gebhart/patrepeval huggingface dataset:
BCH-1868 [(-)-2-R-dihydroxyphosphinoyl-5-(S)-(guanin-9'-yl-methyl) tetrahydrofuran]: a cyclic nucleoside phosphonate with antitumor activity. (2002)

Nucleoside phosphonates are widely used therapeutic agents with a broad spectrum of antiviral activity. However, only a few of them are reported to have antitumor activity. In this study, we show that a tetrahydrofuran phosphonate analogue of guanosine, (-)-2-R-dihydroxyphosphinoyl-5-(S)-(guanin-9'-ylmethyl) tetrahydrofuran (BCH-1868), previously reported as having antiviral activity, also displays antitumor activity. In vitro, BCH-1868 inhibited the proliferation of several murine and human cancer cell lines with IC50s in the microM range independently of the tissue type or the presence of multidrug resistance protein MRP/gp190. In vivo, BCH-1868 was active against a variety of human tumor xenograft models (Caki-1, HT-29, DU 145, COLO 205, and CCRF-CEM). In all tumors tested, a significant tumor growth inhibition was noted at 40-50 mg/kg (daily x 5), but no tumor regression was observed in the settings used. To better understand these results, we partially characterized, at the cellular level, the mechanism of action of this new cyclic nucleoside phosphonate and investigated its pharmacokinetic characteristics in mice. We showed that BCH-1868 exerts its antitumor activity by an inhibitory mechanism at the level of DNA polymerase a, resulting in arrest of DNA synthesis and a block of cell division at the S phase of the cell cycle. Low-circulating plasma concentration (Cmax = 87 microM; area under the curve = 1138 micromol x min/liters; after a bolus i.v. injection of 10 mg/kg) and rapid clearance of the drug (terminal half-life, t1/2 = 16 min) may contribute to the modest antitumor efficacy observed in vivo.
A Novel Variant in the TP53 Gene Causing Li–Fraumeni Syndrome (2023)

Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer syndrome associated with germline pathogenic variants in the tumor protein p53 (<i>TP53</i>) gene and elevated risk of a broad range of early-onset malignancies. Patients with LFS are at risk of a second and third primary tumor. A 15-month-old girl consulted for clitoromegaly and pubic hair. Adrenal ultrasound detected a large left adrenal tumor. Left total adrenalectomy confirmed adrenocortical carcinoma. Family history revealed multiple highly malignant neoplasms at an early age across five generations, and a genetic dominant trait seemed probable. Whole-genome sequencing was performed. Multiple members of the family were found positive for a novel likely pathogenic variant (c. 892delGinsTTT, p. Glu298PhefsX48, NM_000546.6) in the <i>TP53</i> gene, causing the loss of normal protein function through non-sense-mediated mRNA decay. According to the PSV1 supporting criteria and the Auto PVS1 online tool this frameshift variant: hg19/17-7577045-TC-TAAA:NM_000546.6 has a very strong, definitive clinical validity for LFS with autosomal dominant inheritance. Proper guidance resulted in timely diagnosis of a second tumor (primary osteosarcoma) in the index case and in the early detection of breast and cervical cancer in her young mother. Patients with cancer predisposition syndromes like LFS require close multidisciplinary cancer surveillance and appropriate referral to expert centers.
Modified CUK Converter with Two Switched Inductor Module Configurations for Photovoltaic Application: Part-II (2020)

A new member of Modified CUK Converter family with a two-switched inductor module (MCC <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SI</sub> ): Modified CUK Converter with XYL configuration (MCC <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SI</sub> -XYL), Modified CUK Converter with LYZ configuration (MCC <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SI</sub> -LYZ) and Modified CUK Converter with XLZ configuration (MCC <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SI</sub> -XLZ) is introduced in this paper. The highlighting points of the proposed converters are (i) single switch topologies, (ii) continuous input current, (iii) high voltage gain, and (iv) inverted output. The voltage gain analysis of three configurations is carried out in detail. Additionally, the comparison of the three converters is made w.r.t. the component count and voltage gain. The MatLab simulation results meet the mathematical analysis and validate the functionality and feasibility of the presented three converters.
A 130nm SiGe BiCMOS technology for mm-Wave applications featuring HBT with f<inf>T</inf>/f<inf>MAX</inf> of 260/320 GHz (2013)

A manufacturable 130nm SiGe BiCMOS RF technology for high-performance mm-wave analog applications having a high-speed SiGe Heterojunction Bipolar Transistor (HBT) integrated into a full-featured RFCMOS is presented. The technology features a high performance (HP) SiGe HBT with f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</sub> /f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">MAX</sub> of 260/320 GHz, a high breakdown (HB) HBT with BV <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">CEO</sub> of 3.5V, 130nm RF CMOS, and a full suite of passive devices. Specific device results pertaining to this BiCMOS8XP technology are discussed in this paper.
Stromal-Derived Factor 1 Expression in the Human Thymus (2002)

Stromal-derived factor-1 (SDF-1), the only known ligand for the chemokine receptor CXCR4, is broadly expressed in cells of both the immune and central nervous systems, and it can induce the migration of resting leukocytes and hemopoietic progenitors. SDF-1 mRNA was previously detected in human thymus-derived stromal cells, but its role in thymopoiesis was unknown. Here we show that SDF-1 is expressed in medullar epithelial cells forming Hassall's corpuscles (HC). In search of the cell type that may be attracted by SDF-1(+) cells in the medulla, we determined that dendritic cells (DC) could be found in situ in close proximity to SDF-1(+) epithelial cells in HC. In HIV-1-infected SCID-hu thymuses, DC contained apoptotic cells and were located within enlarged HC. It was further demonstrated that uptake of apoptotic thymocytes by immature DC induced an increase in CXCR4 expression and SDF-1-mediated chemotaxis. Our data suggest a role for SDF-1 in the elimination of apoptotic thymocytes.
The synthesis and mesomorphic properties of 4,4″-dialkyl-2,2′,3- and 2,2′,3′-trifluoro-1,1′∶4′,1″-terphenyls for high dielectric biaxiality ferroelectric liquid crystal mixtures (2000)

Two series of liquid crystalline terphenyls with terminal alkyl chains have been synthesised with three lateral fluoro substituents in close proximity to each other. Two terminal alkyl chains were employed to minimise viscosity, maximise solubility and generate low melting points. The first series of materials employs fluoro substituents at an outer-edge position to maximise the smectic phase C phase stability, whereas the second series has the fluoro substituents in the centre of the molecule in an attempt to minimise melting points, but surprisingly the melting points of the former compounds are much lower. The synthetic routes to all of the materials involved low-temperature lithiations to generate arylboronic acids which were then involved in sequential, selective palladium-catalysed cross-coupling reactions. Many of the materials produced have extremely low melting points and some exhibit the smectic C phase at room temperature. In general, the 2,2′,3- and 2,2′,3′-patterns of lateral fluoro substitution in 1,1′∶4′,1′′-terphenyls generate materials of low viscosity and high lateral dipole. In particular, many materials from the first series have low melting points and exhibit the smectic C phase, hence they show great promise for the formulation of ferroelectric mixtures with a high dielectric biaxiality which is very important in τV minimum driving schemes; whereas the materials from the second series are nematogens and hence could be useful for vertically aligned nematic devices.
IR Matrix Isolation Studies of Group IVA Metals With Water (1982)

Silicon, germanium, tin and lead metal atoms and dimers react with water molecules to form an adduct on cocondensation in argon, which can then undergo a photoinsertion reaction of the metal into the 0-H bond. The water molecule V2 bending mode frequency is red shifted in the initially formed M1···0H2 and M2···0H2 adducts by 18.6, 15.9, 15.3 and 8.0 cm-1 for Si, Ge, Sn and Pb and 32.1, 19.9 and 16.0 cm-1 for Ge2, Sn2 and Pb2 respectively. Data suggest that the HMOH and MO species are formed on further reaction of the Si, Ge and Sn metal atom-water molecule adducts. The Ge2 and Sn2 adduct reacts to form a dimetal species containing a bridging hydrogen atom. Lead does not react beyond adduct formation.
WE‐E‐M100F‐05: Evaluation of Respiration‐Correlated Digital Tomosynthesis in the Thorax and Abdomen for Soft Tissue Visualization and Patient Positioning (2007)

Purpose: To find optimal parameters for digital tomosynthesis (DTS) image reconstruction, to evaluate ability of respiration correlated DTS to reduce blur caused by respiratory motion, and to assess DTS imaging for soft tissue localization and patient positioning. Methods and Materials: Image acquisition for DTS used a gantry‐mounted kV on‐board imaging system (Varian Medical Systems). We did not acquire DTS separately, but instead simulated DTS acquisition by using projection images acquired for CBCT. DTS reconstruction consisted of backprojection followed by a deblurring operation removing out‐of‐plane objects. For tumors subject to respiratory motion we selected projection images according to an external respiratory monitor signal (Real‐time Position Management System, Varian Medical Systems). Reconstruction and registration of DTS images used vender research software. Results: Optimal DTS quality is achieved with a 6–9 cm long deblurring volume in the direction perpendicular to the image and 20–30° reconstruction arc lengths. Image blur increases with longer arc lengths, while for shorter arcs out of plane objects become more pronounced. RC DTS reconstruction from disjoint arcs containing 2–3 respiratory cycles is feasible, yields images with less motion blur, and allows visualization of tumor movement. Generally, DTS was capable to visualize lung tumors, bronchi, liver, kidneys and abdominal lymph nodes. Estimated 3D registration error of DTS to reference DTS generated from the plan CT DRRs was 3 mm, relative to cone‐beam CT as a standard. Registration of RC DTS of lung tumors was possible to within 2 mm. Conclusions: DTS is capable of soft tissue visualization and patient positioning, including tumors subject to respiratory motion. With several advantages over full rotation CBCT scan, such as much shorter acquisition time, smaller dose and relaxed clearance requirement, DTS can become an efficient imaging modality for image‐guided radiotherapy. Conflict of Interest: Research sponsored by NCI Grant P01‐CA59017 and Varian Medical Systems.
Linear-Chain Structures of Platinum(II) Diimine Complexes (1997)

The structures of three linear-chain platinum(II) diimine complexes have been determined [Pt···Pt, Å]: Pt(bpm)Cl2·0.5(nmp) (3) [3.411(1), 3.371(1)], Pt(phen)(CN)2 (6) [3.338(1), 3.332(1)], and Pt(bpy)(NCS)2 (7) [3.299(2)] (bpm = 2,2‘-bipyrimidine, phen = 1,10-phenanthroline, bpy = 2,2‘-bipyridine, nmp = 1-methyl-2-pyrrolidinone). The Pt···Pt distances in these and in seven related compounds range from 3.24 to 3.49 Å. While we find evidence of interligand interactions influencing these structures, the Pt···Pt bonds are the most important of the stacking forces. The metal−metal distances are generally consistent with an electronic structural model in which σ-donor/π-acceptor ligands strengthen Pt···Pt bonding interactions (for example, the Pt···Pt distances in 3 are 0.04 and 0.08 Å shorter than in the bpy analogue). We have also found that the yellow form of Pt(dmbpy)(NCO)2 (1b) (4,4‘-dimethyl-2,2‘-bipyridine) has a columnar structure; however, in contrast to the linear-chain form (1), which is orange, the Pt atoms are well separated (>4.9 Å). Interestingly, the yellow form is 7% denser than the orange form; this result is consistent with the concept that directed intermolecular interactions give rise to lower density polymorphs. Crystal data: (3) monoclinic, C2/m (No. 12), a = 12.668(4) Å, b = 15.618(6) Å, c = 6.704(3) Å, β = 93.43(3)°, Z = 4; (6) orthorhombic, Pbca (No. 61), a = 38.731(13) Å, b = 18.569(3) Å, c = 6.628(1) Å, Z = 16; (7) orthorhombic, Pbcm (No. 57), a = 10.349(3) Å, b = 19.927(5) Å, c = 6.572(3) Å, Z = 4; (1b) monoclinic, C2/c (No. 15), a = 17.313(4) Å, b = 12.263(3) Å, c = 14.291(4) Å, β = 114.00(2)°, Z = 8.
Dynamic signature verification using discriminative training (2005)

In this paper we describe a new approach to dynamic signature verification using the discriminative training framework. The authentic and forgery samples are represented by two separate Gaussian Mixture models and discriminative training is used to achieve optimal separation between the two models. An enrollment sample clustering and screening procedure is described which improves the robustness of the system. We also introduce a method to estimate and apply subject norms representing the "typical" variation of the subject's signatures. The subject norm functions are parameterized, and the parameters are trained as an integral part of the discriminative training. The system was evaluated using 480 authentic signature samples and 260 skilled forgery samples from 44 accounts and achieved an equal error rate of 2.25%.
A fully human anti-BMP6 antibody reduces the need for erythropoietin in rodent models of the anemia of chronic disease (2020)

Recombinant erythropoietin (EPO) and iron substitution are a standard of care for treatment of anemias associated with chronic inflammation, including anemia of chronic kidney disease. A black box warning for EPO therapy and concerns about negative side effects related to high-dose iron supplementation as well as the significant proportion of patients becoming EPO resistant over time explains the medical need to define novel strategies to ameliorate anemia of chronic disease (ACD). As hepcidin is central to the iron-restrictive phenotype in ACD, therapeutic approaches targeting hepcidin were recently developed. We herein report the therapeutic effects of a fully human anti-BMP6 antibody (KY1070) either as monotherapy or in combination with Darbepoetin alfa on iron metabolism and anemia resolution in 2 different, well-established, and clinically relevant rodent models of ACD. In addition to counteracting hepcidin-driven iron limitation for erythropoiesis, we found that the combination of KY1070 and recombinant human EPO improved the erythroid response compared with either monotherapy in a qualitative and quantitative manner. Consequently, the combination of KY1070 and Darbepoetin alfa resulted in an EPO-sparing effect. Moreover, we found that suppression of hepcidin via KY1070 modulates ferroportin expression on erythroid precursor cells, thereby lowering potentially toxic-free intracellular iron levels and by accelerating erythroid output as reflected by increased maturation of erythrocyte progenitors. In summary, we conclude that treatment of ACD, as a highly complex disease, becomes more effective by a multifactorial therapeutic approach upon mobilization of endogenous iron deposits and stimulation of erythropoiesis.
A Catheter-Based Acoustic Interrogation Device for Monitoring Motility Dynamics of the Lower Esophageal Sphincter (2014)

This paper presents novel minimally-invasive, catheter-based acoustic interrogation device for monitoring motility dynamics of the lower esophageal sphincter (LES). A micro-oscillator actively emitting sound wave at 16 kHz is located at one side of the LES, and a miniature microphone is located at the other side of the sphincter to capture the sound generated from the oscillator. Thus, the dynamics of the opening and closing of the LES can be quantitatively assessed. In this paper, experiments are conducted utilizing an LES motility dynamics simulator. The sound strength is captured by the microphone and is correlated to the level of LES opening and closing controlled by the simulator. Measurements from the simulator model show statistically significant (p < 0.05) Pearson correlation coefficients (0.905 on the average in quiet environment and 0.736 on the average in noisy environment, D.O.F. = 9). Measuring the level of LES opening and closing has the potential to become a valuable diagnostic technique for understanding LES dysfunction and the disorders associated with it.
Hf-based metal–organic frameworks as acid–base catalysts for the transformation of biomass-derived furanic compounds into chemicals (2018)

Hafnium-based metal–organic frameworks are promising catalysts for upgrading biomass derivatives <italic>via</italic> an aldol condensation reaction.
Microenvironment Impacts the Molecular Architecture and Interactivity of Resident Cells in Marmoset Brain (2021)

Abstract The microenvironments of the brain consist of specialized cell types that together influence physiological functions in health and pathological outcomes in disease. Despite apparent differences in the density of neurons and oligodendrocytes in various milieus, such as gray matter (GM) and white matter (WM), the extent of structural and functional heterogeneity of other resident cells remains unclear. We profiled RNA in ~500,000 nuclei from 19 tissue types across the central nervous system of the healthy adult common marmoset ( Callithrix jacchus ) and mapped 87 identified subclusters (including neurons, glia, and vasculature) spatially onto a 3D MRI atlas. We performed cross-species comparison, explored regulatory pathways, surveyed cellular determinants of neurological disorders, and modeled regional intercellular communication. We found spatially segregated microglia, oligodendrocyte lineage cells, and astrocytes in WM and GM. WM-glia are diverse, are enriched with genes involved in stimulus response and biomolecule modification, and interact with other resident cells more extensively than their GM counterparts. GM-glia preserve the expression of developmental morphogens into adulthood and share 6 differentially enriched transcription factors that restrict the transcriptome complexity. Our work in marmoset, an experimentally tractable animal model with &gt;5 times more WM volume and complexity than mouse, identifies novel WM-glia subtypes and their contributions to different neurological disorders. A companion Callithrix jacchus Primate Cell Atlas (CjPCA) is available through an online portal https://cjpca.ninds.nih.gov to facilitate data exploration.
Simulating Bluff-Body Flameholders: On the Use of Proper Orthogonal Decomposition for Wake Dynamics Validation (2014)

In this article, we describe a novel use of proper orthogonal decomposition (POD) for validation of the structure of dominant flow features in the wake of a bluff-body flameholder. Large-eddy simulations (LES) using both FLUENT and OpenFOAM were conducted based on experiments with planar particle-image velocimetry (PIV) measurements of the same geometry and conditions. With the vision of extending the LES to reacting flows, a validation process is presented that involves a comparison of experimental and computational results, beginning with single-point mean statistics and then extended to the dynamic modes of the data sets as obtained using POD of the instantaneous flow field results. The results exhibit quantitative agreement between both shapes and mode magnitudes for the first POD modes of the measured and simulated data.
Investigation of Nitrogen-Originated NBTI Mechanism in SiON with High-Nitrogen Concentration (2006)

We have investigated the nitrogen-originated NBT degradation mechanism of SiON films by using SiON with high nitrogen concentration. It was found that, threshold voltage shift (DeltaV <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sub> ) under NBT stress is degraded with increasing nitrogen concentration in bulk rather than that at interface. Furthermore, NBTI exponents strongly correlate with the nitrogen concentration in bulk and pre-stressed flat-band voltage shift (AV <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">fb</sub> <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ini</sup> ). From these experimental results, we interpret that there is an additional NBT degradation mechanism with small NBTI exponents (beta > 0.25) and this is originated by pre-existing defects due to nitrogen incorporation. Finally, from the reliability viewpoint, we propose that decreasing the defect in bulk introduced during nitridation is indispensable for the fabrication process of high nitrogen concentration SiON maintaining high reliability
Charge ordering and hopping in a triangular array of quantum dots (1999)

We demonstrate a mapping between the problem of charge ordering in a triangular array of quantum dots and a frustrated Ising spin model. Charge correlation in the low temperature state is characterized by an intrinsic height field order parameter. Different ground states are possible in the system, with a rich phase diagram. We show that electronic hopping transport is sensitive to the properties of the ground state, and describe the singularities of hopping conductivity at the freezing into an ordered state.
Continuous and discontinuous power reduced transmission of speech inactivity for the GSM system (2002)

Discontinuous transmission (DTX) or variable bit rate operation during speech inactivity is applied in various cellular speech communication systems. This is a technique in essence to turn off the transmission during periods of speech silence. The purpose is to reduce interference caused to other users concurrently transmitting on the air interface and to save battery power in the mobile stations. A major problem with this technique arises for emerging communication systems with link adaptation as both continuous channel tracking and continuous inband back channels are disabled when transmission is turned off. This paper presents a novel alternative method to conventional DTX which allows to keep the transmission continuous or almost continuous but which maintains or even exceeds the gain of the conventional method.
A Novel and Efficient Synthesis of a Highly Active Analogue of clasto-Lactacystin β-Lactone (1999)

Herein, we describe a new convergent synthesis of a more potent analogue of clasto-lactacystin β-lactone (2), PS-519 compound 4, which is currently in preclinical development for the treatment of ischemia−reperfusion injury in stroke and myocardial infarction. The synthetic strategy relies on building two intermediates (an oxazoline and an aldehyde) which are joined through a doubly diastereoselective aldol reaction, setting up the requisite unichiral centers in the final product (4). The facial selectivity and ultimate stereocontrol are achieved by employing a trivalent aluminum Lewis acid, Me2AlCl, in a chelation-induced reaction which yields a single aldol adduct. The efficiency of the synthetic approach has allowed for the preparation of multigram quantities of clinical grade material, which will support Phase I studies.
Optimized structure of silane-core containing host materials for highly efficient blue TADF OLEDs (2017)

The TADF OLEDs based on these silane-core host materials showed a maximum EQE of up to 18.8%.