gebhart/patrepeval huggingface dataset:
Achieving High Stereoselectivity in Ruthenium-Catalyzed Olefin Metathesis Reactions for Organic and Polymer Synthesis (2018)

Transition metal-catalyzed olefin metathesis has emerged as a powerful tool for constructing C−C double bonds. This thesis delineates the development of Ru-based catalysts for the stereoselective formation of olefins and mechanistic studies used to examine how catalyst structure influences selectivity and activity. Chapter 2 details the synthesis of Z-selective, cyclometalated catalysts bearing nitrite X-ligands. The activity and selectivity of these catalysts were examined in an array of ring-opening metathesis polymerization and cross metathesis reactions. Comparison of these catalysts with their nitrate-bound analogues is described. Chapter 3 describes the examination of several Z-selective, cyclometalated catalysts in ring-opening metathesis polymerizations. The polymerizations of a variety of norbornene and norbornene derivatives were examined to determine the tacticity and microstructure of the resulting polymer. Computational studies were used to examine the mechanism of the polymerization reactions. Chapter 4 examines the decomposition of Fischer carbene complexes derived from cyclometalated catalysts. In-depth NMR studies are used to determine the identity of the decomposition product, and the decomposition pathway is examined through computational studies. Chapter 5 describes the first example of highly E-selective cross metathesis through kinetic control using stereoretentive, Ru-based catalysts bearing dithiolate catalysts. The preparation of additional stereoretentive catalysts is described for increasing catalyst activity while maintaining or increasing selectivity. A model for the observed stereoselectivity is proposed. Chapter 6 delineates the preparation of a series of fast initiating, stereoretentive catalysts. These catalysts are assessed in an array of cross metathesis reactions, and significantly enhanced activity is observed in E-selective reactions. The examination of the relationships between the structure of a catalyst and its selectivity and activity is described. Chapter 7 examines the use of stereoretentive catalysts in the synthesis of Z-macrocycles from diene starting materials bearing a Z-olefin and a terminal olefin. Initiation rate studies are conducted to examine the activity of these catalysts compared to previously reported cyclometallated catalysts used in this ring-closing metathesis reaction. The synthesis of twelve- to seventeen-membered rings with high Z-selectivity is described. Chapter 8 explores the use of fast-initiating, stereoretentive catalysts for synthesizing E-macrocycles. The preparation of diene starting materials containing two E-olefins is described. Using these catalysts, twelve- to eighteen-membered rings are constructed with high E-selectivity.
Rv0989c encodes a novel (<i>E</i>)-geranyl diphosphate synthase facilitating decaprenyl diphosphate biosynthesis in<i>Mycobacterium tuberculosis</i> (2011)

Mycobacterium tuberculosis (Mtb) has a highly complex cell wall, which is required for both bacterial survival and infection. Cell wall biosynthesis is dependent on decaprenyl diphosphate as a glyco-carrier, which is hence an essential metabolite in this pathogen. Previous biochemical studies indicated (E)-geranyl diphosphate (GPP) is required for the synthesis of decaprenyl diphosphate. Here we demonstrate that Rv0989c encodes the "missing" GPP synthase, representing the first such enzyme to be characterized from bacteria, and which presumably is involved in decaprenyl diphosphate biosynthesis in Mtb. Our investigation also has revealed previously unrecognized substrate plasticity of the farnesyl diphosphate synthases from Mtb, resolving previous discrepancies between biochemical and genetic studies of cell wall biosynthesis.
The Shorter the Better: Reducing Fixed Primer Regions of Oligonucleotide Libraries for Aptamer Selection (2009)

Oligonucleotide aptamers are highly structured DNA or RNA molecules, or modified versions thereof, that can bind to targets with specific affinities comparable to antibodies. They are identified through an in vitro selection process termed SELEX (Systematic Evolution of Ligands by EXponential enrichment) to recognize a wide variety of targets, from small molecules to proteins, and from cultured cells to whole organisms. Aptamers possess a number of desirable properties, such as ease of synthesis, stability, robustness, and lack of immunogenicity. Standard SELEX libraries require two primers, one on each side of a central random domain, to amplify the target-bound sequences via PCR or RT-PCR. However, these primer sequences cause non-specific binding by their nature, and have been reported to lead to large numbers of false-positive binding sequences, or to interfere with binding of sequences within the random regions. This review is focused on methods which have been developed to eliminate fixed primer interference during the SELEX process.
Excitation wavelength optimization of harmonic generation microscopy in human skin enabled by fiber-based femtosecond source tunable in 1.15-1.35 µm (2018)

We demonstrate a fiber-based tunable femtosecond source covering 1.15–1.35 μm based on self-phase modulation enabled spectral selection, which allows us to optimize the excitation wavelength for harmonic generation imaging in ex vivo human skin.
Degradable Hydrogels for Tissue Engineering – Part I: Synthesis by RAFT Polymerization and Characterization of PHEMA Containing Enzymatically Degradable Crosslinks (2010)

A nonapeptide, which is sensitive to enzymatic digestion by collagenase, was modified by the covalent attachment of an acrylamido group at the terminal positions. The functionalized peptide was used as a crosslinking agent during polymerization of 2-hydroxyethyl methacrylate (HEMA). Reversible addition-fragmentation chain transfer (RAFT) method was used to obtain a polymer (PHEMA) with an average theoretical molecular weight of 4000 Da, containing enzymatically labile peptide crosslinks. The functionalized peptide was analyzed in detail by 1H and 13C nuclear magnetic resonance (NMR) spectrometry. The polymerization reaction was monitored by near infrared spectrometry, while the resulting polymer was analyzed by size exclusion chromatography and solid NMR spectrometry. The peptide-crosslinked PHEMA was subjected to an in-vitro degradation assay in the presence of collagenase. At the highest concentration of enzyme used in the study, a weight loss of 35% was recorded after 60 days of incubation in the collagenolytic medium. This suggests that crosslinking with enzymatically degradable peptides is a valid method for inducing biodegradability in polymers that otherwise are not degradable.
Abstract PR03: Global quantitative proteomic and phosphoproteomic analysis of oncogenic Kras-driven mouse pancreatic cancer (2014)

Abstract Background: The most common genetic abnormality in pancreatic cancer is oncogenic mutation of KRAS, which is an initial key event in pancreatic carcinogenesis. Oncogenic KRAS activates downstream signaling pathways, such as PI3K and MAPK pathways, indicating the essential role of phosphorylation in pancreatic cancer. However, the effect of KRAS on the global phosphoproteome in pancreatic cancer has not been fully elucidated. We investigated proteomic and phosphoproteomic alterations induced by oncogenic Kras using mouse pancreatic cancer cell lines established from doxycycline-inducible KrasG12D pancreatic cancer mouse model. Materials and Methods: Three mouse pancreatic cancer cell lines were established from triple transgenic inducible KrasG12D pancreatic cancer mouse model (tetO_LSL- KrasG12D; ROSA26A-LSL-rtTA-IRES-GFP; p48-Cre). To identify direct downstream pathways of Kras, we performed two different experiments for each cell line: (1) 20 hours Kras-off followed by 5 hours Kras-on (designated “Re-on”) vs. 25 hours Kras-off, and (2) Continuous Kras-on (designated “On”) vs. 24 hours Kras-off. Whole cell lysates were fractionated and subjected to analysis with using mass spectrometry. Results and Conclusion: Overall 4,133 phosphorylation sites were identified. Phosphorylation levels of 2,670 sites were quantified in at least one sample, including 2,347 (87.9%) at serine, 293 (11.0%) threonine, and 30 (1.1%) tyrosine residues. Phosphorylation levels were more than 1.25 fold higher at 386 sites (139 proteins) and 558 sites (256 proteins) in “Re-on” and “On” samples, respectively. 190 sites were common between “Re-on” and “On”, 196 sites were “Re-on” unique, and 368 sites were “On” unique. mTOR and MAPK pathways were activated in both “Re-on” and “On”, while Rho kinase, Phospholipase C, and Rac signaling pathways were predominantly associated with “On”, suggestive of differential downstream pathway activation at different phases of Kras signaling. This abstract is also presented as Poster A21. Citation Format: Ayumu Taguchi, Avnish Kapoor, Amin Momin, Hiroyuki Katayama, Wantong Yao, Hong Wang, Haoqiang Ying, Ronald DePinho, Samir Hanash. Global quantitative proteomic and phosphoproteomic analysis of oncogenic Kras-driven mouse pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr PR03. doi: 10.1158/1557-3125.RASONC14-PR03
Recent advances in ultrafast MIXSELs (2014)

A high-power MIXSEL combining 570-fs-pulses and repetition-rate scalability from 5 GHz to record high 101.2 GHz is presented. Additionally, we achieve record low timing jitters of a free-running and piezo-stabilized picosecond MIXSEL.
The differential contribution of tumour necrosis factor to thermal and mechanical hyperalgesia during chronic inflammation (2005)

Therapies directed against tumour necrosis factor (TNF) are effective for the treatment of rheumatoid arthritis and reduce pain scores in this condition. In this study, we sought to explore mechanisms by which TNF contributes to inflammatory pain in an experimental model of arthritis. The effects of an anti-TNF agent, etanercept, on behavioural pain responses arising from rat monoarthritis induced by complete Freund's adjuvant were assessed and compared with expression of TNF receptors (TNFRs) by dorsal root ganglion (DRG) cells at corresponding time points. Etanercept had no effect on evoked pain responses in normal animals but exerted a differential effect on the thermal and mechanical hyperalgesia associated with rat arthritis induced by complete Freund's adjuvant (CFA). Joint inflammation was associated with increased TNFR1 and TNFR2 expression on DRG cells, which was maintained throughout the time course of the model. TNFR1 expression was increased in neuronal cells of the DRG bilaterally after arthritis induction. In contrast, TNFR2 expression occurred exclusively on non-neuronal cells of the macrophage-monocyte lineage, with cell numbers increasing in a TNF-dependent fashion during CFA-induced arthritis. A strong correlation was observed between numbers of macrophages and the development of mechanical hyperalgesia in CFA-induced arthritis. These results highlight the potential for TNF to play a vital role in inflammatory hyperalgesia, both by a direct action on neurons via TNFR1 and by facilitating the accumulation of macrophages in the DRG via a TNFR2-mediated pathway.
The effect of novel mutations on the structure and enzymatic activity of unconventional myosins associated with autosomal dominant non-syndromic hearing loss (2014)

Mutations in five unconventional myosin genes have been associated with genetic hearing loss (HL). These genes encode the motor proteins myosin IA, IIIA, VI, VIIA and XVA. To date, most mutations in myosin genes have been found in the Caucasian population. In addition, only a few functional studies have been performed on the previously reported myosin mutations. We performed screening and functional studies for mutations in the MYO1A and MYO6 genes in Korean cases of autosomal dominant non-syndromic HL. We identified four novel heterozygous mutations in MYO6. Three mutations (p.R825X, p.R991X and Q918fsX941) produce a premature truncation of the myosin VI protein. Another mutation, p.R205Q, was associated with diminished actin-activated ATPase activity and actin gliding velocity of myosin VI in an in vitro analysis. This finding is consistent with the results of protein modelling studies and corroborates the pathogenicity of this mutation in the MYO6 gene. One missense variant, p.R544W, was found in the MYO1A gene, and in silico analysis suggested that this variant has deleterious effects on protein function. This finding is consistent with the results of protein modelling studies and corroborates the pathogenic effect of this mutation in the MYO6 gene.
Void-mediated coherency-strain relaxation and impediment of cubic-to-hexagonal transformation in epitaxial metastable metal/semiconductor <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mrow><mml:mi>TiN</mml:mi><mml:mtext>/</mml:mtext><mml:mi mathvariant="normal">A</mml:mi></mml:mrow><mml:msub><mml:mi mathvariant="normal">l</mml:mi><mml:mrow><mml:mn>0.72</mml:mn></mml:mrow></mml:msub><mml:mi mathvariant="normal">S</mml:mi><mml:msub><mml:mi mathvariant="normal">c</mml:mi><mml:mrow><mml:mn>0.28</mml:mn></mml:mrow></mml:msub><mml:mi mathvariant="normal">N</mml:mi></mml:mrow></mml:math> multilayers (2017)

Bulk metastable phases can be stabilized during thin-film growth by employing substrates with similar crystal structure and lattice parameter, albeit over a thickness range limited by coherency-strain relaxation. Expanding that strategy, growth of superlattices comprising one stable and another metastable compound with similar crystal structure and lattice parameters are known to yield epitaxial stabilization over a few nanometers of thickness. In this work, the high-pressure rocksalt (B1) phase of $\mathrm{A}{\mathrm{l}}_{0.72}\mathrm{S}{\mathrm{c}}_{0.28}\mathrm{N}$ was stabilized epitaxially in a multilayer with TiN with thicknesses of up to 26 nm. In order to investigate the microstructural changes leading to the phase transformation of the metastable B1 phase to its wurtzite allomorph, we demonstrate a design based on a multilayer architecture with systematically varying thicknesses of the metastable compound within a constant-thickness lattice of stable metallic TiN with the cubic rocksalt structure. The multilayer films show an increasing hardness and elastic modulus for decreasing period thickness, in correspondence with both coherency-strain and Koehler hardening. The phase transition is accompanied by an increase of lattice strain with increasing multilayer periods, and resulting ultimately in coherency-strain relaxation upon phase transformation. Further, we show that the phase transformation is mediated by voids decorating the ${130}$ planes that separate regions of different growth rates and act as additional growth fronts for wurtzite growth during the phase transformation. The TiN/(Al,Sc)N interfaces themselves remain atomically sharp and smooth until the interface structure roughens along with the epitaxial rocksalt to wurtzite transition of (Al,Sc)N. These results show the strong influence of the voids on controlling the target thickness of epitaxially stabilized thin-film growth to the range relevant for applications, such as coatings, plasmonic materials, and electronic device technology, where the mechanical integrity of the material is critical.
A semi-analytical model of a near-field optical trapping potential well (2017)

A semi-analytical model is proposed to describe the force generated by a near-field optical trap. The model contains fitting parameters that can be adjusted to resemble a reference force-field. The model parameters for a plasmonic near-field trap consisting of a C-shaped engraving are determined using least squares regression. The reference values required for the regression analysis are calculated using the Maxwell stress tensor method. The speed and accuracy of the proposed model are compared with the conventional method. The model is found to be significantly faster with an acceptable level of accuracy.
ChemInform Abstract: Stereoselective Synthesis of 2,4,5‐Trisubstituted Piperidines by Carbonyl Ene and Prins Cyclizations. (2009)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Role of the Oxidative DNA Damage Repair Gene OGG1 in Colorectal Tumorigenesis (2013)

Biallelic inherited mutations in the oxidative DNA damage repair gene MUTYH predispose to colorectal adenomas and colorectal carcinoma (CRC) with high penetrance. We investigated whether rare inherited variants in other oxidative DNA damage repair genes predisposed to CRC. Single marker association analyses were assessed under an allelic model with Bonferroni correction for multiple testing. All statistical tests were two-sided. A rare inherited nonsynonymous variant in OGG1 (Gly308Glu), the functional partner of MUTYH, was over-represented in case patients with advanced CRC compared with population-based control subjects (n = 36 of 2142 case patients vs n = 15 of 2175 control subjects in the training phase, P = 1.8×10(-3); and n = 22 of 1005 case patients vs n = 8 of 1389 control subjects in the validation phase, P = 4.8×10(-4); P = 1.4×10(-5) combined; odds ratio = 2.92, 95% confidence interval = 1.80 to 4.74). Glycine at residue 308 was highly conserved through evolution, and the glutamic acid substitution was predicted as likely to interfere with function. Biallelic inherited and somatic OGG1 mutations were rarely observed in OGG1 (Gly308Glu) carriers, nor did we find any associated somatic mutator phenotype. These data suggest that OGG1 (Gly308Glu) may act as a low-penetrance allele that contributes to colorectal tumorigenesis.
Clinical Pearls (2009)

Prendergast and colleagues evaluated the oral health status of intubated patients in a neuroscience intensive care unit (ICU) through intubation and 48 hours after extubation, and described the effect of oral care on intracranial pressure (ICP). They found the following:See Article, pp 368–376The systemic inflammatory response syndrome (SIRS) is a severe hyperinflammatory condition frequently observed in critically ill patients. In this issue, NeSmith and colleagues show that the SIRS scores on ICU admission predicted ICU length of stay. The SIRS score is based on the SIRS criteria, where 1 point is assigned to each of 4 criteria:See Article, pp 339–347The relationship between oral care and ventilator-associated pneumonia (VAP) has gained much attention, primarily in adult medical and surgical (especially cardiac and trauma) populations, but there are fewer data in the neuroscience population (see above) and even less focus in pediatric patients. In this issue 2 articles address these underresearched populations. A team from Brazil, Pedreira and colleagues, evaluated the effect of chlorhexidine on the oropharyngeal microbiological profile, length of mechanical ventilation, and pediatric intensive care unit (PICU) length of stay.See Article, pp 319–329
Conservative Tibial Resection and Vertical Cut Minimise Risk of Tibial Plateau Fracture after UKR (2015)

Tibial fracture is a known complication after unicompartmental knee replacement (UKR) [1]. Furthermore, some studies have indicated an increased risk of tibial fracture with cementless UKR [2]. Our aim was to identify surgical factors that contribute to fracture. We examined the influence of tibial saw cuts on the risk of fracture after cementless UKR, to determine if changes in tibial preparation could minimise the risk of fracture. The range and distribution of typical saw cut positions were measured from 23 right tibial Sawbones used as part of an instructional course. Sawbones were prepared by both experienced and unexperienced orthopaedic surgeons but all had received training on the operative technique. Measured parameters were; resection depth, excessive vertical cut anterior/posterior, excessive horizontal cut anterior/posterior, pin depth and pin angle. One hundred finite element models were then created where each parameter was assigned using a random number generator within its measured distribution, and the risk of fracture assessed. Results from a multiple linear regression model indicated that a greater resection depth and a more excessive posterior vertical cut significantly increased the risk of fracture after UKR. Based upon these results, a surgical technique and instrumentation for UKR which minimises inaccuracies in the vertical cut and promotes a more conservative resection depth would be recommended to minimise the risk of tibial plateau fracture after UKR. [1] HG Pandit, DW Murray, CA Dodd, et al. (2007) Orthopedics 30: 28-31 [2] JB Seeger, D Haas, S Jager et al. (2012) Knee Surg Sports Traumatol Arthrosc 20: 1087-1091
A Conserved Family of WD-40 Proteins Binds to the Retinoblastoma Protein in Both Plants and Animals (1997)

Robert A. Ach, Patti Taranto, Wilhelm Gruissem, A Conserved Family of WD-40 Proteins Binds to the Retinoblastoma Protein in Both Plants and Animals, The Plant Cell, Vol. 9, No. 9 (Sep., 1997), pp. 1595-1606
Compressed sensing recovery using computational memory (2017)

Computational memory (CM) is a promising non-von Neumann approach where certain computational tasks are performed within resistive memory units by exploiting their physical attributes. We propose a new method for fast and robust compressed sensing (CS) recovery of sparse signals using CM. For a signal of size N, this method achieves a potential O(N)-fold complexity reduction compared with a standard software approach. Large-scale experimental demonstrations using more than 256k phase-change memory (PCM) devices are presented along with an in-depth device analysis and array-level considerations.
Helminth products modulate innate immune recognition of nucleic acids in systemic lupus erythematosus (2022)

Our data show that ABF has an immunomodulatory effect on the production of key cytokines in the pathogenesis of SLE. These results suggest that ABF or ABF components hold potential as a novel treatment option for SLE.
Lipoprotein Lipase S447X variant associated with VLDL, LDL and HDL diameter clustering in the MetS (2011)

This was the first study this kind to show an association between LPL and large VLDL particle size within the MetS, a pattern associated with higher IR. Future work should extend this to larger samples to confirm these findings, and examine the long term outcomes of those with this lipoprotein diameter pattern.