gebhart/patrepeval huggingface dataset:
Optimizing complex phenotypes through model-guided multiplex genome engineering (2016)

Abstract Optimization of complex phenotypes in engineered microbial strains has traditionally been accomplished by laboratory evolution. However, only a subset of the resulting mutations may affect the phenotype of interest and many others may have unintended effects. Multiplexed genome editing can complement evolutionary approaches by creating diverse combinations of targeted changes, but in both cases it remains challenging to identify which alleles influence the desired phenotype. We present a method for identifying a minimal set of genomic modifications that optimizes a complex phenotype by combining iterative cycles of multiplex genome engineering and predictive modeling. We applied our method to the 63-codon E. coli strain C321.ΔA, which has 676 mutations relative to its wild-type ancestor, and identified six single nucleotide mutations that together recover 59% of the fitness defect exhibited by the strain. The resulting optimized strain, C321.DA.opt, is an improved chassis for production of proteins containing non-standard amino acids. Our data reveal how multiple cycles of multiplex automated genome engineering (MAGE) and inexpensive sequencing can generate rich genotypic and phenotypic diversity that can be combined with linear regression techniques to quantify individual allelic effects. While laboratory evolution relies on enrichment as a proxy for allelic effect, our model-guided approach is less susceptible than enrichment to bias from population dynamics and recombination efficiency. We also show that the method can identify beneficial de novo mutations that arise adventitiously. Beyond improving the fitness of C321, ΔA, our work provides a proof-of-principle for high-throughput quantification of individual allelic effects which can be used with any method for generating targeted genotypic diversity.
Emb15 encodes a plastid ribosomal assembly factor essential for embryogenesis in maize (2021)

Ribosome assembly factors guide the complex process by which ribosomal proteins and the ribosomal RNAs form a functional ribosome. However, the assembly of plant plastid ribosomes is poorly understood. In the present study, we discovered a maize (Zea mays) plastid ribosome assembly factor based on our characterization of the embryo defective 15 (emb15) mutant. Loss of function of Emb15 retards embryo development at an early stage, but does not substantially affect the endosperm, and causes an albino phenotype in other genetic backgrounds. EMB15 localizes to plastids and possesses a ribosome maturation factor M (RimM) domain in the N-terminus and a predicted UDP-GlcNAc pyrophosphorylase domain in the C-terminus. The EMB15 RimM domain originated in bacteria and the UDP-GlcNAc pyrophosphorylase domain originated in fungi; these two domains came together in the ancestor of land plants during evolution. The N-terminus of EMB15 complemented the growth defect of an Escherichia coli strain with a RimM deletion and rescued the albino phenotype of emb15 homozygous mutants. The RimM domain mediates the interaction between EMB15 and the plastid ribosomal protein PRPS19. Plastid 16S rRNA maturation is also significantly impaired in emb15. These observations suggest that EMB15 functions in maize seed development as a plastid ribosome assembly factor, and the C-terminal domain is not important under normal conditions.
<title>Wavelength-multiplexed holograms by persistent spectral hole burning</title> (1997)

We have been investigating wavelength multiplexed holograms in persistent spectral hole burning (PHB) materials. We have examined PHB hologram characteristics in some organic PHB materials to show guides to produce more suitable PHB materials for wavelength multiplexed holograms. The examined characteristics were diffraction efficiency, sensitivity and the capability of wavelength-multiplexing and the distribution of diffraction efficiency at the temperature of 4.2 K. Typical characteristics in the examined materials at 4.2 K were as follows: (1) sensitivity of &gt; 0.1 mJ/cm<SUP>2</SUP>, (2) diffraction efficiency of &lt; 0.3%, and (3) the holograms' intervals of &gt; 15 GHz where adjacent holograms could be formed most closely without cross talk. Hundreds of holograms can be stored without crosstalk with each other in calculation. Furthermore, we showed that wavelength multiplexed holographic storage of tens of 2- and 3-D images could be performed at the different laser frequencies at the temperature of 4.2 K. The continuous 3D retrieval of the images of a moving object could be performed by scanning laser frequency continuously.
Local buried oxide technology for HV transistors integrated in CMOS (2007)

Automotive applications require full dielectric isolation of the high voltage and analog components. Such isolation is typically realized by BCD technologies built on SOI. The drawbacks of using SOI wafers, i.e. deviation from the baseline bulk CMOS and increased overall cost, can be addressed by manufacturing local SOI islands in the standard bulk wafer. This paper presents a method to manufacture a local buried oxide using LoBOX technology and its integration to baseline CMOS. Our LoBOX technology is based on a sacrificial SiGe layer buried in bulk substrate and subsequently replaced with oxide. It is a general isolation solution that allows flexible local SOI and local BOX thickness. We have integrated our LoBOX technology in a 130 nm bulk CMOS process to demonstrate its feasibility. The manufactured HV transistors isolated with local BOX, feature almost identical performance as those manufactured on commercial SOI wafers.
Performance metrics for auto-focus in digital and cell-phone cameras (2010)

Passive auto-focus (AF) is a key component of many digital and cell-phone camera systems. In order to make informed choices in the selection of a passive AF search algorithm, it is essential to have performance metrics. The performance metrics currently utilized do not take into consideration all aspects of auto-focusing. In this paper, four performance metrics which measure all relevant aspects of an AF system is considered at the same time. These metrics include focusing speed, accuracy, power consumption and user experience. Experimental results on a prototype digital camera platform are presented to compare the AF performance of four popular AF search algorithms exhibiting the usefulness of the introduced set of AF performance metrics.
The Core DOM (2018)

In this AFP entry, we formalize the core of the Document Object Model (DOM). At its core, the DOM defines a tree-like data structure for representing documents in general and HTML documents in particular. It is the heart of any modern web browser. Formalizing the key concepts of the DOM is a prerequisite for the formal reasoning over client-side JavaScript programs and for the analysis of security concepts in modern web browsers. We present a formalization of the core DOM, with focus on the node-tree and the operations defined on node-trees, in Isabelle/HOL. We use the formalization to verify the functional correctness of the most important functions defined in the DOM standard. Moreover, our formalization is 1) extensible, i.e., can be extended without the need of re-proving already proven properties and 2) executable, i.e., we can generate executable code from our specification.
Powerful femtosecond laser pulse propagation in the atmosphere and applications (2002)

High-power ultra-short laser pulses can propagate through a significant distance in air after self-focusing and filamentation.. Upon self-focusing, the pulse undergoes self-phase modulation turning into a broadband pulse spectrally ranging from the UV to IR, yet of strong spectral coherence, hence a white light laser pulse. Molecules in the filament will be ionized, fragmented and the resulting particles will fluoresce with well resolved molecular spectra without the interference of a plasma continuum even at atmospheric pressure. This talk gives a summary of some of our recent findings on the above mentioned phenomena as well as on ring formation, etc.
Induction of Apoptosis by Coptisine in Hep3B Hepatocellular Carcinoma Cells through Activation of the ROS-Mediated JNK Signaling Pathway (2020)

Hepatocellular carcinoma (HCC) has a high mortality rate worldwide, and treatment is very limited due to its high recurrence and low diagnosis rate, and therefore there is an increasing need to develop more effective drugs to treat HCC. Coptisine is one of the isoquinoline alkaloids, and it has various pharmacological effects. However, the evidence for the molecular mechanism of the anticancer efficacy is still insufficient. Therefore, this study investigated the antiproliferative effect of coptisine on human HCC Hep3B cells and identified the action mechanism. Our results showed that coptisine markedly increased DNA damage and apoptotic cell death, which was associated with induction of death receptor proteins. Coptisine also significantly upregulated expression of proapoptotic Bax protein, downregulated expression of anti-apoptotic Bcl-2 protein, and activated caspase-3, -8, and -9. In addition, coptisine remarkably increased the generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential (MMP), and release of cytochrome <i>c</i> into the cytoplasm. However, <i>N</i>-acetylcysteine (NAC), a ROS scavenger, significantly attenuated the apoptosis-inducing effect of coptisine. It is worth noting that coptisine significantly upregulated phosphorylation of ROS-dependent c-Jun N-terminal kinase (JNK), whereas treatment with JNK inhibitor could suppress an apoptosis-related series event. Taken together, our results suggest that coptisine has an anticancer effect in Hep3B cells through ROS-mediated activation of the JNK signaling pathway.
An explant model for the investigation of skin adaptation to mechanical stress (2002)

A test apparatus was developed to investigate the effects of mechanical stress application on collagen remodeling in skin. The system maintained a 4.5-cm x 5.5-cm skin explant at an air interface with controlled temperature, relative humidity (RH), and carbon dioxide concentration [CO2] while allowing controlled compressive and shear forces to be applied to the skin surface. For environmental control, a custom-designed flow system under Proportional-Integral-Derivative (PID) control was used. Evaluation tests demonstrated that the system maintained air above the explant at a temperature within 1 degrees C of the 37.5 degrees C set point, RH within 5% of the user-specified set point (range of 5% to 95%), and [CO2] within 1% of the 5% [CO2] set point. Least-squares errors in cyclic compressive and shear forces (0- to 20-Hz bandwidth) delivered to the explant were 0.9% and 2.8%, respectively, of user-specified values. Pig skin samples cyclically stressed for 1 hr/day for 3 days with either compressive force only or a combined compressive and shear force had significantly smaller collagen fibril densities compared with an unstressed control, a result consistent with in vivo test data. Collagen fibril diameters were significantly larger for stressed versus control for some of the samples, but the changes were not as substantial as from in vivo testing. This result may have been due to the shorter study duration in vitro (3 d versus 20 d in vivo). The system allows insight into the mechanisms of skin adaptation to mechanical stress to be investigated on a cellular and molecular level, potentially leading to therapies to encourage adaptation in at-risk patients.
ERG of form deprivation myopia and drug induced ametropia in chicks (1996)

Chick eyes occluded for various periods or treated with various concentrations of kainic acid (KA) or 2-amino-4-phosphonobutylate (APB) during development showed characteristic changes of electroretinography and of refraction. In occluded eyes, oscillatory potential amplitudes (OP-A) were reduced, even with high-intensity stimulation, in proportion to duration of occlusion, but b wave amplitude was unchanged, implying functional changes in inner layers of the deprived retina. OP-A reduction after only 1 week of occlusion and reversibility of this change might reflect retinal changes preceding axial elongation. KA was confirmed to induce myopia with axial elongation and APB to induce hyperopia with axial shortening. KA and APB both suppressed OP-A. KA reduced ON and OFF responses, but low-dose APB suppressed only ON responses. Study results suggest that myopia could be induced by changes of inner retina mediating OP attenuation and degradation of ON and OFF responses. This manuscript reports unpublished work that is not currently under consideration for publication elsewhere.
A Molecular Dynamics Study of Glucose Solvation in the Ionic Liquid 1,3‐Dimethylimidazolium Chloride (2006)

(Chemical Equation Presented) Sweet simulations: Molecular dynamics simulations of the solvation environment of isolated glucose monomers in a choride-based ionic liquid (IL) reveal that the sugar prefers to bind to four chloride anions. Coordination shells involving only three anions, two of which are bridging chlorides, are also observed (see picture). The presence of these lower chloride:glucose ratios explains the unexpected high degree of solvation of glucose in these Ils.
Postpartum Cardiomyopathy (2008)

The early diagnosis and interdisciplinary management of PPCM can often lead to substantial recovery from heart failure and cardiomyopathy.
Bypassing Loss in Plasmonic Modulators (2018)

We show that Ohmic losses in plasmonic modulators can be bypassed by using a resonant scheme. This enables the first modulator that unites low-loss, high-speed, compact footprint and low-electrical energy consumption.
Rapid and robust variable flip angle T1mapping using interleaved two-dimensional multislice spoiled gradient echo imaging (2016)

The derived 2D multislice SPGR protocol offers efficient, highly reproducible, and in particular T<sub>2</sub> -insensitive T<sub>1</sub> quantification of human brain tissues. Magn Reson Med 77:1606-1611, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
(D-Ser2)Oxm[Lys38- and #947;-glu-PAL] improves hippocampal gene expression and cognition in a mouse model of type 1 diabetes (2016)

Objective: Oxyntomodulin (Oxm) is a gastrointestinal hormone with recently noted therapeutic potential for type 1 diabetes mellitus (T1DM).The present study examined the effects of a stable Oxm analogue on anxiety, exploratory behavior, cognitive function, hippocampal gene expression and metabolic control in a mouse model of T1DM.Methods: Effects of twice daily administration of the stable Oxm analogue, (d-Ser 2 )Oxm[Lys 38 -γ-glu-PAL], was assessed in insulin-deficient streptozotocin (STZ)-induced T1DM mice.Results: Induction of diabetes by STZ injection significantly (P < 0.05) impaired learning and memory compared to normal control mice.However, (d-Ser 2 )Oxm[Lys 38 -γ-glu-PAL] treatment completely reversed this detrimental effect.Anxiety levels and exploratory behavior were not significantly different between all groups of mice.Hippocampal gene expression of MASH1, SYP and mTOR were reduced (P < 0.01 to P < 0.001) in T1DM mice, but significantly (P < 0.05 to P < 0.001) enhanced by twice daily (d-Ser 2 )Oxm[Lys 38γ-glu-PAL] intervention.Moreover, expression of SYP, mTOR and IRS-1 were significantly elevated (P < 0.05 to P < 0.001) in (d-Ser 2 )Oxm[Lys 38 -γ-glu-PAL] mice compared to both STZ and lean controls.These effects were accompanied by improved (P < 0.001) glucose tolerance and insulin sensitivity compared to STZ controls.Conclusion: The data highlight the potential of (d-Ser 2 )Oxm[Lys 38 -γ-glu-PAL] for the treatment of T1DM, and reveal the ability of this Oxm analogue to restore the deficits of learning and memory observed in STZ-induced T1DM.
A Bispecific METxMET Antibody–Drug Conjugate with Cleavable Linker Is Processed in Recycling and Late Endosomes (2023)

Most antibody-drug conjugates (ADC) approved for the treatment of cancer contain protease-cleavable linkers. ADCs that traffic to lysosomes traverse highly acidic late endosomes, while ADCs that recycle to the plasma membrane traffic through mildly acidic sorting and recycling endosomes. Although endosomes have been proposed to process cleavable ADCs, the precise identity of the relevant compartments and their relative contributions to ADC processing remain undefined. Here we show that a METxMET biparatopic antibody internalizes into sorting endosomes, rapidly traffics to recycling endosomes, and slowly reaches late endosomes. In agreement with the current model of ADC trafficking, late endosomes are the primary processing site of MET, EGFR, and prolactin receptor ADCs. Interestingly, recycling endosomes contribute up to 35% processing of the MET and EGFR ADCs in different cancer cells, mediated by cathepsin-L, which localizes to this compartment. Taken together, our findings provide insight into the relationship between transendosomal trafficking and ADC processing and suggest that receptors that traffic through recycling endosomes might be suitable targets for cleavable ADCs.
Interferon-αinduces interleukin-18 binding protein in chronic hepatitis C patients (2002)

Interleukin-18 (IL-18), derived from macrophages and Kupffer cells, is the central pro-inflammatory cytokine leading to experimental liver failure. IL-18 binding protein (IL-18BP) is a circulating protein that binds IL-18 and neutralizes its activity. Since IL-18 production is increased in chronic HCV infection, we asked whether IFN-alpha might act on the IL-18/IL-18BP system in HCV patients. IL-18BP, total and free IL-18 plasma levels were determined in 13 HCV patients receiving 1 x 107 IU IFN-alpha subcutaneously daily for 28 days. The in vitro effects of IFN-alpha on macrophage IL-18BP and IL-18 were studied by enzyme-linked immunosorbent assays and Northern analysis. IFN-alpha administration increased IL-18BP plasma levels 3.24 fold 24 h after institution of therapy, resulting in a 67.4% reduction of free IL-18. Total IL-18 levels decreased from day +24 on. In vitro, IFN-alpha diminished IL-18 release from macrophages of healthy volunteers and chronic HCV patients. On top of its inhibitory effects on IL-1 and TNF-alpha release, IFN-alpha also exerts its anti-inflammatory action in vivo by induction of IL-18BP. These anti-inflammatory properties might account - together with its antiviral action - for its clinical efficacy in chronic hepatitis C.
Microplastics in (drink)water? – terugblik op een workshop met de drinkwaterbedrijven (2021)

De drinkwaterbedrijven hebben samen met KWR, HWL en RIVM onderzoek gedaan naar microplastics in water. De resultaten werden onlangs op een workshop gepresenteerd, waarbij werd ingegaan op de oorsprong van microplastics in water, analyse en karakterisering van microplastics en wat ermee gebeurt tijdens het drinkwaterzuiveringsproces. Op dit moment bevat kraanwater nog vrijwel geen meetbare microplastics, maar meer onderzoek is nodig om te kijken of dit zo kan blijven.
Supplementary Figure 2 from Blocked Autophagy Using Lysosomotropic Agents Sensitizes Resistant Prostate Tumor Cells to the Novel Akt Inhibitor AZD5363 (2023)

&lt;p&gt;PDF file - 92 KB, A, AZD5363 fails to induce apoptosis in PC-3 and DU145 cells&lt;/p&gt;
Recent advances in amino acid analysis by capillary electromigration methods: June 2015–May 2017 (2017)

In the tenth edition of this article focused on recent advances in amino acid analysis using capillary electrophoresis, we describe the most important research articles published on this topic during the period from June 2015 to May 2017. This article follows the format of the previous articles published in Electrophoresis. The new developments in amino acid analysis with CE mainly describe improvements in CE associated with mass spectrometry. Focusing on applications, we mostly describe clinical works, although metabolomics studies are also very important. Finally, works focusing on amino acids in food and agricultural applications are also described.
Computing with unreliable information (1990)

Model: Our general model will be a (possibly randomized) computation tree, in which each node gives the correct answer with some probability > p, where p is a fixed constant in (1/2, 1), bounded away from 1/2 and 1. The node faults are independent. We study the depth of the computation tree in terms of a tolerance parameter Q E (0,1/2): on any instance, the computation tree leads to a leaf giving the correct answer on that instance with probability at least 1 -Q. The success probability of the algorithm is computed over the combined probability space of the outcome of individual comparisons The Weizmarm Institute of Science,
Comment on “Single-trial spike trains in parietal cortex reveal discrete steps during decision-making” (2016)

Latimeret al (Reports, 10 July 2015, p. 184) claim that during perceptual decision formation, parietal neurons undergo one-time, discrete steps in firing rate instead of gradual changes that represent the accumulation of evidence. However, that conclusion rests on unsubstantiated assumptions about the time window of evidence accumulation, and their stepping model cannot explain existing data as effectively as evidence-accumulation models.
Design of low-loss one-dimensional planar-photonic crystal coupled-cavity waveguides (2008)

We propose a novel design method for low-loss one-dimensional planar-photonic crystal coupled-cavity waveguide (CCW). The calculated intrinsic losses in the proposed CCW are 2 orders of magnitude lower than those in previously reported CCW structure.
A Protective Vaccine against Chlamydia Genital Infection Using Vault Nanoparticles without an Added Adjuvant (2017)

<i>Chlamydia trachomatis</i> genital infection is the most common sexually transmitted bacterial disease, causing a significant burden to females due to reproductive dysfunction. Intensive screening and antibiotic treatment are unable to completely prevent female reproductive dysfunction, thus, efforts have become focused on developing a vaccine. A major impediment is identifying a safe and effective adjuvant which induces cluster of differentiation 4 (CD4) cells with attributes capable of halting genital infection and inflammation. Previously, we described a natural nanocapsule called the vault which was engineered to contain major outer membrane protein (MOMP) and was an effective vaccine which significantly reduced early infection and favored development of a cellular immune response in a mouse model. In the current study, we used another chlamydial antigen, a polymorphic membrane protein G-1 (PmpG) peptide, to track antigen-specific cells and evaluate, in depth, the vault vaccine for its protective capacity in the absence of an added adjuvant. We found PmpG-vault immunized mice significantly reduced the genital bacterial burden and histopathologic parameters of inflammation following a <i>C. muridarum</i> challenge. Immunization boosted antigen-specific CD4 cells with a multiple cytokine secretion pattern and reduced the number of inflammatory cells in the genital tract making the vault vaccine platform safe and effective for chlamydial genital infection. We conclude that vaccination with a <i>Chlamydia</i>-vault vaccine boosts antigen-specific immunities that are effective at eradicating infection and preventing reproductive tract inflammation.