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For positive rank r elliptic curves E (Q) , we employ ideal class pairings E (Q) × E − D (Q) → CL (− D) , for quadratic twists E − D (Q) with a suitable "small y -height" rational point, to obtain explicit class number lower bounds that improve on earlier work by the authors. For the curves E (a) : y 2 = x 3 − a , with rank r (a) , this gives h (− D) ≥ 1 10 ⋅ | E tor (Q) | R Q (E) ⋅ π r (a) 2 2 r (a) Γ (r (a) 2 + 1) ⋅ log ⁡ (D) r (a) 2 log ⁡ log ⁡ D , representing a general improvement to the classical lower bound of Goldfeld, Gross and Zagier when r (a) ≥ 3. We prove that the number of twists E − D (a) (Q) with such a suitable point (resp. with such a point and rank ≥2 under the Parity Conjecture) is ≫ a , ε X 1 2 − ε. We give infinitely many cases where r (a) ≥ 6. These results can be viewed as an analogue of the classical estimate of Gouvêa and Mazur for the number of rank ≥2 quadratic twists, where in addition we obtain "log-power" improvements to the Goldfeld-Gross-Zagier class number lower bound. [ABSTRACT FROM AUTHOR]

Ideal class pairings map the rational points of rank r ≥ 1 elliptic curves E / Q to the ideal class groups CL (− D) of certain imaginary quadratic fields. These pairings imply that h (− D) ≥ 1 2 (c (E) − ε) (log ⁡ D) r 2 for sufficiently large discriminants − D in certain families, where c (E) is a natural constant. These bounds are effective, and they offer improvements to known lower bounds for many discriminants. [ABSTRACT FROM AUTHOR]

• Phosphonic acids were deposited onto four different platinum catalyst supports. • Deposited modifiers provide Brønsted acid sites, creating an acid-metal catalyst. • The strength of Brønsted acid sites is dependent on the modifier tail functionality. • On supports with weak or no Brønsted acidity, modifiers enhance deoxygenation. • On strongly acidic supports, modification leads to a loss of deoxygenation activity. Bifunctional catalysts comprised of both noble metal and Brønsted acid sites are of growing interest for many reactions, such as the hydrodeoxygenation (HDO) of oxygenates produced by the deconstruction of lignocellulosic biomass. One method of preparing a bifunctional metal-acid catalyst is to modify the supporting material of a metal catalyst with acid-containing ligands, such as phosphonic acids (PAs), which provide tunable Brønsted acid sites at the metal-support interface. Here, we explore the potential for PA modification to improve HDO rates on Al 2 O 3 , TiO 2 , CeO 2 , and SiO 2 -Al 2 O 3 supports. PAs containing either alkyl or carboxylic acid (CA) tails were used to modify Pt catalysts on each support. PA modification improved HDO rates for the model compound benzyl alcohol when applied to Pt supported by Al 2 O 3 , TiO 2 , and CeO 2 , but had a negative effect on the HDO rate of Pt/SiO 2 -Al 2 O 3. Measurements of the relative strength of Brønsted acid sites present on the modified and unmodified catalysts suggested that PAs improved HDO when they provided new or stronger Brønsted acid sites. Additionally, the strength of the Brønsted acid sites provided by PA modifiers were tunable by altering the tail functionality, which affected the rates of HDO. These results suggest that PAs can be used to modify a variety of supports to prepare bifunctional acid-metal catalysts. [ABSTRACT FROM AUTHOR]

We investigate ξ (s) = 1 2 s (s − 1) π − s 2 Γ (s 2) ζ (s) , where ζ (s) is the Riemann zeta function. The Riemann hypothesis (RH) asserts that if ξ (s) = 0 , then Re (s) = 1 2. Pólya proved that RH is equivalent to the hyperbolicity of the Jensen polynomials J d , n (X) constructed from certain Taylor coefficients of ξ (s). For each d ≥ 1 , recent work proves that J d , n (X) is hyperbolic for sufficiently large n. In this paper, we make this result effective. Moreover, we show how the low-lying zeros of the derivatives ξ (n) (s) influence the hyperbolicity of J d , n (X). [ABSTRACT FROM AUTHOR]

[Display omitted] • Small heat-shock proteins populate a monomer–dimer-oligomer equilibrium. • The alpha-crystallin domain binds at fibril ends to inhibit elongation. • Chaperone-activity is inhibited by disulfide crosslinking at the dimer interface. • Monomers of the alpha-crystallin domain are proposed to interact with fibril ends. Small heat-shock proteins (sHSPs) are ubiquitously expressed molecular chaperones present in all kingdoms of life that inhibit protein misfolding and aggregation. Despite their importance in proteostasis, the structure–function relationships of sHSPs remain elusive. Human sHSPs are characterised by a central, highly conserved α-crystallin domain (ACD) and variable-length N- and C-terminal regions. The ACD forms antiparallel homodimers via an extended β-strand, creating a shared β-sheet at the dimer interface. The N- and C-terminal regions mediate formation of higher order oligomers that are thought to act as storage forms for chaperone-active dimers. We investigated the interactions of the ACD of two human sHSPs, αB-crystallin (αB-C) and Hsp27, with apolipoprotein C-II amyloid fibrils using analytical ultracentrifugation and nuclear magnetic resonance spectroscopy. The ACD was found to interact transiently with amyloid fibrils to inhibit fibril elongation and naturally occurring fibril end-to-end joining. This interaction was sensitive to the concentration of fibril ends indicating a 'fibril-capping' interaction. Furthermore, resonances arising from the ACD monomer were attenuated to a greater extent than those of the ACD dimer in the presence of fibrils, suggesting that the monomer may bind fibrils. This hypothesis was supported by mutagenesis studies in which disulfide cross-linked ACD dimers formed by both αB-C and Hsp27 were less effective at inhibiting amyloid fibril elongation and fibril end-to-end joining than ACD constructs lacking disulfide cross-linking. Our results indicate that sHSP monomers inhibit amyloid fibril elongation, highlighting the importance of the dynamic oligomeric nature of sHSPs for client binding. [ABSTRACT FROM AUTHOR]

A majority of well pads for unconventional gas wells that are drilled into the Marcellus shale (northeastern USA) consist of multiple wells (in some cases as many as 12 wells per pad), yet the influence of the evolution of well pad development on the extent of environmental violations and wastewater production is unknown. Although the development of multi-well pads (MWP) at the expense of single well pads (SWP) has been mostly driven by economic factors, the concentrated nature of drilling activities from hydraulic fracturing and horizontal drilling operations on MWP suggests that MWP may create less surface disturbance, produce more volumes of wastewater, and generate more environmental violations than SWP. To explore these hypotheses, we use geospatial techniques and statistical analyses (i.e., regression and Mann–Whitney tests) to assess development of unconventional shale gas wells, and quantify environmental violations and wastewater volumes on SWP and MWP in Pennsylvania. The analyses include assessments of the influence of different types of well pads on potential, minor and major environmental events. Results reveal that (a) in recent years, a majority of pads on which new wells for unconventional gas were drilled are MWP, (b) on average, MWP have about five wells located on each pad and thus, had the transition to MWP not occurred, between two and four times as much land surface disturbance would have occurred per year if drilling was relegated to SWP, (c) there were more environmental violations on MWP than SWP, but when the number of wells were taken into account, fewer environmental violations per well were observed on MWP than on SWP, (d) there were more wastewater and recycled wastewater volumes per pad and per well produced on MWP than on SWP, and (e) the proportion of wastewater that was recycled was higher on MWP than SWP. This study sheds light on how the evolution from SWP to MWP has influenced environmental violations and wastewater production in a field that has undergone rapid development in recent years. [Copyright &y& Elsevier]

Interleukin-11 (IL-11) is a cytokine that has been strongly implicated in the pathogenesis of fibrotic diseases and solid malignancies. Elevated IL-11 expression is also associated with several non-malignant inflammatory diseases where its function remains less well-characterized. Here, we summarize current literature surrounding the contribution of IL-11 to the pathogenesis of autoimmune inflammatory diseases, including rheumatoid arthritis, multiple sclerosis, diabetes and systemic sclerosis, as well as other chronic inflammatory conditions such as periodontitis, asthma, chronic obstructive pulmonary disease, psoriasis and colitis. [ABSTRACT FROM AUTHOR]

[Display omitted] • H2 relaxin has distinct and unique binding sites for RXFP1 and RXFP2. • Both the LDLa module and linker of RXFP1 and RXFP2 are essential for activation. • A conserved motif in the linker adopts different structures in RXFP1 and RXFP2. • These differences lead to distinct mechanisms for relaxin-induced activation. Our poor understanding of the mechanism by which the peptide-hormone H2 relaxin activates its G protein coupled receptor, RXFP1 and the related receptor RXFP2, has hindered progress in its therapeutic development. Both receptors possess large ectodomains, which bind H2 relaxin, and contain an N-terminal LDLa module that is essential for receptor signaling and postulated to be a tethered agonist. Here, we show that a conserved motif (GDxxGWxxxF), C-terminal to the LDLa module, is critical for receptor activity. Importantly, this motif adopts different structures in RXFP1 and RXFP2, suggesting distinct activation mechanisms. For RXFP1, the motif is flexible, weakly associates with the LDLa module, and requires H2 relaxin binding to stabilize an active conformation. Conversely, the GDxxGWxxxF motif in RXFP2 is more closely associated with the LDLa module, forming an essential binding interface for H2 relaxin. These differences in the activation mechanism will aid drug development targeting these receptors. [ABSTRACT FROM AUTHOR]