gebhart/patrepeval huggingface dataset:
Unique marine derived cyanobacterial biosynthetic genes for chemical diversity (2016)

Cyanobacteria are a prolific source of structurally unique and biologically active natural products that derive from intriguing biochemical pathways. Advancements in genome sequencing have accelerated the identification of unique modular biosynthetic gene clusters in cyanobacteria and reveal a wealth of unusual enzymatic reactions involved in their construction. This article examines several interesting mechanistic transformations involved in cyanobacterial secondary metabolite biosynthesis with a particular focus on marine derived modular polyketide synthases (PKS), nonribosomal peptide synthetases (NRPS) and combinations thereof to form hybrid natural products. Further, we focus on the cyanobacterial genus Moorea and the co-evolution of its enzyme cassettes that create metabolic diversity. Progress in the development of heterologous expression systems for cyanobacterial gene clusters along with chemoenzymatic synthesis makes it possible to create new analogs. Additionally, phylum-wide genome sequencing projects have enhanced the discovery rate of new natural products and their distinctive enzymatic reactions. Summarizing, cyanobacterial biosynthetic gene clusters encode for a large toolbox of novel enzymes that catalyze unique chemical reactions, some of which may be useful in synthetic biology.
Selective Synthesis of Monodisperse CoO Nanooctahedra as Catalysts for Electrochemical Water Oxidation (2020)

Thermal decomposition is a promising route for the synthesis of metal oxide nanoparticles because size and morphology can be tuned by minute control of the reaction variables. We synthesized CoO nanooctahedra with diameters of ∼48 nm and a narrow size distribution. Full control over nanoparticle size and morphology could be obtained by controlling the reaction time, surfactant ratio, and reactant concentrations. We show that the particle size does not increase monotonically with time or surfactant concentration but passes through minima or maxima. We unravel the critical role of the surfactants in nucleation and growth and rationalize the observed experimental trends in accordance with simulation experiments. The as-synthesized CoO nanooctahedra exhibit superior electrocatalytic activity with long-term stability during oxygen evolution. The morphology of the CoO particles controls the electrocatalytic reaction through the distinct surface sites involved in the oxygen evolution reaction.
Serverless Programming (Function as a Service) (2017)

In this tutorial, we will present serverless computing, survey existing serverless platforms from industry, academia, and open source projects, identify key characteristics and use cases, and describe technical challenges and open problems. Our tutorial will involve a hands-on experience of using the serverless technologies available from different cloud providers (e.g. IBM, Amazon, Google and Microsoft). We expect our users to have basic knowledge of programming and basic knowledge of cloud computing.
Improved Oncologic Outcomes Following Laparoscopic Surgery for Small T4 Colon Cancer : A Multi-center Comparative Study (2020)

Abstract Background: Laparoscopic surgery for T4 colon cancer may be safe in selected patients. Based on the theory that small tumor size might preoperatively predict a good laparoscopic surgery outcome, we herein compare the clinicopathologic and oncologic outcomes of open and laparoscopic surgery in small T4 colon cancer. Methods: In a retrospective multicenter study, we reviewed the data of 449 patients, including 117 patients with tumors ≤4 cm, who underwent T4 colon cancer surgery between January 2014 and December 2017. We compared the clinicopathologic and 3-year oncologic outcomes between the laparoscopic and open surgery groups. Results: Blood loss, length of hospital stay, and postoperative morbidity were lower in the laparoscopic group than in the open group (86 mL vs. 278 mL, p &lt; 0.001; 10.0 days vs. 12.5 days, p = 0.003; and 18.0% vs. 29.5%, p = 0.005, respectively). There were no intergroup differences in overall survival (OS) and 3-year disease-free survival (DFS; 87.8% vs. 83.2%, p = 0.117; 69.5% vs. 68.1%, p = 0.408, respectively). Among patients with tumors of size ≤4 cm, blood loss was lower in the laparoscopic surgery group than in the open group (80 mL vs. 208 mL, p = 0.001); despite no statistical difference observed in the 3-year OS (84.4% vs 78.7%, p = 0.442), the laparoscopic group had a better 3-year DFS (73.8% vs. 46.0%, p = 0.004). Conclusions: Laparoscopic surgery showed similar outcomes to open surgery in T4 colon cancer patients, and may have favorable short-term oncologic outcomes in patients with small T4 tumors.
Spider Silk Coatings as a Bioshield to Reduce Periprosthetic Fibrous Capsule Formation (2014)

Medical grade silicones have been employed for decades in medical applications. The associated long‐term complications, such as capsule formation and contraction have, however, not been fully addressed yet. The aim of this study is to elucidate if capsule formation and/or contraction can be mitigated by veiling the surface of the silicone during the critical phase after implantation. Medical grade silicone implants are homogeneously coated with a micrometer thin layer of recombinant spider silk proteins. Biocompatibility analysis in vitro and in vivo focuses on specific physiological reactions. Applying quantitative methods for the determination of marker‐specific gene expression and protein concentration, it is detected that the silk coating inhibits fibroblast proliferation, collagen I synthesis, and differentiation of monocytes into CD68‐positive histiocytes. It significantly reduces capsule thickness, post‐operative inflammation, synthesis and re‐modeling of extracellular matrix, and expression of contracture‐mediating factors. Therefore, coatings made of recombinant spider silk proteins considerably reduce major post‐operative complications associated with implantation of silicone‐based alloprosthetics, such as capsular fibrosis and contraction, rendering spider silk coatings a bioshield for such implants.
Asymmetric Bifunctional Catalysis Using Heterobimetallic and Multimetallic Systems in Enantioselective Conjugate Additions (2010)

This chapter contains sections titled: Introduction Dinuclear Zn-Complexes in Catalytic ECAs Heterobimetallic Rare-Earth–Alkali Metal-Binol Complexes in ECAs Heterobimetallic Rare-earth–Alkali Metal-Binol Complexes in ECAs of Heteroatom Nucleophiles Miscellaneous Conclusion References
4 Ongoing Changes and Advanced L2 Use of English: Evidence from New Corpus Resources (2016)

This chapter approaches the global spread of English by charting new ways of studying the expansion and diversification of English to non-native contexts. The research builds on the idea that the o ...
Green's function estimation in speckle using the FDORT method (2008)

The FDORT method (French acronym for Decomposition Of the Time Reversal Operator using Focused beams) is a Time Reversal based method that can detect point-scatterers in a heterogeneous medium and extract their Green's function. It is particularly useful when focusing in a heterogeneous medium. In this presentation, the theory of the FDORT method is generalized to random media (speckle), and it is shown that it is possible to extract Green's functions from speckle signal using this method. Therefore it is possible to achieve a good focusing even if no point scatterers are present. Moreover, a link is made between FDORT and the Van Cittert Zernike theorem. We deduce from this interpretation that the normalized first eigenvalue of the Focused Time Reversal Operator is a well-known focusing criterion. The concept of an equivalent virtual object is introduced, that allows the random problem to be replaced by an equivalent deterministic problem and leads to an intuitive understanding of FDORT in speckle. Applications to aberration correction are presented. The reduction of the variance of the Green's function estimate is discussed.
Pulmonary hamartoma: CT findings. (1986)

Forty-seven patients with a proved (n = 31) or presumed (n = 16) diagnosis of pulmonary hamartoma were studied prospectively by thin-section computed tomography (CT). CT criteria for hamartoma included a diameter of 2.5 cm or less, a smooth edge, and focal collections of fat or fat alternating with areas of calcification. No case of cancer (n = 283) or metastatic disease (n = 72) fulfilled these criteria. Seventeen hamartomas with no detectable calcium or fat were not diagnosed by means of CT. Two other lesions contained diffuse calcium deposits. In 28 lesions, a CT diagnosis of hamartoma was based on the detection of fat (n = 18) or calcium plus fat (n = 10). Twelve such cases were proved histologically by means of thoracotomy or needle biopsy; the remainder, including eight in asymptomatic patients aged 65 years or older, were managed with conservative follow-up.
Human Tissue Kallikrein Gene Delivery Attenuates Cardiac Glycogen Accumulation in Streptozotocin-Induced Diabetic Rats (2000)

P58 The tissue kallikrein-kinin system is locally present in the heart and is reduced under diabetic conditions. In the present study, we explored the effects of kallikrein gene delivery in the heart under diabetic conditions. Intravenous injection of streptozotocin (STZ) (60mg/kg) into 8-week-old male Sprague-Dawley rats produced hyperglycemia (460 ± 10 mg/dl, n=30). Three weeks after STZ treatment, adenovirus containing the human tissue kallikrein gene (Ad.CMV-cHK) or green fluorescence protein gene (Ad.CMV-GFP) under the control of CMV promoter/enhancer were injected via the tail vein into STZ-diabetic rats. Adenovirus-mediated kallikrein gene delivery caused a significant reduction of blood pressure as compared to control rats receiving control virus (170.8 ± 3.5 vs. 187.4 ± 4.2 mmHg, n=8, P&lt;0.01). Rats were sacrificed and tissues were collected for analysis at 16 days after gene delivery. Histological examination of heart sections stained with periodic acid-Schiff (PAS) showed marked accumulation of glycogen in cardiomyocytes of diabetic rats. Kallikrein gene delivery significantly reduced cardiac glycogen accumulation as compared to rats receiving control adenovirus. Quantitative analysis confirmed the morphological observation that kallikrein gene delivery significantly reduced cardiac glycogen levels as compared to control diabetic rats injected withAd.CMV-GFP (0.5 ± 0.07 vs. 2.15 ± 0.83 mg glycogen/mg protein, n=6, P&lt;0.05). Cardiac cAMP levels were significantly increased after kallikrein gene delivery. This is the first study to demonstrate that kallikrein gene delivery exerts a protective effect in the reduction of glycogen accumulation in cardiomyocytes of STZ-induced diabetic rats.
Towards Joule-scale few-cycle pulses - progress and challenges of short-pulse pumped OPCPA (2011)

The Petawatt Field Synthesizer is based on short-pulse-pumped optical parametric amplification (OPA) for generating few-cycle, Joule-scale pulses (~ 5 fs, &gt; 3 J). Stabilizing the pump-seed timing to ±100 fs allowed for the first OPA experiments, which are reported here.
The Foundational Data Initiative for Parkinson Disease: Enabling efficient translation from genetic maps to mechanism (2023)

The Foundational Data Initiative for Parkinson Disease (FOUNDIN-PD) is an international collaboration producing fundamental resources for Parkinson disease (PD). FOUNDIN-PD generated a multi-layered molecular dataset in a cohort of induced pluripotent stem cell (iPSC) lines differentiated to dopaminergic (DA) neurons, a major affected cell type in PD. The lines were derived from the Parkinson's Progression Markers Initiative study, which included participants with PD carrying monogenic PD variants, variants with intermediate effects, and variants identified by genome-wide association studies and unaffected individuals. We generated genetic, epigenetic, regulatory, transcriptomic, and longitudinal cellular imaging data from iPSC-derived DA neurons to understand molecular relationships between disease-associated genetic variation and proximate molecular events. These data reveal that iPSC-derived DA neurons provide a valuable cellular context and foundational atlas for modeling PD genetic risk. We have integrated these data into a FOUNDIN-PD data browser as a resource for understanding the molecular pathogenesis of PD.
Synthesis and SAR development of PD 0325901, a potent and highly bioavailable MEK inhibitor. (2004)

2477 The MAP kinase pathway transmits proliferative signals for a number of growth factors and receptors and plays a central role in the growth of many human cancers. MEK (MAP kinase kinase), a central player in the Ras-MAP kinase pathway, is a critical signaling protein for multiple oncogenic pathways including the ErbB family, VEGF, PDGF, and mutated ras. MEK inhibitors therefore have the potential for a broader spectrum of antitumor activity than agents that inhibit only one portion of a tumor’s redundant proliferative pathways. We have previously described the identification and evaluation of PD 184352 (CI-1040), the first MEK inhibitor reported to modulate phosphorylation of MAP kinase in tumor-bearing animals (Sebolt-Leopold et al, Nature Medicine, 5, 810-816, 1999). CI-1040 was well tolerated in Phase 1 studies and did modulate tumor pERK levels at tolerated doses, although low overall bioavailability of the drug hampered its further development. To increase the bioavailability of CI-1040, we have explored the incorporation of polar, solubilizing substituents into the CI-1040 template. In this presentation, we describe synthesis and structure-activity-relationships (SAR) of a new class of N-aryl anthranilic acid hydroxamates that has led to PD 0325901. A variety of functionalized hydroxamate esters were surveyed and maximal in vitro potency was obtained by the incorporation of hydroxyalkyl esters. Further optimization of three sites on the CI-1040 ring system provided an additional boost in potency. These new sub-nanomolar inhibitors, display exquisite selectivity for MEK, like CI-1040. A recently obtained co-crystal structure of a MEK1 construct with PD 0318088, a PD 0325901 congener, explains the kinase selectivity of Pfizer’s MEK inhibitors and is highlighted here.
Stability-Indicating UPLC Method for Tramadol HCl Impurities in Tramadol Injection After Dilution by Infusion Fluids (5% Dextrose and 0.9% Sodium Chloride) (2013)

A novel, rapid, and sensitive ultra-performance liquid chromatography (UPLC) method has been developed and validated as per ICH guidelines for the determination of tramadol HCl impurities in the tramadol HCl injection after reconstitution by infusion fluids (5% dextrose and 0.9% sodium chloride). The tramadol HCl injection is for the treatment of patients with moderate-to-severe pain. The stability of the reconstituted solution is critical before intravenous injection. The literature search resulted in few published articles on assays of tramadol in infusion fluids by conventional HPLC. No attempts have yet been made to determine the impurities in infusion fluids, as the concentration of tramadol after reconstitution is extremely low (0.4 mg/mL) and that of impurities is even lower. The proposed method is novel as it allows the quantitation of the impurities of tramadol HCl and is based on modern chromatographic techniques like UPLC. The method was developed using the Waters Acquity BEH C18 column with a mobile phase consisting of a gradient mixture of solvent A (trifluroacetic acid buffer) and solvent B (methanol: acetonitrile). The model stability study was designed by diluting the tramadol HCl injection in the 5% dextrose injection and 0.9% sodium chloride injection. Each mixture was kept under storage at room temperature (25 ± 2°C) for testing at initial, 2, 4, 8, 12, 18 & 24 hours. The validation study illustrates that the proposed method is suitable for the determination of tramadol and its impurities. The proposed method makes use of the LC-MS-compatible mobile phase. It can be useful for the determination of tramadol HCl and its impurities in plasma samples and other pharmaceutical dosage forms.
Investigation of plasma hydrogenation and trapping mechanism for layer transfer (2005)

Hydrogen ion implantation is conventionally used to initiate the transfer of Si thin layers onto Si wafers coated with thermal oxide. In this work, we studied the feasibility of using plasma hydrogenation to replace high dose H implantation for layer transfer. Boron ion implantation was used to introduce H-trapping centers into Si wafers to illustrate the idea. Instead of the widely recognized interactions between boron and hydrogen atoms, this study showed that lattice damage, i.e., dangling bonds, traps H atoms and can lead to surface blistering during hydrogenation or upon postannealing at higher temperature. The B implantation and subsequent processes control the uniformity of H trapping and the trap depths. While the trap centers were introduced by B implantation in this study, there are many other means to do the same without implantation. Our results suggest an innovative way to achieve high quality transfer of Si layers without H implantation at high energies and high doses.
Sclerostin antibody treatment improves fracture outcomes in a Type I diabetic mouse model (2015)

Type 1 diabetes mellitus (T1DM) patients have osteopenia and impaired fracture healing due to decreased osteoblast activity. Further, no adequate treatments are currently available that can restore impaired healing in T1DM; hence a significant need exists to investigate new therapeutics for treatment of orthopedic complications. Sclerostin (SOST), a WNT antagonist, negatively regulates bone formation, and SostAb is a potent bone anabolic agent. To determine whether SOST antibody (SostAb) treatment improves fracture healing in streptozotocin (STZ) induced T1DM mice, we administered SostAb twice weekly for up to 21days post-fracture, and examined bone quality and callus outcomes at 21days and 42days post-fracture (11 and 14weeks of age, respectively). Here we show that SostAb treatment improves bone parameters; these improvements persist after cessation of antibody treatment. Markers of osteoblast differentiation such as Runx2, collagen I, osteocalcin, and DMP1 were reduced, while an abundant number of SP7/osterix-positive early osteoblasts were observed on the bone surface of STZ calluses. These results suggest that STZ calluses have poor osteogenesis resulting from failure of osteoblasts to fully differentiate and produce mineralized matrix, which produces a less mineralized callus. SostAb treatment enhanced fracture healing in both normal and STZ groups, and in STZ+SostAb mice, also reversed the lower mineralization seen in STZ calluses. Micro-CT analysis of calluses revealed improved bone parameters with SostAb treatment, and the mineralized bone was comparable to Controls. Additionally, we found sclerostin levels to be elevated in STZ mice and β-catenin activity to be reduced. Consistent with its function as a WNT antagonist, SostAb treatment enhanced β-catenin activity, but also increased the levels of SOST in the callus and in circulation. Our results indicate that SostAb treatment rescues the impaired osteogenesis seen in the STZ induced T1DM fracture model by facilitating osteoblast differentiation and mineralization of bone.
Burnar: Involuntary heat sensations in augmented reality (2013)

Augmented Reality systems that run interactively and in real time, using high quality graphical displays and sensational cues, can create the illusion of virtual objects appearing to be real. This paper presents the design, implementation, and evaluation of BurnAR, a novel demonstration which enables users to experience the illusion of seeing their own hands burning, which we achieve by overlaying virtual flames and smoke on their hands. Surprisingly, some users reported an involuntary warming sensation of their hands. Based on these comments, we hypothesized that stimulation of multiple sensory modalities presented in this AR environment can induce an involuntary experience in an additional sensory pathway: observation of virtual flames resulting in a heat sensation. This cross-modal transfer, known as virtual synesthe-sia, is a temporary experience which affects some people who are not synesthetes and only lasts for a short time during the illusory experience. To verify our hypothesis, we conducted an exploratory study where participants experienced the BurnAR demonstration under controlled conditions.
Identification of Genes and Genomic Islands Correlated with High Pathogenicity in Streptococcus suis Using Whole Genome Tilling Microarrays (2011)

Streptococcus suis is an important zoonotic pathogen that can cause meningitis and sepsis in both pigs and humans. Infections in humans have been sporadic worldwide but two severe outbreaks occurred in China in recent years, while infections in pigs are a major problem in the swine industry. Some S. suis strains are more pathogenic than others with 2 sequence types (ST), ST1 and ST7, being well recognized as highly pathogenic. We analyzed 31 isolates from 23 serotypes and 25 STs by NimbleGen tiling microarray using the genome of a high pathogenicity (HP) ST1 strain, GZ1, as reference and a new algorithm to detect gene content difference. The number of genes absent in a strain ranged from 49 to 225 with a total of 632 genes absent in at least one strain, while 1346 genes were found to be invariably present in all strains as the core genome of S. suis, accounting for 68% of the GZ1 genome. The majority of genes are located in chromosomal blocks with two or more contiguous genes. Sixty two blocks are absent in two or more strains and defined as regions of difference (RDs), among which 26 are putative genomic islands (GIs). Clustering and statistical analyses revealed that 8 RDs including 6 putative GIs and 21 genes within these RDs are significantly associated with HP. Three RDs encode known virulence related factors including the extracellular factor, the capsular polysaccharide and a SrtF pilus. The strains were divided into 5 groups based on population genetic analysis of multilocus sequence typing data and the distribution of the RDs among the groups revealed gain and loss of RDs in different groups. Our study elucidated the gene content diversity of S. suis and identified genes that potentially promote HP.
Non equilibrium plasmas: from dusty plasmas to nanotechnology (2022)

International audience
Evaluation of the relationship between aging and the renin-angiotensin system using direct radioimmunoassay with monoclonal antibodies. (1988)

加齢に伴うレニン-アンジオテンシン系の変化を, モノクローナル抗体を用いたレニン直接ラジオイムノアッセイ法, および従来法 Plasma renin activity (以下PRA), Total renin activity (以下TRA) で検討した. 60歳以下16名, 60歳以上14名の健常者に対し, 常食30分臥位後に採血を行い, PRA及びトリプシン活性化法によるTRAを測定, 更に我々の開発したモノクローナル抗体を用いた総レニン直接RIA法とパスツール研の活性型レニン直接RIA法で測定を行った. PRAによるレニン値は加齢により減少 (60歳以下2.2±0.5ng/ml/h, 60歳以上0.7±0.1ng/ml/h; mean±SE, p<0.01) し, 活性型レニン直接RIA法によるレニン値も加齢により減少した (60歳以下35±5pg/ml, 60歳以上17±2pg/ml, p<0.01). 一方, TRAと総レニン直接RIA法によるレニン値 (Plasma total renin concentration; PTRC) は加齢による変化はなかった (TRA; 60歳以下10.3±1.6ng/ml/h, 60歳以上7.7±1.0ng/ml/h, PTRC; 60歳以下442±128pg/ml, 60歳以上250±52pg/ml). 従来法で求めた活性型レニン (PRA)の総レニン (TRA) に対する比 (A/T比) は, 加齢と共に減少し (相関係数r=-0.683, p<0.01), 直接RIA法によるA/T比も, 加齢により減少した (相関係数r=-0.535, p<0.01). モノクローナル抗体を用いた新しいレニン直接RIA法により, 加齢に伴うレニン活性の低下が活性型レニン濃度の低下を反映していることを確認した. 更に, 血中総レニン量は加齢により低下せず, A/T比が減少することから, 老人ではプロレニンのプロセッシングに異常がある可能性も示唆された.