gebhart/patrepeval huggingface dataset:
Structures of the first and second double‐stranded RNA‐binding domains of human TAR RNA‐binding protein (2010)

The TAR RNA-binding Protein (TRBP) is a double-stranded RNA (dsRNA)-binding protein, which binds to Dicer and is required for the RNA interference pathway. TRBP consists of three dsRNA-binding domains (dsRBDs). The first and second dsRBDs (dsRBD1 and dsRBD2, respectively) have affinities for dsRNA, whereas the third dsRBD (dsRBD3) binds to Dicer. In this study, we prepared the single domain fragments of human TRBP corresponding to dsRBD1 and dsRBD2 and solved the crystal structure of dsRBD1 and the solution structure of dsRBD2. The two structures contain an α-β-β-β-α fold, which is common to the dsRBDs. The overall structures of dsRBD1 and dsRBD2 are similar to each other, except for a slight shift of the first α helix. The residues involved in dsRNA binding are conserved. We examined the small interfering RNA (siRNA)-binding properties of these dsRBDs by isothermal titration colorimetry measurements. The dsRBD1 and dsRBD2 fragments both bound to siRNA, with dissociation constants of 220 and 113 nM, respectively. In contrast, the full-length TRBP and its fragment with dsRBD1 and dsRBD2 exhibited much smaller dissociation constants (0.24 and 0.25 nM, respectively), indicating that the tandem dsRBDs bind simultaneously to one siRNA molecule. On the other hand, the loop between the first α helix and the first β strand of dsRBD2, but not dsRBD1, has a Trp residue, which forms hydrophobic and cation-π interactions with the surrounding residues. A circular dichroism analysis revealed that the thermal stability of dsRBD2 is higher than that of dsRBD1 and depends on the Trp residue.
The mechanisms of sodium absorption in the human small intestine (1968)

The present studies were designed to characterize sodium transport in the jejunum and ileum of humans with respect to the effects of water flow, sodium concentration, addition of glucose and galactose, and variations in aniomic composition of luminal fluid. In the ileum, sodium absorption occurred against very steep electrochemical gradients (110 mEq/liter, 5-15 mv), was unaffected by the rate or direction of water flow, and was not stimulated by addition of glucose, galactose, or bicarbonate. These findings led to the conclusion that there is an efficiently active sodium transport across a membrane that is relatively impermeable to sodium. In contrast, jejunal sodium (chloride) absorption can take place against only the modest concentration gradient of 13 mEq/liter, was dramatically influenced by water movement, and was stimulated by addition of glucose, galactose, and bicarbonate. The stimulatory effect of glucose and galactose was evident even when net water movement was inhibited to zero by mannitol. These observations led to the conclusion that a small fraction of jejunal sodium absorption was mediated by active transport coupled either to active absorption of bicarbonate or active secretion of hydrogen ions. The major part of sodium absorption, i.e. sodium chloride absorption, appeared to be mediated by a process of bulk flow of solution along osmotic pressure gradients. The stimulatory effect of glucose and galactose, even at zero water flow, was explained by a model in which the active transport of monosaccharide generates a local osmotic force for the absorption of solution (NaCl and water) from the jejunal lumen, which, in the presence of mannitol, is counterbalanced by a reverse flow of pure solvent (H(2)O) through a parallel set of channels which are impermeable to sodium. Support for the model was obtained by the demonstration that glucose and bicarbonate stimulated the absorption of the nonactively transported solute urea even when net water flow was maintained at zero by addition of mannitol to luminal contents.
Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala (2020)

Serotonin (5-hydroxytryptamine; 5-HT) is a neurotransmitter that has an essential role in the regulation of emotion. The precise circuits through which aversive states are orchestrated by 5-HT, however, have not yet been defined. Here we show that 5-HT from the dorsal raphe nucleus (5-HTDRN) enhances fear and anxiety and activates a subpopulation of corticotropin-releasing factor (CRF) neurons in the bed nucleus of the stria terminalis (CRFBNST). Specifically, 5-HTDRN projections to the BNST, via actions at 5-HT2C receptors (5-HT2CRs), engage a CRFBNST inhibitory microcircuit that silences anxiolytic BNST outputs to the ventral tegmental area (VTA) and lateral hypothalamus (LH). Further, we demonstrate that this CRFBNST inhibitory circuit underlies aversive behavior following acute exposure to selective serotonin reuptake inhibitors (SSRIs). This early aversive effect is mediated via the corticotrophin releasing factor type 1 receptor (CRF1R) given that CRF1R antagonism is sufficient to prevent acute SSRI-induced enhancements in aversive learning. These results reveal an essential 5-HTDRN→CRFBNST circuit governing fear and anxiety and provide a potential mechanistic explanation for the clinical observation of early adverse events to SSRI treatment in some patients with anxiety disorders1,2.
Representation of Swept Volumes in a Parametric CAD System Using Trajectory Information From Virtual Environments (1999)

Abstract Swept volumes are the volumes created by a part moving in space during the process of assembly, disassembly, service, etc. Swept volumes represent important manufacturing, maintainability, and serviceability data. Several graphical and implicit modeling techniques are currently available to create and represent swept volumes as three-dimensional polygonal blobs. In this paper, we present a method for generating swept volumes from trajectory data created in a virtual graphics environment during an assembly/disassembly scenario. The individual instances can be edited in the virtual environment by swept instance removal and modification of position and orientation of instances. Using a synchronous link between the virtual environment and the CAD system, the trajectory information from the virtual environment is used along with the parametric model in the CAD system to create swept volume geometry directly in a parametric CAD system as a feature of the assembly. In addition, using the synchronous link, this swept volume (not just instances along the trajectory) can then be exported back to the original virtual environment and displayed. This method can handle any sweeping trajectory and does not restrict the geometry or the topology requirement of the sweeping object. The swept volumes generated this way are accurate, concise, and can be easily processed by CAD systems.
The public's dilemma: race and political evaluations of police killings (2020)

This paper explores perceptions of the killings of African-Americans by police officers. We show how characteristics of the victim, officer and surrounding environment, as well as political cues, shape such perceptions. In the first study, we employ a conjoint survey experiment, wherein subjects are exposed to descriptions of hypothetical police killings. Focusing on subjects who score high on the Symbolic Racism Scale (SRS), we identify what leads such subjects to view shootings as more justified. We replicate and extend these effects in a second study in which subjects read fictitious newspaper articles. We find that exposing high SRS subjects to primes related to Black Lives Matter can decrease their belief in shootings' justifiability.
Optimizations for the Electrically-Evoked Stapedial Reflex Threshold Measurement in Cochlear Implant Recipients (2016)

The results of this investigation demonstrate that the use of a standard 226 Hz probe tone is not ideal for measurement of the eSRT. The use of higher probe tone frequencies (i.e., 678 or 1000 Hz) resulted in lower eSRT levels when compared with the eSRT levels obtained with use of a 226 probe tone. In addition, 4 of the 23 participants included in this study did not have a measureable eSRT with use of a 226 Hz probe tone, but all of the participants had measureable eSRT with use of both the 678 and 1000 Hz probe tones. Additional work is required to understand the clinical implication of these changes in the context of cochlear implant programming.
Minimum degree reordering based graph partitioning method for distributed fault section estimation system in power networks (2002)

In order to make fault section estimation (FSE) in large-scale power networks use a distributed artificial intelligence approach, we an efficient way to partition the large-scale power network into desired number of connected subnetworks has to developed, such that each sub-network should have quasi-balanced working burden in performing FSE. In this paper, an efficient minimum degree reordering based graph partitioning method is suggested for the partitioning task. The method consists of two basic steps: partitioning the power network into connected, quasi-balanced and frontier minimized sub-networks based on minimum degree reordering; and minimizing the number of the frontier nodes of the sub-networks through iterations so as to reduce the interaction of FSE in adjacent sub-networks. The partitioning procedure and characteristic analysis is presented. The method has been implemented with sparse storage technique and tested in the IEEE 14-bus, 30-bus and 118-bus systems respectively. Computer simulation results show that the proposed multiple-way graph partitioning method is suitable for FSE in large-scale power networks and is compared favorably with other graph partitioning methods suggested in references.
IrMn based spin-filter spin-valves (2000)

As recording densities increase, the sense layer (free layer) thickness in a recording head (whether spin-valve or otherwise) must also decrease so that the sense layer can be effectively saturated by the transitions on the media. However, in a traditional spin-valve structure, reducing the sense layer (free layer) thickness below ∼50 Å results in a rapid reduction in ΔR/R. One of the solutions for this is the spin-filter spin-valve, having a free layer composed of a very thin magnetic layer and an adjacent thin enhancing conduction layer. The advantage of the spin-filter spin-valve is high ΔR/R and easy control of the bias point while keeping the free layer very thin (10–30 Å). The present work reports the results on sputtered IrMn top and bottom spin-filter spin-valves. The data clearly show that ΔR/R has been significantly improved when reducing the free layer CoFe down to 10 Å. ΔR/R&amp;gt;8.0% remains for free layer thickness between 10 and 20 Å using a Cu enhancing layer, while ΔR/R decreased rapidly to 4.0% with no Cu enhancing layer for the same free layer thickness range. An optimized ΔR/R of ∼10% was obtained for an enhancing layer of tCu∼13 Å, as a result of the balance between the increase in electron mean free path difference and current shunting through the very conducting enhancement layer. It was also found that the softness of the CoFe free layer was improved when sandwiched by Cu layers, showing similar soft properties and magnetostriction to conventional free layers. Such a soft, thin CoFe free layer is particularly attractive for high density (30–50 Gb/in2) read sensor applications.
Notice of Removal: Assessment of corneal biomechanical properties using the ultrasonic micro-elastography (2017)

Removed.
Differential intracellular calcium influx, nitric oxide production, ICAM-1 and IL8 expression in primary bovine endothelial cells exposed to nonesterified fatty acids (2016)

These findings strongly suggest that each individual NEFA stimulates endothelial cells in a different way, with clearly different effects on intracellular calcium mobilization, NO production, and IL-8 and ICAM-1 expression in primary BUVECs. These findings not only extend our understanding of NEFA-mediated diseases in ruminants, but also provide new insight into the different molecular mechanisms involved during endothelial cell activation by NEFAs.
Effect of Oral Supplementation with Iron (III)-hydroxide Polymaltose Complex on the Immunological Profile of Adolescents with Varying Iron Status (2011)

IPC supplementation for eight months led to significant improvements of immunological parameters in iron deficient adolescents with and without anemia.
Combining free and aggregated cellulolytic systems in the cellulosome-producing bacterium Ruminiclostridium cellulolyticum (2015)

Our study shows that the cellulolytic capacity of R. cellulolyticum can be augmented by supplementing the cellulosomes with a free cellulase originating from L. phytofermentans, whereas integration of the heterologous enzyme in the cellulosomes is rather unfavorable.
Human Embryonic Stem Cell-Derived Hematopoietic Cells Maintain Core Epigenetic Machinery of the Polycomb Group/Trithorax Group Complexes Distinctly from Functional Adult Hematopoietic Stem Cells (2012)

Hematopoietic cells derived from human embryonic stem cells (hESCs) have a number of potential utilities, including the modeling of hematological disorders in vitro, whereas the use for cell replacement therapies has proved to be a loftier goal. This is due to the failure of differentiated hematopoietic cells, derived from human pluripotent stem cells (hPSCs), to functionally recapitulate the in vivo properties of bona fide adult hematopoietic stem/progenitor cells (HSPCs). To better understand the limitations of differentiation programming at the molecular level, we have utilized differential gene expression analysis of highly purified cells that are enriched for hematopoietic repopulating activity across embryonic, fetal, and adult human samples, including in vivo explants of human HSPCs 8-weeks post-transplantation. We reveal that hESC-derived hematopoietic progenitor cells (eHPCs) fail to express critical transcription factors which are known to govern self-renewal and myeloid/lymphoid development and instead retain the expression of Polycomb Group (PcG) and Trithorax Group (TrxG) factors which are more prevalent in embryonic cell types that include EZH1 and ASH1L, respectively. These molecular profiles indicate that the differential expression of the core epigenetic machinery comprising PcGs/TrxGs in eHPCs may serve as previously unexplored molecular targets that direct hematopoietic differentiation of PSCs toward functional HSPCs in humans.
Why Are the Majority of Active Compounds in the CNS Domain Natural Products? A Critical Analysis (2018)

Small-molecule natural products (NPs) have a long and successful track record of providing first-in-class drugs and pharmacophore (scaffolds) in all therapeutic areas, serving as a bridge between modern and traditional medicine. This trajectory has been remarkably successful in three key areas of modern therapeutics: cancers, infections, and CNS diseases. Beginning with the discovery of morphine 200 years ago, natural products have remained the primary source of new drugs/scaffolds for CNS diseases. In this perspective, we address the question: why are the majority of active compounds in the CNS domain natural products? Our analysis indicates that ∼84% approved drugs for CNS diseases are NPs or NP-inspired, and interestingly, 20 natural products provided more than 400 clinically approved CNS drugs. We have discussed unique physicochemical properties of NPs and NP-inspired vis-à-vis synthetic drugs, isoform selectivity, and evolutionary relationship, providing a rationale for increasing focus on natural product driven discovery for next-generation drugs for neurodegenerative diseases.
Ex vivo gene transfer to mature skeletal muscle by using adenovirus helper cells (2004)

We achieved more efficient adenoviral gene transduction by using 293 and E32 helper cells than by myoblast-mediated gene transfer and direct viral injection. These helper cells also enabled adenoviral gene transfer to mature myofibers. The mechanisms by which this method facilitated adenoviral gene transfer to mature myofibers remains unclear; however, we hypothesize that the in vivo occurrence of cytopathic effects (CPE) in the transduced 293 and E32 helper cell populations facilitated the improved adenoviral transduction of myofibers.
<title>Investigations of laser damage in KDP using light-scattering techniques</title> (1997)

Interest in producing high damage threshold KH<SUB>2</SUB>PO<SUB>4</SUB> (KDP) and (D<SUB>x</SUB>H<SUB>1-x</SUB>)<SUB>2</SUB>PO<SUB>4</SUB> (DKDP) for frequency conversion and optical switching applications is driven by the requirements of the National Ignition Facility (NIF) at the Lawrence Livermore National Laboratory. At present only the best crystals meet the NIF system requirements at the third harmonic and only after a laser conditioning process. Neither the mechanism for damage in bulk KDP nor the mechanism for conditioning ins understood. As part of ta development effort to increase the damage thresholds of KDP and DKDP, we have been developing techniques to pinpoint the locations where damage will initiate in the bulk material. After we find these locations we will use other measurement techniques to determine how these locations differ from the other surrounding materials and why they cause damage. This will allow crystal growers to focus their efforts to improve damage thresholds. Historically, damage thresholds have increased it is believed as a consequence of increased purity of the growth solution and through the use of constant filtration during the growth process. As a result we believe that damage is caused by defects in the crystals and have conducted a series of experiments using light scatter to locate these defects and to determine when and where damage occurs. In this paper we present results which show a low correlation between light scatter from bulk defects in KDP and the initiation sites for damage. We have also studied the effects of thermal conditioning on light scatter, strain induced birefringence and damage threshold. We have seen evidence that regions of high strain also exhibit lower damage threshold than the surrounding lower strain material. When thermally conditioned, these crystals show a decrease in some of the strong linear scattering features and a decrease in the strain birefringence while the damage threshold in these regions increased to that of the surrounding bulk material.
Two‐Dimensional Antimonene‐Based Photonic Nanomedicine for Cancer Theranostics (2018)

Antimonene (AM) is a recently described two-dimensional (2D) elemental layered material. In this study, a novel photonic drug-delivery platform based on 2D PEGylated AM nanosheets (NSs) is developed. The platform's multiple advantages include: i) excellent photothermal properties, ii) high drug-loading capacity, iii) spatiotemporally controlled drug release triggered by near-infrared (NIR) light and moderate acidic pH, iv) superior accumulation at tumor sites, v) deep tumor penetration by both extrinsic stimuli (i.e., NIR light) and intrinsic stimuli (i.e., pH), vi) excellent multimodal-imaging properties, and vii) significant inhibition of tumor growth with no observable side effects and potential degradability, thus addressing several key limitations of cancer nanomedicines. The intracellular fate of the prepared NSs is also revealed for the first time, providing deep insights that improve cellular-level understanding of the nano-bio interactions of AM-based NSs and other emerging 2D nanomaterials. To the best of knowledge, this is the first report on 2D AM-based photonic drug-delivery platforms, possibly marking an exciting jumping-off point for research into the application of 2D AM nanomaterials in cancer theranostics.
Advanced wafer bonding and laser debonding (2014)

This paper describes the development of a wafer debonding process and tooling based on 355 nm UV laser ablation. While laser-assisted debonding of polyimide-based materials at shorter UV wavelengths has been described previously, this work describes a method having two major advantages over earlier methods: 1) a significantly more compact and affordable diode-pumped solid state 355 nm laser source is combined with a high-speed optical scanner to create a rapid debonding module with a small footprint, and 2) the addition of a very thin UV ablation layer to the glass handler ensures that release will occur, independently of the adhesive used to bond the wafer. The first enhancement is designed to enable high-throughput debonding at lower cost than earlier laser tools, while the second enhancement is designed to greatly expand the adhesive choices available to device manufacturers. Flexibility in material choice for both the release layer and the adhesive layer permits the manufacturer to meet post-wafer thinning process and temperature compatibility needs. In this research paper, the many benefits of this novel room-temperature debonding technology are reported along with examples of successfully demonstrated adhesives and release layers.
IFN-gamma production by adoptively transferred CD8+ T lymphocytes and host cells contributes to successful tumor immunotherapy (2004)

Finkelstein, Steven MD; Klebanoff, Christopher BS; Antony, Paul MD; Gattinoni, Luca MD; Heimann, David MD; Hinrichs, Christian MD; Hwang, Leroy PhD; Palmer, Douglas BA; Spiess, Paul BA; Rosenberg, Steven MD, PhD; Restifo, Nicholas MD Author Information
Prospective, Randomized, Multicenter, Controlled Trial (TRIATHRON 1) on a New Antithrombogenic Hydrophilic Dialysis Membrane (2017)

The NV dialyzer series is safe with no adverse events reported. Further studies are required to understand the mechanisms of anti-thrombogenic effects.
Phenylation of PVC with triphenylaluminum and related model reactions (1974)

Abstract It was theorized that the heat stability of PVC may be improved by exchanging the “weak” (allylic and tertiary) chlorines by groups of higher bond strength, e.g., phenyl. Thus PVC was phenylated by ϕ 3 Al in carbon disulfide slurry for various times (1 to 5 hrs) and temperatures (from −30 to +45°C). The ϕ 3 Al concentration, temperature and time of ϕ 3 Al treatment greatly affect the ultimate heat stability of PVC. Significant improvement in the heat stability was obtained by treating PVC in carbon disulfide at 25°C for 1 hr. The mechanism of phenylation was studied by model experiments in which the possible structural irregularities in PVC were simulated by small molecule chlorine compounds, i.e., 3‐chloro‐1‐butene, 1,3‐dichloro‐1‐butene, 4‐choro‐2‐pentene were models for terminal and inchain allylic chlorines, t‐butyl chloride was the model for tertiary chlorine at branch site, and isopropyl chloride simulated regular secondary chlorines. The reactions between ϕ 3 Al and these chlorides were carried out at 35°C for various times and the NMR spectra were analyzed. The ϕ 3 Al + tBuCl reaction in carbon disulfide gives t‐butylbenzene (Wurtz coupling) and isobutylene oligomers. Evidently ϕ 3 Al (or the ϕ 2 AlCl formed) dehydrochlorinates tBuCl to isobutylene which rapidly oligomerizes in the presence of Lewis acids. In aromatic diluents, i.e., benzene, chlorobenzene, and o‐chlorotoluene, Friedel‐Crafts t‐butylation of the diluent occurs; in mesitylene t‐butylation is absent presumably because of steric hindrance and small amounts of t‐butylbenzene are formed by Wurtz coupling. All the allyl chlorides examined are rapidly phenylated by ϕ 3 Al in carbon disulfide at 35°C and yield the expected products: 3‐chloro‐1‐butene → 1‐phenyl‐2‐butene; 1,3‐dichloro‐1‐butene → 1‐chloro‐3‐phenyl‐1‐butene; 4‐chloro‐2‐pentene → 4‐phenyl‐2‐pentene. The kinetics of phenylation by ϕ 3 Al of model compounds have been studied and the following rate constants were obtained: k allyl = too fast to measure, k tBuCl = 1.0, and k iPrCl = 9 × 10 −4 l/mole min. Evidently the rate of the ϕ 3 Al + RCl reaction is mainly determined by the stability of the R ⊕ intermediate: substituted allylic ⊕ ≫ tertiary ⊕ ≫ secondary ⊕ .