Higher Binding Affinity and In Vitro Potency of Reslizumab for Interleukin-5 Compared With Mepolizumab

Mark Liddament,Jean Husten,Tanya Estephan,David Laine,David Mabon,Laurie Pukac,Jacquelyn Lyons,Adam W. Clarke,Anthony Doyle 대한천식알레르기학회 2019 Allergy, Asthma & Immunology Research Vol.11 No.2

Reslizumab and mepolizumab are recently approved monoclonal antibodies for the treatment of severe (uncontrolled) eosinophilic asthma. Both are effective in neutralizing the function of interleukin-5 (IL-5). This study is the first to compare the binding affinity and in vitro potency of both antibodies in head-to-head assays. Two assays assessed binding affinity (using the equilibrium dissociation constant [KD]) of each drug for human IL-5. In the Biacore surface plasmon resonance assay, the association constant (kon) values for human IL-5 for reslizumab and mepolizumab were 3.93 × 106 and 1.83 × 105, respectively. The dissociation constant (koff) values were 4.29 × 10−4 and 2.14 × 10−4, respectively. Calculated KD values for human IL-5 for reslizumab and mepolizumab were 109 and 1,170 pM, respectively, representing an approximately 11-fold stronger binding affinity with reslizumab. In the Kinetic Exclusion Assay, the kon values for human IL-5 for reslizumab and mepolizumab were 3.17 × 106 and 1.32 × 105, respectively. The koff values were 1.36 × 10−5 and 1.48 × 10−5, respectively. Measured KD values for human IL-5 for reslizumab and mepolizumab were 4.3 and 112 pM, respectively, representing an approximately 26-fold stronger binding affinity for reslizumab. A human-IL-5-dependent cell proliferation assay was developed to assess in vitro potency, based on a human cell line selected for enhanced surface expression of IL-5 receptor-alpha and consistent proliferation response to IL-5. The concentration at which 50% inhibition occurred (IC50) was determined for both antibodies. Reslizumab and mepolizumab inhibited IL-5-dependent cell proliferation, with IC50 values of approximately 91.1 and 286.5 pM, respectively, representing on average 3.1-fold higher potency with reslizumab. In conclusion, comparative assays show that reslizumab has higher affinity binding for and in vitro potency against human IL-5 compared with mepolizumab. However, these results do not take into consideration the different methods of administration of reslizumab and mepolizumab.

Are tropical butterflies more colorful?

Adams, Jonathan M.,Kang, Changku,June‐,Wells, Mark Springer Japan 2014 Ecological research Vol.29 No.4

<P><B>Abstract</B></P><P>There is a common and long‐standing belief that tropical butterflies are more striking in their coloration than those of cooler climates. It has been suggested that this is due to more intense biotic selection or mate selection in the tropics. We tested whether there were differences in coloration by examining the dorsal surface color properties of male butterflies from three regions of the western hemisphere: the Jatun‐Satcha Reserve in lowland Ecuador (tropical), the state of Florida, USA (subtropical) and the state of Maine, USA (cool temperate). We digitally photographed the dorsal wing and body surface of male butterfly specimens from Maine, Florida, and Ecuador. For each photograph, we analyzed the mean and variation for the color‐parameters that are thought to be related to colorfulness; namely Hue, saturation and intensity. Overall, the Ecuadorian sample exhibited more varied intensity, saturation, and Hue compared to the other regions. These results suggest a more complex assemblage of colors and patterns regionally and on a butterfly‐by‐butterfly basis in the tropics. The greater complexity of colors within each butterfly in our Ecuadorian sample suggests that tropical butterflies are indeed more ‘colorful’, at least by some measures. Possible reasons for this include stronger predation pressure selecting for aposematism, greater species diversity selecting for camouflage or warning coloration against potential predators, and easier recognition of potential mates in a species rich environment.</P>

Multimessenger observations of a flaring blazar coincident with high-energy neutrino IceCube-170922A

Aartsen, Mark,Ackermann, Markus,Adams, Jenni,Aguilar, Juan Antonio,Ahlers, Markus,Ahrens, Maryon,Al Samarai, Imen,Altmann, David,Andeen, Karen,Anderson, Tyler,Ansseau, Isabelle,Anton, Gisela,Argü American Association for the Advancement of Scienc 2018 Science Vol.361 No.6398

<P>Previous detections of individual astrophysical sources of neutrinos are limited to the Sun and the supernova 1987A, whereas the origins of the diffuse flux of high-energy cosmic neutrinos remain unidentified. On 22 September 2017, we detected a high-energy neutrino, IceCube-170922A, with an energy of ~290 tera-electron volts. Its arrival direction was consistent with the location of a known γ-ray blazar, TXS 0506+056, observed to be in a flaring state. An extensive multiwavelength campaign followed, ranging from radio frequencies to γ-rays. These observations characterize the variability and energetics of the blazar and include the detection of TXS 0506+056 in very-high-energy γ-rays. This observation of a neutrino in spatial coincidence with a γ-ray-emitting blazar during an active phase suggests that blazars may be a source of high-energy neutrinos.</P>

Reducing the Burden on the Poor: Household Costs of Basic Education in Gansu, China

Don Adams,Mark Bray,Ding Xiaohao,Huang Ping 서울대학교 교육연구소 2005 Asia Pacific Education Review Vol.6 No.2

Neutrino emission from the direction of the blazar TXS 0506+056 prior to the IceCube-170922A alert

Aartsen, Mark,Ackermann, Markus,Adams, Jenni,Aguilar, Juan Antonio,Ahlers, Markus,Ahrens, Maryon,Al Samarai, Imen,Altmann, David,Andeen, Karen,Anderson, Tyler,Ansseau, Isabelle,Anton, Gisela,Arguelles American Association for the Advancement of Scienc 2018 Science Vol.361 No.6398

<P><B>Neutrino emission from a flaring blazar</B></P><P>Neutrinos interact only very weakly with matter, but giant detectors have succeeded in detecting small numbers of astrophysical neutrinos. Aside from a diffuse background, only two individual sources have been identified: the Sun and a nearby supernova in 1987. A multiteam collaboration detected a high-energy neutrino event whose arrival direction was consistent with a known blazar—a type of quasar with a relativistic jet oriented directly along our line of sight. The blazar, TXS 0506+056, was found to be undergoing a gamma-ray flare, prompting an extensive multiwavelength campaign. Motivated by this discovery, the IceCube collaboration examined lower-energy neutrinos detected over the previous several years, finding an excess emission at the location of the blazar. Thus, blazars are a source of astrophysical neutrinos.</P><P><I>Science</I>, this issue p. 147, p. eaat1378</P><P>A high-energy neutrino event detected by IceCube on 22 September 2017 was coincident in direction and time with a gamma-ray flare from the blazar TXS 0506+056. Prompted by this association, we investigated 9.5 years of IceCube neutrino observations to search for excess emission at the position of the blazar. We found an excess of high-energy neutrino events, with respect to atmospheric backgrounds, at that position between September 2014 and March 2015. Allowing for time-variable flux, this constitutes 3.5σ evidence for neutrino emission from the direction of TXS 0506+056, independent of and prior to the 2017 flaring episode. This suggests that blazars are identifiable sources of the high-energy astrophysical neutrino flux.</P>

Use of Reverse Genetics to Enhance the Oncolytic Properties of Newcastle Disease Virus

Vigil, Adam,Park, Man-Seong,Martinez, Osvaldo,Chua, Mark A.,Xiao, Sa,Cros, Jerome F.,Martí,nez-Sobrido, Luis,Woo, Savio L.C.,Garcí,a-Sastre, Adolfo American Association for Cancer Research 2007 Cancer research Vol.67 No.17

<P>Naturally occurring strains of Newcastle disease virus (NDV) have shown oncolytic therapeutic efficacy in preclinical studies and are currently in clinical trials. Here, we have evaluated the possibility to enhance the cancer therapeutic potential of NDV by means of reverse genetics. Mice bearing s.c. implanted CT26 tumors were treated with intratumoral (i.t.) injections of a recombinant NDV modified to contain a highly fusogenic F protein. These treated mice exhibited significant reduction in tumor development compared with mice treated with the unmodified virus. Furthermore, mice in a CT26 metastatic tumor model treated with an i.v. injection of the genetically engineered NDV exhibited prolonged survival compared with wild-type control virus. In addition, we examined whether the oncolytic properties of NDV could be improved by expression of immunostimulatory molecules. In this regard, we engineered several NDVs to express granulocyte macrophage colony-stimulating factor, IFN-gamma, interleukin 2 (IL-2), or tumor necrosis factor alpha, and evaluated their therapeutic potential in an immunocompetent colon carcinoma tumor model. Mice bearing s.c. CT26 tumors treated with i.t. injections of recombinant NDV expressing IL-2 showed dramatic reductions in tumor growth, with a majority of the mice undergoing complete and long-lasting remission. Our data show the use of reverse genetics to develop enhanced recombinant NDV vectors as effective therapeutic agents for cancer treatment.</P>

An alternative to cyanide leaching of waste activated carbon ash for gold and silver recovery via synergistic dual-lixiviant treatment

Charlie R. Adams,Christopher P. Porter,Thomas J. Robshaw,James P. Bezzina,Victoria R. Shields,Alan Hides,Richard Bruce,Mark D. Ogden 한국공업화학회 2020 Journal of Industrial and Engineering Chemistry Vol.92 No.-

This study reports the development of a hydrometallurgical treatment for activated carbon ash (ACA); awaste product of the carbon-in-pulp (CIP) process used in the gold mining industry, rich in adsorbedprecious metals. After an initial screening of known leaching chemistries, the research focusses on duallixiviant(thiourea and thiocyanate) and thiourea systems, both of which have lower environmentalimpact than traditional cyanide leaches. Comparing ferric sulfate and hydrogen peroxide as oxidantsshowed that a thiourea leach is more suited to ferric sulfate whereas the dual-lixiviant leach achievedgreater extraction with hydrogen peroxide. This was believed to be due to a more favourable effective[thiourea]:[thiocyanate] molar ratio in solution. The latter demonstrated faster kinetics and improvedefficiency for dissolution of gold and silver. However, both leaches had issues with silver extraction due toformation of passivating layers on the surface of the silver nanoparticles. Kinetic modelling showed bothsystems tended towards a mixed-controlled process. Gold extraction of 89%, with leaching reachingequilibrium within 100 min, using the dual-lixiviant process demonstrated that there is an alternative tocyanide leaches employed in gold recovery.

Biomechanical Comparison of Fixed- versus Variable-Angle Locking Screws for Distal Humerus Comminuted Fractures

Ali Nourbakhsh,Adam G. Hirschfeld,Sravan Dhulipala,William Hutton,Timothy Ganey,Luis Lozada,Daniel Schlatterer,Gary Mark Lourie 대한정형외과학회 2019 Clinics in Orthopedic Surgery Vol.11 No.3

Background: To compare the stability of fixed- versus variable-angle locking constructs for the comminuted distal humerus fracture (AO/OTA 13-A3). Methods: Eight pairs of complete humeri harvested from eight fresh frozen cadavers were used for the study. We fixed the intact humeri using 2.7-mm/3.5-mm locking VA-LCP stainless steel distal humerus posterolateral (nine-hole) and medial (seven-hole) plates. An oscillating saw was used to cut a 1-cm gap above the olecranon fossa. The specimens were loaded in axial mode with the rate of 1 mm per 10 seconds to failure, and stress-strain curves were compared in each pair. The mode of failure was recorded as well as the load needed for 2- and 4-mm displacement at the lateral end of the gap. Results: The stiffness of the constructs, based on the slope of the stress-strain curve, did not show any difference between the fixed- versus variable-angle constructs. Likewise, there was no difference between the force needed for 2- or 4-mm displacement at the lateral gap between the fixed- and variable-angle constructs. The mode of failure was bending of both plates in all specimens and screw pull-out in four specimen pairs in addition to the plate bending. Conclusions: Our results did not show any difference in the biomechanical stability of the fixed- versus variable-angle constructs. There was not any screw breakage or failure of the plate-screw interface.

Dose dependence of DNA repair in rainbow trout (Oncorhynchus mykiss) larvae exposed to UV-B radiation

Mitchell, David L.,Adams-Deutsch, Tristan,Olson, Mark H. Korean Society of Photoscience 2009 Photochemical & photobiological sciences Vol.8 No.1

We examined survival and DNA damage in rainbow trout larvae (Oncorhynchus mykiss) resulting from a range of sublethal to lethal ultraviolet-B exposures in the presence and absence of photoreactivating radiation. We found that after low, sublethal UV-B exposures trout larvae are quite proficient at photoenzymatic repair but that this capacity decreases exponentially with the total incident UV-B dose. The relationship between the dose dependence of PER and trout development and vulnerability in fisheries and in the natural environment are discussed.

Impact of Sb Incorporation on MOVPE-Grown “Bulk” InGaAs(Sb)N Films for Solar Cell Application

Kim, Taewan,Wood, Adam,Kim, Honghyuk,Kim, Youngjo,Lee, Jaejin,Peterson, Mark,Sin, Yongkun,Moss, Steven,Kuech, Thomas F.,Babcock, Susan,Mawst, Luke J. IEEE 2016 IEEE journal of photovoltaics Vol.6 No.6

<P>We have investigated the impacts of Sb incorporation on the microstructural, optical, electrical, and carrier dynamics properties of bulk InGaAsSbN films in a comparative study of In-GaAsN and InGaAsSbN materials grown by metal-organic vapor phase epitaxy (MOVPE). These films were grown at the relatively high temperature of 600 degrees C and annealed at 800 degrees C for 30 min. Transmission electron microscopy studies indicate compositional and structural homogeneity of the InGaAsN and InGaAsSbN films. Low-temperature time-resolved photoluminescence measurements of the MOVPE-grown InGaAsN film show a longer minority carrier lifetime (similar to 40 ns) than observed for the InGaAsSbN film (similar to 26 - 27 ns). In addition, single-junction solar cells with an InGaAsN (In-GaAsSbN) base layer exhibit an open-circuit voltage of 0.64 (0.58) V, a short-circuit current of 17.13 (16.89) mA/cm2, a fill factor (FF) of 77.55 (74.29)%, and an efficiency of 8.57 (7.31)%. Sb incorporation in InGaAsN adversely affects solar cell performance due to a reduced minority carrier lifetime correlated with the formation of defects and narrow depletion region width resulting from a higher background carbon impurity level.</P>