gebhart/patrepeval huggingface dataset:
Structure analysis of the receptor binding of 2019-nCoV (2020)

2019-nCoV is a newly identified coronavirus with high similarity to SARS-CoV. We performed a structural analysis of the receptor binding domain (RBD) of spike glycoprotein responsible for entry of coronaviruses into host cells. The RBDs from the two viruses share 72% identity in amino acid sequences, and molecular simulation reveals highly similar ternary structures. However, 2019-nCoV has a distinct loop with flexible glycyl residues replacing rigid prolyl residues in SARS-CoV. Molecular modeling revealed that 2019-nCoV RBD has a stronger interaction with angiotensin converting enzyme 2 (ACE2). A unique phenylalanine F486 in the flexible loop likely plays a major role because its penetration into a deep hydrophobic pocket in ACE2. ACE2 is widely expressed with conserved primary structures throughout the animal kingdom from fish, amphibians, reptiles, birds, to mammals. Structural analysis suggests that ACE2 from these animals can potentially bind RBD of 2019-nCoV, making them all possible natural hosts for the virus. 2019-nCoV is thought to be transmitted through respiratory droplets. However, since ACE2 is predominantly expressed in intestines, testis, and kidney, fecal-oral and other routes of transmission are also possible. Finally, antibodies and small molecular inhibitors that can block the interaction of ACE2 with RBD should be developed to combat the virus.
Stable secondary structures at the 3'‐end of the genome of yellow fever virus (17 <i>D</i> vaccine strain) (1985)

The sequence of the 3'-terminal 565 nucleotides of yellow fever virus has been determined from a cloned cDNA. Several structures are detectable: three tandemly repeated sequences, a series of inverted repeats and a stable secondary structure involving the 3'-terminal 120 nucleotides.
Type VI collagen is a major component of the human cornea (1986)

Collagen type VI is shown to be present in the human cornea. This finding is based on comparative peptide mapping relative to type VI collagen isolated from placenta and on immunoblotting using antibodies specific for human type VI collagen. Scanning of polyacrylamide gels indicates that type VI collagen comprises as much as one quarter of the dry weight of the cornea. Indirect immunofluorescence shows this collagen to be distributed throughout the corneal stroma. Thus, type VI collagen must be considered a major component of the extracellular matrix of the human cornea.
Oligonucleotide Analogues as Potential Chemotherapeutic Agents (1989)

In principle, relatively short oligonucleotides (ca. 15-20 bases in length) can specifically hybridize with DNA or RNA and thus be used for novel drug design strategies involving targeted interference of genetic expression at the level of transcription or translation. Conceivable chemotherapeutic applications predicated on sequence-specific hybridization ("antisense" inhibition) require oligonucleotide analogues that are resistant to in vivo degradation by enzymes such as nucleases. Nuclease-resistant analogues having modified internucleoside linkages (e.g., methylphosphonates or phosphorothioates) or modified nucleosides (e.g., 2'-O-methylribose or 1'-alpha-anomers) are now readily available by means of automated synthesis. Through collaborative investigations of various different backbone-modified oligonucleotides, we have comparatively studied hybridization (Tm), in vitro inhibition of gene expression (CAT and ras genes), and in vitro inhibition of HIV. Phosphorothioate oligomers at ca. 1 uM exhibited potent anti-HIV activity. The mechanism(s) for this anti-retroviral activity is (are) under further investigation.
Efficient modeling of 3-D photonic crystals for integrated optical devices (2005)

We propose a full-wave numerical model of a three-dimensional (3-D) photonic crystal with the absolute photonic bandgap (PBG) centered at /spl lambda//spl sim/1.6 μm. The analyzed structure is widely used in integrated optical circuitry. The electromagnetic analysis is performed by using the finite-element method (FEM) and transmission line matrix-integral equation (TLMIE) method. We analyze the reflection properties and compare theoretical results to experimental data. Due to its exact boundary conditions, TLMIE shows much higher accuracy with respect to FEM in the PBG optical band. As a demonstration, we have realized and analyzed a holographic polymer dispersed liquid crystal grating.
Wall position and thickness estimation from sequences of echocardiographic images (1996)

Presents a new method for endocardial (inner) and epicardial (outer) contour estimation from sequences of echocardiographic images. The framework herein introduced is fine-tuned for parasternal short axis views at the papillary muscle level. The underlying model is probabilistic; it captures the relevant features of the image generation physical mechanisms and of the heart morphology. Contour sequences are assumed to be two-dimensional noncausal first-order Markov random processes; each variable has a spatial index and a temporal index. The image pixels are modeled as Rayleigh distributed random variables with means depending on their positions (inside endocardium, between endocardium and pericardium, or outside pericardium). The complete probabilistic model is built under the Bayesian framework. As estimation criterion the maximum a posteriori (MAP) is adopted. To solve the optimization problem, one is led to (joint estimation of contours and distributions' parameters), the authors introduce an algorithm herein named iterative multigrid dynamic programming (IMDP). It is a fully data-driven scheme with no ad-hoc parameters. The method is implemented on an ordinary workstation, leading to computation times compatible with operational use. Experiments with simulated and real images are presented.
Subtle alternating electrocardiographic morphology as an indicator of decreased cardiac electrical stability. (1985)

Observations from finite-element computer models, together with analytic developments based on percolation theory have suggested that subtle fluctuations of ECG morphology might serve as an indicator diminished cardiac electrical stability. With fixed-rate atrial pacing in canines, we have previously observed a pattern of alternation in T wave energy which correlated with cardiac electrical stability. We report here on a series of 20 canine experiments in which cardiac electrical stability (measured via Ventricular Fibrillation Threshold determination) was compared to a non-degenerate, multidimensional measurement of the degree of alternating activity present in the ECG complex morphology. The decrease in cardiac electrical stability brought on by both coronary artery occlusion and systemic hypothermia was consistently accompanied by subtle alternation in ECG morphology, with the absolute degree of alternating activity being significantly (negatively) correlated with cardiac electrical stability.
Oral delivery of PND-1186 FAK inhibitor decreases tumor growth and spontaneous breast to lung metastasis in pre-clinical models (2010)

Tumor metastasis is a leading cause of cancer-related death. Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase recruited to integrin-mediated matrix attachment sites where FAK activity is implicated in the control of cell survival, migration, and invasion. Although genetic studies support the importance of FAK activity in promoting tumor progression, it remains unclear whether pharmacological FAK inhibition prevents tumor metastasis. Here, we show that the FAK inhibitor PND-1186 blocks FAK Tyr-397 phosphorylation in vivo and exhibits anti-tumor efficacy in orthotopic breast carcinoma mouse tumor models. PND-1186 (100 mg/kg intraperitoneal, i.p.) showed promising pharmacokinetics (PK) and inhibited tumor FAK Tyr-397 phosphorylation for 12 hours. Oral administration of 150 mg/kg PND-1186 gave a more sustained PK profile verses i.p., and when given twice daily, PND-1186 significantly inhibited sygeneic murine 4T1 orthotopic breast carcinoma tumor growth and spontaneous metastasis to lungs. Moreover, low-level 0.5 mg/ml PND-1186 ad libitum administration in drinking water prevented oncogenic KRAS- and BRAF-stimulated MDA-MB-231 breast carcinoma tumor growth and metastasis with inhibition of tumoral FAK and p130Cas phosphorylation. Although PND-1186 was not cytotoxic to cells in adherent culture, tumors from animals receiving PND-1186 exhibited increased TUNEL staining, decreased leukocyte infiltrate and reduced tumor-associated splenomegaly. In vitro, PND-1186 reduced tumor necrosis factor-a triggered interleukin-6 cytokine expression, indicating that FAK inhibition may impact tumor progression via effects on both tumor and stromal cells. As oral administration of PND-1186 also decreased experimental tumor metastasis, PND-1186 may therefore be useful clinically to curb breast tumor progression.
Distribution of Sulfate Ions in Spherical Ice Crystals and Elution Phenomena. (1996)

春先の最初の雪解け水中の水素イオン濃度は高い傾向にある。大気中を落下する雪は酸性物質を捕捉する。大地に積もった新雪は, 圧縮され, 溶解と再結晶を繰り返し, 氷状のザラメ雪となる。この繰り返しで, 硫酸, 硝酸, 塩化物イオンは粒状ザラメ雪の表面に濃縮される。硫酸イオンを含む溶液から球状結晶を生成し, それらを溶解し, この濃縮現象を実験室的に検討した。溶解実験により氷結晶中の硫酸イオン濃度とその分布を測定した。有機溶媒中で結晶を表面から溶解した場合, 硫酸イオンの分布は偏っていて, 表面付近により多く存在した。結晶生成時の硫酸イオン濃度が高い程一様な分布になる傾向にあることが分かった。氷結晶をカラム中に詰め室温でそれを溶解した場合, 最初の流出液中の硫酸イオン濃度が高いことを認めた。又, その濃度比は有機溶媒を使用して得た球表面付近の値よりも高くなった。ザラメ雪を溶解した場合, 同じような結果が得られ, 最初の流出液中の硫酸イオン濃度は後のものより高いことも分かった。
Expression of the Long Form of Human FLIP by Retroviral Gene Transfer of Hemopoietic Stem Cells Exacerbates Experimental Autoimmune Encephalomyelitis (2003)

Subsidence of inflammation and clinical recovery in experimental autoimmune encephalomyelitis (EAE) is postulated to involve apoptosis of inflammatory cells. To test this concept, we examined the effects of overexpressing the long form of human FLICE-inhibitory protein, a potent inhibitor of death receptor-mediated apoptosis, in myelin oligodendrocyte glycoprotein-induced EAE in DBA/1 mice. We found that overexpression of the long form of human FLICE-inhibitory protein by retroviral gene transfer of hemopoietic stem cells led to a clinically more severe EAE in these mice compared with control mice receiving the retroviral vector alone. The exacerbated disease was evident by an enhanced and prolonged inflammatory reaction in the CNS of these animals compared with control mice. The acute phase of EAE was characterized by a massive infiltration of macrophages and granulocytes and a simultaneous increase in TNF-alpha production in the CNS. In the chronic phase of the disease, there was a prolonged inflammatory response in the form of persistent CD4(+) T and B cells in the CNS and a peripheral Th1 cytokine bias caused by elevated levels of IFN-gamma and reduced levels of IL-4 in the spleen. Our findings demonstrate that death receptor-mediated apoptosis can be important in the pathogenesis of EAE and further emphasize the need for effective apoptotic elimination of inflammatory cells to achieve disease remission.
Stability constants of magnesium and cadmium complexes of adenine nucleotides and thionucleotides and rate constants for formation and dissociation of magnesium-ATP and magnesium-ADP (1984)

Stability constants for the Mg2+ and Cd2+ complexes of ATP, ADP, ATP alpha S, ATP beta S, and ADP alpha S have been determined at 30 degrees C and mu = 0.1 M by 31P NMR. Besides being of the utmost importance for determining species distributions for enzymatic studies, these constants allow an estimation of the preference of Cd2+ for sulfur vs. oxygen coordination in phosphorothioate complexes. Stability constants for Mg2+ complexes decreases when sulfur replaces oxygen (log K: ADP, 4.11; ADP alpha S, 3.66; ATP, 4.70; ATP alpha S, 4.47; ATP beta S, 4.04) because of (a) a statistical factor resulting from the loss of one potential phosphate oxygen ligand and (b) either an alteration in the charge distribution between oxygen and sulfur or destabilization of the chelate ring structure by loss of an internal hydrogen bond between an oxygen of coordinated phosphate and metal-bound water. Cd2+ complexes with sulfur-substituted nucleotides are more stable than those without sulfur (log K: ADP, 3.58; ADP alpha S, 4.95; ATP, 4.36; ATP alpha S, 4.42; ATP beta S, 5.44) because of the preferential binding of Cd2+ to sulfur rather than oxygen, which we estimate to be approximately 60 in CdADP alpha S and CdATP beta S. The proportion of tridentate coordination is estimated to be 50-60% in MgATP and MgATP beta S, approximately 27% in MgATP alpha S, approximately 16% in CdATP or CdATP beta S, but approximately 75% in CdATP alpha S. By analysis of the data of Jaffe and Cohn [Jaffe, E. K., & Cohn, M. (1979) J. Biol. Chem. 254, 10839], we conclude that the preference for oxygen over sulfur coordination to ATP beta S is 31 000 for Mg2+, 3100-3900 for Ca2+, and 158-193 for Mn2+. Proton NMR demonstrates that bidentate Cd2+ complexes form intramolecular chelates with the N-7 of adenine while Mg2+ nucleotides and the tridenate CdATP alpha S do not. An analysis of the 31P NMR line widths shows that the rate constants for dissociation of MgADP and MgATP are both 7000 s-1 while the association rate constants are 7 X 10(7) and 4 X 10(8) M-1 s-1, respectively. The observed dependence of the line width on nucleotide concentration is best explained by a base-stacking model at nucleotide concentrations above 5 mM.
Somatosensory processes subserving perception and action (2007)

The functions of the somatosensory system are multiple. We use tactile input to localize and experience the various qualities of touch, and proprioceptive information to determine the position of different parts of the body with respect to each other, which provides fundamental information for action. Further, tactile exploration of the characteristics of external objects can result in conscious perceptual experience and stimulus or object recognition. Neuroanatomical studies suggest parallel processing as well as serial processing within the cerebral somatosensory system that reflect these separate functions, with one processing stream terminating in the posterior parietal cortex (PPC), and the other terminating in the insula. We suggest that, analogously to the organisation of the visual system, somatosensory processing for the guidance of action can be dissociated from the processing that leads to perception and memory. In addition, we find a second division between tactile information processing about external targets in service of object recognition and tactile information processing related to the body itself. We suggest the posterior parietal cortex subserves both perception and action, whereas the insula principally subserves perceptual recognition and learning.
Two Activities of Long-Chain Acyl-Coenzyme A Synthetase Are Involved in Lipid Trafficking between the Endoplasmic Reticulum and the Plastid in Arabidopsis (2014)

In plants, fatty acids are synthesized within the plastid and need to be distributed to the different sites of lipid biosynthesis within the cell. Free fatty acids released from the plastid need to be converted to their corresponding coenzyme A thioesters to become metabolically available. This activation is mediated by long-chain acyl-coenzyme A synthetases (LACSs), which are encoded by a family of nine genes in Arabidopsis (Arabidopsis thaliana). So far, it has remained unclear which of the individual LACS activities are involved in making plastid-derived fatty acids available to cytoplasmic glycerolipid biosynthesis. Because of its unique localization at the outer envelope of plastids, LACS9 was regarded as a candidate for linking plastidial fatty export and cytoplasmic use. However, data presented in this study show that LACS9 is involved in fatty acid import into the plastid. The analyses of mutant lines revealed strongly overlapping functions of LACS4 and LACS9 in lipid trafficking from the endoplasmic reticulum to the plastid. In vivo labeling experiments with lacs4 lacs9 double mutants suggest strongly reduced synthesis of endoplasmic reticulum-derived lipid precursors, which are required for the biosynthesis of glycolipids in the plastids. In conjunction with this defect, double-mutant plants accumulate significant amounts of linoleic acid in leaf tissue.
Modeling Study of Seasonal Variation of the Pelagic-Benthic Ecosystem Characteristics of the Bohai Sea (2006)

在 1998 和 1999 在 Bohai 海基于中国德语的全面调查的实验数据，一个简单联合 pelagic-benthic 生态系统多盒子模型被用来模仿生态系统季节变异。远洋的亚模型由七个州的变量组成：浮游植物，浮游动物，锡，尖端，文档，停靠港和溶解的氧() 。benthicsub 模型在沉积包括宏底生生物， meiobenthos，细菌，岩屑，听和尖端。除从海底部渗出的太阳辐射，水温和营养素的效果以外，以地为基地的输入被考虑。在盒子之间的移流术语的影响也被考虑。同时， micro-bial-loop 的效果与 simpleparameterization 被介绍。季节变异和生态系统的水平分布声明 Bohai 海的变量被模仿。与观察相比， themulti 盒子模型的结果是合理的。建模的结果证明大约 13% 光合作用初级生产量去主要食物环， 20% 转到 benthic 领域， 44% 被浮游植物的呼吸消费，并且剩余的去文档。模型结果也在 Bohai 海，和它对年度浮游动物生产的贡献的生态系统显示出微生物引起的食物环的重要性能是 60%-64% 。
Alphavirus vectors: development and potential therapeutic applications (2001)

AbstractAlphaviruses are RNA enveloped viruses that are proving their value as expression vectors. They are particularly well-suited for this role as they are easily and quickly engineered and can be used to produce high levels of proteins of interest. A promising and important use is as vaccines against disease-causing agents such as HIV. The three alphaviruses now serving as vectors are Sindbis virus, Semliki Forest virus (SFV) and Venezuelan equine encephalitis (VEE) virus. Sindbis virus and SFV are well-known models for studies in molecular and cell biology; VEE virus is a human pathogen and had received some previous notoriety as a potential biological weapon. It is now becoming a potentially valuable vaccine vector. All three viruses are being tested as vaccines but, at present, only Sindbis virus and SFV have been considered for other uses. Sindbis virus vectors have been developed to screen libraries for the identification of new proteins and to devise sensitive assays to detect viruses more difficult to grow in culture. Both Sindbis virus and SFV vectors are serving as tools for fundamental studies in biology, examples include development in insects and analysis of protein functions in neuronal cells. In this article the replication strategy of alphaviruses and the different ways they can be engineered to serve as expression vectors is described. This provides an introduction to the ways these vectors have been used and illustrates the promise these vectors offer.Keywordsalphavirusesexpression vectorsRNA virusesSemliki Forest virusSindbis virusvaccinesVenezuelan equine encephalitisvirus detection assays
The Clock is Still Ticking (2015)

Web-based timing attacks have been known for over a decade, and it has been shown that, under optimal network conditions, an adversary can use such an attack to obtain information on the state of a user in a cross-origin website. In recent years, desktop computers have given way to laptops and mobile devices, which are mostly connected over a wireless or mobile network. These connections often do not meet the optimal conditions that are required to reliably perform cross-site timing attacks. In this paper, we show that modern browsers expose new side-channels that can be used to acquire accurate timing measurements, regardless of network conditions. Using several real-world examples, we introduce four novel web-based timing attacks against modern browsers and describe how an attacker can use them to obtain personal information based on a user's state on a cross-origin website. We evaluate our proposed attacks and demonstrate that they significantly outperform current attacks in terms of speed, reliability, and accuracy. Furthermore, we show that the nature of our attacks renders traditional defenses, i.e., those based on randomly delaying responses, moot and discuss possible server-side defense mechanisms.
Strong Kochen-Specker theorem and incomputability of quantum randomness (2012)

The Kochen-Specker theorem shows the impossibility for a hidden variable theory to consistently assign values to certain (finite) sets of observables in a way that is noncontextual and consistent with quantum mechanics. If we require noncontextuality, the consequence is that many observables must not have pre-existing definite values. However, the Kochen-Specker theorem does not allow one to determine which observables must be value indefinite. In this paper we present an improvement on the Kochen-Specker theorem which allows one to actually locate observables which are provably value indefinite. Various technical and subtle aspects relating to this formal proof and its connection to quantum mechanics are discussed. This result is then utilized for the proposal and certification of a dichotomic quantum random number generator operating in a three-dimensional Hilbert space.
THROWING ARM MOTION TO DETERMINE SPIN AXIS OF PITCHED BASEBALL (2006)

The purpose of the present study was to investigate a throwing arm kinematics to determine the direction of spin axis of pitched baseball. The baseball was filmed immediately after ball release using a high-speed video camera (250 Hz). The direction of the spin axis and the spin rate were calculated based on the positional changes of the marks on the ball. The throwing motion was recorded with 3-D motion analysis system (Vicon), and angles of wrist flexion/extension, radial/ulnar deviation, and forearm pronation/supination were calculated as kinematic parameters. The direction of the hand segment in global reference frame was also obtained. The spin axis direction significantly correlated with the hand direction, while, there were no special relationship between the spin axis of the ball and joint angular kinematics obtained in this study. It follows from what has been reported that pitched ball trajectory is associated with attitude of the hand when a ball was released from the fingertip. KEY WORDS: baseball, spin, kinematics. INTRODUCTION: Kreighbaum (1978) proposed that the trajectory of a pitched ball is
Monitoring Light-induced Structural Changes of Channelrhodopsin-2 by UV-visible and Fourier Transform Infrared Spectroscopy (2008)

Channelrhodopsin-2 (ChR2) is a microbial type rhodopsin and a light-gated cation channel that controls phototaxis in Chlamydomonas. We expressed ChR2 in COS-cells, purified it, and subsequently investigated this unusual photoreceptor by flash photolysis and UV-visible and Fourier transform infrared difference spectroscopy. Several transient photoproducts of the wild type ChR2 were identified, and their kinetics and molecular properties were compared with those of the ChR2 mutant E90Q. Based on the spectroscopic data we developed a model of the photocycle comprising six distinguishable intermediates. This photocycle shows similarities to the photocycle of the ChR2-related Channelrhodopsin of Volvox but also displays significant differences. We show that molecular changes include retinal isomerization, changes in hydrogen bonding of carboxylic acids, and large alterations of the protein backbone structure. These alterations are stronger than those observed in the photocycle of other microbial rhodopsins like bacteriorhodopsin and are related to those occurring in animal rhodopsins. UV-visible and Fourier transform infrared difference spectroscopy revealed two late intermediates with different time constants of tau = 6 and 40 s that exist during the recovery of the dark state. The carboxylic side chain of Glu(90) is involved in the slow transition. The molecular changes during the ChR2 photocycle are discussed with respect to other members of the rhodopsin family.