability in the vicinity of the chief. The work assumes that the Clohessy―Wiltshire closeness assumption between the deputy and chief is valid. Using the new methodology developed in this work, feasible closed- and nonclosed-relative orbits are found and evaluated based on a fuel criterion and are compared with an easily calculated continuous-thrust baseline. It is shown that in certain scenarios (generally corresponding to a smaller total time of flight) a discrete-thrust solution provides a lower overall fuel cost than a continuous-thrust solution. A simple check is proposed that enables the mission planner to make the correct strategy choice.
ChemInform Abstract: Discovery of L‐740,515, a Potent Thienopyridine cysLT1 Receptor (LTD4 Receptor) Antagonist. (1996)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Finite-state transducer-based statistical machine translation using joint probabilities. (2006)

In this paper, we present our system for statistical machine translation that is based on weighted finite-state transducers. We describe the construction of the transducer, the estimation of the weights, acquisition of phrases (locally ordered tokens) and the mechanism we use for global reordering. We also present a novel approach to machine translation that uses a maximum entropy model for parameter estimation and contrast its performance to the finite-state translation model on the IWSLT Chinese-English data sets. 1.
Food allergen detection by mass spectrometry: the role of systems biology (2016)

Food allergy prevalence is rising worldwide, motivating the development of assays that can sensitively and reliably detect trace amounts of allergens in manufactured food. Mass spectrometry (MS) is a promising alternative to commonly employed antibody-based assays owing to its ability to quantify multiple proteins in complex matrices with high sensitivity. In this review, we discuss a targeted MS workflow for the quantitation of allergenic protein in food products that employs selected reaction monitoring (SRM). We highlight the aspects of SRM method development unique to allergen quantitation and identify opportunities for simplifying the process. One promising avenue identified through a comprehensive survey of published MS literature is the use of proteotypic peptides, which are peptides whose presence appears robust to variations in food matrix, sample preparation protocol, and MS instrumentation. We conclude that proteotypic peptides exist for a subset of allergenic milk, egg, and peanut proteins. For less studied allergens such as soy, wheat, fish, shellfish, and tree nuts, we offer guidance and tools for peptide selection and specificity verification as part of an interactive web database, the Allergen Peptide Browser (http://www.AllergenPeptideBrowser.org). With ongoing improvements in MS instrumentation, analysis software, and strategies for targeted quantitation, we expect an increasing role of MS as an analytical tool for ensuring regulatory compliance.
Destruction behavior of power diodes beyond the SOA limit (2012)

Simulation results show how cathode-side filaments may trigger a thermal runaway at the end of a reverse-recovery period of diodes turned off with extremely high current rates. The mechanism is not essentially affected by the edge termination if an appropriate design is chosen. While multiple avalanche-induced filaments may appear during the reverse-recovery period, at the end of the turn-off phase a single “winning” filament carries the total current. This can result in a local melting of the diode. The appearance of a cathode-side filament by itself does not necessarily lead to the diode destruction. However, a high thermal carrier generation rate can result in an uncontrollable increase of the current density in a single filament connecting the anode and the cathode contact. It is shown t hat the reverse-recovery charge as a function of the dc-link voltage shows a characteristic super-linear increase below the critical value dc-link voltage at which the diode current increases uncontrollably.