gebhart/patrepeval huggingface dataset:
Substrate Channeling in an Artificial Metabolon: A Molecular Dynamics Blueprint for an Experimental Peptide Bridge (2017)

Natural enzyme cascades utilize electrostatic guidance as an effective technique to control the diffusion of charged reaction intermediates between catalytic active sites in a process known as substrate channeling. However, the limited understanding of channeling mechanisms has abated the application of this technique in artificial catalytic cascades. In this work, we utilize molecular dynamics simulations to describe the transport of anionic intermediates (e.g., oxalate and glucose-6-phosphate) on a theoretical cationic α-helix peptide bridge and identify rules for molecular-level design of electrostatic channeling. These simulations allowed us to elucidate a surface diffusion mechanism whereby the anionic intermediate undergoes discrete hydrogen-bonding interactions along adjacent cationic residues on the peptide bridge. Using MD simulations as a foundational blueprint, we synthesized an enzyme complex using a poly(lysine) peptide chain as a cationic bridge between glucose-6-phosphate dehydrogenase and hexokinase. Stopped-flow lag time experiments demonstrate the ability of the artificially linked enzyme complex to facilitate electrostatic substrate channeling, while an analogous neutral poly(glycine)-bridged complex was used as a control to isolate proximity effects from artificial substrate channeling.
Ecological Genomics of<i>Trichoderma</i> (2013)

Species of Trichoderma (teleomorph Hypocrea, Hypocreales, Ascomycota, Dikarya) are among the most frequent mitosporic fungi commonly detected in cultivation-based surveys. They have been isolated from an innumerable diversity of natural and artificial substrata that demonstrates their high opportunistic potential and adaptability to various ecological conditions. Most recently, Trichoderma spp. have increasingly been described as symptomless associates of plants or endophytes, a phenomenon that is common among bacteria and fungi. The ecology of the genus and an overview the genetic background that allows Trichoderma to thrive in its natural habitats and serve multiple applications is presented in this chapter. The availability of the genome sequence of T. atroviride and T. virens has enabled full genome arrays to be used to study the sequential events occurring during confrontation of these Trichoderma spp. with Rhizoctonia solani at a genome-wide transcriptomic level.
Deep Gaussian Processes with Importance-Weighted Variational Inference (2019)

Deep Gaussian processes (DGPs) can model complex marginal densities as well as complex mappings. Non-Gaussian marginals are essential for modelling real-world data, and can be generated from the DGP by incorporating uncorrelated variables to the model. Previous work on DGP models has introduced noise additively and used variational inference with a combination of sparse Gaussian processes and mean-field Gaussians for the approximate posterior. Additive noise attenuates the signal, and the Gaussian form of variational distribution may lead to an inaccurate posterior. We instead incorporate noisy variables as latent covariates, and propose a novel importance-weighted objective, which leverages analytic results and provides a mechanism to trade off computation for improved accuracy. Our results demonstrate that the importance-weighted objective works well in practice and consistently outperforms classical variational inference, especially for deeper models.
Human Immunodeficiency Virus Type 1 Capsid Mutation N74D Alters Cyclophilin A Dependence and Impairs Macrophage Infection (2012)

The antiviral factor CPSF6-358 interferes with the nuclear entry of human immunodeficiency virus type 1 (HIV-1). HIV-1 acquires resistance to CPSF6-358 through the N74D mutation of the capsid (CA), which alters its nuclear entry pathway. Here we show that compared to wild-type (WT) HIV-1, N74D HIV-1 is more sensitive to cyclosporine, has increased sensitivity to nevirapine, and is impaired in macrophage infection prior to reverse transcription. These phenotypes suggest a difference in the N74D reverse transcription complex that manifests early after infection and prior to interaction with the nuclear pore. Overall, our data indicate that N74D HIV-1 replication in transformed cells requires cyclophilin A but is dependent on other interactions in macrophages.
Artificial intelligence and algorithmic bias: implications for health systems (2019)

Algorithmic bias occurs when the application of an algorithm compounds existing inequities in socioeconomic status, race, ethnic background, religion, gender, disability or sexual orientation to amplify them and adversely impact equity in health systems.
Survival and functional outcomes of molecularly defined childhood posterior fossa ependymoma: Cure at a cost (2019)

Data from a molecularly informed large cohort of patients with PFE clearly indicate improved survival over time, related to more aggressive surgery and upfront radiotherapy. However, to the best of the authors' knowledge, the current study is the first, in a subgrouped cohort, to demonstrate that this approach results in reduced neurocognitive outcomes over time.
Effects on QRS-waveforms and ST-T-segment by changes in body position during continuous 12-lead ECG: a preliminary report (2002)

ST-segment monitoring by Holter or by continuous 12-lead ECG-monitoring have prognostic value in unstable angina and myocardial infarction. However, "pseudo-changes" due to changes in body position may cause problems during monitoring for indicators of silent ischemia. Therefore, ischemia-monitoring with continuous 12-lead ECG was performed in 36 clinically stable patients in different body positions. Using the ECG in supine position as reference, ST-segment changes were usually small but reached significant levels in some patients, especially in the left lateral decubital position. However these deviations of the ST-segment seemed to arise under certain circumstances, which are possible to recognize in the clinical setting.
&lt;title&gt;Performance Efficiency Of InSb Charge Injection Devices (CID)&lt;/title&gt; (1979)

This paper describes the factors governing the Performance Efficiency (PE) of Indium Antimonide Charge Injection Devices (CID) arrays. Factors influencing PE in both line and area arrays are considered and compared to experimental results. An important factor re-lates to the signal charge loss of a dual gate array operating in the charge sharing mode (CSM). The chief advantages of the CSM are that it overcomes charge transfer problems that might be present in practical arrays, and it is believed to be radiation damage resistant. The chief limitation is that only the charge residing under the sensing gate of the dual gate site is read out. This loss can be lessened by designing the sensing gate to be a large fraction of the total storage area. Performance data of lx32, lx64 line arrays, 24x16 and 32x32 dual gate area arrays are presented. Line arrays FE up to 56 percent, responsivity variation below 10 percent, and D* of about 3x10<sup>11</sup> cm HZ&frac12;/watt have been measured.
Stability, electronic structures, and mechanical properties of Fe–Mn–Al system from first-principles calculations (2017)

The stability, electronic structures, and mechanical properties of the Fe–Mn–Al system were determined by first-principles calculations. The formation enthalpy and cohesive energy of these Fe–Mn–Al alloys are negative and show that the alloys are thermodynamically stable. Fe3Al, with the lowest formation enthalpy, is the most stable compound in the Fe–Mn–Al system. The partial density of states, total density of states, and electron density distribution maps of the Fe– Mn–Al alloys were analyzed. The bonding characteristics of these Fe–Mn–Al alloys are mainly combinations of covalent bonding and metallic bonds. The stress-strain method and Voigt–Reuss–Hill approximation were used to calculate the elastic constants and moduli, respectively. Fe2.5Mn0.5Al has the highest bulk modulus, 234.5 GPa. Fe1.5Mn1.5Al has the highest shear modulus and Young's modulus, with values of 98.8 GPa and 259.2 GPa, respectively. These Fe–Mn–Al alloys display disparate anisotropies due to the calculated different shape of the three-dimensional curved surface of the Young's modulus and anisotropic index. Moreover, the anisotropic sound velocities and Debye temperatures of these Fe–Mn–Al alloys were explored.
Porous material and process development for electrospray propulsion applications (2014)

Thesis: S.M., Massachusetts Institute of Technology, Department of Aeronautics and Astronautics, 2014.
Randomized Positional Encodings Boost Length Generalization of Transformers (2023)

Transformers have impressive generalization capabilities on tasks with a fixed context length. However, they fail to generalize to sequences of arbitrary length, even for seemingly simple tasks such as duplicating a string. Moreover, simply training on longer sequences is inefficient due to the quadratic computation complexity of the global attention mechanism. In this work, we demonstrate that this failure mode is linked to positional encodings being out-of-distribution for longer sequences (even for relative encodings) and introduce a novel family of positional encodings that can overcome this problem. Concretely, our randomized positional encoding scheme simulates the positions of longer sequences and randomly selects an ordered subset to fit the sequence's length. Our large-scale empirical evaluation of 6000 models across 15 algorithmic reasoning tasks shows that our method allows Transformers to generalize to sequences of unseen length (increasing test accuracy by 12.0% on average).
Adaptive harmonic generation microscopy of mammalian embryos (2009)

Adaptive optics is implemented in a harmonic generation microscope using a wavefront sensorless correction scheme. Both the second- and third-harmonic intensity signals are used as the optimization metric. Aberration correction is performed to compensate both system- and specimen-induced aberrations by using an efficient optimization routine based upon Zernike polynomial modes. Images of live mouse embryos show an improved signal level and resolution.
Comment on "The Sex Ratio: A Scientific Glimpse of the Holy Qur'an" and Authors' Response (1991)

DOI: http://dx.doi.org/10.5915/23-3-15224 This letter is in regards to an article published in Volume 23, No 1: Sex Ration: A Scientific Glimpse of the Holy Qur'an by S. M. Bakir and Hossam E. Fadel. It is available at DOI: http://dx.doi.org/10.5915/23-1-15223. The authors' response is included.
Studies of Icebergs, Ice Fronts and Ice Walls using Side-Scanning Sonar (1980)

During the Norwegian Antarctic Research Expedition of 1978–79, a number of experiments were carried out using side-scanning solar techniques for under-water mapping of icebergs, ice fronts, and ice walls, and for studies of active ploughing areas off ice fronts. This paper presents the techniques and some results, together with views on operational and environmental aspects of using side-scanning sonar in the Antarctic. From the sonographs it is possible to measure depths of icebergs and ice fronts, and to estimate the magnitudes of shape anomalies. Vertical profiles of ice fronts show great variations depending on whether they are grounded or floating. Also, the acoustic signatures vary according to the elapsed time since calving.
In vitro analysis reveals necroptotic signaling does not provoke DNA damage or HPRT mutations (2020)

Most anticancer drugs provoke apoptotic signaling by damaging DNA or other means. Genotoxic therapies may enhance a patient's risk of developing "therapy-related cancers" due to the accumulation of oncogenic mutations that may occur in noncancerous cells. Mutations can also form upon apoptotic signaling due to sublethal caspase activity, implying that apoptosis activating drugs may also be oncogenic. Necroptosis is a different way of killing cancer cells: this version of caspase-independent cell death is characterized by receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase-like domain protein (MLKL) activation, leading to cell membrane rupture and controlled cell lysis. The mutagenic potential of sublethal necroptotic signaling has not yet been directly investigated. Smac mimetics drugs, which activate apoptotic or necroptotic cell death, do not induce mutations but the mechanistic basis for this lack of mutagenic activity has not been determined. In this study, we compared the mutagenic potential of these two cell death pathways by engineering cells to activate either apoptotic or necroptotic signaling by exposing them to Smac mimetics with or without TNFα, and/or enforcing or preventing expression of apoptotic or necroptotic regulators. We discovered that sublethal concentrations of Smac mimetics in contexts that activated apoptotic signaling provoked DNA damage and mutations in surviving cells. Mutagenesis was dependent on executioner caspase activation of the nuclease CAD. In contrast, RIPK3- and MLKL-dependent necroptotic signaling following Smac mimetic treatment was not mutagenic. Likewise, DNA damage was not provoked in cells expressing a lethal constitutively active MLKL mutant. These data reveal that cells surviving sublethal necroptotic signaling do not sustain genomic damage and provide hope for a reduced risk of therapy-related malignancies in patients treated with necroptosis-inducing drugs.
[Flow cytometric DNA analysis of uterine endometrial carcinoma]. (1991)

The DNA content in individual cells from 40 cases of histopathologically normal endometria, 15 of endometrial hyperplasia and 68 of endometrial adenocarcinoma was measured by flow cytometry. An aneuploid cell population was found in 50% of malignant endometria, but in the remaining endometrial carcinomas, the flow cytometrical findings showed no difference from those of benign tissue. Aneuploidy was more common (77.8%) in poorly differentiated tumors than in highly differentiated tumors (35.5%). Two and more aneuploid cell populations were found in 8 cases of 34. The DNA indices of aneuploid tumors were classified into 3 groups: hyperdiploidy, low hyperdiploidy (DNA index range: 1.04-1.2) and high hyperdiploidy (DNA index range: More than 1.2). The proportion of tumors with a high DNA index tended to increase as tumors became less differentiated. In normal endometria the fraction of cells with DNA content corresponding to the s-phase (s-fraction) was 8 +/- 3% on average in the proliferative phase. In well differentiated diploid tumors the s-fraction was 12 +/- 6%, but in moderately and poorly differentiated tumors it was higher (16.0% and 19.0%).
Chemical Modifications and Design Influence the Potency of <i>Huntingtin</i> Anti-Gene Oligonucleotides (2023)

Huntington's disease is a neurodegenerative, trinucleotide repeat (TNR) disorder affecting both males and females. It is caused by an abnormal increase in the length of CAG•CTG TNR in exon 1 of the <i>Huntingtin</i> gene (<i>HTT</i>). The resultant, mutant HTT mRNA and protein cause neuronal toxicity, suggesting that reduction of their levels would constitute a promising therapeutic approach. We previously reported a novel strategy in which chemically modified oligonucleotides (ONs) directly target chromosomal DNA. These anti-gene ONs were able to downregulate both <i>HTT</i> mRNA and protein. In this study, various locked nucleic acid (LNA)/DNA mixmer anti-gene ONs were tested to investigate the effects of varying ON length, LNA content, and fatty acid modification on <i>HTT</i> expression. Altering the length did not significantly influence the ON potency, while LNA content was critical for activity. Utilization of palmitoyl-modified LNA monomers enhanced the ON activity relatively to the corresponding nonmodified LNA under serum starvation conditions. Furthermore, the number of palmitoylated LNA monomers and their positioning greatly affected ON potency. In addition, we performed RNA sequencing analysis, which showed that the anti-gene ONs affect the "immune system process, mRNA processing, and neurogenesis." Furthermore, we observed that for repeat containing genes, there is a higher tendency for antisense off-targeting. Taken together, our findings provide an optimized design of anti-gene ONs that could potentially be developed as DNA-targeting therapeutics for this class of TNR-related diseases.
Multimodal analysis of drug transporter expression in gastrointestinal tissue (2017)

Lack of agreement between analytical techniques suggests that resources should be focused on generating downstream measures of protein expression to predict drug exposure. Taken together, these data inform the use of preclinical models for studying ART distribution and the design of targeted therapies for HIV eradication.
Stable Lithium Deposition Generated from Ceramic-Cross-Linked Gel Polymer Electrolytes for Lithium Anode (2016)

In this work, a composite gel electrolyte comprising ceramic cross-linker and poly(ethylene oxide) (PEO) matrix is shown to have superior resistance to lithium dendrite growth and be applicable to gel polymer lithium batteries. In contrast to pristine gel electrolyte, these nanocomposite gel electrolytes show good compatibility with liquid electrolytes, wider electrochemical window, and a superior rate and cycling performance. These silica cross-linkers allow the PEO to form the lithium ion pathway and reduce anion mobility. Therefore, the gel not only features lower polarization and interfacial resistance, but also suppresses electrolyte decomposition and lithium corrosion. Further, these nanocomposite gel electrolytes increase the lithium transference number to 0.5, and exhibit superior electrochemical stability up to 5.0 V. Moreover, the lithium cells feature long-term stability and a Coulombic efficiency that can reach 97% after 100 cycles. The SEM image of the lithium metal surface after the cycling test shows that the composite gel electrolyte with 20% silica cross-linker forms a uniform passivation layer on the lithium surface. Accordingly, these features allow this gel polymer electrolyte with ceramic cross-linker to function as a high-performance lithium-ionic conductor and reliable separator for lithium metal batteries.
Repeated resections of extrahepatic metastases after hepatic resection: an aggressive approach to hepatocellular carcinoma. (2004)

Survival following curative hepatic resection for hepatocellular carcinoma is limited by a high incidence of recurrence. Resection of extrahepatic recurrences has been shown to prolong survival in selected patients. We report two cases in whom repeated resections of extrahepatic metastases achieved good palliation and survival. The first patient had cerebral, pulmonary and splenic metastases that appeared more than four years following an extended left hepatectomy for a 4-cm hepatocellular carcinoma. Resection of the metastases in the three organs was performed in sequence, and the patient remained alive and asymptomatic 12 months after the metastatic recurrence. The second patient developed pulmonary metastases after an extended right hepatectomy for a 16-cm hepatocellular carcinoma. Following two resections of pulmonary metastases, he was alive and disease-free for seven years. These two cases illustrate that an aggressive surgical approach of repeated resections of extrahepatic recurrences after curative resection of hepatocellular carcinoma can result in long-term survival in selected patients.
A new CRONE suspension: more compact and more efficient - Part 2: Synthesis and achievement (2009)

International audience
Dye Sensitised Solar Cells Using High Mobility, Transparent Conducting Oxides for Tandem Solar Cell Applications (2008)

Dye sensitised solar cells are suitable for use as a top cell in a tandem solar cell structure, with a bottom CIGS solar cell, because their transmission characteristics can be adjusted by changing the particle size of the mesoporous TiO2 layer, and the photosensitising dye used. However, optical losses also occur from the fluorine doped tin oxide electrode, due to free carrier absorption in the NIR region of the solar spectrum, and lower the light available to the bottom cell. To solve this problem, a high mobility transparent conducting oxide (titanium doped indium oxide) has been used as the conducting layer to lower the optical loses in the near infrared through the cell. This increases light transmission from 800nm onwards, whilst maintaining high conductivity in the layer, which could be used in a tandem device. A device efficiency of 6.77% has been fabricated, whilst problems of porous layer delamination, and low temperature stability of the conducting layer have been solved.
Explosive instabilities: from solar flares to edge localized modes in tokamaks (2003)

The mechanisms for the explosive loss of plasma confinement that occurs in solar flares, magnetospheric sub-storms, tokamak disruptions and edge localized modes remain largely unexplained. Modelling the rapid onset of such events provides a considerable challenge to theory. A possible explanation for these events, nonlinear explosive ballooning, is discussed. In this mechanism a narrow finger of plasma erupts from inside the plasma growing explosively and pushing aside other field lines—the instability spreads from a small region until it disturbs lines across a large section of plasma. The model predicts the observed features of some high β tokamak disruptions.
The Characterization and Role of Zinc Binding in Yeast Cox4 (2007)

Yeast Cox4 is a zinc binding subunit of cytochrome c oxidase. Cox4 is the only cofactor-containing subunit that is not directly part of the catalytic core of the enzyme located in the mitochondrial inner membrane. The Zn(II) site is shown to be distinct from the bovine ortholog, as it results from the x-ray structure of the entire cytochrome c oxidase in having a single histidyl residue and three conserved cysteines residues in the coordination sphere. Substitutions at the Cys ligand positions result in non-functional Cox4 proteins that fail to lead to cytochrome oxidase assembly. Limited function exists in His-119 mutants when overexpressed. Zn(II) binding in Cox4 is, therefore, important for the stability of the complex. The solution structure of yeast Cox4 elucidated by multidimensional NMR reveals a C-terminal globular domain consisting of two beta sheets analogous to the bovine ortholog except the loop containing the coordinating His in the yeast protein and the fourth Cys in the bovine protein are in different positions in the two structures. The conformation of this loop is dictated by the different sequence position of the fourth coordinating zinc ligand. The Zn(II) ion is buried within the domain, consistent with its role in structural stability. Potential functions of this matrix-facing subunit are discussed.
2P1-B05 Description of Humanoid's Object Manipulation and Execution of Motion using Autonomous Phase Transition based on Object-environment-robot Contact States(Humanoid) (2013)

In the case of object manipulation by a humanoid robot, it is important to deal with object-robot-environment contact states both to avoid falling down and achieve objective manipulations. We propose a method to describe and execute uniformly various object manipulations by a humanoid robot. We focus on the contact states as description of manipulation and define manipulation phases according to the contact states. In execution of motion, humanoid's controller obtains information for manipulation from force and contact point sensing, estimates changes of contact states, autonomously switches manipulation phases, and substantiate force-based controller. We evaluated our proposed method through experiments in which a humanoid robot manipulates four objects without information about object's mass and necessary operational force.
Real‐world efficacy of prescription and over‐the‐counter nicotine replacement therapy (2002)

Smoking cessation rates achieved with nicotine gum and patch under OTC conditions were as good as those under real-world prescribing conditions.