gebhart/patrepeval huggingface dataset:
Assessment of heterologous butyrate and butanol pathway activity by measurement of intracellular pathway intermediates in recombinant Escherichia coli (2010)

In clostridia, n-butanol production from carbohydrates at yields of up to 76% of the theoretical maximum and at titers of up to 13 g/L has been reported. However, in Escherichia coli, several groups have reported butyric acid or butanol production from recombinant expression of clostridial genes, at much lower titers and yields. To pinpoint deficient steps in the recombinant pathway, we developed an analytical procedure for the determination of intracellular pools of key pathway intermediates and applied the technique to the analysis of three sets of E. coli strains expressing various combinations of butyrate biosynthesis genes. Low expression levels of the hbd-encoded S-3-hydroxybutyryl-CoA dehydrogenase were insufficient to convert acetyl-CoA to 3-hydroxybutyryl-CoA, indicating that hbd was a rate-limiting step in the production of butyryl-CoA. Increasing hbd expression alleviated this bottleneck, but in resulting strains, our pool size measurements and thermodynamic analysis showed that the reaction step catalyzed by the bcd-encoded butyryl-CoA dehydrogenase was rate-limiting. E. coli strains expressing both hbd and ptb-buk produced crotonic acid as a byproduct, but this byproduct was not observed with expression of related genes from non-clostridial organisms. Our thermodynamic interpretation of pool size measurements is applicable to the analysis of other metabolic pathways.
Modulation of trigeminal sensory neuron activity by the dual cannabinoid–vanilloid agonists anandamide, <i>N</i>‐arachidonoyl‐dopamine and arachidonyl‐2‐chloroethylamide (2004)

1. Peripheral cannabinoids have been shown to suppress nociceptive neurotransmission in a number of behavioral and neurophysiological studies. It is not known, however, whether cannabinoids exert this action through direct interactions with nociceptors in the periphery and/or if other processes are involved. To gain a better understanding of the direct actions of cannabinoid-vanilloid agonists on sensory neurons, we examined the effects of these compounds on trigeminal ganglion (TG) neurons in vitro. 2. AEA (EC(50)=11.0 microM), NADA (EC(50)=857 nM) and arachidonyl-2-chloroethylamide ACEA (EC(50)=14.0 microM) each evoked calcitonin gene-related peptide (CGRP) release from TG neurons. The TRPV1 antagonists iodo-resiniferatoxin (I-RTX) and capsazepine (CPZ) each obtunded AEA-, NADA-, ACEA- and capsaicin (CAP)-evoked CGRP release with individually equivalent IC(50)'s for each of the compounds (I-RTX IC(50) range=2.6-4.0 nM; CPZ IC(50) range=523-1140 microM). 3. The pro-inflammatory mediator prostaglandin E(2) significantly increased the maximal effect of AEA-evoked CGRP release without altering the EC(50). AEA, ACEA and CAP stimulated cAMP accumulation in TG neurons in a calcium- and TRPV1-dependent fashion. Moreover, the protein kinase inhibitor staurosporine significantly inhibited AEA- and CAP-evoked CGRP release. 4. The pungency of AEA, NADA, ACEA and CAP in the rat eye-wipe assay was also assessed. Interestingly, when applied intraocularly, NADA or CAP each produced nocifensive responses, while AEA or ACEA did not. 5. Finally, the potential inhibitory effects of these cannabinoids on TG nociceptors were evaluated. Neither AEA nor ACEA decreased CAP-evoked CGRP release. Furthermore, neither of the cannabinoid receptor type 1 antagonists SR141716A nor AM251 had any impact on either basal or CAP-evoked CGRP release. AEA also did not inhibit 50 mM K(+)-evoked CGRP release and did not influence bradykinin-stimulated inositol phosphate accumulation. 6. We conclude that the major action of AEA, NADA and ACEA on TG neurons is excitatory, while, of these, only NADA is pungent. These findings are discussed in relation to our current understanding of interactions between the cannabinoid and vanilloid systems and nociceptive processing in the periphery.
A comprehensive empirical comparison of modern supervised classification and feature selection methods for text categorization (2014)

An important aspect to performing text categorization is selecting appropriate supervised classification and feature selection methods. A comprehensive benchmark is needed to inform best practices in this broad application field. Previous benchmarks have evaluated performance for a few supervised classification and feature selection methods and limited ways to optimize them. The present work updates prior benchmarks by increasing the number of classifiers and feature selection methods order of magnitude, including adding recently developed, state‐of‐the‐art methods. Specifically, this study used 229 text categorization data sets/tasks, and evaluated 28 classification methods (both well‐established and proprietary/commercial) and 19 feature selection methods according to 4 classification performance metrics. We report several key findings that will be helpful in establishing best methodological practices for text categorization.
Cranioplasty with polymethylmethacrylate prostheses fabricated by hand using original bone flaps: Technical note and surgical outcomes (2013)

Prefabrication of custom PMMA prostheses by hand when original bone flaps are available is an excellent alternative to newer 3-D printing techniques, because it is relatively cheaper, less time consuming, and offers excellent results in terms of anatomical reconstruction and improvement of neurological function in long-term follow-ups.
Ketamine suppresses intestinal NF-kappa B activation and proinflammatory cytokine in endotoxic rats (2004)

Ketamine can suppress endotoxin-induced production of proinflammatory cytokines such as TNF-alpha and IL-6 production in the intestine. This suppressive effect may act through inhibiting NF-kappa B.
Novel HLA-B27-restricted Epitopes from Chlamydia trachomatis Generated upon Endogenous Processing of Bacterial Proteins Suggest a Role of Molecular Mimicry in Reactive Arthritis (2013)

Reactive arthritis (ReA) is an HLA-B27-associated spondyloarthropathy that is triggered by diverse bacteria, including Chlamydia trachomatis, a frequent intracellular parasite. HLA-B27-restricted T-cell responses are elicited against this bacterium in ReA patients, but their pathogenetic significance, autoimmune potential, and relevant epitopes are unknown. High resolution and sensitivity mass spectrometry was used to identify HLA-B27 ligands endogenously processed and presented by HLA-B27 from three chlamydial proteins for which T-cell epitopes were predicted. Fusion protein constructs of ClpC, Na(+)-translocating NADH-quinone reductase subunit A, and DNA primase were expressed in HLA-B27(+) cells, and their HLA-B27-bound peptidomes were searched for endogenous bacterial ligands. A non-predicted peptide, distinct from the predicted T-cell epitope, was identified from ClpC. A peptide recognized by T-cells in vitro, NQRA(330-338), was detected from the reductase subunit. This is the second HLA-B27-restricted T-cell epitope from C. trachomatis with relevance in ReA demonstrated to be processed and presented in live cells. A novel peptide from the DNA primase, DNAP(211-223), was also found. This was a larger variant of a known epitope and was highly homologous to a self-derived natural ligand of HLA-B27. All three bacterial peptides showed high homology with human sequences containing the binding motif of HLA-B27. Molecular dynamics simulations further showed a striking conformational similarity between DNAP(211-223) and its homologous and much more flexible human-derived HLA-B27 ligand. The results suggest that molecular mimicry between HLA-B27-restricted bacterial and self-derived epitopes is frequent and may play a role in ReA.
Lossless point cloud geometry compression via binary tree partition and intra prediction (2017)

Characterized by geometry and photometry attributes, point cloud has become widely applied in the real-time presentation of various 3D objects and scenes. The development of even more precise capture devices and the increasing requirements for vivid rendering inevitably induce huge point capacity, thus making the point cloud compression a demanding issue. Considering the non-uniform sampling and time-variant geometry, appropriate structural representation for point cloud is important. In this paper, we propose a lossless geometry compression algorithm for 3D point cloud which serves as the basis of future adaptive improvement. We utilize the binary tree structure for effectively partitioning unorganized points into block structure. This hierarchical representation obtains roughly the same quantity level for each leaf node. Further analysis is conducted on an intra-geometry prediction via extended Travelling Salesman Problem (TSP), achieving an impressive performance in eliminating point-wise redundancy while preserving one single reference position for each block. The residual encoding is accomplished via a shallow neural network-based lossless compression algorithm, PAQ. Simulation results confirm the lossless compression of geometry from high quality capture, achieving approximately 3.5 times efficiency gain over the state of art algorithm implemented as MPEG Point Cloud Compression (PCC) reference software.
Defects in mouse mammary gland development caused by conditional haploinsufficiency of <i>Patched-1</i> (1999)

In vertebrates, the hedgehog family of cell signaling proteins and associated downstream network components play an essential role in mediating tissue interactions during development and organogenesis. Loss-of-function or misexpression mutation of hedgehog network components can cause birth defects, skin cancer and other tumors. The mammary gland is a specialized skin derivative requiring epithelial-epithelial and epithelial-stromal tissue interactions similar to those required for development of other organs, where these interactions are often controlled by hedgehog signaling. We have investigated the role of the Patched-1 (Ptc1) hedgehog receptor gene in mammary development and neoplasia. Haploinsufficiency at the Ptc1 locus results in severe histological defects in ductal structure, and minor morphological changes in terminal end buds in heterozygous postpubescent virgin animals. Defects are mainly ductal hyperplasias and dysplasias characterized by multilayered ductal walls and dissociated cells impacting ductal lumens. This phenotype is 100% penetrant. Remarkably, defects are reverted during late pregnancy and lactation but return upon involution and gland remodeling. Whole mammary gland transplants into athymic mice demonstrates that the observed dysplasias reflect an intrisic developmental defect within the gland. However, Ptc1-induced epithelial dysplasias are not stable upon transplantation into a wild-type epithelium-free fat pad, suggesting stromal (or epithelial and stromal) function of Ptc1. Mammary expression of Ptc1 mRNA is both epithelial and stromal and is developmentally regulated. Phenotypic reversion correlates with developmentally regulated and enhanced expression of Indian hedgehog (Ihh) during pregnancy and lactation. Data demonstrate a critical mammary role for at least one component of the hedgehog signaling network and suggest that Ihh is the primary hedgehog gene active in the gland.
25-Gb/s broadband silicon modulator with 031-V·cm VπL based on forward-biased PIN diodes embedded with passive equalizer (2015)

We investigated the broadband operations of a silicon Mach-Zehnder modulator (MZM) based on a forward-biased-PIN diode. The phase shifter was integrated with a passive-circuit equalizer to compensate for the narrowband characteristics of the diodes, which consists of a simple resistance of doped silicon and a parallel-plate metal capacitance. The device structure was simple and fabricated using standard CMOS processes. The measured results for a 50-Ω driver indicated there was a small VπL of 0.31 V·cm and a flat frequency response for a 3-dB bandwidth (f(3dB)) of 17 GHz, which agree well with the designed values. A 25-Gb/s large-signal operation was obtained using binary signals without pre-emphasis. The modulator showed a linear modulation property to the applied voltage, due to the metal capacitance of the equalizer.
Scientific Charge-Coupled Devices (1987)

The charge-coupled device dominates an ever-increasing variety of scientific imaging and spectroscopy applications. Recent experience indicates, however, that the full potential of CCD performance lies well beyond that realized in devices currently available. Test data suggest that major improvements are feasible in spectral response, charge collection, charge transfer, and readout noise. These properties, their measurement in existing CCDs, and their potential for future improvement are discussed in this paper.
Bark-stripping of tankan orange, Citrus tankan, by the roof rat, Rattus rattus, on Amami Oshima Island, southern Japan. (1998)

In 1997, roof rats, Rattus rattus, damaged the bark of cultivated tankan orange, Citrus tankan Hayata, trees over a wide area of the central part of Amami Oshima, an island in the Nansei Shoto archipelago of southern Japan.'This was the first time that tankan farmers had experienced such damage in more than 30 years of cultivation of the fruit.At first, it was believed that the introduced mongoose, Herpestes sp., had damaged the trees, but later, from the appearance of the tooth marks on the trees, it was surmised that the rats were responsible.The damage which occurred from early April until early October 1997 was found in an area where other potential mammalian culprits such as R. norvegicus, Tokudaia osimensis and Diplothrix legata were known to be absent.
Mechanism of cytokine-induced modulation of beta-adrenoceptor responsiveness in airway smooth muscle. (1996)

To elucidate the role of specific proinflammatory cytokines in regulating airway responsiveness, we examined the effects and mechanisms of action of IL-1beta, TNF-alpha, and IL-2 on the beta-adrenoceptor- and postreceptor-coupled transmembrane signaling mechanisms regulating relaxation in isolated rabbit tracheal smooth muscle (TSM) segments. During half-maximal isometric contraction of the tissues with acetylcholine, relaxation responses to isoproterenol, PGE2, and forskolin were separately compared in control (untreated) TSM and tissues incubated for 18 h with IL-1beta (10 ng/ml), TNF-(alpha (100 ng/ml), or IL-2 (200 ng/ml). Relative to controls, IL-1beta- and TNF-alpha-treated TSM, but not IL-2-treated tissues, depicted significant attenuation of their maximal relaxation and sensitivity (i.e., -log dose producing 50% maximal relaxation) to isoproterenol (P < 0.001) and PGE2 (P < 0.05); whereas the relaxation responses to direct stimulation of adenylate cyclase with forskolin were similar in the control and cytokine-treated tissues. Further, the attenuated relaxation to isoproterenol and PGE2 was ablated in the IL-1beta-treated TSM that were pretreated with either the muscarinic M2-receptor antagonist, methoctramine (10(-6) M), or pertussis toxin (100 ng/ml). Moreover, Western immunoblot analysis demonstrated that: (a) Gi protein expression was significantly enhanced in membrane fractions isolated from IL-1beta-treated TSM; and (b) the latter was largely attributed to induced enhanced expression of the Gi alpha2 and Gi alpha3 subunits. Collectively, these observations provide new evidence demonstrating that IL-lbeta and TNF-alpha induce impaired receptor-coupled airway relaxation in naive TSM, and that the latter effect is associated with increased muscarinic M2-receptor/Gi protein-coupled expression and function.
Balance Computation of Objects Transported on a Tray by a Humanoid Robot Based on 3D Dynamic Slopes (2018)

Humanoid robots are designed to perform tasks in the same way than humans do. One of these tasks is to act as a waiter serving drinks, food, etc. Transporting all these items can be considered a manipulation task. In this application, the objects are transported over a tray, without grasping them. The consequence is that the objects are not firmly attached to the robot, which is the case in grasping. Then, the complexity of robotics grasping is avoided but stability issues arise. The problem of keeping balance of the object transported by a robot over a tray is discussed in this paper. The approach presented is based on the computation of the Zero Moment Point (ZMP) of the object, which is modelled as a three dimensional Linear Inverted Pendulum Model (3D-LIPM). The use of force-torque sensors located at the wrist enables ZMP computation, but the main problem to be solved is how the robot should react when the object losses balance. One strategy is to rotate the tray to counteract the rotation of the object. This rotation has to be proportional to the ZMP variation and the object's rotation angle. This issue is solved by applying the concept of three dimensional dynamic slopes. It helps to avoid kinematic problems and make balance computation independent from the angle of the tray.
Inhibition of the Tyrosine Phosphatase SHP-2 Suppresses Angiogenesis in vitro and in vivo (2007)

Endothelial cell survival is indispensable to maintain endothelial integrity and initiate new vessel formation. We investigated the role of SHP-2 in endothelial cell survival and angiogenesis in vitro as well as in vivo. SHP-2 function in cultured human umbilical vein and human dermal microvascular endothelial cells was inhibited by either silencing the protein expression with antisense-oligodesoxynucleotides or treatment with a pharmacological inhibitor (PtpI IV). SHP-2 inhibition impaired capillary-like structure formation (p < 0.01; n = 8) in vitro as well as new vessel growth ex vivo(p < 0.05; n = 10) and in vivo in the chicken chorioallantoic membrane (p < 0.01, n = 4). Additionally, SHP-2 knock-down abrogated fibroblast growth factor 2 (FGF-2)-dependent endothelial proliferation measured by MTT reduction (p < 0.01; n = 12). The inhibitory effect of SHP-2 knock-down on vessel growth was mediated by increased endothelial apoptosis (annexin V staining, p < 0.05, n = 9), which was associated with reduced FGF-2-induced phosphorylation of phosphatidylinositol 3-kinase (PI3-K), Akt and extracellular regulated kinase 1/2 (ERK1/2) and involved diminished ERK1/2 phosphorylation after PI3-K inhibition (n = 3). These results suggest that SHP-2 regulates endothelial cell survival through PI3-K-Akt and mitogen-activated protein kinase pathways thereby strongly affecting new vessel formation. Thus, SHP-2 exhibits a pivotal role in angiogenesis and may represent an interesting target for therapeutic approaches controlling vessel growth.
MicroRNA-204 regulates vascular smooth muscle cell calcification in vitro and in vivo (2012)

Our study has shown that down-regulation of miR-204 may contribute to β-glycerophosphate-induced VSMC calcification through regulating Runx2. miR-204 represents an important new regulator of VSMC calcification and a potential therapeutic target in medial artery calcification.
DNA 5-Methylcytosine-Specific Amplification and Sequencing (2020)

DNA 5-methylcytosine (5mC)-specific mapping has been hampered by severe DNA degradation and the presence of 5-hydroxymethylcytosine (5hmC) using the conventional bisulfite sequencing approach. Here, we present a 5mC-specific whole-genome amplification method (5mC-WGA), with which we achieved 5mC retention during DNA amplification from limited input down to 10 pg scale with limited interference from 5hmC signals, providing DNA 5mC methylome with high reproducibility and accuracy.
Fault Tolerance using Whole-Process Migration and Speculative Execution (2003)

This thesis examines programming language concepts that facilitate fault-tolerant distributed programming. New language primitives are introduced for whole-process migration, which allows an active process to be transferred from one machine to another, and speculative execution, which enables optimistic computing based on an unverified assumption. These primitives are developed in the context of the Mojave Compiler Collection, a multi-language multi-architecture compiler with ties to the MetaPRL theorem prover.

The new primitives are first discussed from a theoretical perspective. The primitives are implemented as part of a functional intermediate language in the Mojave compiler, which has a formal operational semantics and complete typing rules. The operational semantics and typing rules are extended to accommodate whole-process migration and speculative execution, and the implications these primitives have for program safety are discussed.

The primitives are implemented as part of the Mojave compiler. The runtime safety checks that are required to ensure these primitives are safe are presented, along with runtime invariants used to justify the safety of the system. The primitives are also integrated with a novel compacting, generational garbage collector whose algorithm is presented.
A Lewis Acid Palladium(II)-Catalyzed Three-Component Synthesis of α-Substituted Amides (2013)

A Lewis acid palladium-catalyzed reaction of amides, aryl aldehydes, and arylboronic acids is described. This new method allows for a practical and general synthesis of α-substituted amides from simple, readily available building blocks.
High-Throughput, High-Resolution Interferometric Light Microscopy of Biological Nanoparticles (2020)

Label-free, visible light microscopy is an indispensable tool for studying biological nanoparticles (BNPs). However, conventional imaging techniques have two major challenges: (i) weak contrast due to low-refractive-index difference with the surrounding medium and exceptionally small size and (ii) limited spatial resolution. Advances in interferometric microscopy have overcome the weak contrast limitation and enabled direct detection of BNPs, yet lateral resolution remains as a challenge in studying BNP morphology. Here, we introduce a wide-field interferometric microscopy technique augmented by computational imaging to demonstrate a 2-fold lateral resolution improvement over a large field-of-view (>100 × 100 μm<sup>2</sup>), enabling simultaneous imaging of more than 10<sup>4</sup> BNPs at a resolution of ∼150 nm without any labels or sample preparation. We present a rigorous vectorial-optics-based forward model establishing the relationship between the intensity images captured under partially coherent asymmetric illumination and the complex permittivity distribution of nanoparticles. We demonstrate high-throughput morphological visualization of a diverse population of Ebola virus-like particles and a structurally distinct Ebola vaccine candidate. Our approach offers a low-cost and robust label-free imaging platform for high-throughput and high-resolution characterization of a broad size range of BNPs.