gebhart/patrepeval huggingface dataset:
On the Influence of Nucleic Acid Backbone Modifications on Lipid Nanoparticle Morphology (2022)

Nucleic acid therapeutics represent a major advance toward treating diseases at their root cause. However, nucleic acids are prone to degradation by serum endonucleases, clearance through the immune system, and rapid degradation in complex medium. To overcome these barriers, nucleic acids frequently include chemical modifications to improve stability or decrease immune responses. Lipid nanoparticles (LNPs) have enabled a dramatic reduction in the dose required to achieve a therapeutic effect by protecting these nucleic acids and improving their intracellular delivery. It has been assumed thus far that nonspecific ionic interactions drive LNP formation and chemical modifications to the nucleic acid backbone to confer improved stability do not impact LNP delivery in any way. Here, we demonstrate that these chemical modifications do impact LNP morphology substantially, and phosphorothioate modifications produce stronger interactions with ionizable amino lipids, resulting in enhanced entrapment. This work represents a major first step toward greater understanding of the interaction between the lipid components and nucleic acids within an LNP.
Data from Targeting DNA Damage Repair Functions of Two Histone Deacetylases, HDAC8 and SIRT6, Sensitizes Acute Myeloid Leukemia to NAMPT Inhibition (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;Nicotinamide phosphoribosyltransferase (NAMPT) inhibitors (NAMPTi) are currently in development, but may be limited as single-agent therapy due to compound-specific toxicity and cancer metabolic plasticity allowing resistance development. To potentially lower the doses of NAMPTis required for therapeutic benefit against acute myeloid leukemia (AML), we performed a genome-wide CRISPRi screen to identify rational disease-specific partners for a novel NAMPTi, KPT-9274.&lt;/p&gt;Experimental Design:&lt;p&gt;Cell lines and primary cells were analyzed for cell viability, self-renewal, and responses at RNA and protein levels with loss-of-function approaches and pharmacologic treatments. &lt;i&gt;In vivo&lt;/i&gt; efficacy of combination therapy was evaluated with a xenograft model.&lt;/p&gt;Results:&lt;p&gt;We identified two histone deacetylases (HDAC), &lt;i&gt;HDAC8&lt;/i&gt; and &lt;i&gt;SIRT6&lt;/i&gt;, whose knockout conferred synthetic lethality with KPT-9274 in AML. Furthermore, HDAC8-specific inhibitor, PCI-34051, or clinical class I HDAC inhibitor, AR-42, in combination with KPT-9274, synergistically decreased the survival of AML cells in a dose-dependent manner. AR-42/KPT-9274 cotreatment attenuated colony-forming potentials of patient cells while sparing healthy hematopoietic cells. Importantly, combined therapy demonstrated promising &lt;i&gt;in vivo&lt;/i&gt; efficacy compared with KPT-9274 or AR-42 monotherapy. Mechanistically, genetic inhibition of SIRT6 potentiated the effect of KPT-9274 on PARP-1 suppression by abolishing mono-ADP ribosylation. AR-42/KPT-9274 cotreatment resulted in synergistic attenuation of homologous recombination and nonhomologous end joining pathways in cell lines and leukemia-initiating cells.&lt;/p&gt;Conclusions:&lt;p&gt;Our findings provide evidence that HDAC8 inhibition- or shSIRT6-induced DNA repair deficiencies are potently synergistic with NAMPT targeting, with minimal toxicity toward normal cells, providing a rationale for a novel–novel combination-based treatment for AML.&lt;/p&gt;&lt;/div&gt;
Outgassing of organic vapors from 193 nm photoresists: Impact on atmospheric purity near the lens optics (1999)

Fourteen different 193 nm photoresists were tested for organic vapor outgassing after exposure and their outgassing rates were measured to be between 1011 and 1013 molecules cm−2 s−1, with the primary compounds being isobutene and benzylic photoacid generator fragments. Rough estimates indicate that for an outgassing rate of 1011 molecules cm−2 s−1 and a well purged tool, organic vapor partial pressures between 10 ppb and 1 ppm are likely, depending on the lens working distance. Higher levels of outgassing combined with poor ventilation can result in partial pressures in excess of 1 Torr. These values exceed the residual ambient levels expected in a fab and hence constitute an increased risk of contamination to the final optical element of 193 nm exposure tools.
The human gamma interferon receptor accessory factor encoded by chromosome 21 transduces the signal for the induction of 2',5'-oligoadenylate-synthetase, resistance to virus cytopathic effect, and major histocompatibility complex class I antigens (1993)

Mouse fibroblasts, and human-mouse hybrid fibroblasts carrying only human chromosome 21, were transfected with cDNA encoding full-length human gamma interferon (IFN-gamma) receptor or chimeric IFN-gamma receptor (extracellular domain of the human receptor; transmembrane and intracellular domains of mouse origin). These transfected mouse cells were sensitive to human IFN-gamma only when human chromosome 21 was present. These results show that the species-specific accessory protein encoded by human chromosome 21 interacts with the extracellular domain of human IFN-gamma receptor and transduces the IFN-gamma signal not only for up-regulation of mouse major histocompatibility complex class I antigen expression but also for the induction of 2',5'-oligoadenylate-synthetase and resistance to virus cytopathic effect.
NOTES: Education and Training (2009)

The concept of minimally invasive surgery has gained widespread acceptance because of significant reduction in the patient postoperative morbidity that is associated with these surgical procedures. Natural orifice translumenal endoscopic surgery (NOTES) could theoretically maximize the advantages of minimally invasive surgery by performing intra-abdominal surgery in an "incisionless" manner. NOTES requires a new surgical skill set that would need to be taught to urologists to ensure its safe implementation. Several fundamental issues must be determined regarding safety and efficacy before any widespread implementation of this new technology to urologic surgery can be entertained. The development of specialized instruments designed for NOTES will certainly be crucial. Human ingenuity will undoubtedly succeed in this endeavor. Therefore, development of guidelines for training will be necessary for the safe adoption of this technique by urologists in their clinical practice. As previously demonstrated in laparoscopic surgery, a dedicated curriculum with clearly delineated objectives and teaching strategies will govern the success of postgraduate courses and residency training in urologic NOTES. These types of comprehensive educational programs will provide the basic foundation for the acquisition of the necessary knowledge and the development of the appropriate surgical skills. Animal and cadaveric laboratories will provide realistic interaction with tissue. Mentoring and surgical simulators will facilitate progressive acquisition and maintenance of NOTES skills in the future.
Application Of ERT For Tracking CO2 Plume Growth And Movement At The SECARB Cranfield Site (2009)

Electrical Resistance Tomography (ERT) installed to track the development of an injected subsurface CO{sub 2} plume at the SECARB Cranfield, MS. sequestration site will be the deepest subsurface application of this method to date. ERT utilizes vertical arrays of electrodes, usually in a cross-well arrangement, to perform four-electrode measurements of changes in the spatial distribution of electrical resistance within a subsurface formation. Because a formation containing super-critical CO{sub 2} is approximately five times as resistive as its surroundings, significant resistance changes are anticipated during plume growth and movement within a brine-filled formation. ERT has also been shown to be quite sensitive to CO{sub 2} saturation changes. The Cranfield ERT electrode arrays will be emplaced at a depth exceeding 10,000 ft. (3280 m); the system design and installation must address significant challenges associated with both the depth and borehole conditions including temperatures of 258 F (126 C), pressures exceeding 5000 psi and a groundwater pH of 3. In addition, the system must allow co-located emplacement and concurrent operation with other monitoring techniques that utilize the same boreholes. ERT electrode and cabling will be attached to the outside of the well casing, allowing free access to the interior of the well, which is required by some of the other monitoring techniques being fielded. We will highlight these design challenges along with preliminary simulations indicating the anticipated level of imaging and the advantages of applying the technique in conjunction with other methods (such as cross-well seismics) to more accurately track the properties, location and movement of CO{sub 2} plumes.
Simultaneous observations of current and voltage waveforms of Gunn oscillators (1967)

Simultaneous observations were made of current and voltage waveforms of Gunn oscillators mounted in a resistive circuit. From the results of the observations, the efficiency of resistively loaded Gunn oscillators is studied for applied voltages and load resistances, and some quantities for a high-field domain are also discussed for applied voltages.
A low-power integrated magneto-optic modulator on silicon for cryogenic\n applications (2021)

A fundamental challenge of the quantum revolution is to efficiently interface\nthe quantum computing systems operating at cryogenic temperatures with room\ntemperature electronics and media for high data-rate communication. Current\napproaches to control and readout of such cryogenic computing systems use\nelectrical cables, which prevent scalability due to their large size, heat\nconduction, and limited bandwidth1. A more viable approach is to use optical\nfibers which allow high-capacity transmission and thermal isolation. A key\ncomponent in implementing photonic datalinks is a cryogenic optical modulator\nfor converting data from the electrical to the optical domain at high speed and\nwith low power consumption, while operating at temperatures of 4 K or lower.\nCryogenic modulators based on the electro-optic effect have been demonstrated\nin a variety of material platforms, however they are voltage driven components\nwhile superconducting circuits are current based, resulting in a large\nimpedance mismatch. Here, we present the first demonstration of an integrated\ncurrent-driven modulator based on the magneto-optic effect operating over a\nwide temperature range that extends down to less than 4 K. The modulator works\nat data rates up to 2 Gbps with energy consumption below 4 pJ/bit, and we show\nthat this figure can be reduced to less than 40 fJ/bit with optimized design\nand fabrication. This modulator is a hybrid device, where a current-driven\nmagneto-optically active crystal (cerium substituted yttrium iron garnet, or\nCe:YIG) is bonded to a high-quality silicon microring resonator. Because of its\npotential for extremely low power consumption under cryogenic conditions, the\nclass of magneto-optical modulators demonstrated here has the potential to\nenable efficient data links in large-scale systems for quantum information\nprocessing.\n
Beamforming and power allocation for physical-layer security in hybrid RF/VLC wireless networks (2017)

Visible light communication (VLC) has emerged as a promising candidate to complement and enhance the performance of the existing radio frequency (RF) networks in indoor environments. Due to the broadcast nature of both RF and VLC channels, improving the transmission confidentiality is a requirement in practical wireless networks. Physical-layer security has emerged to provide a first line of defense against eavesdropping attacks. In this paper, we study the physical layer security problem of a hybrid RF/VLC system. First, we formulate the minimization problem of the consumed electrical power in the hybrid RF/VLC network while satisfying the user's required secrecy rate. Then, we propose a zero forcing beamforming strategy and a minimum power allocation algorithm. Simulations results show that the proposed power allocation and beamforming algorithms outperform the benchmark algorithms in terms of the average consumed electrical power in various indoor scenarios.
Microbiota in Reflux Esophagitis and Peptic Ulcer Disease (2023)

Gastroesophageal reflux disease (GERD), reflux esophagitis (RE), and peptic ulcer disease (PUD) are commonly encountered in clinical practice. More than simple anatomic abnormalities, these conditions are tethered to a variety of external influences as well as those related to genomics, transcriptomics, and metabolomics. Furthermore, each of these conditions is clearly related to abnormalities of the microbiota of the oropharynx, esophagus, and gastrointestinal tract. Certain therapeutics used to address these conditions such as antibiotic agents and proton pump inhibitors worsen microbiome dysbiosis while pursuing clinical benefit. Therapeutics that protect, shape adaptively, or restore microbiota balance are key aspects of current and future therapy to pursue. How the microbiota is involved in clinical condition genesis and progression, as well as how therapeutic support or derange the microbiota are herein explored.
Learning Separable Filters (2013)

Learning filters to produce sparse image representations in terms of over complete dictionaries has emerged as a powerful way to create image features for many different purposes. Unfortunately, these filters are usually both numerous and non-separable, making their use computationally expensive. In this paper, we show that such filters can be computed as linear combinations of a smaller number of separable ones, thus greatly reducing the computational complexity at no cost in terms of performance. This makes filter learning approaches practical even for large images or 3D volumes, and we show that we significantly outperform state-of-the-art methods on the linear structure extraction task, in terms of both accuracy and speed. Moreover, our approach is general and can be used on generic filter banks to reduce the complexity of the convolutions.
Control of Group Delay Spread in Randomly-Coupled Multicore Fibers (2020)

The impact of core-to-core distance, bending condition, and number of cores on the group delay spread (GDS) in randomly-coupled multicore fibers (MCFs) is investigated for designing low GDS coupled MCFs. It is shown that the control of group index difference between different modes along the propagation direction in bent and twisting MCFs has strong impact on the GDS reduction.
Chiral Diaminodiamide Copper(II) Complexes for the Enantioselective Recognition of Amino Acids: Synthesis of the Ligands and Formation Constants (1986)

Abstract ( S , S )‐ N , N ′ ‐Bis(aminoacyl)ethane‐ and ( S , S )‐ N , N ′ ‐bis(aminoacyl)propanediamines (AA‐NN‐2 and AA‐NN‐3, respectively, AA = alanine, phenylalanine, valine) were synthesized as the dihydrochlorides, and their complexes with Cu(II) studied potentiometrically. Since these ligands in the presence of Cu(II) are able to perform chiral resolution of D , L ‐dansylamino acids in HPLC (reversed phase), in a certain pH range (6.5–8.5), it is important to know the equilibria existing between ligands and copper in aqueous solution. For AA‐NN‐2, four species, CuLH 3+ , CuL 2+ , Cu 2 L 2 H , and CuLH −2 , were detected, whereas for AA‐NN‐3, only CuLH 3+ , CuL 2+ , and CuLH −2 were found. The aim is to find out which complexes may be involved in the recognition process.
Realization of robust photonic crystal waveguides designed to reduce out-of-plane scattering (2002)

We have realized environmentally stable silicon-on-insulator based photonic crystal waveguides. The waveguide structure is designed to minimize scattering at semiconductor/hole interfaces. Transmission measurements and IR pictures indicate efficient guiding through straight and bent waveguides.
GENE-01. THE MUTATIONAL LANDSCAPE OF PRIMARY CHORDOMAS AND THEIR SENSITIVE DETECTION IN PLASMA ctDNA BY MULTIPLE NEXT GENERATION SEQUENCING TECHNOLOGIES (2019)

Abstract CNS-associated tumors are notoriously difficult to detect in plasma. Chordomas are the most common primary spinal column malignancy, and extensive surgical procedures, along with chemotherapy and radiation are required to reduce recurrence. Currently CT, MRI, and PET are used to monitor for recurrence but are limited by surgical sequalae. In addition, needle biopsy risks tumor seeding along the biopsy track. In the largest cohort of chordomas described thus far, we characterize the mutational landscape of these tumors and show that liquid biopsy is a sensitive method for detecting cancers. 34 patients with a biopsy-confirmed diagnosis of chordoma had blood drawn before surgery, at the time of surgery, and/or at follow up appointments. Mutations in the primary tumor were identified by whole exome sequencing (WES) and droplet digital PCR (ddPCR) and/or Rapid Amplification of cDNA Ends Sequencing (RACE-Seq) was used to detect one or more of these mutations in plasma ctDNA at concurrent or later time points. The primary endpoint was detection of mutations in ctDNA in biopsy-confirmed chordoma samples. 87.9% of patients were ctDNA positive at the time of initial blood draw (p &amp;lt; 0.001). Follow up blood draws in twenty of the patients demonstrated that ctDNA levels reflected the clinical status of the disease. Patients with positive ctDNA levels were more likely to undergo radiotherapy (p = 0.004), and the presence of ctDNA may predict response to systemic chemotherapy and/or disease recurrence. Given the significant sequelae of biopsy and spinal surgery, liquid biopsy may be the best tool for detection and monitoring of chordomas.
Automated Tandem Mass Spectrometry for Mass Newborn Screening for Disorders in Fatty Acid, Organic Acid, and Amino Acid Metabolism (1999)

Development of acylcarnitine and amino acid profiling using tandem mass spectrometry, and its application for use with dried blood specimens collected on filter-paper cards, has introduced an innovative new technology for detecting inborn errors of fatty acid, organic acid, and amino acid metabolism. From November 1, 1992 through June 30, 1999 we screened more than 700,000 newborns in Pennsylvania, Ohio, North Carolina, and Louisiana. We have prospectively detected 163 inborn errors of metabolism. Eighty-six patients have amino acid metabolism errors. Among them are phenylketonuria, hyperphenylalaninemia, maple syrup urine disease, and several urea cycle disorders. Thirty-two have organic acid metabolism errors, including glutaric aciduria type 1; 3-methylcrotonyl coenzyme A (CoA) carboxylase deficiency, propionic acidemia, methylmalonic acidemia, and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency; and 45 have fatty acid oxidation errors, including 36 with medium-chain acyl-CoA dehydrogenase deficiency. Details of the methodology are presented and the potential of this screening technology is discussed. (J Child Neurol 1999;14(Suppl 1):S4-S8).
Welding and Quality Control for the Consolidation of the LHC Superconducting Magnets and Circuits (2014)

The first LHC long shutdown was driven by the need to consolidate the 13 kA splices between the superconducting magnets to safely attain its center of mass design energy of 14 TeV. Access to the splices requires the opening of welded sleeves by machining. After consolidation, the sleeves are re-welded using a TIG orbital welding. The welding process has been modified from the original “as-new” installation in order to better adapt to the “as repaired” situation. The intervention has been thoroughly prepared through qualifications, organisation of teams, their training and follow-up. Quality control is based on the qualification of equipment, process and operators; the recording of production parameters; regular process audits and production witness samples; visual inspection through an official certifying body. The paper also describes welding and quality control of special intervention cases, with issues of difficult access requiring innovative solutions. This work concerns over 10 000 welds and a team of 40 engineers and technicians over a period of 18 months. The experience and lessons learnt will be applicable to similar large complex projects.
ChemInform Abstract: A New Biarylphosphine Ligand for the Pd‐Catalyzed Synthesis of Diaryl Ethers under Mild Conditions. (2012)

Abstract TCP in combination with [PdCl(cinnamyl)] 2 is highly efficient in the reaction of various aromatic and heteroaromatic bromides with phenols.
BGP Dissemination of L2 Flow Specification Rules (1999)

This document defines a Border Gateway Protocol (BGP) Flow
Specification (flowspec) extension to disseminate Ethernet Layer 2
(L2) and Layer 2 Virtual Private Network (L2VPN) traffic filtering
rules either by themselves or in conjunction with L3 flowspecs.
AFI/SAFI 6/133 and 25/134 are used for these purposes. New component
types and an extended community also are defined.
HybridTreeMiner: an efficient algorithm for mining frequent rooted trees and free trees using canonical forms (2004)

Tree structures are used extensively in domains such as computational biology, pattern recognition, XML databases, computer networks, and so on. In this paper, we present HybridTreeMiner, a computationally efficient algorithm that discovers all frequently occurring subtrees in a database of rooted unordered trees. The algorithm mines frequent subtrees by traversing an enumeration tree that systematically enumerates all subtrees. The enumeration tree is defined based on a novel canonical form for rooted unordered trees - the breadth-first canonical form (BFCF). By extending the definitions of our canonical form and enumeration tree to free trees, our algorithm can efficiently handle databases of free trees as well. We study the performance of our algorithms through extensive experiments based on both synthetic data and datasets from real applications. The experiments show that our algorithm is competitive in comparison to known rooted tree mining algorithms and is faster by one to two orders of magnitudes compared to a known algorithm for mining frequent free trees.
Endogenous Peptides for Delta Opioid Receptors and Analogues (2003)

The discoveryofthe endogenous opioid peptidesleucine-enkephalin(H-Tyr-Gly-Gly-Phe-Leu-OH) and methionine-enkephalin (H-Tyr-Gly-Gly-Phe-Met-OH) [1] (Fig. 1) and the suggestion, ﬁrst from pharmacological studies[2,3] and later from molecular cloning [4–7], that there are three opioidreceptors(mu,delta,andkappa)havehadanenormousimpactonthesearchfor better opioid analgesics that would not possess the severe toxicities andother undesirable biological activities of the alkaloid morphine and relatedcompounds. The delta opioid receptor, and selective ligands for this receptorthatalsohaveminimalsideeﬀects,havebeenamajortargetinopioidresearchever since.Most of the early work, much of it done in industry, sought to modifythe enkephalin structures to make them morestable in relation to proteolyticbreakdown and improve their bioavailability. The conversion of enkephalinto [D-Ala
Supplementary Methods from Multilevel Whole-Genome Analysis Reveals Candidate Biomarkers in Clear Cell Renal Cell Carcinoma (2023)

Supplementary Methods from Multilevel Whole-Genome Analysis Reveals Candidate Biomarkers in Clear Cell Renal Cell Carcinoma
ChemInform Abstract: A Novel Synthesis of K‐13. (1995)

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.