gebhart/patrepeval huggingface dataset:
1 General Principles (2003)

The fundamental blueprint for any cell or organism is encoded in its genetic material, its deoxyribonucleic acid (DNA). The linear order of bases in a segment of DNA is termed its DNA sequence and determines its function. A gene is a segment of DNA whose sequence directly determines its translated protein product. Molecular biology makes extensive use of the DNA-modifying enzymes employed by cells during replication, translation, repair, and protection from foreign DNA. Recombinant DNA technology affords biologists the capability to manipulate and analyze DNA sequences. Many of the techniques employed take advantage of a basic property of DNA, the molecular complementarity of the two strands of the double helix. Cloning is a recombinant procedure that has two main purposes: First, it allows selection of a single DNA fragment from a complex mixture, and second, it provides a means to store, manipulate, propagate, and produce large numbers of identical molecules having this single ancestor.
Trade-offs between tRNA abundance and mRNA secondary structure support smoothing of translation elongation rate (2015)

Translation of protein from mRNA is a complex multi-step process that occurs at a non-uniform rate. Variability in ribosome speed along an mRNA enables refinement of the proteome and plays a critical role in protein biogenesis. Detailed single protein studies have found both tRNA abundance and mRNA secondary structure as key modulators of translation elongation rate, but recent genome-wide ribosome profiling experiments have not observed significant influence of either on translation efficiency. Here we provide evidence that this results from an inherent trade-off between these factors. We find codons pairing to high-abundance tRNAs are preferentially used in regions of high secondary structure content, while codons read by significantly less abundant tRNAs are located in lowly structured regions. By considering long stretches of high and low mRNA secondary structure in Saccharomyces cerevisiae and Escherichia coli and comparing them to randomized-gene models and experimental expression data, we were able to distinguish clear selective pressures and increased protein expression for specific codon choices. The trade-off between secondary structure and tRNA-concentration based codon choice allows for compensation of their independent effects on translation, helping to smooth overall translational speed and reducing the chance of potentially detrimental points of excessively slow or fast ribosome movement.
Aerodynamic Performance of a Centrifugal Compressor With Vaned Diffusers (1980)

An experimental investigation to improve the stage efficiency through the use of vaned diffusers is presented. Sixteen different vaned diffusers were tested on a model compressor rig. The results showed that the pressure recovery of the vaned diffuser increased up to the critical diffusion ratio, which was shown to be approximately 0.5. The measured pressure distribution around vanes of the well-designed diffusers which had the fair diffusion ratios, were found to agree well with the potential flow solutions. Finally, the importance of the diffuser inlet configuration to the improvement of the stage efficiency is discussed.
Selective phase modulation of NiSi using N-ion implantation for high performance dopant-segregated source/drain n-channel MOSFETs (2006)

We have developed a novel dual phase-modulated Ni silicide for Schottky barrier and series resistance reduction in dopant-segregated source/drain (DSS) n-MOSFETs. Using pre-silicide N2 + implant (thereafter N-implant), it is possible to selectively form interfacial epitaxial Si-rich NiSi2, reducing electron Schottky barrier(SB) from 0.7 eV to 0.34 eV while maintaining a low resistive bulk NiSi, at the same silicide formation temperature. Dual phase-modulated NiSi shows enhanced thermal stability up to 750degC, low rhos of 26 muOmegacm and SB modulation DeltaphiBn = 0.36 eV (expected 81% reduction in contact resistance Rc). Saturation gm for phase-modulated N-modulated DSS n-FETs shows 32% improvement over control NiSi with 22% reduction in series resistance Rext, while still maintaining CMOS integratability.
QTL Associated with Maize Kernel Oil, Protein, and Starch Concentrations; Kernel Mass; and Grain Yield in Illinois High Oil × B73 Backcross‐Derived Lines (2008)

Illinois long‐term selection strains of maize ( Zea mays L.) have been useful for identifying genomic regions controlling kernel oil, protein, and starch concentrations. To identify kernel trait quantitative trait loci (QTL) in a genetic background more relevant to practical breeding, 150 BC 1 ‐derived S 1 lines (BC 1 S 1 s) were produced from Illinois High Oil and recurrent parent B73. Oil, protein, and starch were measured in BC 1 S 1 s and in Mo17‐topcross hybrids (TCs). Kernel mass of BC 1 S 1 s and grain yield of TCs were also determined. Starch was positively correlated with mass in BC 1 S 1 s (r p = 0.67**, α ≤ 0.01) and with yield in TCs (r p = 0.59**). Oil was negatively correlated with mass in BC 1 S 1 s (r p = −0.29**) and with yield in TCs (r p = −0.30**). Oil was negatively correlated with starch in BC 1 S 1 s (r p = −0.75**) and TCs (r p = −0.66**). A genetic map with length = 1486 cM was created with 110 markers. Multiple regression models with QTL detected by composite interval mapping (CIM) explained 46.9, 45.2, 44.3, and 17.7% of phenotypic variance for oil, protein, starch, and mass, respectively, in BC 1 S 1 s and 17.5, 22.9, 40.1, and 28.7% for oil, protein, starch, and yield, respectively, in TCs. A 22 cM‐interval on chromosome 6 in BC 1 S 1 s included oil, protein, and starch QTL, including a QTL explaining 36.7% of the BC 1 S 1 phenotypic variation for oil. No yield QTL were detected in this region. Introgression of this QTL into breeding lines might increase oil while maintaining yield.
Results of the WMO/CAS NWP data study and intercomparison project for forecasts for the Northern Hemisphere in 1979-80 (1981)

Moment arm-angle functions (MA-a-functions) are commonly used to estimate in vivo muscle forces in humans. However, different MA-a-functions might not only influence the magnitude of the estimated muscle forces but also change the shape of the muscle's estimated force-angle relationship (F-a-r). Therefore, we investigated the influence of different literature based Achilles tendon MA-a-functions on the triceps surae muscle-tendon unit F-a-r. The individual in vivo triceps torque-angle relationship was determined in 14 participants performing maximum voluntary fixed-end plantarflexion contractions from 18.3° ± 3.2° plantarflexion to 24.2° ± 5.1° dorsiflexion on a dynamometer. The resulting F-a-r were calculated using 15 literature-based in vivo Achilles tendon MA-a-functions. MA-a-functions affected the F-a-r shape and magnitude of estimated peak active triceps muscle-tendon unit force. Depending on the MA-a-function used, the triceps was solely operating on the ascending limb (n = 2), on the ascending limb and plateau region (n = 12), or on the ascending limb, plateau region and descending limb of the F-a-r (n = 1). According to our findings, the estimated triceps muscle-tendon unit forces and the shape of the F-a-r are highly dependent on the MA-a-function used. As these functions are affected by many variables, we recommend using individual Achilles tendon MA-a-functions, ideally accounting for contraction intensity-related changes in moment arm magnitude.
ChemInform Abstract: SENSITIVITY OF POLYPEPTIDE CONFORMATION TO GEOMETRY. THEORETICAL CONFORMATIONAL ANALYSIS OF OLIGOMERS OF α‐AMINOISOBUTYRIC ACID (1981)

Abstract Die bevorzugten Konformationen von Ac(Aib)nNHCH3 (Aib: α‐Aminoisobutyryl‐Rest; n: 1, 2, 3) wurden durch empirische Berechnung der Konformationsenergie bestimmt.
Global Representations of Goal-Directed Behavior in Distinct Cell Types of Mouse Neocortex (2017)

The successful planning and execution of adaptive behaviors in mammals may require long-range coordination of neural networks throughout cerebral cortex. The neuronal implementation of signals that could orchestrate cortex-wide activity remains unclear. Here, we develop and apply methods for cortex-wide Ca<sup>2+</sup> imaging in mice performing decision-making behavior and identify a global cortical representation of task engagement encoded in the activity dynamics of both single cells and superficial neuropil distributed across the majority of dorsal cortex. The activity of multiple molecularly defined cell types was found to reflect this representation with type-specific dynamics. Focal optogenetic inhibition tiled across cortex revealed a crucial role for frontal cortex in triggering this cortex-wide phenomenon; local inhibition of this region blocked both the cortex-wide response to task-initiating cues and the voluntary behavior. These findings reveal cell-type-specific processes in cortex for globally representing goal-directed behavior and identify a major cortical node that gates the global broadcast of task-related information.
Cell type‐specific enhancer‐promoter connectivity maps in the human brain and associations with Alzheimer’s disease risk (2020)

Abstract Background There is no clear genetic cause for most cases of late‐onset Alzheimer’s disease (AD), however, genome‐wide association studies have identified multiple genetic variants associated with increased risk of AD. These AD‐risk variants are often located in non‐coding DNA regulatory regions called enhancers, which upon transcription factor binding, modulate the expression of nearby genes. One of the major challenges facing the field of AD research is the assignment of cell‐type specificity and functionality to these genetic variants. Method Nuclei of microglia, neurons, astrocytes and oligodendrocytes were isolated from frozen human cortical tissue. Sorted nuclei were processed using chromatin immunoprecipitation and sequencing (ChIP‐seq) to define cell type promoter and enhancer regions. The assay for transposase accessible chromatin sequencing (ATAC‐seq) was used to define open chromatin regions, which indicates likely transcription factor binding sites. Proximity Ligation‐Assisted ChIP‐seq (PLAC‐seq) is a chromatin conformation assay that was used to link distal enhancers to target genes. Enhancers were validated by CRISPR‐mediated deletion of putative regions in induce‐pluripotent stem cells (iPSCs) that were derived into neurons, microglia and astrocytes followed by gene expression analysis. Result Genetic variants associated with increased risk of AD were largely confined to microglia enhancers, whereas genetic variants for psychiatric disorders such as autism and schizophrenia were enriched in neuronal enhancers. Enhancer‐promoter interactome maps connected disease‐risk variants located in enhancers to gene promoters. Integrative analysis of promoter‐enhancer interactome maps has not only revised and expanded the gene repertoire influenced by AD‐risk variants but has also revealed the probable cell types in which they function. Lastly, the BIN1 locus, the second highest putative AD‐risk gene after APOE, has a microglia‐specific enhancer that harbors AD‐risk variants. CRISPR‐deletion of the microglia BIN1 enhancer in iPSCs ablated BIN1 gene expression in iPSC‐derived microglia and not neurons or astrocytes. Conclusion There has been intense interest in elucidating mechanisms that link human non‐coding genetic variation to risk of neurodegenerative and psychiatric diseases. Towards this effort, enhancer‐promoter connectivity maps in the human brain has enabled an initial cell‐type‐specific interpretation of human genetic variation associated with disease risk for AD and other brain disorders.
Mechanism-guided repurposing: Effect of deferiprone on the eIF5A hydroxylation-dependent synthesis of proline cluster-containing proteins (PccPs) in uterine serous carcinoma (USC). (2016)

e23159 Background: Hydroxylation of eIF5A by deoxyhypusyl hydroxylase (DOHH) forms its hypusine residue, which relieves stalling within the ribosomal exit tunnel of a subset of nascent, cellular or viral PccPs. We tested the hypothesis that NIH 353, an antibody selectively recognizing hydroxylated eIF5A (OH-eIF5A) in tumor biopsies, can identify PccP-dependent cancers and thus guide the development of oncologically relevant eIF5A hydroxylation inhibitors by low-risk drug-based lead discovery (DBLD) or high-risk de novo drug development. Methods: Receptor-guided drug discovery; immunohistochemistry; Western; cell culture; flow cytometry; drug spectrometry. Results: DOHH active site mapping, confirmed by crystallography (Structure 23: 882-892 [2015]), identified deferiprone as a docking-compliant drug. NIH-353, immunoreative only to OH-eIF5A (Gynecol Oncol 94: 217-222 [2004]), prominently stained biopsies of USC, but not of endometrioid carcinomas. In the USC cell line ARK-1, deferiprone at clinically relevant concentration for 48 hours inhibited eIF5A hydroxylation ( ≥ -80%) along with the synthesis of the PccP Hsp27/HSPB1 ( ≥ -60%; Cancer Res 74: 552-562 [2013]). Cyclin B2 and stathmin-1, both representative for the USC gene expression subtype of endometrial carcinomas (Nature 497: 67-73 [2013]), were also inhibited ( ≥ -60%), whereas actin was unaffected. Deferiprone caused cell cycle arrest and transient epithelial differentiation of ARK-1, followed by rapid lethality after 72 hours of exposure. The same concentration had no deleterious effect on non-malignant uterine epithelial cells (ECC-1) even after 144 hours, assessed by transepithelial resistance. Conclusions: The library of FDA-approved drugs contains medicines with DOHH inhibitor side activity that disrupt the aggressive gene expression subtype involving PccP synthesis, as in USC. The DBLD approach, guided by the atomic level 3D resolution of the DOHH active site, facilitates targeted proof-of-principle trials and targeted optimization of drug pioneers to derive next-generation compounds.
Differential processing of a chemosensory cue across life stages sharing the same valence state in Caenorhabditis elegans (2023)

Many chemosensory cues evoke responses of the same valence under widely varying physiological conditions. It remains unclear whether similar or distinct neural mechanisms are involved in the detection and processing of such chemosensory cues across contexts. We show that in <i>Caenorhabditis elegans</i>, a chemosensory cue is processed by distinct neural mechanisms at two different life stages that share the same valence state. Both starved adults and dauer larvae are attracted to carbon dioxide (CO<sub>2</sub>), but CO<sub>2</sub> evokes different patterns of neural activity and different motor outputs at the two life stages. Moreover, the same interneuron within the CO<sub>2</sub> microcircuit plays a different role in driving CO<sub>2</sub>-evoked motor output at the two life stages. The dauer-specific patterns of CO<sub>2</sub>-evoked activity in this interneuron require a dauer-specific gap junction complex and insulin signaling. Our results demonstrate that functionally distinct microcircuits are engaged in response to a chemosensory cue that triggers the same valence state at different life stages, revealing an unexpected complexity to chemosensory processing.
Structural insights into the extracellular recognition of the human serotonin 2B receptor by an antibody (2020)

Highly selective monoclonal antibodies recognizing the extracellular 3D epitope of G protein-coupled receptors represent valuable tools for elucidating receptor function and localization in the cell and show promise for a range of therapeutic applications. Here we present the structure of a complex between the human serotonin 2B receptor, captured in an active-like state, and an antibody Fab fragment, bound to the extracellular side of the receptor. The structure uncovers the mechanisms of receptor activation and of extracellular receptor recognition by antibodies.
THE CONFORMATIONS OF INSULIN AND INSULIN-LIKE GROWTH FACTORS AND THEIR RELATION TO RECEPTOR BINDING. (1979)

Journal Article THE CONFORMATIONS OF INSULIN AND INSULIN-LIKE GROWTH FACTORS AND THEIR RELATION TO RECEPTOR BINDING Get access T L Blundell, T L Blundell Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet Street, London WC1E 7HX, United Kingdom Search for other works by this author on: Oxford Academic Google Scholar R Horuk, R Horuk Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet Street, London WC1E 7HX, United Kingdom Search for other works by this author on: Oxford Academic Google Scholar S Bedarkar, S Bedarkar Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet Street, London WC1E 7HX, United Kingdom Search for other works by this author on: Oxford Academic Google Scholar S P Wood S P Wood Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet Street, London WC1E 7HX, United Kingdom Search for other works by this author on: Oxford Academic Google Scholar Acta Endocrinologica (Norway), Volume 92, Issue 2_Supplement_b, Aug 1979, Pages S434–S441, https://doi.org/10.1530/acta.0.091S434 Published: 01 August 1979
The capacity of a class of 3-receiver broadcast channels with degraded message sets (2007)

Korner and Marton established the capacity region for the 2-receiver broadcast channel with degraded message sets. Recent results and conjectures suggest that a straightforward extension of the Korner-Marton region to more than 2 receivers is optimal. This paper shows that this is not the case. We establish the capacity region for a class of 3-receiver broadcast channels with 2 degraded message sets and show that it can be strictly larger than the straightforward extension of the Korner-Marton region. The key new idea is indirect decoding, whereby a receiver who cannot directly decode a cloud center, finds it indirectly by decoding satellite codewords. This idea is then used to establish new inner and outer bounds on the capacity region of the general 3-receiver broadcast channel with 2 and 3 degraded message sets. We show that these bounds are tight for some nontrivial cases. The results suggest that the capacity of the 3-receiver broadcast channel with degraded message sets is as at least as hard to find as the capacity of the general 2-receiver broadcast channel with common and private message.
Proceedings of the 16th ACM SIGPLAN/SIGBED Conference on Languages, Compilers and Tools for Embedded Systems 2015 CD-ROM (2015)

Welcome to LCTES 2015, the 16th ACM SIGPLAN/SIGBED Conference on Languages, Compilers, Tools and Theory for Embedded Systems.
Neuropilin 1 is not a marker of human Foxp3+ regulatory T cells. (2009)

International audience
Polymeric cantilevered piezotronic strain microsensors processed by Atomic Layer Deposition (2020)

We propose an original and reliable method for processing cantilevered piezotronic strain microsensors based on diode junctions made of dominant wurtzite zinc oxide (ZnO) polycrystalline thin film by atomic layer deposition (ALD). These strain sensitive microsensors are integrated into millimetre-sized polyimide cantilevers by means of maskless laser lithography on the polymer foil, where the zinc oxide thin film is microstructured on top of patterned interdigitated platinum microelectrodes. We show how the structural and transducing properties are strongly influenced by the ALD deposition parameters, leading to the expected Schottky barrier modulation by electromechanical coupling. The linearity, sensitivity, frequency response and noise figure of the created piezotronic strain sensors are reported, leading to measured gauge factors as high as 150. Electrical power consumption inferior to 50 μW is reported.
Organic/Inorganic Hybrid Polymer/Clay Nanocomposites (2003)

A novel class of polymer/clay nanocomposites has been invented in an attempt to develop transparent, lightweight, durable materials for a variety of aerospace applications. As their name suggests, polymer/ clay nanocomposites comprise organic/ inorganic hybrid polymer matrices containing platelet-shaped clay particles that have sizes of the order of a few nanometers thick and several hundred nanometers long. Partly because of their high aspect ratios and high surface areas, the clay particles, if properly dispersed in the polymer matrix at a loading level of 1 to 5 weight percent, impart unique combinations of physical and chemical properties that make these nanocomposites attractive for making films and coatings for a variety of industrial applications. Relative to the unmodified polymer, the polymer/ clay nanocomposites may exhibit improvements in strength, modulus, and toughness; tear, radiation, and fire resistance; and lower thermal expansion and permeability to gases while retaining a high degree of optical transparency.
Fully-Addressable Varactor-Based Reflecting Metasurface with Dual-Linear Polarisation for Low Power Reconfigurable Intelligent Surfaces (2023)

This work explores the performance of a 1-bit dual-linear polarised varactor-based metasurface design at sub-6 GHz. A modified particle swarm optimisation algorithm was utilised to determine the element geometry resulting in minimum reflection loss and phase error, and maximum cross-polarisation isolation. Unit cells may be individually addressed and with independent polarisation control over 3.3 to 3.7 GHz. A prototype consisting of an arrangement 48 x 16 unit cells has been fabricated for deployment in a reconfigurable intelligent surface-aided wireless communication channel sounding campaign.