Apoptosis is a crucial process by which multicellular organisms control tissue growth, removal and inflammation. Disruption of the normal apoptotic function is often observed in cancer, where cell death is avoided by the overexpression of anti-apoptotic proteins of the Bcl-2 (B-cell lymphoma 2) family, including Mcl-1 (myeloid cell leukaemia 1). This makes Mcl-1 a potential target for drug therapy, through which normal apoptosis may be restored by inhibiting the protective function of Mcl-1. Here, the discovery and biophysical properties of an anti-Mcl-1 antibody fragment are described and the utility of both the scFv and Fab are demonstrated in generating an Mcl-1 crystal system amenable to iterative structure-guided drug design.

A versatile, compact heater designed at National Synchrotron Light Source-II for in situ X-ray nano-imaging in a full-field transmission X-ray microscope is presented. Heater design for nano-imaging is challenging, combining tight spatial constraints with stringent design requirements for the temperature range and stability. Finite-element modeling and analytical calculations were used to determine the heater design parameters. Performance tests demonstrated reliable and stable performance, including maintaining the exterior casing close to room temperature while the heater is operating at above 1100°C, a homogenous heating zone and small temperature fluctuations. Two scientific experiments are presented to demonstrate the heater capabilities: (i) in situ 3D nano-tomography including a study of metal dealloying in a liquid molten salt extreme environment, and (ii) a study of pore formation in icosahedral quasicrystals. The progression of structural changes in both studies were clearly resolved in 3D, showing that the new heater enables powerful capabilities to directly visualize and quantify 3D morphological evolution of materials under real conditions by X-ray nano-imaging at elevated temperature during synthesis, fabrication and operation processes. This heater design concept can be applied to other applications where a precise, compact heater design is required.

The optical design of a Hettrick–Underwood-style soft X-ray spectrometer with Wolter type 1 mirrors is presented. The spectrometer with a nominal length of 3.1 m can achieve a high resolving power (resolving power higher than 10000) in the soft X-ray regime when a small source beam (<3 µm in the grating dispersion direction) and small pixel detector (5 µm effective pixel size) are used. Adding Wolter mirrors to the spectrometer before its dispersive elements can realize the spatial imaging capability, which finds applications in the spectroscopic studies of spatially dependent electronic structures in tandem catalysts, heterostructures, etc. In the pump–probe experiments where the pump beam perturbs the materials followed by the time-delayed probe beam to reveal the transient evolution of electronic structures, the imaging capability of the Wolter mirrors can offer the pixel-equivalent femtosecond time delay between the pump and probe beams when their wavefronts are not collinear. In combination with some special sample handing systems, such as liquid jets and droplets, the imaging capability can also be used to study the time-dependent electronic structure of chemical transformation spanning multiple time domains from microseconds to nanoseconds. The proposed Wolter mirrors can also be adopted to the existing soft X-ray spectrometers that use the Hettrick–Underwood optical scheme, expanding their capabilities in materials research.

Elucidating the structural dynamics of small molecules and proteins in the liquid solution phase is essential to ensure a fundamental understanding of their reaction mechanisms. In this regard, time-resolved X-ray solution scattering (TRXSS), also known as time-resolved X-ray liquidography (TRXL), has been established as a powerful technique for obtaining the structural information of reaction intermediates and products in the liquid solution phase and is expected to be applied to a wider range of molecules in the future. A TRXL experiment is generally performed at the beamline of a synchrotron or an X-ray free-electron laser (XFEL) to provide intense and short X-ray pulses. Considering the limited opportunities to use these facilities, it is necessary to verify the plausibility of a target experiment prior to the actual experiment. For this purpose, a program has been developed, referred to as S-cube, which is short for a Solution Scattering Simulator. This code allows the routine estimation of the shape and signal-to-noise ratio (SNR) of TRXL data from known experimental parameters. Specifically, S-cube calculates the difference scattering curve and the associated quantum noise on the basis of the molecular structure of the target reactant and product, the target solvent, the energy of the pump laser pulse and the specifications of the beamline to be used. Employing a simplified form for the pair-distribution function required to calculate the solute–solvent cross term greatly increases the calculation speed as compared with a typical TRXL data analysis. Demonstrative applications of S-cube are presented, including the estimation of the expected TRXL data and SNR level for the future LCLS-II HE beamlines.

Double-sided Fresnel zone plates are diffractive lenses used for high-resolution hard X-ray microscopy. The double-sided structures have significantly higher aspect ratios compared with single-sided components and hence enable more efficient imaging. The zone plates discussed in this paper are fabricated on each side of a thin support membrane, and the alignment of the zone plates with respect to each other is critical. Here, a simple and reliable way of quantifying misalignments by recording efficiency maps and measuring the absolute diffraction efficiency of the zone plates as a function of tilting angle in two directions is presented. The measurements are performed in a setup based on a tungsten-anode microfocus X-ray tube, providing an X-ray energy of 8.4 keV through differential measurements with a Cu and an Ni filter. This study investigates the sources of the misalignments and concludes that they can be avoided by decreasing the structure heights on both sides of the membrane and by pre-programming size differences between the front- and back-side zone plates.

The program Mercury, developed at the Cambridge Crystallographic Data Centre, was originally designed primarily as a crystal structure visualization tool. Over the years the fields and scientific communities of chemical crystallography and crystal engineering have developed to require more advanced structural analysis software. Mercury has evolved alongside these scientific communities and is now a powerful analysis, design and prediction platform which goes a lot further than simple structure visualization.

Single-crystalline-like thin films composed of crystallographically aligned grains are a new prototype of 2D materials developed recently for low-cost and high-performance flexible electronics as well as second-generation high-temperature superconductors. In this work, significant texture improvement in single-crystalline-like materials is achieved through growth of a 330 nm-thick silver layer.

The new agreement, effective immediately through Dec. 5, 2015, stipulates that the Smithsonian's National Zoological Park will conduct research in the areas of giant panda breeding and cub behavior.

The post Smithsonian signs new giant panda agreement with China appeared first on Smithsonian Insider.

The male’s fluke design helps it overcome the drag caused by their long tusks, the scientists determined. The female’s fluke design gives them increased speed for diving while foraging.

The post Narwhal fluke design helps compensate for drag caused by tusk appeared first on Smithsonian Insider.

In recent research on Santa Rosa Island off the coast of Southern California, isotope readings of carbon and nitrogen found in the bones of Chumash Indians and domestic dogs excavated from archaeological sites show that both humans and dogs have nearly identical signatures of stable isotopes.

The post Ancient bond between humans and dogs revealed in isotopic signatures of their bones appeared first on Smithsonian Insider.

Invertebrates make up more than 80 percent of all known species and provide humans with a myriad of valuable services—from crop pollination to their use as food—yet they are overlooked and underrepresented in conservation decisions and on priority lists of threatened and endangered species.

The post Invertebrates are ignored, overlooked by conservationists, policymakers and the public appeared first on Smithsonian Insider.

“Ignition Sequence,” 1968, Vincent Cavallaro, oil on canvas. The power of the ignition and launch sequence of a NASA rocket is portrayed in an abstract […]

The post “Ignition Sequence,” by Vincent Cavallaro appeared first on Smithsonian Insider.

A mysterious X-ray signal has been found in a detailed study of galaxy clusters using NASA’s Chandra X-ray Observatory and ESA’s XMM-Newton. One intriguing possibility […]

The post Mysterious X-ray signal from space appeared first on Smithsonian Insider.

When it’s time for a meal of katydids, bats use their ears. When hunting and eating male katydids, different bat species locate their prey by […]

The post To hunt, bats listen for signals in prey mating calls appeared first on Smithsonian Insider.

When astronomers study protoplanetary disks of gas and dust that surround young stars, they sometimes spot a dark gap like the Cassini division in Saturn’s […]

The post Disk Gaps Don’t Always Signal Planets appeared first on Smithsonian Insider.

In conflicts between predators and prey, speed is a decided advantage, and evolution has given the trap-jaw ant a distinct advantage with spring-loaded jaws that […]

The post Locked and loaded: unique trigger design fires this ant’s snapping jaws appeared first on Smithsonian Insider.

With a non-stop babble of hums, grunts and shrill squeals as they argue over fish and defend their territories, the Amazon’s giant otters are one […]

The post With voices joined in chorus, giant otter families create a distinct sound signature appeared first on Smithsonian Insider.

Well known for its collection of children’s books, the Cooper Hewitt Library holds a rare 19th century illustrated German nursery rhyme children’s book titled Paradiesfibel, written and illustrated […]

The post Learning to sign: Rare book appeared first on Smithsonian Insider.

Scott J. Neal, Qingxiang Zhou, and Francesca Pignoni

The specification of organs, tissues and cell types results from cell fate restrictions enacted by nuclear transcription factors under the control of conserved signaling pathways. The progenitor epithelium of the Drosophila compound eye, the eye imaginal disc, is a premier model for the study of such processes. Early in development, apposing cells of the eye disc are established as either retinal progenitors or support cells of the peripodial epithelium (PE), in a process whose genetic and mechanistic determinants are poorly understood. We have identified Protein Phosphatase 2A (PP2A), and specifically a STRIPAK-PP2A complex that includes the scaffolding and substrate-specificity components Cka, Strip and SLMAP, as a critical player in the retina-PE fate choice. We show that these factors suppress ectopic retina formation in the presumptive PE and do so via the Hippo signaling axis. STRIPAK-PP2A negatively regulates Hpo kinase, and consequently its substrate Wts, to release the transcriptional co-activator Yki into the nucleus. Thus, a modular higher-order PP2A complex refines the activity of this general phosphatase to act in a precise specification of cell fate.

Olivia R. Grafinger, Genya Gorshtein, Tyler Stirling, Megan I. Brasher, and Marc G. Coppolino

Malignant cancer cells can invade extracellular matrix (ECM) through the formation of F-actin-rich subcellular structures termed invadopodia. ECM degradation at invadopodia is mediated by matrix metalloproteinases (MMPs), and recent findings indicate that membrane-anchored membrane type 1-matrix metalloproteinase (MT1-MMP) has a primary role in this process. Maintenance of an invasive phenotype is dependent on internalization of MT1-MMP from the plasma membrane and its recycling to sites of ECM remodeling. Internalization of MT1-MMP is dependent on its phosphorylation, and here we examine the role of β1 integrin-mediated signaling in this process. Activation of β1 integrin using the antibody P4G11 induced phosphorylation and internalization of MT1-MMP and resulted in increased cellular invasiveness and invadopodium formation in vitro. We also observed phosphorylation of Src and epidermal growth factor receptor (EGFR) and an increase in their association in response to β1 integrin activation, and determined that Src and EGFR promote phosphorylation of MT1-MMP on Thr⁵⁶⁷. These results suggest that MT1-MMP phosphorylation is regulated by a β1 integrin-Src-EGFR signaling pathway that promotes recycling of MT1-MMP to sites of invadopodia formation during cancer cell invasion.

Kristina Drizyte-Miller, Jing Chen, Hong Cao, Micah B. Schott, and Mark A. McNiven

Epithelial cells such as liver-resident hepatocytes rely heavily on the Rab family of small GTPases to perform membrane trafficking events that dictate cell physiology and metabolism. Not surprisingly, disruption of several Rabs can manifest in metabolic diseases or cancer. Rab32 is expressed in many secretory epithelial cells but its role in cellular metabolism is virtually unknown. In this study, we find that Rab32 associates with lysosomes and regulates proliferation and cell size of Hep3B hepatoma and HeLa cells. Specifically, we identify that Rab32 supports mTORC1 signaling under basal and amino acid stimulated conditions. Consistent with inhibited mTORC1, an increase in nuclear TFEB localization and lysosome biogenesis is also observed in Rab32-depleted cells. Finally, we find that Rab32 interacts with mTOR kinase and that loss of Rab32 reduces the association of mTOR and mTORC1 pathway proteins with lysosomes, suggesting that Rab32 regulates lysosomal mTOR trafficking. In summary, these findings suggest that Rab32 functions as a novel regulator of cellular metabolism through supporting mTORC1 signaling.

Thomas O'Loughlin, Antonina J. Kruppa, Andre L. R. Ribeiro, James R. Edgar, Abdulaziz Ghannam, Andrew M. Smith, and Folma Buss

Optineurin (OPTN) is a multifunctional protein involved in autophagy, secretion as well as NF-B and IRF3 signalling and OPTN mutations are associated with several human diseases. Here we show that, in response to viral RNA, OPTN translocates to foci in the perinuclear region, where it negatively regulates NF-B and IRF3 signalling pathways and downstream pro-inflammatory cytokine secretion. These OPTN foci consist of a tight cluster of small membrane vesicles, which are positive for ATG9A. Disease mutations linked to POAG cause aberrant foci formation in the absence of stimuli, which correlates with the ability of OPTN to inhibit signalling. Using proximity labelling proteomics, we identify the LUBAC complex, CYLD and TBK1 as part of the OPTN interactome and show that these proteins are recruited to this OPTN-positive perinuclear compartment. Our work uncovers a crucial role for OPTN in dampening NF-B and IRF3 signalling through the sequestration of LUBAC and other positive regulators in this viral RNA-induced compartment leading to altered pro-inflammatory cytokine secretion.

Cooper Hewitt, Smithsonian Design Museum, the only museum in the U.S. devoted exclusively to design, reopens after a 3-year makeover with 60 percent more exhibition […]

The post Smithsonian Design Museum in NYC Reopens with High Tech Makeover appeared first on Smithsonian Insider.

Judy Garland’s iconic ruby slippers from “The Wizard of Oz” are one of the most popular attractions at the National Museum of American History. But […]

The post Crowdfunding campaign to restore Ruby Slippers surpasses mark appeared first on Smithsonian Insider.

Hidden in the thick foliage of tropical forests a subfamily of colorful beetles–the Chrysomelidae–may be hiding the secrets to the earliest stages of social behavior. […]

The post Beetle moms show clear signs of maternal instincts and care appeared first on Smithsonian Insider.

Smithsonian’s MarineGEO (Marine Global Earth Observatory) conducts long-term research around the world on coastal marine ecosystems, including at their field station on Carrie Bow Cay […]

The post MarineGEO Field Campaign: Belize appeared first on Smithsonian Insider.

When the Signal Editor is saving data, the indicator that the save is occurring does not appear.  You might notice a delay when saving large data files.This bug exists in the following release(s):
R2020a

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Video of the B9 robot from "Lost In Space" and his most famous catchphrases.; Credit: timtomp (via YouTube)

Robert Kinoshita, the Los Angeles native who designed the iconic robots from "Lost in Space" and "Forbidden Planet," has passed away. He was 100 years old.

Konishita died Dec. 9 at a Torrance nursing home, according to the Hollywood Reporter, citing family friend Mike Clark. His creations included "Forbidden Planet's" Robby the Robot, the B9 robot from "Lost in Space," Tobor from "Tobor the Great" and more. Kinoshita also created "Lost in Space's" iconic flying-saucer-shaped Jupiter 2 spaceship.

Kinoshita built the original miniature prototype of Robby the Robot out of wood and plastic by combining several different concepts, according to the Reporter; the Rafu Shimpo reported that he struggled with the design.

"I thought, what the hell. We’re wasting so much time designing and drawing one sketch after another. I said to myself, I’m going to make a model," Kinoshita told the Rafu Shimpo in a 2004 interview. "Then one day, the art director sees the model. He says, ‘Give me that thing.’ He grabbed it and ran. ... Ten minutes later, he comes running back and puts the model back on my desk and says, ‘Draw it!’"

Watch Kinoshita and his colleagues talking about the construction of Robby the Robot:

Robby the Robot's construction

The 1956 classic sci-fi movie "Forbidden Planet" — based on Shakespeare's "The Tempest" — went on to be nominated for a special effects Oscar.

Kinoshita later served as art director on the 1960s sci-fi TV series "Lost in Space," creating the arm-flailing robot — named B9 — who delivered the classic line "Danger! Danger, Will Robinson!" That robot received as much fan mail as the actual humans on the show, according to the Reporter.

Watch the robot's feud with "Lost in Space's" Dr. Smith:

The robot vs. Dr. Smith

The "Lost in Space" robot even inspired a B9 Robot Builders Club, featured in Forbes. Kinoshita sent a message in 2000 to the club, thanking them for their support for the robot he originally nicknamed "Blinky."

"I'm truly flabbergasted and honored by your support for 'Blinky!' It's a well-designed little beauty," Kinoshita wrote. "Your thoughtful remembrance is something we designers seldom are lucky enough to receive."

Kinoshita described the thought process behind its design in a 1998 interview.

"You're laying in bed, and something comes to you," he said. "Until, finally, you get to a point where you say, 'This could work,' 'OK, let's see what the boss man says.' And you present it to him."

He told the Rafu Shimpo that he tried to create his robots to disguise the fact that there was a person inside. "I tried to camouflage it enough so you’d wonder where the hell the human was," he said.

Both the Japanese-American Kinoshita and his wife, Lillian, were sent to an Arizona internment camp during World War II, though they were able to get out before the end of the war and moved to Wisconsin, according to the Reporter.

While in Wisconsin, Kinoshita learned industrial design and plastic fabrication, designing washing machines for the Army and Air Force before returning to California, according to the Rafu Shimpo.

Kinoshita said that he had to overcome racial prejudice to break into working in Hollywood.

Kinoshita attributed his long life to clean living — along with daily doses of apple cider vinegar, family friend Clark told the Reporter.

Kinoshita also worked as a designer and art director on numerous classic TV shows, including "Kojak," "Barnaby Jones," "Hawaii Five-O," "Bat Masterson," "Sea Hunt," "Tombstone Territory," "Star Trek" creator Gene Roddenberry's "Planet Earth" and more, according to his IMDB. His last TV show was 1984's "Cover Up."

Kinoshita grew up in Boyle Heights, according to the Reporter, attending Maryknoll Japanese Catholic School, Roosevelt High School and USC's School of Architecture. His career began with work on 1937's "100 Men and a Girl." Kinoshita graduated cum laude from USC, according to the Rafu Shimpo.

Watch Kinoshita speak at his 95th birthday gathering with the B9 Robot Builders Club. He said he hoped to make it to 100, and he ended up doing so.

Kinoshita's 95th birthday speech

This content is from Southern California Public Radio. View the original story at SCPR.org.

Quaternion methods for obtaining solutions to the problem of finding global rotations that optimally align pairs of corresponding lists of 3D spatial and/or orientation data are critically studied. The existence of multiple literatures and historical contexts is pointed out, and the algebraic solutions of the quaternion approach to the classic 3D spatial problem are emphasized. The treatment is extended to novel quaternion-based solutions to the alignment problems for 4D translation and orientation data.

Kristina Drizyte-Miller
Apr 15, 2020; 0:jcs.236661v1-jcs.236661
Articles

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Bridges make travel faster and more convenient, but, in an earthquake, these structures are subject to forces that can cause extensive damage and make them unsafe. Now civil and environmental engineer Petros Sideris of Texas A&M University is leading a National Science Foundation (NSF)-funded research project to investigate the performance of hybrid sliding-rocking (HSR) columns. HSR columns provide the same support as conventional bridge infrastructure columns but are more earthquake-resistant. HSR columns are a series of individual concrete segments held together by steel cables that allow for controlled sliding and rocking. This allows the columns to shift without damage, while post-tensioning strands ensure that at the end of an earthquake the columns are pushed back to their original position. Conventional bridges are cast-in-place monolithic concrete elements that are strong but inflexible. Structural damage in these bridge columns, typically caused by a natural disaster, often forces a bridge to close until repairs are completed. But bridges with HSR columns can withstand large earthquakes with minimal damage and require minor repairs, likely without bridge closures. Such infrastructure helps with post-disaster response and recovery and can save thousands in taxpayer dollars. In an earthquake, HSR columns provide "multiple advantages to the public," Sideris said. "By preventing bridge damage, we can maintain access to affected areas immediately after an event for response teams to be easily deployed, and help affected communities recover faster. In mitigating losses related to post-event bridge repairs and bridge closures, more funds can be potentially directed to supporting the recovery of the affected communities." According to Joy Pauschke, NSF program director for natural hazards engineering, "NSF invests in fundamental engineering research so that, in the future, the nation's infrastructure can be more resilient to earthquakes, hurricanes, and other forces of nature."

Image credit: Texas A&M University

A bold national initiative is needed to reduce the enormous health burden of sexually transmitted diseases (STDs) in the United States, according to a new report from a committee of the Institute of Medicine.

While every mode of transportation in the U.S. will be affected as the climate changes, potentially the greatest impact on transportation systems will be flooding of roads, railways, transit systems, and airport runways in coastal areas because of rising sea levels and surges brought on by more intense storms, says a new report from the National Research Council.

The National Academy of Engineering (NAE) has elected 67 new members and 11 foreign associates, announced NAE President C.D. (Dan) Mote Jr. today. This brings the total U.S. membership to 2,250 and the number of foreign associates to 214.

Given the minimal impact of long prison sentences on crime prevention and the negative social consequences and burdensome financial costs of U.S. incarceration rates, which have more than quadrupled in the last four decades, the nation should revise current criminal justice policies to significantly reduce imprisonment rates, says a new report from the National Research Council.

Veterans who participated in a series of tests during the 1960s known as Project SHAD (Shipboard Hazard and Defense) show no significant increase in adverse health outcomes, specific causes of death, or death rates compared with a similar group of veterans who were not involved in the tests, says a new report from a committee of the National Academies of Sciences, Engineering, and Medicine.

Conducting clinical investigations of mitochondrial replacement techniques (MRT) in humans is ethically permissible as long as significant conditions and principles are met, says a new report from the National Academies of Sciences, Engineering, and Medicine.

Although individual anglers – people who fish recreationally – generally take small numbers of fish, collectively, a large number of them can have a substantial impact on the overall stock.

A new book from the National Academies of Sciences, Engineering, and Medicine outlines how educators can develop and adapt student assessments for the classroom that reflect the approach to learning and teaching science described in the Next Generation Science Standards (NGSS) and similar standards.

The U.S. DRIVE Partnership – a government-industry partnership that fosters the development of precompetitive and innovative technologies for clean and efficient light-duty vehicles – has made significant progress in many technical areas including advanced combustion technologies, durability and cost of hydrogen fuel cells, and electric drive systems such as motors, power electronics, and batteries, says a new report by the National Academies of Sciences, Engineering, and Medicine.

Cognitive training, blood pressure management for people with hypertension, and increased physical activity all show modest but inconclusive evidence that they can help prevent cognitive decline and dementia, but there is insufficient evidence to support a public health campaign encouraging their adoption, says a new report from the National Academies of Sciences, Engineering, and Medicine.

The U.S. lacks icebreaking capability in the Arctic and Antarctic and should build four polar icebreakers with heavy icebreaking capability to help minimize the life-cycle costs of icebreaker acquisition and operations, says a new congressionally mandated letter report from the National Academies of Sciences, Engineering, and Medicine.

Although the process used to develop the Dietary Guidelines for Americans (DGA) has become more evidence-based since its inception more than 30 years ago, it is not currently positioned to effectively adapt to changes such as food diversity and chronic disease prevalence, while also ensuring the integrity of the process, says a new congressionally mandated report from the National Academies of Sciences, Engineering, and Medicine.

A new report from the National Academies of Sciences, Engineering, and Medicine calls for an international, multi-institutional comprehensive campaign of research, observation, and analysis activities that would help improve understanding and prediction of the Gulf of Mexico’s Loop Current System (LCS).

The National Academy of Engineering has elected 83 new members and 16 foreign members, announced NAE President C. D. (Dan) Mote, Jr., today.

The National Academy of Sciences elected 84 new members and 21 foreign associates in recognition of their distinguished and continuing achievements in original research.