gebhart/patrepeval huggingface dataset:
Of Mitochondrial Eve and Steve (2015)

Maternal inheritance of mitochondria and their genes is a developmental paradigm sometimes referred to as The Mitochondrial Eve.Propagation of paternal-sperm-contributed mitochondrial genes, resulting in heteroplasmy, is seldom observed in mammals due to post-fertilization targeting and degradation of sperm mitochondria, referred to as "sperm mitophagy".Early observations suggested that sperm mitophagy utilized the ubiquitin proteasome system (UPS), the major protein-turnover pathway that degrades proteins one molecule at the time rather than removing them in bulk or as a part of whole-organelle degradation (Sutovsky et al. 1999.Nature 25:371-2).Yet how can a single-molecule proteolytic pathway degrade dozens of sperm mitochondria inside a fertilized oocyte?Recent studies in insect and nematode models have provided the missing link between UPS and autophagic machinery that is responsible for removal of damaged organelles via authophagyassociated ubiquitin-receptor proteins and ubiquitin-like protein modifi ers (reviewed by
ChemInform Abstract: Task‐Specific Ionic Liquids for the Extraction of Metal Ions from Aqueous Solutions (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.
Degeneration Patterns in the Organ of Corti and Spiral Lamina (1987)

The relation between organ of Corti degeneration and radial nerve fibre degeneration in the osseous spiral lamina was studied in two human cochleas.
Extraction of Silver by Glucose (2016)

Unprecedented silver ion leaching, in the range of 0.7 ppm was seen when metallic silver was heated in water at 70 °C in presence of simple carbohydrates, such as glucose, making it a green method of silver extraction. Extraction was facilitated by the presence of anions, such as carbonate and phosphate. Studies confirm a two-step mechanism of silver release, first forming silver ions at the metal surface and later complexation of ionic silver with glucose; such complexes have been detected by mass spectrometry. Extraction leads to microscopic roughening of the surface making it Raman active with an enhancement factor of 5×10(8) .
ChemInform Abstract: DDQ Oxidation of Ring‐A Methoxylated 11b‐Methoxycarbonyl‐2,3,5,6,11, 11b‐hexahydro‐3‐oxo‐1H‐indolizino(8,7‐b)indoles. (1992)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.
Markers of Accelerated Skeletal Muscle Regenerative Response in Murphy Roths Large Mice: Characteristics of Muscle Progenitor Cells and Circulating Factors (2018)

The "super-healing" Murphy Roths Large (MRL/MpJ) mouse possesses a superior regenerative capacity for repair of many tissues, which makes it an excellent animal model for studying molecular and cellular mechanisms during tissue regeneration. As the role of muscle progenitor cells (MPCs) in muscle-healing capacity of MRL/MpJ mice has not been previously studied, we investigated the muscle regenerative capacity of MRL/MpJ mice following muscle injury, and the results were compared to results from C57BL/6J (B6) age-matched control mice. Our results show that muscle healing upon cardiotoxin injury was accelerated in MRL/MpJ mice and characterized by reduced necrotic muscle area, reduced macrophage infiltration, and more regenerated myofibers (embryonic myosin heavy chain+/centronucleated fibers) at 3, 5, and 12 days postinjury, when compared to B6 age-matched control mice. These observations were associated with enhanced function of MPCs, including improved cell proliferation, differentiation, and resistance to stress, as well as increased muscle regenerative potential when compared to B6 MPCs. Mass spectrometry of serum proteins revealed higher levels of circulating antioxidants in MRL/MpJ mice when compared to B6 mice. Indeed, we found relatively higher gene expression of superoxide dismutase 1 (Sod1) and catalase (Cat) in MRL/MpJ MPCs. Depletion of Sod1 or Cat by small interfering RNA impaired myogenic potential of MRL/MpJ MPCs, indicating a role for these antioxidants in muscle repair. Taken together, these findings provide evidence that improved function of MPCs and higher levels of circulating antioxidants play important roles in accelerating muscle-healing capacity of MRL/MpJ mice. Stem Cells 2019;37:357-367.
Tension wood provides insight into structural changes in biomass resulting from chemical pretreatment (2018)

Plant cell walls comprise the bulk of lignocellulosic biomass. Therefore, a greater understanding of the chemistry, architecture, physical and mechanical properties of cell walls is essential to improve biomass-based biofuel production. The work presented here furthers understanding of biomass properties underlying recalcitrance to enzyme-based sugar (ethanol substrate) release. The spatiotemporal progression in chemical and anatomical changes that occur in growing plants under tension stress is investigated. An earlier neutron diffraction study of hydrogenated and partially deuterated poplar tension wood found that, unlike fibers from the ramie plant, the characteristic diffraction peaks were not present. The authors postulated that the contribution of laterally aligned microfibrils complicated the signal from the majority of the microfibrils, which are longitudinally aligned, but did not further investigate the tension wood structure. Here, we report structural studies of tension wood using small-angle neutron scattering at the Bio-SANS instrument. We used intact microtomed samples of normal and tension wood that resulted in anisotropic scattering. A crystalline core (Rg = 10 ~ 11 ) is observed for normal wood. 2 Meanwhile, the tension side showed evidence of different levels of associations between elementary fibrils, forming different aggregate sizes. Most interestingly, these aggregates are multiples of the elementary fibril. This propensity to associate due to the application of mechanical stress (also called tension) produces identical effects on the plant nanostructure as observed during most thermochemical pretreatments, especially dilute acid pretreatment.
The first oasts and hop kilns in England (2021)

Evidence of hops imported from Continental Europe for brewing in England at least 100 years before hop growing introduced in Kent by Huguenot refugees from the Low Countries. Disputes about flavouring ale with hops. Evidence from 16<sup>th</sup> century books, notably Scot A Perfecte Platorme of a Hoppe Garden, about the design and building of the first oasts. Surviving examples at Golford near Cranbrook, Kent match the books well. Plans of these oasts as they were in 1960. Rapid expansion of beer drinking drove need for new oasts. The differences between hop oasts and malt kilns.
Flt3 ligand expands CD4+FoxP3+ regulatory T cells in human subjects (2012)

CD4(+) CD25(+) FoxP3(+) naturally occurring regulatory T (Treg) cells play a crucial role in the maintenance of immune tolerance and in preventing autoimmune pathology. Interventions that expand Treg cells are highly desirable, as they may offer novel treatment options in a variety of autoimmune and transplantation settings. Paralleling previous preclinical studies, we demonstrate here that administration of the hematopoietic growth factor Flt3L to human subjects increases the frequency and absolute number of Treg cells, and reduces the ratio of CD8(+) T cells to Treg cells in the peripheral blood. The increase in Treg cells was due to enhanced Treg-cell proliferation rather than release of Treg cells from the thymus. Further studies revealed that Flt3L-induced proliferation of Treg cells was an indirect effect that occurred via the interaction of Treg cells with the Flt3L-expanded pool of CD1c(+) myeloid dendritic cells. On the basis of these findings, Flt3L may represent a promising agent for promoting immune tolerance in a variety of clinical settings.
Volcanic activities triggered or inhibited by resonance of volcanic edifices to large earthquakes (2019)

The existence of a causal link between large earthquakes and volcanic unrest is widely accepted. Recent observations have also revealed counterintuitive negative responses of volcanoes to large earthquakes, including decreased gas emissions and subsidence in volcanic areas. In order to explore the mechanisms that could simultaneously explain both the positive and negative responses of volcanic activity to earthquakes, we here focus on the role played by topography. In the laboratory, we shook a volcanic edifice analogue, made of gel, previously injected with a buoyant fluid. We find that shaking triggers rapid migration of the buoyant fluid upward, downward, or laterally, depending on the fluid’s buoyancy and storage depth; bubbly fluids stored at shallow depth ascend, while low-buoyancy fluids descend or migrate laterally. The migration of fluids induced by shaking is two orders of magnitude faster than without shaking. Downward or lateral fluid migration may decrease volcanic gas emissions and cause subsidence as a negative response, while upward migration is consistent both with an increase in volcanic activity and immediate unrest (deformation and seismicity) after large earthquakes. The fluid migration is more efficient when the oscillation frequency is close to the resonance frequency of the edifice. The resonance frequency for a 30-km-wide volcanic mountain range, such as those where subsidence was observed, is ∼0.07 Hz. Only large earthquakes are able to cause oscillation at such low frequencies.
Structure of the GcpE (IspG)–MEcPP complex from Thermus thermophilus (2012)

Isoprenoid precursor biosynthesis occurs through the mevalonate or the methylerythritol phosphate (MEP) pathway, used i.e., by humans and by many human pathogens, respectively. In the MEP pathway, 2‐ C ‐methyl‐ d ‐erythritol‐2,4‐cyclo‐diphosphate (MEcPP) is converted to ( E )‐1‐hydroxy‐2‐methyl‐but‐2‐enyl‐4‐diphosphate (HMBPP) by the iron–sulfur cluster enzyme HMBPP synthase (GcpE). The presented X‐ray structure of the GcpE–MEcPP complex from Thermus thermophilus at 1.55 Å resolution provides valuable information about the catalytic mechanism and for rational inhibitor design. MEcPP binding inside the TIM‐barrel funnel induces a 60° rotation of the [4Fe–4S] cluster containing domain onto the TIM‐barrel entrance. The apical iron of the [4Fe–4S] cluster ligates with the C3 oxygen atom of MEcPP.
Assessment of the persistence of anacetrapib and evacetrapib concentrations using two pharmacokinetic modeling approaches (2015)

Anacetrapib, a cholesterol ester transfer protein (CETP) inhibitor, has been reported to have longer elimination half-life after longer treatment. Two pharmacokinetic model-based approaches were used to assess whether evacetrapib, another CETP inhibitor, could behave similarly. Using population pharmacokinetic (PopPK) modeling, evacetrapib and anacetrapib pharmacokinetics were characterized using available concentration-time data, and steady-state conditions were simulated. Published 2-compartment models for each compound were adapted to include a hypothetical third compartment representing a depot into which drug could partition. Physiologically based pharmacokinetic (PBPK) modeling was used to predict steady-state conditions and terminal half-life based on known physicochemical and dispositional properties. The PopPK model described the anacetrapib data well, showing a likely third compartment with estimated apparent volume of 40,700 L. Anacetrapib's estimated half-life for this compartment was 550 days. Simulations for evacetrapib using a hypothetical 3-compartment model, the third compartment being consistent with that of the anacetrapib model, produced predictions inconsistent with reported results, indicating that evacetrapib did not substantially accumulate into a large compartment. The PBPK simulations were consistent with PopPK results, predicting accumulation for anacetrapib (but not evacetrapib) followed by very slow elimination. Based on available data and known physicochemical properties, evacetrapib is not expected to accumulate substantially during long-term treatment.
2-MPPA, a selective inhibitor of PSMA, delays prostate cancer growth and attenuates taxol-induced neuropathy in mice (2005)

8054 Background: Docetaxel is a standard of care treatment for patients with progression castration resistant prostate cancer, from which peripheral neuropathy may be dose limiting. A selective inhibitor of PSMA, termed 2-(3-mercaptopropyl) pentanedioic acid (2-MPPA), both prevents and reverses taxol-induced neuropathy in murine models, as indicated by deficits in sensory nerve conduction velocity (SNCV). 2-MPPA, a potent (IC50 of 90 nM) and selective inhibitor of glutamate carboxypeptidase (GCPII), also known as PSMA or NAALADase was also able to delay tumor growth in a prostate cancer model expressing high levels of PSMA. Of importance, there was no change in efficacy when taxol was administered with 2-MPPA in this model. Methods: Neuropathy: Female DBA2 mice received 5 mg/kg taxol (5 i.p. doses in two weeks) or 25 mg/kg taxol (4 i.p. doses in two weeks) with daily 30 mg/kg 2-MPPA or vehicle. Neuropathy was indicated by a SNCV deficit compared to baseline (pre-chemotherapy) values. Cancer: nu/nu mice with or with out testosterone supplements were inoculated with CWR22 or CWR22RS tumor. When tumors reached 50mm3, mice were dosed with 2-MPPA (10 to 750 mg/kg) bid PO for two weeks and tumor volume was monitored. Results: 2-MPPA significantly prevented the deficit in SNCV induced by both 5 and 25 mg/kg taxol by 96.3 ± 4.4% and 98.3± 11.6% respectively (p<0.001). Moreover, 7-day p.o. treatment with 30 mg/kg 2-MPPA given after a persistent SNCV deficit was established reversed the decline in SNCV by 98.3±8.0% (p<0.05). Peripheral nerve histopathology evaluations are ongoing. In a separate study, 10 mg/kg 2-MPPA inhibited tumor growth in the high expressor PSMA model CWR22RS by 70% (p<0.03). Lastly, 2-MPPA was dosed concomitantly with a therapeutic dose of taxol in the hormone-dependent model of prostate cancer, CWR22, and no effect on taxol efficacy was observed. Conclusions: Inhibition of GCPII/PSMA may have a therapeutic potential both as an anti-cancer agent, as well as to reduce chemotherapy-induced neuropathy No significant financial relationships to disclose.
Correlation of pncA Sequence with Pyrazinamide Resistance Level in BACTEC™ for 21 Mycobacterium tuberculosis Clinical Isolates (2000)

Mutations in the pncA gene, encoding pyrazinamidase, are considered the major mechanism of pyrazinamide (PZA) resistance in Mycobacterium tuberculosis, but resistant strains containing the wild-type gene have been described. The correlation of pncA sequence with PZA resistance level was examined for 21 M. tuberculosis clinical isolates. Susceptibility patterns were determined for 100, 300, and 900 microg/ml concentrations of the drug in BACTEC. Insertions and deletions and a substitution in the putative promoter region led to high-level resistance, whereas substitutions within the open reading frame seemed to confer variable levels of resistance. Variable resistance levels and PZase activities were also observed among isolates lacking pncA mutations. The high-level resistance (900 microg/ml) in pncA wild-type isolates highlights the clinical significance of these isolates. These data also suggest that there may still be more than one alternative mechanism leading to PZA resistance in M. tuberculosis isolates.
The Moraxella catarrhalis phase-variable DNA methyltransferase ModM3 is an epigenetic regulator that affects bacterial survival in an in vivo model of otitis media (2019)

Phase variation of ModM3 epigenetically regulates the expression of a phasevarion containing multiple genes that are potentially important in the progression of otitis media.
Reverse recovery failure modes in modern fast recovery diodes (2002)

In this paper, reverse recovery failure modes in modern fast power diodes are investigated. By the aid of semiconductor device simulation tools, a better view is obtained for the physical process, and operating conditions at which both diode snappy recovery and dynamic avalanching phenomenas occur during the recovery period in modern high frequency power electronic applications. The paper shows that the control of the carrier gradient and the remaining stored charge in the drift region during the recovery phase influence both failure modes and determine if the diode exhibits a soft, snappy or dynamic avalanche recovery characteristics.
Cloned receptors and cardiovascular responses to adenosine (1993)

Four subtypes of adenosine receptors have recently been cloned from thyroid, brain and testis. In this review we have summarised properties of these purinergic receptors. The cloned A1 and A2 subtypes are probably similar or identical to receptors that exist on cardiac and vascular tissues, respectively. A comparison of the amino acid sequences of A1, A2a, and A2b receptors reveals several stretches of conserved amino acids that are unique to adenosine receptors, primarily in the membrane spanning regions. Species differences in A1 receptors indicate that minor changes in receptor structure can produce marked changes in ligand binding properties and may facilitate the identification of amino acids involved in ligand recognition. A confusing A1 receptor subclassification system of putative A1a, A1b, and A3 subtypes has emerged based on subtle rank order potency differences for various ligands among tissues. cDNAs corresponding to these A1 subtypes have not yet been isolated. Atrial A1 receptors activate K+ channels and inhibit adenylyl cyclase. These two pathways appear to be independently up and down regulated, suggesting the existence either of atrial A1 receptor subtypes or of differential regulation of the coupling of a single receptor to distinct GTP binding proteins. An adenosine receptor distinct from A1 and A2 receptors has been cloned from testis and designated TGPCR, or A3, although it differs from the pharmacologically defined A3 receptor. We suggest that the current A1/A3 receptor subtype nomenclature be abandoned and superseded by a nomenclature based solely on receptor cDNAs. In addition to the cloned adenosine receptors, a novel A4 subtype has been proposed based on pharmacological and electrophysiological criteria.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibitors of cullin-RING E3 ubiquitin ligase 4 with antitumor potential (2021)

Cullin-RING (really intersting new gene) E3 ubiquitin ligases (CRLs) are the largest E3 family and direct numerous protein substrates for proteasomal degradation, thereby impacting a myriad of physiological and pathological processes including cancer. To date, there are no reported small-molecule inhibitors of the catalytic activity of CRLs. Here, we describe high-throughput screening and medicinal chemistry optimization efforts that led to the identification of two compounds, 33-11 and KH-4-43, which inhibit E3 CRL4 and exhibit antitumor potential. These compounds bind to CRL4's core catalytic complex, inhibit CRL4-mediated ubiquitination, and cause stabilization of CRL4's substrate CDT1 in cells. Treatment with 33-11 or KH-4-43 in a panel of 36 tumor cell lines revealed cytotoxicity. The antitumor activity was validated by the ability of the compounds to suppress the growth of human tumor xenografts in mice. Mechanistically, the compounds' cytotoxicity was linked to aberrant accumulation of CDT1 that is known to trigger apoptosis. Moreover, a subset of tumor cells was found to express cullin4 proteins at levels as much as 70-fold lower than those in other tumor lines. The low-cullin4-expressing tumor cells appeared to exhibit increased sensitivity to 33-11/KH-4-43, raising a provocative hypothesis for the role of low E3 abundance as a cancer vulnerability.
Ligand-Accelerated Stereoretentive Suzuki–Miyaura Coupling of Unprotected 3,3′-Dibromo-BINOL (2016)

An efficient synthesis of the enantiomerically pure 3,3'-bis-arylated BINOL derivatives is accomplished through the palladium-catalyzed Suzuki-Miyaura coupling of the unprotected 3,3'-dibromo-BINOL with complete retention of enantiopurity. The active catalyst system Pd(OAc)2/BI-DIME has enabled mild reaction conditions at palladium loads as low as 500 ppm.
Bio‐Based Aliphatic Polyurethanes Through ADMET Polymerization in Bulk and Green Solvent (2013)

A new route to α,ω-diene urethane monomer is proposed by converting 10-undecenoic acid into the corresponding acyl azide, followed by urethanization with 10-undecenol. ADMET polymerizations of this α,ω-diene urethane monomer as well as other bio-based α,ω-dienes bearing various organic functions (ester, carbonate, ether, amide) were carried out in bulk and solution conditions. A screening of the most commonly used metathesis catalysts allows to evaluate their tolerance toward the urethane function as well as toward Polarclean, a "green" and nontoxic high boiling point solvent. The influence of the nature of the central organic function in these α,ω-diene monomers on the thermomechanical properties is investigated.
Combined inhibition of MEK and nuclear ERK translocation has synergistic antitumor activity in melanoma cells (2017)

Genetic alterations in BRAF, NRAS and NF1 that activate the ERK cascade, account for over 80% of metastatic melanomas. However, ERK cascade inhibitors have been proven beneficial almost exclusively for BRAF mutant melanomas. One of the hallmarks of the ERK cascade is the nuclear translocation of ERK1/2, which is important mainly for the induction of proliferation. This translocation can be inhibited by the NTS-derived peptide (EPE) that blocks the ERK1/2-importin7 interaction, inhibits the nuclear translocation of ERK1/2, and arrests active ERK1/2 in the cytoplasm. In this study, we found that the EPE peptide significantly reduced the viability of not only BRAF, but also several NRAS and NF1 mutant melanomas. Importantly, combination of the EPE peptide and trametinib showed synergy in reducing the viability of some NRAS mutant melanomas, an effect driven by the partial preservation of negative feedback loops. The same combination significantly reduced the viability of other melanoma cells, including those resistant to mono-treatment with EPE peptide and ERK cascade inhibitors. Our study indicates that targeting the nuclear translocation of ERK1/2, in combination with MEK inhibitors can be used for the treatment of different mutant melanomas.