cssi/SciSciGPT-SciSciNet huggingface dataset:
Control Capacity

Feedback control actively dissipates uncertainty from a dynamical system by means of actuation. We develop a notion of “control capacity” that gives a fundamental limit (in bits) on the rate at which a controller can dissipate the uncertainty from a system, i.e., stabilize to a known fixed point. We give a computable single-letter characterization of control capacity for memoryless stationary scalar multiplicative actuation channels. Control capacity allows us to answer questions of stabilizability for scalar linear systems: a system with actuation uncertainty is stabilizable if and only if the control capacity is larger than the log of the unstable open-loop eigenvalue. For second-moment senses of stability, we recover the classic uncertainty threshold principle result. However, our definition of control capacity can quantify the stabilizability limits for any moment of stability. Our formulation parallels the notion of Shannon’s communication capacity and thus yields both a strong converse and a way to compute the value of side information in control.
Government financial institutions and capital allocation efficiency in Japan

Abstract This paper uses the industry-level panel data from 1975–2005 and estimates Wurgler's η, the elasticity of industry investment to value-added, for each of Japan's 47 prefectures. We find that Wurgler's η varies considerably across prefectures even though there is no regulatory restriction on inter-regional flow of financial capital. Moreover, exploiting cross-prefecture variation in Wurgler's η, we show that the share of government loans is strongly and negatively correlated with the quality of capital allocation. We also find that this negative correlation is robust to controlling for local economic and financial development, and more pronounced in declining industries than growing industries. Moreover, the share of government loans is positively correlated with investment-to-output ratio but negatively correlated with total factor productivity growth. Taken as a whole, the results are broadly consistent with the view that Japan's government financial institutions stimulate investment in declining industries while distorting capital allocation and reducing overall productivity growth.
Why Propensity Scores Should Not Be Used for Matching

We show that propensity score matching (PSM), an enormously popular method of preprocessing data for causal inference, often accomplishes the opposite of its intended goal—thus increasing imbalance, inefficiency, model dependence, and bias. The weakness of PSM comes from its attempts to approximate a completely randomized experiment, rather than, as with other matching methods, a more efficient fully blocked randomized experiment. PSM is thus uniquely blind to the often large portion of imbalance that can be eliminated by approximating full blocking with other matching methods. Moreover, in data balanced enough to approximate complete randomization, either to begin with or after pruning some observations, PSM approximates random matching which, we show, increases imbalance even relative to the original data. Although these results suggest researchers replace PSM with one of the other available matching methods, propensity scores have other productive uses.
Simplified protocol for faster transformation of (a large number of) Pichia pastoris strains.

During the last couple of decades, the methylotrophic yeast, Pichia pastoris, has emerged as an important yeast species owing to its increasing importance both in industry and in basic research. The presently available methods for P. pastoris transformation necessitate the preparation of competent cells, which requires lots of resource, space, time, and efforts. This limits the number of transformations that can be performed by an individual in a given time. This paper is reporting a modification in the available protocols, which makes P. pastoris transformation hassle-free. In the present, modified procedure, cells were grown in patches on YPD plate(s), and the rest of the steps were carried out in small Eppendorf tubes. This modified protocol does not require a big centrifuge and shaker. This modified procedure of P. pastoris transformation with its unique way of competent cells preparation will be helpful for those working with this yeast species.
Total synthesis of (±)-dysidiolide

Abstract The total synthesis of (±)-dysidiolide was accomplished with a high level of intramolecular stereo-induction. Methylation of 6-carboethoxy-3-chloro-5-methyl-cyclohex-2-enone provided 33 bearing the 6,7- trans -dimethyl substitution of the C6–C11 B-ring. Diastereoselective conjugate addition upon enone 34 installed the C11 stereogenic center. Annulation then provided an A-ring enone ( 23 ), a substrate for a challenging conjugate addition of the branched pentenyl side chain. The combination of tri- n -butylphosphine, boron trifluoride etherate, and a dialkylcuprate uniquely effected conjugate addition to yield 58 . Incorporation of the hydroxybutenolide-containing side chain completed the total synthesis and established the viability of a general approach for the preparation of the isolabdanoid terpene system.
Clockless Spin-based Look-Up Tables with Wide Read Margin

In this paper, we develop a 6-input fracturable non-volatile Clockless LUT (C-LUT) using spin Hall effect (SHE)-based Magnetic Tunnel Junctions (MTJs) and provide a detailed comparison between the SHE-MTJ-based C-LUT and Spin Transfer Torque (STT)-MTJ-based C-LUT. The proposed C-LUT offers an attractive alternative for implementing combinational logic as well as sequential logic versus previous spin-based LUT designs in the literature. Foremost, C-LUT eliminates the sense amplifier typically employed by using a differential polarity dual MTJ design, as opposed to a static reference resistance MTJ. This realizes a much wider read margin and the Monte Carlo simulation of the proposed fracturable C-LUT indicates no read and write errors in the presence of a variety of process variations scenarios involving MOS transistors as well as MTJs. Additionally, simulation results indicate that the proposed C-LUT reduces the standby power dissipation by 5.4-fold compared to the SRAM-based LUT. Furthermore, the proposed SHE-MTJ-based C-LUT reduces the area by 1.3-fold and 2-fold compared to the SRAM-based LUT and the STT-MTJ-based C-LUT, respectively.
A congruent topology for deep gastropod relationships.

Gastropod molluscs are among the most diverse and abundant animals in the oceans, and are successful colonizers of terrestrial and freshwater environments. Past phylogenetic efforts to resolve gast...
The Stellar CME–Flare Relation: What Do Historic Observations Reveal?

NASA Living [NNX16AC11G]; NASA [NAS8-03060]; NASA Astrobiology Institute [NNX15AE05G]; Chandra [AR4-15000X, GO5-16021X]; SI Grand Challenges grant "Lessons from Mars: Are Habitable Atmospheres on Planets around M Dwarfs Viable?"
"This Girl is on Fire": Sensemaking in an Online Health Community for Vulvodynia

Online health communities (OHCs) allow people living with a shared diagnosis or medical condition to connect with peers for social support and advice. OHCs have been well studied in conditions like diabetes and cancer, but less is known about their role in enigmatic diseases with unknown or complex causal mechanisms. In this paper, we study one such condition: Vulvodynia, a chronic pain syndrome of the vulvar region. Through observations of and interviews with members of a vulvodynia Facebook group, we found that while the interaction types are broadly similar to those found in other OHCs, the women spent more time seeking basic information and building individualized management plans. They also encounter significant emotional and interpersonal challenges, which they discuss with each other. We use this study to extend the field's understanding of OHCs, and to propose implications for the design of self-tracking tools to support sensemaking in enigmatic conditions.
Explicit two-source extractors and resilient functions

We explicitly construct an extractor for two independent sources on n bits, each with polylogarithmic min-entropy. Our extractor outputs one bit and has polynomially small error. The best previous extractor, by Bourgain, required each source to have min-entropy .499n. A key ingredient in our construction is an explicit construction of a monotone, almost-balanced Boolean functions that are resilient to coalitions. In fact, our construction is stronger in that it gives an explicit extractor for a generalization of non-oblivious bit-fixing sources on n bits, where some unknown n-q bits are chosen almost polylogarithmic-wise independently, and the remaining q bits are chosen by an adversary as an arbitrary function of the n-q bits. The best previous construction, by Viola, achieved q quadratically smaller than our result. Our explicit two-source extractor directly implies improved constructions of a K-Ramsey graph over N vertices, improving bounds obtained by Barak et al. and matching independent work by Cohen.
The allometry of brain size in mammals

Why some animals have big brains and others do not has intrigued scholars for millennia. Yet, the taxonomic scope of brain size research is limited to a few mammal lineages. Here, we present a brain size dataset compiled from the literature for 1,552 species with representation from 28 extant taxonomic orders. The brain–body size allometry across all mammals is (Brain) = –1.26 (Body)⁰.⁷⁵. This relationship shows strong phylogenetic signal. Thus, we conducted additional allometries using median species values for each order, family, and genus to ensure evolutionary independence. Slopes from these analyses at different taxonomic levels all approximate ∼0.75 scaling. Why brain size scales to the 3/4 power to body size across mammals is to our knowledge unknown. Slopes within taxonomic orders, exhibiting smaller size ranges, are generally shallower than 0.75 and range from 0.24 to 0.81 with a median slope of 0.64. Published data on brain size are lacking for the majority of extant mammals (> 70% of species) with strong bias in representation from Primates, Carnivora, Perissodactyla, and Australidelphian marsupials (orders Dasyuromorphia, Diprotodontia, Peramelemorphia). Several orders are particularly underrepresented. For example, data on brain size are available for less than 20% of species in each of the following speciose lineages: Soricomorpha, Rodentia, Lagomorpha, Didelphimorphia, and Scandentia. Use of museum collections can decrease the current taxonomic bias in mammal brain size data and tests of hypothesis.
Relative reactivity of anti- and syn-oximino carbonates and carbamates of 2-pyridylacetic acid esters.

anti-Oximes of 2-pyridylacetic acid esters are rapidly transformed to pyridine-2-carbonitrile under a variety of conditions while syn-oximes bearing tert-butyl esters can be conveniently deprotected to the corresponding carboxylic acid with subsequent fragmentation to the nitrile.
Nuisance effects and the limitations of nuisance regression in dynamic functional connectivity fMRI

In resting-state fMRI, dynamic functional connectivity (DFC) measures are used to characterize temporal changes in the brain's intrinsic functional connectivity. A widely used approach for DFC estimation is the computation of the sliding window correlation between blood oxygenation level dependent (BOLD) signals from different brain regions. Although the source of temporal fluctuations in DFC estimates remains largely unknown, there is growing evidence that they may reflect dynamic shifts between functional brain networks. At the same time, recent findings suggest that DFC estimates might be prone to the influence of nuisance factors such as the physiological modulation of the BOLD signal. Therefore, nuisance regression is used in many DFC studies to regress out the effects of nuisance terms prior to the computation of DFC estimates. In this work we examined the relationship between seed-specific sliding window correlation-based DFC estimates and nuisance factors. We found that DFC estimates were significantly correlated with temporal fluctuations in the magnitude (norm) of various nuisance regressors. Strong correlations between the DFC estimates and nuisance regressor norms were found even when the underlying correlations between the nuisance and fMRI time courses were relatively small. We then show that nuisance regression does not necessarily eliminate the relationship between DFC estimates and nuisance norms, with significant correlations observed between the DFC estimates and nuisance norms even after nuisance regression. We present theoretical bounds on the difference between DFC estimates obtained before and after nuisance regression and relate these bounds to limitations in the efficacy of nuisance regression with regards to DFC estimates.
Tandem organochromium-coupling and epoxide ring opening: a direct approach for the synthesis of cyclic ethers

Abstract A two-step protocol for the convergent formation of cyclic ethers has been demonstrated. This involves the chemoselective 1,2-addition of vinylchromium species to a 4,5-epoxy aldehyde to generate γ,δ-epoxy alcohols followed by acid-induced transetherification to generate substituted tetrahydrofuran and pyran products.
Charge-remote fragmentation: an account of research on mechanisms and applications

Abstract Charge-remote fragmentation is one class of decomposition reactions of gas-phase ions. Their discovery and applications had to await the development of soft ionization, particularly fast atom bombardment, and tandem mass spectrometry. The decompositions are particularly informative and allow functional groups to be identified and located in fatty acids, surfactants, steroids, complex lipids, and related materials. These are difficult structure assignments to make by other mass-spectrometry methods or by nuclear magnetic resonance and other spectroscopic techniques. Thus, charge-remote fragmentation fills an important need in structural chemistry. The mechanisms of charge-remote fragmentation underpin their structural utility, and they are still a matter of some debate. In this account, we discuss the discovery of charge-remote fragmentation in our laboratory. Further, we describe our efforts to understand their mechanism and to exploit their high information content in structure determinations of fatty acid and related materials.
Synthesis and Characterization of Three New Layered Phosphates, Na2MnP2O7, NaCsMnP2O7, and NaCsMn0.35Cu0.65P2O7

Three new layered phosphates were isolated by employing high-temperature, solid-state reactions. These compounds belong to the AI2BIIP2O7 family. Na2MnP2O7, 1, crystallizes in the triclinic space group P1 (No. 2) with a = 5.316(2) A, b = 6.580(2) A, c = 9.409(3) A, α = 109.65(3)°, β = 95.25(3)°, γ = 106.38(3)°, and Z = 2; NaCsMnP2O7, 2, crystallizes in the orthorhombic space group Cmc21 (No. 36) with a = 5.332(2) A, b = 15.009(2) A, c = 9.808(2) A, and Z = 4; NaCsMn0.35Cs0.65P2O7, 3, also crystallizes in the orthorhombic space group Cmc21 (No. 36) with a = 5.208(2) A, b = 15.073(5) A, c = 9.708(3) A, and Z = 4. 1 possesses a new structure type composed of slabs of fused Mn4P4O26 cages, and 2 and 3 are isostructural with K2CuP2O7. The unique cage structure found in 1 is made of two edge-sharing Mn2O10 dimers and two P2O7 pyrophosphate groups. These units, arranged in parallel with respect to Mn−Mn and P−P vectors, are linked in an alternating fashion through corner-sharing oxygen atoms. Incorporation of l...
Organotin polymers as anticancer and antiviral agents

Abstract Organotin polymers are easily synthesized employing interfacial polymerization systems involving the reaction of difunctional Lewis bases and organotin halides. A wide variety of organotin-containing polymeric products have been synthesized including the first water soluble organotin polymers. The organotin polymers exhibit a wide range of biological activities including the inhibition of a wide variety of cancer cell lines including cell lines associated with ovarian, colon, lung, prostrate, pancreatic and breast cancer. Some also inhibit a variety of viruses including those responsible for herpes infections and smallpox. The synthesis, structural characterization, and biological characterization of these materials are described in this review.
The REgolith X-Ray Imaging Spectrometer (REXIS) for OSIRIS-REx: identifying regional elemental enrichment on asteroids

The OSIRIS-REx Mission was selected under the NASA New Frontiers program and is scheduled for launch in September of 2016 for a rendezvous with, and collection of a sample from the surface of asteroid Bennu in 2019. 101955 Bennu (previously 1999 RQ36) is an Apollo (near-Earth) asteroid originally discovered by the LINEAR project in 1999 which has since been classified as a potentially hazardous near-Earth object. The REgolith X-Ray Imaging Spectrometer (REXIS) was proposed jointly by MIT and Harvard and was subsequently accepted as a student led instrument for the determination of the elemental composition of the asteroid's surface as well as the surface distribution of select elements through solar induced X-ray fluorescence. REXIS consists of a detector plane that contains 4 X-ray CCDs integrated into a wide field coded aperture telescope with a focal length of 20 em for the detection of regions with enhanced abundance in key elements at 50 m scales. Elemental surface distributions of approximately 50-200 m scales can be detected using the instrument as a simple collimator. An overview of the observation strategy of the REXIS instrument and expected performance are presented here.
Quasi-nature catalysis: conjugated addition of unsaturated carbonyl compounds with aryl and vinyltin reagents catalyzed by rhodium in air and water

Abstract In air and water, trialkylphenyl- or trialkylvinylstannanes react with α,β-unsaturated esters and ketones to give the corresponding conjugated addition products in high yields in the presence of a rhodium catalyst.
Synthesis of Asialo GM1. New Insights in the Application of Sulfonamidoglycosylation in Oligosaccharide Assembly: Subtle Proximity Effects in the Stereochemical Governance of Glycosidation

The total synthesis of asialo GM1 (1a) has been accomplished. Using related chemistry, the methyl glycoside of the asialo compound (1b) has also been synthesized. These kinds of compounds have been identified as potential ligands for bacterial and viral infection sites. A simpler structure, which has also been identified for its infection attracting structure in the context of glycopeptides and glycolipids (methyl glycoside 2), has also been synthesized. The key common phase in the syntheses involves the sulfonamidoglycosidation reaction which is used to create a β-linkage leading to a galNAc residue joined to the C4 hydroxyl group of a galactose unit either as a monosaccharide (see compound 2) or as C4‘ in the context of a lactosyl moiety. During the course of these studies there was encountered an unusual “proximal hydroxyl” directing effect. Thus, when C4 on the galactose ring of an azaglycosylating donor bears a free hydroxyl (see, for instance, compound 13), β-glycoside formation predominates. When t...
7-Deaza-5′-noraristeromycin derivatives resembling L-toyocamycin and L-sangivamycin

The synthesis of the 7-cyano and 7-carboxamido derivatives of 7-deaza-5′-noraristeromycin have been prepared in 3 and 4 steps, respectively, for evaluation as anti-trypanosomal agents. Neither compound was active in the latter assay.
Physician agency in China: Evidence from a drug-percentage incentive scheme

Abstract This paper examines how physicians respond to financial incentives in China. Faced with the requirement to lower drug expenditure as a percentage of the total medical expenditure, physicians increased non-drug expenditure in addition to decreasing drug expenditure, keeping the total expenditure at the historical level. This shift in the expenditure mix was observed only among insured patients, highlighting the role of patient insurance status in affecting the extent to which physician agency drives medical decision making.
Synthesis of thiol-derivatized porphyrin dimers and trimers for studies of architectural effects on multibit information storage

We present the rational design and synthesis of multiporphyrin arrays containing thiol-derivatized linkers for the purpose of multibit molecular information storage. Porphyrin dimers and trimers were synthesized by the Pd-mediated coupling of iodo-substituted and ethynyl-substituted porphyrin building blocks in 5−51% yields. Each porphyrin dimer bears one S-acetylthio group. The architecture of the trimers incorporates a trans-substituted porphyrin (central) bearing two S-acetylthio groups and two diphenylethyne-linked porphyrins (wings) in a trans geometry. The central porphyrin and the wing porphyrins bear distinct substituents and central metals, thereby affording different oxidation potentials. The S-acetylthio groups provide a means for attachment of the arrays to an electroactive surface. The dimers are designed for vertical orientation on an electroactive surface while the trimers are designed for horizontal orientation of the central porphyrin. Altogether seven different arrays were synthesized. E...
Observations regarding the first step of the Julia-Lythgoe olefin synthesis

Abstract Using DME as a solvent in the addition of metallated sulfones to aldehydes can increase yields in the first step of the Julia-Lythgoe olefin synthesis. The addition of metallated sulfones to ketones is also discussed.
Chimie douce synthesis of a layered ammonium zinc molybdate

A layered ammonium zinc molybdate material was derived by a novel room-temperature chimie douce synthesis technique from a metastable mixed oxide prepared by calcination of a layered double hydroxide (LDH). The compound obtained, (NH4)HZn2(OH)2(MoO4)2, is highly crystalline and retains the rhombohedral symmetry of the LDH precursor. The crystal structure of this material was determined by Rietveld refinement of an isostructural ammonium nickel molybdate. The structure is trigonal, with hexagonal unit-cell parameters of a = 6.10767(15) A and c = 21.6409(6) A. The host structure consists of divalent cation octahedra which share edges to form layers perpendicular to the c axis, analogous to the LDH precursor. The tetrahedral molybdate species, however, are not merely intercalated within the interlayer domain but are bonded to the layers themselves through shared Mo−O−Zn bonds. This arrangement results in the formation of a net negative charge on the host structure, leading to incorporation of ammonium ions b...
Altered motor development following late gestational alcohol and cannabinoid exposure in rats.

Abstract Cannabis is the most commonly used illicit drug among pregnant women, and rates are likely to increase given recent legalization. In addition, half of pregnant women who report consuming cannabis also report drinking alcohol. However, little is known about the consequences of prenatal cannabis alone or in combination with alcohol, particularly with cannabis products that are continually increasing in potency of the primary psychoactive constituent in cannabis, Δ9-tetrahydrocannabinol (THC). The current study investigated the effects of early exposure to cannabinoids during the brain growth spurt on early physical and motor development alone (Experiment 1) or in combination with alcohol (Experiment 2). In Experiment 1, Sprague-Dawley rat pups were exposed to a cannabinoid receptor agonist (CP-55,940 [CP]; 0.1, 0.25, 0.4 mg/kg/day), the drug vehicle, or a saline control from postnatal days (PD) 4–9. In Experiment 2, rat pups were exposed to CP (0.4 mg/kg/day) or the vehicle, and were additionally intubated with alcohol (11.9% v/v; 5.25 g/kg/day) or received a sham intubation. Subjects in both experiments were tested on a motor development task (PD 12–20) and a motor coordination task during adolescence (PD 30–32). Both developmental cannabinoid and alcohol exposure separately decreased body growth throughout development, and combined exposure exacerbated these effects, although only alcohol exposure induced long-term body weight reductions. Developmental cannabinoid exposure advanced early motor development, whereas alcohol exposure delayed development, and subjects given combined exposure did not differ from controls on some measures. Alcohol exposure impaired motor coordination later in life. In contrast, cannabinoid exposure, by itself, did not significantly affect long-term motor coordination, but did exacerbate alcohol-related impairments in motor coordination among females. These results suggest that cannabinoid exposure may not only alter development by itself, but may exacerbate alcohol's teratogenic effects in specific behavioral domains. These findings have important implications not only for individuals affected by prenatal exposure, but also for establishing public policy for women regarding cannabis use during pregnancy.
Far-UVC light: A new tool to control the spread of airborne-mediated microbial diseases

Airborne-mediated microbial diseases such as influenza and tuberculosis represent major public health challenges. A direct approach to prevent airborne transmission is inactivation of airborne pathogens, and the airborne antimicrobial potential of UVC ultraviolet light has long been established; however, its widespread use in public settings is limited because conventional UVC light sources are both carcinogenic and cataractogenic. By contrast, we have previously shown that far-UVC light (207–222 nm) efficiently inactivates bacteria without harm to exposed mammalian skin. This is because, due to its strong absorbance in biological materials, far-UVC light cannot penetrate even the outer (non living) layers of human skin or eye; however, because bacteria and viruses are of micrometer or smaller dimensions, far-UVC can penetrate and inactivate them. We show for the first time that far-UVC efficiently inactivates airborne aerosolized viruses, with a very low dose of 2 mJ/cm2 of 222-nm light inactivating >95% of aerosolized H1N1 influenza virus. Continuous very low dose-rate far-UVC light in indoor public locations is a promising, safe and inexpensive tool to reduce the spread of airborne-mediated microbial diseases.
Synthesis of 9-(4-Thioxylofuranosyl)adenine via a novel glycosylation reaction

Abstract 9-β-(4-Thioxylofuranosyl)adenine was synthesized through direct glycosylation of adenine with a 4-thio-2′,3′,5′-tri-O-benzyl-1-thiobenzyl intermediate. We report a novel, streamlined synthetic pathway to the targeted compound, involving direct addition of a poor nucleophile to a thioether intermediate. Based on our initial observations, we propose an iodium ion promoted elimination/addition reaction mechanism.
TMSCl‐Mediated Catalytic Carbocupration of Alkynoates: An Unprecedented and Remarkable Effect of Catalyst Loading on Highly Selective Stereochemical Induction via a TMS‐Allenoate Intermediate

The TMSCl-mediated catalytic carbocupration of alkynoates has been investigated. It has been shown that catalyst loadings as low as 30 mol% readily allow for high yields and diastereoselectivities for a series of Grignard reagents. In addition, an unprecedented and remarkable effect of catalyst loading on stereochemical induction has been observed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Direct Transformations of Ketones to γ-Unsaturated Thiols via [2,3]-Sigmatropic Rearrangement of Allyl Sulfinyl Carbanions: A Combined Experimental and Computational Study

The reaction of a series of ketones with dimsylsodium in dimethyl sulfoxide resulting in the formation of γ-unsaturated thiols was studied experimentally. [2,3]-Sigmatropic rearrangements of β-unsaturated sulfinyl carbanions are involved at the key step of those transformations. DFT computations at the B3LYP/6-31+G* level indicated that such rearrangements, as well as some typical [2,3]-sigmatropic rearrangements, e.g., thermal rearrangements of allyl sulfoxides and Wittig rearrangements of sulfur ylides and lithiated allyloxy methyl anions, are concerted and moderately synchronous processes. Negative (diatropic) nucleus-independent chemical shifts (NICS) and high diamagnetic susceptibility exaltations indicate that the transition structures of these [2,3]-sigmatropic migrations are aromatic.
Interleukin-8/CXCR2 signaling regulates therapy-induced plasticity and enhances tumorigenicity in glioblastoma.

Emerging evidence reveals enrichment of glioma-initiating cells (GICs) following therapeutic intervention. One factor known to contribute to this enrichment is cellular plasticity—the ability of glioma cells to attain multiple phenotypes. To elucidate the molecular mechanisms governing therapy-induced cellular plasticity, we performed genome-wide chromatin immunoprecipitation sequencing (ChIP-Seq) and gene expression analysis (gene microarray analysis) during treatment with standard of care temozolomide (TMZ) chemotherapy. Analysis revealed significant enhancement of open-chromatin marks in known astrocytic enhancers for interleukin-8 (IL-8) loci as well as elevated expression during anti-glioma chemotherapy. The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project data demonstrated that IL-8 transcript expression is negatively correlated with GBM patient survival (p = 0.001) and positively correlated with that of genes associated with the GIC phenotypes, such as KLF4, c-Myc, and HIF2α (p < 0.001). Immunohistochemical analysis of patient samples demonstrated elevated IL-8 expression in about 60% of recurrent GBM tumors relative to matched primary tumors and this expression also positively correlates with time to recurrence. Exposure to IL-8 significantly enhanced the self-renewing capacity of PDX GBM (average threefold, p < 0.0005), as well as increasing the expression of GIC markers in the CXCR2 population. Furthermore, IL-8 knockdown significantly delayed PDX GBM tumor growth in vivo (p < 0.0005). Finally, guided by in silico analysis of TCGA data, we examined the effect of therapy-induced IL-8 expression on the epigenomic landscape of GBM cells and observed increased trimethylation of H3K9 and H3K27. Our results show that autocrine IL-8 alters cellular plasticity and mediates alterations in histone status. These findings suggest that IL-8 signaling participates in regulating GBM adaptation to therapeutic stress and therefore represents a promising target for combination with conventional chemotherapy in order to limit GBM recurrence.
Expression of the eight GABAA receptor α subunits in the developing zebrafish central nervous system.

GABA is a robust regulator of both developing and mature neural networks. It exerts many of its effects through GABAA receptors, which are heteropentamers assembled from a large array of subunits encoded by distinct genes. In mammals, there are 19 different GABAA subunit types, which are divided into the α, β, γ, δ, e, π, θ and ρ subfamilies. The immense diversity of GABAA receptors is not fully understood. However, it is known that specific isoforms, with their distinct biophysical properties and expression profiles, tune responses to GABA. Although larval zebrafish are well-established as a model system for neural circuit analysis, little is known about GABAA receptors diversity and expression in this system. Here, using database analysis, we show that the zebrafish genome contains at least 23 subunits. All but the mammalian θ and e subunits have at least one zebrafish ortholog, while five mammalian GABAA receptor subunits have two zebrafish orthologs. Zebrafish contain one subunit, β4, which does not have a clear mammalian ortholog. Similar to mammalian GABAA receptors, the zebrafish α subfamily is the largest and most diverse of the subfamilies. In zebrafish there are eight α subunits, and RNA in situ hybridization across early zebrafish development revealed that they demonstrate distinct patterns of expression in the brain, spinal cord, and retina. Some subunits were very broadly distributed, whereas others were restricted to small populations of cells. Subunit-specific expression patterns in zebrafish resembled were those found in frogs and rodents, which suggests that the roles of different GABAA receptor isoforms are largely conserved among vertebrates. This study provides a platform to examine isoform specific roles of GABAA receptors within zebrafish neural circuits and it highlights the potential of this system to better understand the remarkable heterogeneity of GABAA receptors.
Mixed-Valent Neptunium(IV/V) Compound with Cation–Cation-Bound Six-Membered Neptunyl Rings

A new mixed-valent neptunium(IV/V) compound has been synthesized by evaporation of a neptunium(V) acidic solution. The structure of the compound features cation–cation-bound six-membered neptunyl(V) rings. These rings are further connected by NpIV ions through cation–cation interactions (CCIs) into a three-dimensional neptunium cationic open framework. This example illustrates the possibility of isolating neptunyl(V) CCI oligomers in inorganic systems using other cations to compete with NpV in bonding with the neptunyl oxygen.
Leucascandrolide A: A Second Generation Formal Synthesis

A convergent, second generation formal synthesis of (+)-Leucascandrolide A (1) has been efficiently achieved by providing a flexible, enantiocontrolled strategy toward the bioactive macrolactone component. Advancements for stereocontrol in asymmetric allylation methodology are discussed. Efforts feature novel results for reductions using the Terashima hydride reagent.
Chemical synthesis of proteins

The manipulation of protein structure enables a better understanding of the principles of protein folding, as well as the development of novel therapeutics and drug-delivery vehicles. Chemical synthesis is the most powerful approach for constructing proteins of novel design and structure, allowing for variation of covalent structure without limitations. Here we describe the various chemical methods that are currently used for creating proteins of unique architecture and function.
A scalable method for automatically measuring pharyngeal pumping in C. elegans.

Abstract Background The nematode Caenorhabditis elegans is widely used for studying small neural circuits underlying behavior. In particular, the rhythmic feeding motions collectively termed pharyngeal pumping are regulated by a nearly autonomous network of 20 neurons of 14 types. Despite much progress achieved through laser ablation, genetics, electrophysiology, and optogenetics, key questions regarding the regulation of pumping remain open. New method We describe the implementation and application of a scalable automated method for measuring pumping in controlled environments. Our implementation is affordable and flexible: key hardware and software elements can be modified to accommodate different requirements. Results We demonstrate prolonged measurements under controlled conditions and the resulting high quality data. We show the scalability of our method, enabling high throughput, and its suitability for maintaining static and dynamic conditions. When food availability was oscillated, pumping rates were low as compared to steady conditions and pumping activity was not reliably modulated in response to changes in food concentration. Comparison with existing method The prevailing method for measuring rates of pumping relies on scoring by visual inspection of short recordings. Our automated method compares well with manual scoring. It enables detailed statistical characterization under experimental conditions not previously accessible and minimizes unintentional bias. Conclusions Our approach adds a powerful tool for studying pharyngeal pumping. It enhances the experimental versatility of assaying genetic and pharmacological manipulations and the ability to characterize the resulting behavior. Both the experimental setup and the analysis can be readily adapted to additional challenging motion detection problems.
Electrophilic Cyclization of Allylic 1,1- Dimethylisoureas with N-Iodosuccinimide and Phenylselenenyl Triflate

Abstract New procedures are described for the cyclization of allylic 1, 1-dimethylisoureas. Efficient cyclization of the isoureas to give substituted oxazolines occurs with both N-iodosuccinimide and phenylselenenyl triflate. Reductive dehalogenation can be carried out with lithium aluminum hydride.
Zero-shot Entity Linking by Reading Entity Descriptions

We present the zero-shot entity linking task, where mentions must be linked to unseen entities without in-domain labeled data. The goal is to enable robust transfer to highly specialized domains, and so no metadata or alias tables are assumed. In this setting, entities are only identified by text descriptions, and models must rely strictly on language understanding to resolve the new entities. First, we show that strong reading comprehension models pre-trained on large unlabeled data can be used to generalize to unseen entities. Second, we propose a simple and effective adaptive pre-training strategy, which we term domain-adaptive pre-training (DAP), to address the domain shift problem associated with linking unseen entities in a new domain. We present experiments on a new dataset that we construct for this task and show that DAP improves over strong pre-training baselines, including BERT. The data and code are available at https://github.com/lajanugen/zeshel.
Modulation of the rate, enantioselectivity, and substrate specificity of semisynthetic transaminases based on lipid binding proteins using site directed mutagenesis

Abstract Fatty acid binding proteins are a class of small 15 kDa proteins with a simple architecture that forms a large solvent sequestered cavity. In previous work, we demonstrated that reductive amination reactions could be performed in this cavity by covalent attachment of a pyridoxamine cofactor to the protein. Here, we report the results of experiments in which the position of pyridoxamine attachment has been varied by site directed mutagenesis. The conjugate IFABP-PX60 reacts at least 9.4-fold more rapidly than our original conjugate ALBP-PX, while IFABP-PX72 inverts the enantioselectivity of reactions (compared to ALBP-PX) and IFABP-PX104 displays very selective substrate specificty. These results indicate that site-directed mutagenesis can be used to tune the rate, enantioselectivity, and substrate specificity of semisynthetic transaminases based on fatty acid binding proteins.
Impact of oxygen partial pressure on the Ruddlesden-Popper series Nd2-2xSr1+2xMn2O7: Oxygen vacancy formation and ordering

The phase diagram of the Nd 2-2x Sr 1+2x Mn 2 O 7+δ n = 2 Ruddlesden-Popper series has been investigated as a function of composition and oxygen partial pressure at 1400 °C. The regions of phase stability for 0.10 ≤ x ≤ 0.70 and 10 -6 ≤p(O 2 )/atm ≤ 1.0 have been mapped out and a systematic relationship between x and oxygen partial pressure established. At high p(O 2 ) (near 1 atm) the upper solubility limit is fixed by an average Mn oxidation state of +3.5, while the lower limit of stability is a strong function of p(O 2 ). Phases synthesized at low p(O 2 ) are associated with the introduction of oxygen vacancies that can be filled at low temperature to yield metastable phases with formal Mn oxidation states beyond +3.5. The oxygen vacancy structures are highly dependent on the Nd/Sr ratio, with the location of the vacancies changing from in-plane to axial as a function of both x and temperature. Systematic study of the Mn-O bonding framework reveals a subtle dependence of the crystal structure on both the Mn oxidation state and vacancy location. The unusual crystal chemistry of these phases suggests a more general synthetic technique for accessing layered manganite phases as potential CMR candidates.
A Subset of Mycobacteria-Specific CD4+ IFN-γ+ T Cell Expressing Naive Phenotype Confers Protection against Tuberculosis Infection in the Lung.

Failure of the most recent tuberculosis (TB) vaccine trial to boost bacillus Calmette-Guerin-mediated anti-TB immunity despite the induction of Th1-specific central memory cell and effector memory cell responses highlights the importance of identifying optimal T cell targets for protective vaccines. In this study, we describe a novel, Mycobacterium tuberculosis-specific IFN-γ+CD4+ T cell population expressing surface markers characteristic of naive-like memory T cells (TNLM), which were induced in both human (CD45RA+CCR7+CD27+CD95-) and murine (CD62L+CD44-Sca-1+CD122-) systems in response to mycobacteria. In bacillus Calmette-Guerin-vaccinated subjects and those with latent TB infection, TNLM were marked by the production of IFN-γ but not TNF-α and identified by the absence of CD95 expression and increased surface expression CCR7, CD27, the activation markers T-bet, CD69, and the survival marker CD74. Increased tetramer-positive TNLM frequencies were noted in the lung and spleen of ESAT-61-20-specific TCR transgenic mice at 2 wk postinfection with M. tuberculosis and progressively decreased at later time points, a pattern not seen with TNF-α+CD4+ T cells expressing naive cell surface markers. Importantly, adoptive transfer of highly purified TNLM alone, from vaccinated ESAT-61-20-specific TCR transgenic mice, conferred equivalent protection against M. tuberculosis infection in the lungs of Rag-/- mice when compared with total memory populations (central and effector memory cells). Thus, TNLM may represent a memory T cell population that, if optimally targeted, may significantly improve future TB vaccine responses.
Unique Structural Features of the Mitochondrial AAA+ Protease AFG3L2 Reveal the Molecular Basis for Activity in Health and Disease

Mitochondrial AAA+ quality-control proteases regulate diverse aspects of mitochondrial biology through specialized protein degradation, but the underlying mechanisms of these enzymes remain poorly defined. The mitochondrial AAA+ protease AFG3L2 is of particular interest, as genetic mutations localized throughout AFG3L2 are linked to diverse neurodegenerative disorders. However, a lack of structural data has limited our understanding of how mutations impact enzymatic function. Here, we used cryoelectron microscopy (cryo-EM) to determine a substrate-bound structure of the catalytic core of human AFG3L2. This structure identifies multiple specialized structural features that integrate with conserved motifs required for ATP-dependent translocation to unfold and degrade targeted proteins. Many disease-relevant mutations localize to these unique structural features of AFG3L2 and distinctly influence its activity and stability. Our results provide a molecular basis for neurological phenotypes associated with different AFG3L2 mutations and establish a structural framework to understand how different members of the AAA+ superfamily achieve specialized biological functions.
VARX-L: Structured regularization for large vector autoregressions with exogenous variables

Abstract The vector autoregression (VAR) has long proven to be an effective method for modeling the joint dynamics of macroeconomic time series, as well as for forecasting. One major shortcoming of the VAR that has limited its applicability is its heavy parameterization: the parameter space grows quadratically with the number of series included, quickly exhausting the available degrees of freedom. Consequently, using VARs for forecasting is intractable for low-frequency, high-dimensional macroeconomic data. However, empirical evidence suggests that VARs that incorporate more component series tend to result in more accurate forecasts. Most conventional methods that allow for the estimation of large VARs either require ad hoc subjective specifications or are computationally infeasible. Moreover, as global economies become more intricately intertwined, there has been a substantial interest in incorporating the impact of stochastic, unmodeled exogenous variables. Vector autoregression with exogenous variables (VARX) extends the VAR to allow for the inclusion of unmodeled variables, but faces similar dimensionality challenges. This paper introduces the VARX-L framework, a structured family of VARX models, and provides a methodology that allows for both efficient estimation and accurate forecasting in high-dimensional analysis. VARX-L adapts several prominent scalar regression regularization techniques to a vector time series context, which greatly reduces the parameter space of VAR and VARX models. We also highlight a compelling extension that allows for shrinking toward reference models, such as a vector random walk. We demonstrate the efficacy of VARX-L in both low- and high-dimensional macroeconomic forecasting applications and simulated data examples. Our methodology is easy to reproduce in a publicly available R package.
Inferring Phylogenetic Networks with Maximum Pseudolikelihood under Incomplete Lineage Sorting

Phylogenetic networks are necessary to represent the tree of life expanded by edges to represent events such as horizontal gene transfers, hybridizations or gene flow. Not all species follow the paradigm of vertical inheritance of their genetic material. While a great deal of research has flourished into the inference of phylogenetic trees, statistical methods to infer phylogenetic networks are still limited and under development. The main disadvantage of existing methods is a lack of scalability. Here, we present a statistical method to infer phylogenetic networks from multi-locus genetic data in a pseudolikelihood framework. Our model accounts for incomplete lineage sorting through the coalescent model, and for horizontal inheritance of genes through reticulation nodes in the network. Computation of the pseudolikelihood is fast and simple, and it avoids the burdensome calculation of the full likelihood which can be intractable with many species. Moreover, estimation at the quartet-level has the added computational benefit that it is easily parallelizable. Simulation studies comparing our method to a full likelihood approach show that our pseudolikelihood approach is much faster without compromising accuracy. We applied our method to reconstruct the evolutionary relationships among swordtails and platyfishes (Xiphophorus: Poeciliidae), which is characterized by widespread hybridizations.
On the capacity of the slotted strongly asynchronous channel with a bursty user

The slotted strongly asynchronous channel with a bursty user consists of a window of A n = enα blocks of length n channel uses. A user transmits a randomly selected message among M n = enR different ones in exactly K n = env randomly selected but distinct blocks in the window. The receiver must locate and decode, with vanishing error probability in n, each one of the transmitted messages. The optimal tradeoff between (R, α, ν) is derived.
Estimating the unseen from multiple populations

Given samples from a distribution, how many new elements should we expect to find if we continue sampling this distribution? This is an important and actively studied problem, with many applications ranging from unseen species estimation to genomics. We generalize this extrapolation and related unseen estimation problems to the multiple population setting, where population $j$ has an unknown distribution $D_j$ from which we observe $n_j$ samples. We derive an optimal estimator for the total number of elements we expect to find among new samples across the populations. Surprisingly, we prove that our estimator's accuracy is independent of the number of populations. We also develop an efficient optimization algorithm to solve the more general problem of estimating multi-population frequency distributions. We validate our methods and theory through extensive experiments. Finally, on a real dataset of human genomes across multiple ancestries, we demonstrate how our approach for unseen estimation can enable cohort designs that can discover interesting mutations with greater efficiency.