gebhart/patrepeval huggingface dataset:
18F-XTRA PET for Enhanced Imaging of the Extrathalamic α4β2 Nicotinic Acetylcholine Receptor (2018)

Reduced density of the α4β2 nicotinic acetylcholine receptor (α4β2-nAChR) in the cortex and hippocampus of the human brain has been reported in aging and patients with neurodegenerative disease. This study assessed the pharmacokinetic behavior of <sup>18</sup>F-(-)-JHU86428 (<sup>18</sup>F-XTRA), a new radiotracer for in vivo PET imaging of the α4β2-nAChR, particularly in extrathalamic regions of interest in which the α4β2-nAChR is less densely expressed than in thalamus. <sup>18</sup>F-XTRA was also used to evaluate the α4β2-nAChR in the hippocampus in human aging. <b>Methods:</b> Seventeen healthy nonsmoker adults (11 men, 6 women; age, 30-82 y) underwent PET neuroimaging over 90 or 180 min in a high-resolution research tomograph after bolus injection of <sup>18</sup>F-XTRA. Methods to quantify binding of <sup>18</sup>F-XTRA to the α4β2-nAChR in the human brain were compared, and the relationship between age and binding in the hippocampus was tested. <b>Results:</b><sup>18</sup>F-XTRA rapidly entered the brain, and time-activity curves peaked within 10 min after injection for extrathalamic regions and at approximately 70 min in the thalamus. The 2-tissue-compartment model (2TCM) predicted the regional time-activity curves better than the 1-tissue-compartment model, and total distribution volume (V<sub>T</sub>) was well identified by the 2TCM in all ROIs. V<sub>T</sub> values estimated using Logan analysis with metabolite-corrected arterial input were highly correlated with those from the 2TCM in all regions, and values from 90-min scan duration were on average within 5% of those values from 180 min of data. Parametric images of V<sub>T</sub> were consistent with the known distribution of the α4β2-nAChR across the brain. Finally, an inverse correlation between V<sub>T</sub> in the hippocampus and age was observed. <b>Conclusion:</b> Our results extend support for use of <sup>18</sup>F-XTRA with 90 min of emission scanning in quantitative human neuroimaging of the extrathalamic α4β2-nAChR, including in studies of aging.
Establishing Suitability of RNA Preparations for Crystallization: Determination of Polydispersity (2003)

Successful crystallization of ribozymes and ribozyme domains depends on covalent homogeneity of the sample, conformational homogeneity of the preparation, and an efficient and broad sampling of solution conditions where crystals might nucleate and grow. Chapter 38 presents methods to prepare multimilligram quantities of pure RNA, and Chapter 40 describes strategies for determining crystallization conditions. This chapter presents two methods to determine the conformational homogeneity (polydispersity) of RNA preparations. These methods have been successfully used to determine which of several related constructs of a given target molecule are likely to crystallize, enabling the experimenter to focus on the most promising candidate, and constitute an important step in a successful strategy for crystallization.
Monitoring of tracer dispersion in porous media by NMR imaging (1991)

The dispersion of a paramagnetic tracer has been measured by NMR imaging in a non-consolidated porous medium made of 2 and 6 mm diameter glass beads. The technique allows one to obtain 3D images of the tracer repartition as well as instantaneous 1D concentration profiles along the flow axis. Flow reversibility was checked by examining concentration profile variations in both forward and backward flows. Dispersion coefficients were obtained by fitting 1D profiles with the solutions of the convection diffusion equation. They are completely consistent with usual results on bead packings for experiments performed with tracer injection stable with respect to gravity. Moreover, a total irreversibility of the dispersion is established after displacement lengths of a few bead diameters. The tracer distributions as observed from 3D images differ markedly in stable and unstable experiments. For gravitationally unstable injections, on both profiles and images, an additional, partly reversible, convective spreading was observed-it is probably due to permeability inhomogeneities of the bead packing.
The H Ratio for Address Assignment Efficiency (1994)

This document was submitted to the IETF IPng area in response to RFC
1550. This memo provides information for the Internet community. This
memo does not specify an Internet standard of any kind.
ChemInform Abstract: Metathesis by Molybdenum and Tungsten Catalysts (2016)

Abstract Review: 74 refs.
Combination of PDMS microfilters and micromixers based on flexible thermoplastic films for size sorting and mixing of microparticles (2015)

ABSTRACT We present a study for the development of flexible microfilters based on sealing microstructured poly(dimethylsiloxane) (PDMS) to different functionalized thermoplastic films [polyimide (PI), polyethylene naphthalate (PEN), and polyethylene terephthalate (PET)]. The microfilter was manufactured by soft‐lithography and replica molding and then combined with plasma activation and chemical treatment using 3 ‐( aminopropyl )triethoxysilane (APTES). To demonstrate the functionality of the PDMS microfilters, poly(lactic‐ co ‐glycolic acid) (PLGA) microparticles (MPS) were filtered through the microfluidic device based on the three thermoplastic films. Subsequently, the mixing capabilities of a passive PDMS micromixer was observed with the injection of polymeric MPS (fluorescent and nonfluorescent) as fluidic mixers are not generally effective at mixing particles. On mixing nonfluorescent MPS (∼&lt;10–30 µm in diameter) a mixing performance of 13.3% at 5 mm was observed. Therefore, a PDMS microfiltering device was integrated with a PDMS micromixer using a simple and cost effective home‐made polymeric connector for filtration at a size sorting of 11 µm. The results exhibit that the combination of the two microfluidic devices can be achieved with size sorting and mixing of MPS with an improved mixing performance of 62.5% at 3 mm. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132 , 42088.
Investigation of layered and porous nanomaterials by diffraction tomography, simulations and HRTEM (2016)

Figure 1. Intergrown polymorphic mixture of Zeolite Beta A and B: HRTEM hologram combined with structure solution models.
Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation (2015)

A central mechanism of tumour progression and metastasis involves the generation of an immunosuppressive 'macroenvironment' mediated in part through tumour-secreted factors. Here we demonstrate that upregulation of the Inhibitor of Differentiation 1 (Id1), in response to tumour-derived factors, such as TGFβ, is responsible for the switch from dendritic cell (DC) differentiation to myeloid-derived suppressor cell expansion during tumour progression. Genetic inactivation of Id1 largely corrects the myeloid imbalance, whereas Id1 overexpression in the absence of tumour-derived factors re-creates it. Id1 overexpression leads to systemic immunosuppression by downregulation of key molecules involved in DC differentiation and suppression of CD8 T-cell proliferation, thus promoting primary tumour growth and metastatic progression. Furthermore, advanced melanoma patients have increased plasma TGFβ levels and express higher levels of ID1 in myeloid peripheral blood cells. This study reveals a critical role for Id1 in suppressing the anti-tumour immune response during tumour progression and metastasis.
Gel transformation as a general strategy for fabrication of highly porous multiscale MOF architectures (2023)

The structure and chemistry of metal-organic frameworks or MOFs dictate their properties and functionalities. However, their architecture and form are essential for facilitating the transport of molecules, the flow of electrons, the conduction of heat, the transmission of light, and the propagation of force, which are vital in many applications. This work explores the transformation of inorganic gels into MOFs as a general strategy to construct complex porous MOF architectures at nano, micro, and millimeter length scales. MOFs can be induced to form along three different pathways governed by gel dissolution, MOF nucleation, and crystallization kinetics. Slow gel dissolution, rapid nucleation, and moderate crystal growth result in a pseudomorphic transformation (pathway 1) that preserves the original network structure and pores, while a comparably faster crystallization displays significant localized structural changes but still preserves network interconnectivity (pathway 2). MOF exfoliates from the gel surface during rapid dissolution, thus inducing nucleation in the pore liquid leading to a dense assembly of percolated MOF particles (pathway 3). Thus, the prepared MOF 3D objects and architectures can be fabricated with superb mechanical strength (>98.7 MPa), excellent permeability (>3.4 × 10<sup>-10</sup> m<sup>2</sup>), and large surface area (1100 m<sup>2</sup> g<sup>-1</sup>) and mesopore volumes (1.1 cm<sup>3</sup> g<sup>-1</sup>).
Estrogen Receptor Covalent Antagonists: The Best Is Yet to Come (2019)

The development of tamoxifen and subsequent estrogen receptor alpha (ERα) antagonists represents a tremendous therapeutic breakthrough in the treatment of breast cancer. Despite the ability of ERα antagonists to increase survival rates, resistance to these therapies is an all-too-common occurrence. The majority of resistant tumors, including those with hotspot mutations in the ligand-binding domain of ERα, remain dependent on ERα signaling, indicating that either a more potent or novel class of antagonist could have clinical benefit. With this thought in mind, we developed a novel ERα antagonist that exhibits enhanced potency due to its ability to covalently target a unique cysteine in ER. This review describes the design of this antagonist, H3B-5942, and discusses opportunities for future improvements, which could reduce the risk of escape mutations to this therapeutic modality.
On the [2,3] Sigmatropic Rearrangement of Allylic Nitro Compounds (2005)

Allylic nitro compounds undergo relatively clean [2,3] sigmatropic rearrangement upon heating in refluxing 1,2-dichlorobenzene in the presence of DABCO to give the corresponding allylic alcohols via the intermediate allylic nitrite. [reaction: see text]
Multispectral color filters based on self-aligned dual plasmonic gratings fabricated by nano-imprint lithography (2022)

Multispectral plasmonic color filters were fabricated using nano-imprint lithography and benchmarked to similar filters fabricated with standard CMOS processing. The self-aligned process yields devices with narrow linewidths below 30nm and up to 50% transmission efficiency.
Exploiting diverse chemical collections to uncover novel antifungals (2021)

The rise in drug resistance amongst pathogenic fungi, paired with the limited arsenal of antifungals available is an imminent threat to our medical system. To address this, we screened two distinct compound libraries to identify novel strategies to expand the antifungal armamentarium. The first collection wasthe RIKEN Natural Product Depository (NPDepo), which was screened for antifungal activity against four major human fungal pathogens: Candida albicans, Candida glabrata, Candida auris, and Cryptococcus neoformans. Through a prioritization pipeline, one compound, NPD6433, emerged as having broad-spectrum antifungal activity and minimal mammalian cytotoxicity. Chemical-genetic and biochemical assays demonstrated that NPD6433 inhibits the essential fungal enzyme fatty acid synthase 1 (Fas1). Treatment with NPD6433 inhibited various virulence traits in C. neoformans and C. auris , and rescued mammalian cell growth in a co-culture model with C. auris . The second compound library screened was adiversity-oriented collectionfrom Boston University. This chemical screen was focused on identifying novel molecules that enhance the activity of the widely deployed antifungal, fluconazole, against C. auris . Through this endeavour, we discovered a potent compound that enhanced fluconazole efficacy against C. auris through increasing azole intracellular accumulation. This activity was dependent on expression of the multidrug transporter geneCDR1, suggesting that this compound targets efflux mechanisms. Furthermore, this molecule significantly reduced fungal burden alone and in combination with fluconazole in a murine model of C. auris disseminated infection. Overall, this work identifies novel compounds with bioactivity against fungal pathogens, revealing important biology, and paving the way for the critical development of therapeutic strategies.
Comparison of the SF6D, the EQ5D, and the oswestry disability index in patients with chronic low back pain and degenerative disc disease (2013)

This study indicates that the difference in important measurement properties between EQ5D and SF6D is too large to consider them interchangeable. Since the similarity with the "gold standard" (the disease-specific instrument) was quite different, this could indicate that the choice of index should be determined by the diagnosis.
Wafer-Scale Growth of Single-Crystal Monolayer Graphene on Reusable Hydrogen-Terminated Germanium (2014)

The uniform growth of single-crystal graphene over wafer-scale areas remains a challenge in the commercial-level manufacturability of various electronic, photonic, mechanical, and other devices based on graphene. Here, we describe wafer-scale growth of wrinkle-free single-crystal monolayer graphene on silicon wafer using a hydrogen-terminated germanium buffer layer. The anisotropic twofold symmetry of the germanium (110) surface allowed unidirectional alignment of multiple seeds, which were merged to uniform single-crystal graphene with predefined orientation. Furthermore, the weak interaction between graphene and underlying hydrogen-terminated germanium surface enabled the facile etch-free dry transfer of graphene and the recycling of the germanium substrate for continual graphene growth.
Materials, technology and reliability of advanced interconnects - 2005 : symposium held March 28-April 1, 2005, San Francisco, California, U.S.A. (2005)

This book, first published in 2005, brings together leading modelers and experimentalists to discuss the plethora of process and reliability issues associated with depositing, characterizing and integrating novel and existing barriers, metals and ultralow-k dielectrics into reliable high-performance interconnects that can be robustly packaged. Section I focuses on low-k dielectric integration. Manuscripts highlight the importance of interface integrity and adhesion, the issue of process-induced dielectric damage and the need for pore sealing methods for low-k films. Channel cracking is addressed by several contributions. Cu metallization and barrier challenges are discussed in a section on metallization. Mechanical stress is highlighted in a reliability section. Contributions here provide a fundamental understanding of the issues of stress and stress relaxation in Cu films and lines encapsulated in low-k dielectrics. Presentations on electromigration, leakage and time-dependent dielectric breakdown, as well as thermal and mechanical fatigue, are also featured.
Optimum detection of differentially-encoded MPSK in a dispersive aeronautical channel (2002)

Several different waveforms have been proposed for use in aeronautical data links in the next-generation National Airspace System (NAS). Reliability of the links, expressed in terms of the assurance of a very low probability of message error, is crucial. Hence, optimal detection schemes are of interest. The performance of the proposed waveforms in multipath channels has not been thoroughly studied to date, and this work aims to begin filling the gap for a specific candidate modulation scheme: DPSK. This modulation scheme is the one that will be used for two of the modes of the VHF digital link family. The use of multiple symbol differential detection has long been known to improve the performance of differentially-encoded PSK on the additive white Gaussian noise (AWGN) channel, but its performance has not been thoroughly studied on dispersive channels. Related work has addressed the more complicated case of Rayleigh fading for generally very dispersive channels. The aeronautical channel typically lies between the AWGN and these "random" dispersive channels in that the rate of change of the channel is slow and essentially deterministic, and the dispersion is typically limited to two multipath "rays". Optimum noncoherent detection rules for PSK have not been derived for this moderately difficult but important special ease. Using a simple channel model for the aeronautical environment at VHF, we re-visit the derivation of the optimum sequence metric for this dispersive channel, and obtain a new sequence metric for use in detection. Performance of the new detectors is compared via simulations.
Discovery and Characterization of Potent Pan-Genotypic HCV NS5A Inhibitors Containing Novel Tricyclic Central Core Leading to Clinical Candidate (2019)

The identification of a novel class of potent pan-genotypic NS5A inhibitors with good pharmacokinetic profile suitable for potential use in treating HCV infections is disclosed here. The present series of compounds are with less complex tricyclic central core, identified through a systematic SAR study carried out on biphenyl moiety. The SAR outcome has confirmed the requirement of near planar and linear conformation of the molecule to achieve the best pan-genotypic activity. In addition, SAR with substituted imidazoles on improvement of antiviral activity is disclosed. The newly identified compounds <b>12</b>, <b>16</b>, <b>19</b>-<b>21</b> have shown desirable pharmacokinetic profiles with a favorable uptake of compounds in liver and maintained a significant concentration for up to 8 h in the liver. In addition, compounds <b>20</b> and <b>21</b> have shown superior pan-genotypic anti-HCV activity compared to ledipasvir and daclatasvir. Additional characterization and preliminary safety assessment resulted in the identification of compound <b>20</b> as a potential clinical candidate.
Axisymmetric wall jet development in confined jet impingement (2017)

The flow field surrounding an axisymmetric, confined, impinging jet was investigated with a focus on the early development of the triple-layered wall jet structure. Experiments were conducted using stereo particle image velocimetry at three different confinement gap heights (2, 4, and 8 jet diameters) across Reynolds numbers ranging from 1000 to 9000. The rotating flow structures within the confinement region and their interaction with the surrounding flow were dependent on the confinement gap height and Reynolds number. The recirculation core shifted downstream as the Reynolds number increased. For the smallest confinement gap height investigated, the strong recirculation caused a disruption of the wall jet development. The radial position of the recirculation core observed at this small gap height was found to coincide with the location where the maximum wall jet velocity had decayed to 15% of the impinging jet exit velocity. After this point, the self-similarity hypothesis failed to predict the evolution of the wall jet further downstream. A reduction in confinement gap height increased the growth rates of the wall jet thickness but did not affect the decay rate of the wall jet maximum velocity. For jet Reynolds numbers above 2500, the decay rate of the maximum velocity in the developing region of the wall jet was approximately −1.1, which is close to previous results reported for the fully developed region of radial wall jets. A much higher decay rate of −1.5 was found for the wall jet formed by a laminar impinging jet at Re = 1000.
Fetal Hox11 expression patterns predict defective target organs: a novel link between developmental biology and autoimmunity (2008)

Developmental biology has long been ignored in the etiology and diverse manifestations of autoimmune diseases. Yet a role for development is suggested by intriguing overlaps in particular organs targeted in autoimmune diseases, in this case type 1 diabetes and Sjogren's syndrome. Patients with type 1 diabetes have high rates of co-occurring Sjogren's syndrome, and both conditions are associated with hearing loss and tongue abnormalities. All of these co-occurrences are found in organs tracing their lineage to the developmental transcription factor Hox11, which is expressed in embryonic cells destined for the pancreas, salivary glands, tongue, cranial nerves and cochlea. To determine whether development contributes to autoimmunity, we compared four target organs in NOD mice (an animal model for type 1 diabetes and Sjogren's syndrome) with NOD-SCID mice (which lack lymphocytes) and normal controls. We examined the structure and/or function of the cochlea, salivary glands, pancreas and tongue at early time points after birth. Before the usual time of the onset of type 1 diabetes or Sjogren's syndrome, we show that all four Hox11-derived organs are structurally abnormal in both NOD mice and NOD-SCID mice versus controls. The most striking functional defect is near complete hearing loss occurring before the normal time of the onset of autoimmunity. The hearing loss is associated with severe structural defects in the cochlea, suggesting that near-deafness occurs independent of autoimmune attack. The pancreas and salivary glands are also structurally abnormal in NOD and NOD-SCID mice, but they are functionally normal. This suggests that autoimmune attack of these two organs is required for functional failure. We conclude that a developmental lineage of cells contributes to autoimmunity and predicts which organs may be targeted, either structurally and/or functionally. Taken together, our findings challenge the orthodoxy that autoimmunity is solely caused by a defective immune system.
ChemInform Abstract: 3,7‐Dideazapurine Nucleosides. Synthesis and Antitumor Activity of 1‐Deazatubercidin and 2‐Chloro‐2′‐deoxy‐3,7‐dideazaadenosine. (1989)

Abstract The pyrrolopyridine (I) reacts with the protected furanose (II) to give the nucleosides (III) and (IV).
High mobility p-channel germanium MOSFETs with a thin Ge oxynitride gate dielectric (2003)

We report Ge p-channel MOSFETs with a thin gate stack of Ge oxynitride and LTO on bulk Ge substrate without a Si cap layer. Excellent device characteristics (IV and CV) are achieved with subthreshold slope 82mV/dec. /spl sim/40% hole mobility enhancement is obtained over the Si control with a thermal SiO/sub 2/ gate dielectric. To our knowledge, this is the first demonstration of Ge MOSFETs with less than 10nm thick gate dielectric and less than 100mV/dec subthreshold slope.
Lower Airway Dysbiosis Exacerbates Lung Cancer (2021)

Accumulating evidence supports the impact of the gut microbiota on the clinical efficacy of cancer immunotherapies against extraintestinal tumors, but it has not yet been addressed whether local commensals could also dictate the prognosis of patients with cancer. In this issue of <i>Cancer Discovery</i>, Tsay and colleagues demonstrate that the lower airway microbiota may harbor oral commensals that turn on IL17-mediated inflammatory pathways and reprogram host transcription to exacerbate lung cancer progression.<i>See related article by Tsay et al., p. 293</i>.