gebhart/patrepeval huggingface dataset:
Molecular Dynamics Simulations Reveal the Mechanisms of Allosteric Activation of Hsp90 by Designed Ligands (2016)

Controlling biochemical pathways through chemically designed modulators may provide novel opportunities to develop therapeutic drugs and chemical tools. The underlying challenge is to design new molecular entities able to act as allosteric chemical switches that selectively turn on/off functions by modulating the conformational dynamics of their target protein. We examine the origins of the stimulation of ATPase and closure kinetics in the molecular chaperone Hsp90 by allosteric modulators through atomistic molecular dynamics (MD) simulations and analysis of protein-ligand interactions. In particular, we focus on the cross-talk between allosteric ligands and protein conformations and its effect on the dynamic properties of the chaperone's active state. We examine the impact of different allosteric modulators on the stability, structural and internal dynamics properties of Hsp90 closed state. A critical aspect of this study is the development of a quantitative model that correlates Hsp90 activation to the presence of a certain compound, making use of information on the dynamic adaptation of protein conformations to the presence of the ligand, which allows to capture conformational states relevant in the activation process. We discuss the implications of considering the conformational dialogue between allosteric ligands and protein conformations for the design of new functional modulators.
Integrating Metabolic Modeling and High‐Throughput Data to Characterize Diatoms Metabolism (2023)

Metabolic modeling is a quantitative tool that uses genome-scale networks to predict growth phenotypes with high accuracy. During the reconstruction of metabolic networks of diatoms the genome annotation is manually improved by including new gene-protein-reaction associations of organelle-specific pathways, as well as intra- and extracellular transporters. Metabolic modeling combined with omic data of diatoms has been applied to identify suitable culture conditions, unravel interwoven regulatory mechanisms, explore genetic enhancement strategies for bioproduction, and quantify changes in resource allocation under nutrients limitation. Computational models offer insights into the function of pathways critical for diatom physiology, from central carbon metabolism to lipid, pigment, and pathways involved in photon uptake. Here, we review the state-of-the-art of metabolic modeling of diatoms and how recently developed control biosystems can be applied to optimize rational culture cultivation conditions. We also discuss how metabolic models of diatoms and heterotrophs can be linked in a community framework to better understand the interactions of diatoms in natural environments.
[Clinical characteristics and therapeutic strategy for acute myocardial infarction in the elderly]. (1996)

Many randomized studies have revealed that reperfusion therapy is an epochmaking treatment for acute myocardial infarction (AMI). However, it is no clear whether it is equally beneficial in the elderly or not. In this study, we elucidated the clinical characteristics and effectiveness of reperfusion therapy and discussed the optimal treatment for AMI in the elderly. The study population comprised 1,891 consecutive patients with AMI. The reinfarction rates and the rates of Killip class III or IV on admission increased with age. The mortality was significantly higher in the older subgroups. In the patients with first AMI within 24 hours of the onset and who underwent emergency catheterization, those accompanied by hypercholesterolemia or with habitual smoking were significantly fewer in the older group. Although the Q-wave MI rate, the peak CPK level and the reperfusion rate were no different, the low cardiac output condition, multi vessel disease and short-term mortality were significantly greater in the older group. The patients over 80-year-old were subdivided into three groups; those treated conventionally (G-C), those treated with intracoronary thrombolysis (G-T) and those treated with direct PTCA (G-A). The overall mortality did not differ among the three groups. However, in patients hospitalized after 1990, the mortality in G-A was significantly lower than in G-C. The prevalence of bleeding complications between G-A and G-T did not differ. The patients in G-A showed greater improvement of the left ventricular wall motion and lower incidence of postinfarctional angina than other groups. Reperfusion therapy by direct PTCA appears to be the optimal strategy for treatment of elder patients with AMI.
The influence of hydrogen on the chemical, mechanical, optical/electronic, and electrical transport properties of amorphous hydrogenated boron carbide (2015)

Because of its high electrical resistivity, low dielectric constant (κ), high thermal neutron capture cross section, and robust chemical, thermal, and mechanical properties, amorphous hydrogenated boron carbide (a-BxC:Hy) has garnered interest as a material for low-κ dielectric and solid-state neutron detection applications. Herein, we investigate the relationships between chemical structure (atomic concentration B, C, H, and O), physical/mechanical properties (density, porosity, hardness, and Young's modulus), electronic structure [band gap, Urbach energy (EU), and Tauc parameter (B1/2)], optical/dielectric properties (frequency-dependent dielectric constant), and electrical transport properties (resistivity and leakage current) through the analysis of a large series of a-BxC:Hy thin films grown by plasma-enhanced chemical vapor deposition from ortho-carborane. The resulting films exhibit a wide range of properties including H concentration from 10% to 45%, density from 0.9 to 2.3 g/cm3, Young's modulus from 10 to 340 GPa, band gap from 1.7 to 3.8 eV, Urbach energy from 0.1 to 0.7 eV, dielectric constant from 3.1 to 7.6, and electrical resistivity from 1010 to 1015 Ω cm. Hydrogen concentration is found to correlate directly with thin-film density, and both are used to map and explain the other material properties. Hardness and Young's modulus exhibit a direct power law relationship with density above ∼1.3 g/cm3 (or below ∼35% H), below which they plateau, providing evidence for a rigidity percolation threshold. An increase in band gap and decrease in dielectric constant with increasing H concentration are explained by a decrease in network connectivity as well as mass/electron density. An increase in disorder, as measured by the parameters EU and B1/2, with increasing H concentration is explained by the release of strain in the network and associated decrease in structural disorder. All of these correlations in a-BxC:Hy are found to be very similar to those observed in amorphous hydrogenated silicon (a-Si:H), which suggests parallels between the influence of hydrogenation on their material properties and possible avenues for optimization. Finally, an increase in electrical resistivity with increasing H at &amp;lt;35 at. % H concentration is explained, not by disorder as in a-Si:H, but rather by a lower rate of hopping associated with a lower density of sites, assuming a variable range hopping mechanism interpreted in the framework of percolation theory.
Three-dimensional imaging with arrays of Geiger-mode avalanche photodiodes (2004)

Lincoln Laboratory has developed 32 x 32-pixel ladar focal planes comprising silicon geiger-mode avalanche photodiodes and high-speed all-digital CMOS timing circuitry in each pixel. In Geiger mode operation, the APD can detect as little as a single photon, producing a digital CMOS-compatible voltage pulse. This pulse is used to stop a high-speed counter in the pixel circuit, thus digitizing the time of arrival of the optical pulse. This "photon-to-digital conversion" simultaneously achieves single-photon sensitivity and 0.5-ns timing. We discuss the development of these focal planes and present imagery from ladar systems that use them.
Adenoviral B7-H3 therapy induces tumor specific immune responses and reduces secondary metastasis in a murine model of colon cancer (2007)

Introduction: Current cancer gene therapies aim for the induction of systemic antitumor immune responses. Tumors may deliver antigens to T cells, but may lack the costimulatory signals necessary for mounting an effective response.
Hypoxia-Selective Antitumor Agents. 13. Effects of Acridine Substitution on the Hypoxia-Selective Cytotoxicity and Metabolic Reduction of the Bis-bioreductive Agent Nitracrine N-Oxide (1996)

A series of nuclear-substituted derivatives of nitracrine N-oxide (2; a bis-bioreductive hypoxia-selective cytotoxin) were prepared and evaluated, seeking analogues of lower nitroacridine reduction potential. Disubstitution with Me or OMe groups at the 4- and 5-positions did not provide analogues with one-electron reduction potentials significantly lower than those of the corresponding monosubstituted derivatives (E(1) ca. -350 mV for both the 4-OMe and 4,5-diOMe compounds). This appears not to be due to a concomitant raising of the acridine pKa but to a lack of direct electronic effect of substituents in the ring not bearing the nitro group. Conversely, placing two OMe groups in the nitro-bearing ring does result in a substantial further lowering of reduction potential (the 2,4-diOMe analogue has an E(1) of -401 mV). The mono- and disubstituted N-oxides have substantially lower cytotoxicities than the parent nitracrine N-oxide 2 but generally retain very high hypoxic selectivity. The OMe-substituted N-oxides all showed greater metabolic stability than 2 in hypoxic AA8 cell cultures, and the 4-OMe compound 6 had improved activity in EMT6 multicellular spheroids suggesting that this metabolic stabilization may allow more efficient diffusion in tumor tissue. The parent compound 2 was selectively toxic to hypoxic cells in KHT tumors in vivo and clearly superior to nitracrine itself (although only at doses which would eventually be lethal to the host). The analogues of lower E(1), including 6, were not superior to 2 in vivo, indicating that metabolic stabilization of the nitro group is not alone sufficient to improve therapeutic utility.
Efficient narrow-band light emission from a single carbon nanotube p-n\n diode (2010)

Electrically-driven light emission from carbon nanotubes could be exploited\nin nano-scale lasers and single-photon sources, and has therefore been the\nfocus of much research. However, to date, high electric fields and currents\nhave been either required for electroluminescence, or have been an undesired\nside effect, leading to high power requirements and low efficiencies. In\naddition, electroluminescent linewidths have been broad enough to obscure the\ncontributions of individual optical transitions. Here, we report\nelectrically-induced light emission from individual carbon nanotube p-n diodes.\nA new level of control over electrical carrier injection is achieved, reducing\npower dissipation by a factor of up to 1000, and resulting in zero threshold\ncurrent, negligible self-heating, and high carrier-to- photon conversion\nefficiencies. Moreover, the electroluminescent spectra are significantly\nnarrower (ca. 35 meV) than in previous studies, allowing the identification of\nemission from free and localized excitons.\n
Epstein-Barr virus induced lymphoproliferative tumors in severe combined immunodeficient mice are oligoclonal (1992)

Severe combined immunodeficient (SCID) mice reconstituted with lymphocytes from Epstein-Barr virus (EBV) negative human donors develop aggressive tumors after the chimeric mice are infected with EBV. The tumors were composed of human B cells that expressed EBV encoded antigens (latent membrane protein and EBV nuclear antigen2). Southern blot analysis of DNA from 16 SCID/hu tumors with human Ig gene probes showed that each tumor contained multiple heavy and light chain gene rearrangements. Ig kappa gene rearrangements were frequent, while clonal lambda gene rearrangements were infrequent. Analysis of EBV terminal repeat sequences indicated two or more fused termini in each tumor, consistent with a multiclonal origin. Linear terminal repeat segments and viral antigens (EA-D and EA-R) associated with EBV replication were not detected in the tumors. High levels of human Igs in the SCID/hu serum were oligoclonal and primarily contained kappa light chains. Before the appearance of overt tumors, circulating cells with human and EBV DNA could be detected in the SCID/hu mice by the polymerase chain reaction. We conclude that EBV infection in SCID/hu chimeric mice produces a limited number of transformation events, which give rise to oligoclonal tumors resembling EBV-associated lymphoproliferative disorders in some immune-deficient patients.
Tertiary Oil Recovery and CO2 Sequestration by Carbonated Water Injection (CWI) (2010)

Abstract The increasing availability of the anthropogenic carbon dioxide (CO2) and the drives to reduce its concentration in the atmosphere has increased the interest in CO2 injection for improving the oil recovery in maturing oil reservoirs. Many of these reservoirs are being waterflooded to sustain the oil production. Instead of injecting plain water, injecting carbonated (CO2-enriched) water could bring additional oil recovery and added benefit of safe storage of CO2. In carbonated water injection (CWI), CO2 is dissolved in the injected brine prior to injection and then transported through the reservoir by the flood water. As a single phase, carbonated water mobility contrast with oil is more favourable than in the CO2 gas-oil system thus improves sweep efficiency and retards CO2 breakthrough. The slightly higher density of the carbonated water than the unadulterated water would induce the injected CO2 to slump towards the bottom of the reservoir, eliminating the risk of buoyancy-driven leakage thus securing storage. This paper presents the results of an integrated experimental and numerical simulation study of tertiary CWI. A series of high pressure flow visualisation and coreflood experiments as well as compositional simulation have been carried out to evaluate the process. A North Sea crude oil and brine were used at a pressure typical of real reservoir conditions. The visualisation experiments in high-pressure glass micromodels reveal that the oil swelling from CO2 diffusion into the oil and the subsequent oil viscosity reduction, coalescence of the isolated oil ganglia and flow diversion due to flow restriction in some of the pores as a result of oil swelling and the resultant fluid redistribution are the main mechanisms of oil recovery by the tertiary CWI. There was also evidence of micromodel surface becoming more water wet that could also play a role in the oil recovery. The coreflood tests results clearly show that the post waterflood CWI could remobilize the remaining trapped oil in the watered-out core that leads to significant additional oil recovery. A very gradual (dissolved) CO2 breakthrough exhibited in this process is a significant advantage over the sudden CO2 breakthrough problem commonly faced in the conventional CO2 flooding. CWI is also highly potential as CO2 storage injection strategy as demonstrated by almost 50% of the total volume of CO2 injected (in carbonated water) was being stored at the end of the test. There is a challenge in simulating the physics of the CWI process using the commercially available reservoir simulators which will also be discussed.
New Candidaspongiolides, Tedanolide Analogues That Selectively Inhibit Melanoma Cell Growth (2011)

Extracts of the sponge genus &lt;i&gt;Candidaspongia&lt;/i&gt; showed selective cytotoxicity toward melanoma cells in the NCI 60-cell-line screen. Continued investigation of the &lt;i&gt;Candidaspongia &lt;/i&gt;sp&lt;i&gt;.&lt;/i&gt; extracts led to the isolation of three new tedanolide analogues, precandidaspongiolides A (&lt;b&gt;1&lt;/b&gt;) and B (&lt;b&gt;2&lt;/b&gt;) and candidaspongiolide B (&lt;b&gt;4&lt;/b&gt;), as well as candidaspongiolide A (&lt;b&gt;3&lt;/b&gt;) and tedanolide (&lt;b&gt;5&lt;/b&gt;). Semisynthetic derivatives were also generated to develop SAR. Candidaspongiolides A/B were the most potent and showed low nanomolar activity against several melanoma cell lines.
AT&T RESEARCH AT TRECVID 2007 (2006)

ATT more training data that includes 2004, 2005, and 2006 SBD data; no SVM boundary adjustment; training SVM with high generalization capability (e.g., a smaller value of C). As a pilot task, rushes summarization aims to show the main objects and events in the raw material with least redundancy while maximizing the usability. We proposed a multimodal rushes summarization method that relies on both face and speech information. Evaluation results show that the new SBD system is highly effective and the human centric rushes summarization approach is concise and easy to understand.
L-shaped monopole slot antenna for Circular Polarization (2011)

A wideband circularly polarized L-shaped monopole slot antenna is designed and fabricated. The measured results demonstrate that the antenna has an Axial Ratio <; 3 dB and a reflection coefficient <; -10 dB and 23% Circular Polarization bandwidth. As the monopole quarter-wavelength slot antenna occupies half of the area on the corner of circuit board as compared to a half-wavelength slot antenna, this antenna is attractive for compact wireless devices that operate at low frequencies in which planning for the smallest circuit board area combined with the shortest length for signal routing are the two major concerns.
The MoAb reloaded? Is alemtuzumab the one? (2003)

Multiple myeloma remains an incurable B-cell malignancy whose victims survive a median of about 4 years. Over the past decade new therapies and supportive measures have provided incremental gains. No effective monoclonal antibody therapy exists for myeloma, but that is not for want of trying.
Reforming Science: Methodological and Cultural Reforms (2011)

Contemporary science has brought about technological advances and an unprecedented understanding of the natural world. However, there are signs of dysfunction in the scientific community as well as threats from diverse antiscience and political forces. Incentives in the current system place scientists under tremendous stress, discourage cooperation, encourage poor scientific practices, and deter new talent from entering the field. It is time for a discussion of how the scientific enterprise can be reformed to become more effective and robust. Serious reform will require more consistent methodological rigor and a transformation of the current hypercompetitive scientific culture.
"i read my Twitter the next morning and was astonished" (2013)

We present the results of an online survey of 1,221 Twitter users, comparing messages individuals regretted either saying during in-person conversations or posting on Twitter. Participants generally reported similar types of regrets in person and on Twitter. In particular, they often regretted messages that were critical of others. However, regretted messages that were cathartic/expressive or revealed too much information were reported at a higher rate for Twitter. Regretted messages on Twitter also reached broader audiences. In addition, we found that participants who posted on Twitter became aware of, and tried to repair, regret more slowly than those reporting in-person regrets. From this comparison of Twitter and in-person regrets, we provide preliminary ideas for tools to help Twitter users avoid and cope with regret.
Interference effects in non-analog pion double charge exchange (1994)

For (${\mathrm{\ensuremath{\pi}}}^{+}$,${\mathrm{\ensuremath{\pi}}}^{\mathrm{\ensuremath{-}}}$) double charge exchange on $^{27}\mathrm{Al}$, an excitation function at 5\ifmmode^\circ\else\textdegree\fi{} has been measured over a range of incident pion energies from 100 to 293 MeV for transitions to both the ground state and to a doublet at 1.75 MeV of excitation in the final nucleus $^{27}\mathrm{P}$. The shapes of these excitation functions are strikingly different, with the g.s. data exhibiting an interferencelike dip near 150 MeV and the excited state falling smoothly above 150 MeV.
Génie des procédés appliqué à l'électrophorèse : études numérique et expérimentale d'une cellule de focalisation isoélectrique (1989)

La focalisation isolelectrique est un mode d'electrophorese dans lequel les particules chargees sont separees selon leur point isoelectrique. Cette technique de haut pouvoir de resolution est adaptee afin de traiter des quantites importantes de produits: le support utilise est alors une veine liquide. De nombreus phenomenes parasites perturbent la separation: ce sont principalement l'electro-osmose, provoquee par le champ electrique et les gradients thermiques causes par effet joule. L'objectif de ce travail est de cerner les principaux parametres affectant une separation afin d'optimiser la cellule de focalisation isoelectrique. Pour cela, une etude theorique est menee concernant l'hydrodynamique de la cellule: la vitesse d'ecoulement du fluide est calculee a partir des equations de continuite, de mouvement et d'energie. Ce modele est complete par un second modele mathematique qui simule la trajectoire de proteines dans la cellule a partir de l'expression de la mobilite electrophoretique en fonctions du ph. La geometrie particuliere et le procede original de la cellule etudiee presence de reservoirs agites et d'un recyclage sont alors pris en consideration. Il est ainsi possible de determiner pour un probleme de separation pose les conditions optimales de fonctionnement. Une validation des modeles est effectuee a partir de resultats experimentaux portant sur la separation de melanges proteiques simples. Ainsi ce modele valide permet-il de simuler de comportement d'une cellule sous gravite reduite en vue d'experimentations en vol
Kisspeptin Regulation of Genes Involved in Cell Invasion and Angiogenesis in First Trimester Human Trophoblast Cells (2014)

The precise regulation of extravillous trophoblast invasion of the uterine wall is a key process in successful pregnancies. Kisspeptin (KP) has been shown to inhibit cancer cell metastasis and placental trophoblast cell migration. In this study primary cultures of first trimester human trophoblast cells have been utilized in order to study the regulation of invasion and angiogenesis-related genes by KP. Trophoblast cells were isolated from first trimester placenta and their identity was confirmed by immunostaining for cytokeratin-7. Real-time quantitative RT-PCR demonstrated that primary trophoblast cells express higher levels of GPR54 (KP receptor) and KP mRNA than the trophoblast cell line HTR8Svneo. Furthermore, trophoblast cells also expressed higher GPR54 and KP protein levels. Treating primary trophoblast cells with KP induced ERK1/2 phosphorylation, while co-treating the cells with a KP antagonist almost completely blocked the activation of ERK1/2 and demonstrated that KP through its cognate GPR54 receptor can activate ERK1/2 in trophoblast cells. KP reduced the migratory capability of trophoblast cells in a scratch-migration assay. Real-time quantitative RT-PCR demonstrated that KP treatment reduced the expression of matrix metalloproteinase 1, 2, 3, 7, 9, 10, 14 and VEGF-A, and increased the expression of tissue inhibitors of metalloproteinases 1 and 3. These results suggest that KP can inhibit first trimester trophoblast cells invasion via inhibition of cell migration and down regulation of the metalloproteinase system and VEGF-A.