cssi/SciSciGPT-SciSciNet huggingface dataset:
Synthesis and antibacterial activity of 2,3-dehydroofloxacin

The 2,3-dehydro analog 2 of the potent quinolone antibacterial agent ofloxacin (1) was synthesized by an efficient six step route beginning with ethyl 2,3,4,5-tetrafluorobenzoylacetate. Formation of the oxazine ring of 2 was accomplished by ozonolysis of 1-(1-buten-3-yl)quinolone 5 to the corresponding aldehyde, which cyclized upon treatment with base via intramolecular displacement of the C-8 fluorine to afford tricyclic ester 6. The antibacterial activities of 2,3-dehydroofloxacin (2) and ofloxacin (1) are compared.
Heat‐shock‐inducible CRISPR/Cas9 system generates heritable mutations in rice

Transient expression of CRISPR/Cas9 is an effective approach for limiting its activities and improving its precision in genome editing. Here, we describe the heat-shock-inducible CRISPR/Cas9 for controlled genome editing, and demonstrate its efficiency in the model crop, rice. Using the soybean heat-shock protein gene promoter and the rice U3 promoter to express Cas9 and sgRNA, respectively, we developed the heat-shock (HS)-inducible CRISPR/Cas9 system, and tested its efficacy in targeted mutagenesis. Two loci were targeted in rice, and the presence of targeted mutations was determined before and after the HS treatment. Only a low rate of targeted mutagenesis was detected before HS (~16%), but an increased rate of mutagenesis was observed after the HS treatment among the transgenic lines (50-63%). Analysis of regenerated plants harboring HS-CRISPR/Cas9 revealed that targeted mutagenesis was suppressed in the plants but induced by HS, which was detectable by Sanger sequencing after a few weeks of HS treatments. Most importantly, the HS-induced mutations were transmitted to the progeny at a high rate, generating monoallelic and biallelic mutations that independently segregated from the Cas9 gene. Additionally, off-target mutations were either undetectable or found at a lower rate in HS-CRISPR/Cas9 lines as compared to the constitutive-overexpression CRISPR/Cas9 lines. Taken together, this work shows that HS-CRISPR/Cas9 is a controlled and reasonably efficient platform for genome editing, and therefore, a promising tool for limiting genome-wide off-target effects and improving the precision of genome editing.
A facile and practical preparation of 5,7‐dihydroxy‐3‐(4‐nitrophenyl)‐4H‐1‐benzopyran‐4‐one

In spite of the fact that several preparative methods for the synthesis of hydroxylated isoflavones were reported during the past fifty years, none is suitable for the preparation of isoflavones containing 5,7-dihydroxyl functions. This paper reports a simple, large scale preparation of 5,7-dihydroxy-3-(4-nitrophenyl)-4H-1-benzopyran-4-one (2a) by the condensation of the readily available 4-nitrobenzyl 2,4,6-trihydroxyphenyl ketone (1a) and acetic-formic anhydride in high yields. Similar isoflavones, such as 7-hydroxy-3-(4-nitrophenyl)-4H-1-benzopyran-4-one (2b) can also be obtained in good yields in analogous manner.
TETRAPYRROLE PRODUCTS FROM ELECTROCHEMICAL CYCLIZATION OF 1',8'-DISUBSTITUTED-A,C-BILADIENE SALTS

Abstract Anodic oxidation of 1′,8′-dimethyl- and other 1′,8′-disubstituted a.c -biladiene salts affords novel cyclized products. In addition to porphyrin, an unconjugated macrocyclic intermediate product resulting from oxidadve cyclizatfon during porphyrin synthesis is isolated, structurally identified, and characterized with regard to its spectroscopy, electrochemical behavior and chemical reactivity. The formation of a novel homoporphyrin from a 1′-ethoxycarbonylmethy-8′-(2-methoxycarbonylethyl)- a,c -biladiene salt is also briefly discussed.
Electrostatic repulsion causes anticooperative DNA binding between tumor suppressor ETS transcription factors and JUN-FOS at composite DNA sites.

Many different transcription factors (TFs) regulate gene expression in a combinatorial fashion, often by binding in close proximity to each other on composite cis-regulatory DNA elements. Here, we investigated how ETS TFs bind with the AP1 TFs JUN–FOS at composite DNA-binding sites. DNA-binding ability with JUN–FOS correlated with the phenotype of ETS proteins in prostate cancer. We found that the oncogenic ETS-related gene (ERG) and ETS variant (ETV) 1/4/5 subfamilies co-occupy ETS–AP1 sites with JUN–FOS in vitro, whereas JUN–FOS robustly inhibited DNA binding by the tumor suppressors ETS homologous factor (EHF) and SAM pointed domain–containing ETS TF (SPDEF). EHF bound ETS–AP1 DNA with tighter affinity than ERG in the absence of JUN–FOS, possibly enabling EHF to compete with ERG and JUN–FOS for binding to ETS–AP1 sites. Genome-wide mapping of EHF- and ERG-binding sites in prostate epithelial cells revealed that EHF is preferentially excluded from closely spaced ETS–AP1 DNA sequences. Structural modeling and mutational analyses indicated that adjacent positively charged surfaces from EHF and JUN–FOS use electrostatic repulsion to disfavor simultaneous DNA binding. Conservation of positive residues on the JUN–FOS interface identified E74-like ETS TF 1 (ELF1) as an additional ETS TF exhibiting anticooperative DNA binding with JUN–FOS, and we found that ELF1 is frequently down-regulated in prostate cancer. In summary, divergent electrostatic features of ETS TFs at their JUN–FOS interface enable distinct binding events at ETS–AP1 DNA sites, which may drive specific targeting of ETS TFs to facilitate distinct transcriptional programs.
Redox chemistry of chromium (IV) complexes

Abstract A short introduction summarizes scattered preparations of chromium(V) and chromium(IV) derivatives before 1975 and places these unusual states in perspective with respect to the more usual oxidation states of this element. Preparations of peroxo complexes of Cr(IV), known since the turn of the century, are described and their redox reactions, as investigated since 1988, are treated. Systems in which Cr(IV) has been detected in the course of reductions of water-soluble Cr(V) complexes are enumerated and the role of Cr(IV) in some autocatalytic systems and “clock reactions” is considered. The stabilization of Cr(IV) via chelation with the anions of α-hydroxy acids is described and the reactions of this type of chelate are discussed. The recent preparations of aqua-substituted Cr(IV) are mentioned and the role of the 2e− change Cr(IV)→Cr(II) in the oxidations of organic substrates by Cr(VI) is indicated. Finally, experimental values for the standard potential and electron self-exchange rate for the Cr(III/IV) couple are compared with the corresponding parameters for Cr(IV/V) in a similar medium and structural implications are drawn from these rates.
Sc9Te2: A Two-Dimensional Distortion Wave in the Scandium-Richest Telluride

Sc9Te2 was prepared by high-temperature solid-state techniques, and the structure was determined by single-crystal X-ray diffraction to be monoclinic, Cc (No. 9, Z = 8) with a = 7.7576(1) A, b = 15.654(3) A, c = 17.283(3) A, and β = 90.01(3)° at 23 °C. The structure of metallic Sc9Te2 can be viewed as columns built either from distorted 3 × 3 bcc metal atoms or from distorted edge-sharing octahedra along a that are joined via intercolumn bonds on opposite sides into two-dimensional layers along b. A corrugated layer of Te atoms separates the metal layers in the c direction. This structure derives from the Ti9Se2 structure, with doubled a and b dimensions and a lower symmetry. Magnetic susceptibility measurements on Sc9Te2 show a substantially temperature-independent paramagnetism that is much smaller per metal atom than those for other scandium-rich tellurides or scandium metal. Extended Huckel band calculations reveal a clear distinction between high overlap populations for Sc−Sc interactions in the in...
The palladium(II)-catalyzed Nazarov reaction.

The PdCl2-catalyzed cyclization of α-alkoxy dienones leads to 2-hydroxycyclopentenones, whereas the Pd(OAc)2-catalyzed reaction leads to cross-conjugated cyclopentenones through an oxidative process.
1,3-Dipolar cycloreversion of a 1,3,4-oxadiazolidine as a controlled azomethine imine surrogate for pyrazolidine synthesis

Abstract Azomethine imines were generated in a controlled manner through a thermally allowed 1,3-dipolar cycloreversion of 1,3,4-oxadiazolidines and subsequently trapped with dipolarophiles. This method results in the construction of the pyrazolidine heterocycles. A new method for the selective formation of the key semicarbazide substrate, from benzylidene hydrazone, is also disclosed.
A concise route to enantiomerically pure 2-arylcyclohexenones of relevance to the pancratistatin problem

Abstract A transformation involving a 6-aryl “exo” glycal is used to prepare the target structures from carbohydrate starting materials.
Vanadium (V) oxide mediated bromolactonization of alkenoic acids

Abstract A full account of our recently communicated method for the V 2 O 5 mediated bromolactonization of alkenoic acids is presented. Here we describe the extensive evaluation of the metal oxide catalyst, terminal oxidant, halide source, solvent system, and reaction temperature that resulted in optimal conditions employing 0.05 equiv V 2 O 5 , 3 equiv urea-hydrogen peroxide complex (UHP), and 3 equiv of NH 4 Br in an acetone:H 2 O (6:1) solvent system at room temperature. Additionally, we have expanded the substrate scope of the reaction with the aim of evaluating the functional group tolerance of the transformation. Further, we present preliminary data of a related halogenation of β-diketones with our optimal conditions. Finally, we probed the role of urea in the transformation.
Generation of o-quinodimethanes via the electrocyclic reaction of (4Z)-1,2,4,6,7-octapentaenes derived from the organoborate complexes and their subsequent reactions

Abstract Treatment of allenyldicyclohexylborane ( 20 ) with 1-lithio-3,4-pentadien-1-yne 21 produced the organoborate complex 22 , which on further treatment with trimethyltin chloride furnished the enediallene 23 in situ. The subsequent electrocyclic reaction then generated the o -quinodimethane 24 , which underwent a [1,5]-sigmatropic hydrogen shift to afford 25 . Oxidative work-up followed by protonation gave the phenol 26 . The presence of a boron group and a tin group in 25 also provides handles to allow their transformations to an allyl substituent and an iodo substituent in 27 . Attempts to capture the o -quinodimethane in 32 with the carbon–carbon double bond intramolecularly afforded the tricyclic phenol 34 in low yield (6%). By using the combination of the organoborane 36 and 1-lithio-1,2-heptadiene ( 37 ) to form the organoborate complex 38 , the o -quinodimethane 40 could also be generated in situ, leading to the phenol 42 and the styrene 43 .
Syntheses, Structures, and Theoretical Study of LaCuSTe and SmCuSTe.

Two mixed-chalcogen compounds LaCuSTe and SmCuSTe have been synthesized by the reactions of the elements at 1123 K. LaCuSTe crystallizes in a cell of dimensions a = 6.4955(8) A, b = 7.7692(9) A, c = 7.4665(9) A, and β = 95.045(2)° (T = 153 K) with four formula units in space group C2h5-P21/c of the monoclinic system. Its structure is closely related to that of LaCuS2. SmCuSTe crystallizes as a new structure type in a cell of dimensions a = 7.5195(8) A, b = 12.6370(14) A, and c = 7.5287(8) A (T = 153 K) with eight formula units in space group D2h15-Pbca of the orthorhombic system. In LaCuSTe, the La atom is coordinated by a bicapped trigonal prism of four S atoms and four Te atoms; in SmCuSTe, the Sm atom is coordinated by a monocapped trigonal prism of four S atoms and three Te atoms. In both structures, the Cu atom is coordinated by a tetrahedron of one S atom and three Te atoms, These structures are built from (CuSTe)n sheets that are separated by the rare-earth-metal atoms. In LaCuSTe, a sheet comprise...
Application of Arene-Ruthenium Chemistry to a Formal Total Synthesis of OF 4949 III.

A convergent formal total synthesis of OF 4949 III is described. Arene−ruthenium chemistry was used in the construction of the diaryl ether linkage in high yield, and cycloamidation under high dilution conditions (0.005 M) was achieved using DPPA as coupling reagent. SmI2 was used to reductively remove the 2-iodoethyl ester protecting group in the presence of DMPU or HMPA.
Dietary advanced glycation end-product consumption leads to mechanical stiffening of murine intervertebral discs

Back pain is a leading cause of disability and is strongly associated with intervertebral disc (IVD) degeneration. Reducing structural disruption and catabolism in IVD degeneration remains an important clinical challenge. Pro-oxidant and structure-modifying advanced glycation end-products (AGEs) contribute to obesity and diabetes, which are associated with increased back pain, and accumulate in tissues due to hyperglycemia or ingestion of foods processed at high heat. Collagen-rich IVDs are particularly susceptible to AGE accumulation due to their slow metabolic rates, yet it is unclear whether dietary AGEs can cross the endplates to accumulate in IVDs. A dietary mouse model was used to test the hypothesis that chronic consumption of high AGE diets results in sex-specific IVD structural disruption and functional changes. High AGE diet resulted in AGE accumulation in IVDs and increased IVD compressive stiffness, torque range and failure torque, particularly for females. These biomechanical changes were likely caused by significantly increased AGE crosslinking in the annulus fibrosus, measured by multiphoton imaging. Increased collagen damage measured with collagen hybridizing peptide did not appear to influence biomechanical properties and may be a risk factor as these animals age. The greater influence of high AGE diet on females is an important area of future investigation that may involve AGE receptors known to interact with estrogen. We conclude that high AGE diets can be a source for IVD crosslinking and collagen damage known to be important in IVD degeneration. Dietary modifications and interventions that reduce AGEs warrant further investigation and may be particularly important for diabetics, in whom AGEs accumulate more rapidly.
NHC–copper hydrides as chemoselective reducing agents: catalytic reduction of alkynes, alkyl triflates, and alkyl halides

Abstract The NHC–copper-catalyzed Z -selective semi-reduction of terminal and internal alkynes, as well as the NHC–copper-catalyzed reduction of primary alkyl triflates and primary and secondary alkyl iodides and bromides are described. The high chemoselectivity demonstrated in these examples illustrates the mild nature of copper hydride complexes as reducing agents, which have applications in synthetic chemistry beyond their traditional role in the reduction of activated alkenes and carbonyl compounds.
Electrocatalytic reactions: anion radical cyclobutanation reactions and electrogenerated base reactions

Abstract Intermolecular anion radical [2+2] cyclobutanation reactions have been observed between vinyl sulfones and vinyl/propenyl ketones. The products are novel and formed electrocatalytically, although yields are at best modest (11–45%). Competing mechanisms are discussed. Additionally, the electrochemical reduction of vinyl alkyl sulfones in acetonitrile leads to near quantitative formation of cyanomethylation product cyano-sulfones. The single step approach has electrocatalytic factors in excess of thirty.
Comparative modeling of transcranial magnetic and electric stimulation in mouse, monkey, and human

Transcranial magnetic stimulation (TMS) and transcranial electric stimulation (TES) are increasingly popular methods to noninvasively affect brain activity. However, their mechanism of action and dose-response characteristics remain under active investigation. Translational studies in animals play a pivotal role in these efforts due to a larger neuroscientific toolset enabled by invasive recordings. In order to translate knowledge gained in animal studies to humans, it is crucial to generate comparable stimulation conditions with respect to the induced electric field in the brain. Here, we conduct a finite element method (FEM) modeling study of TMS and TES electric fields in a mouse, capuchin and macaque monkeys, and a human model. We systematically evaluate the induced electric fields and analyze their relationship to head and brain anatomy. We find that with increasing head size, TMS-induced electric field strength first increases and then decreases according to a two-term exponential function. TES-induced electric field strength strongly decreases from smaller to larger specimen with up to 100x fold differences across species. Our results can serve as a basis to compare and match stimulation parameters across studies in animals and humans.
Distinct effects of tubulin isotype mutations on neurite growth in Caenorhabditis elegans.

Different tubulin isotypes perform different functions in the regulation of microtubule (MT) structure and neurite growth, and missense mutations of tubulin genes have three types of distinct effec...
The Exported Chaperone PfHsp70x Is Dispensable for the Plasmodium falciparum Intraerythrocytic Life Cycle.

ABSTRACT Export of parasite proteins into the host erythrocyte is essential for survival of Plasmodium falciparum during its asexual life cycle. While several studies described key factors within the parasite that are involved in protein export, the mechanisms employed to traffic exported proteins within the host cell are currently unknown. Members of the Hsp70 family of chaperones, together with their Hsp40 cochaperones, facilitate protein trafficking in other organisms, and are thus likely used by P. falciparum in the trafficking of its exported proteins. A large group of Hsp40 proteins is encoded by the parasite and exported to the host cell, but only one Hsp70, P. falciparum Hsp70x (PfHsp70x), is exported with them. PfHsp70x is absent in most Plasmodium species and is found only in P. falciparum and closely related species that infect apes. Herein, we have utilized clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 genome editing in P. falciparum to investigate the essentiality of PfHsp70x. We show that parasitic growth was unaffected by knockdown of PfHsp70x using both the dihydrofolate reductase (DHFR)-based destabilization domain and the glmS ribozyme system. Similarly, a complete gene knockout of PfHsp70x did not affect the ability of P. falciparum to proceed through its intraerythrocytic life cycle. The effect of PfHsp70x knockdown/knockout on the export of proteins to the host red blood cell (RBC), including the critical virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1), was tested, and we found that this process was unaffected. These data show that although PfHsp70x is the sole exported Hsp70, it is not essential for the asexual development of P. falciparum . IMPORTANCE Half of the world’s population lives at risk for malaria. The intraerythrocytic life cycle of Plasmodium spp. is responsible for clinical manifestations of malaria; therefore, knowledge of the parasite’s ability to survive within the erythrocyte is needed to combat the deadliest agent of malaria, P. falciparum . An outstanding question in the field is how P. falciparum undertakes the essential process of trafficking its proteins within the host cell. In most organisms, chaperones such as Hsp70 are employed in protein trafficking. Of the Plasmodium species causing human disease, the chaperone PfHsp70x is unique to P. falciparum , and it is the only parasite protein of its kind exported to the host (S. Kulzer et al., Cell Microbiol 14:1784–1795, 2012). This has placed PfHsp70x as an ideal target to inhibit protein trafficking and kill the parasite. However, we show that PfHsp70x is not required for export of parasite effectors and it is not essential for parasite survival inside the RBC.
Comments on the chemistry of low-valent alkylidyne complexes of the group 6 transition metals

Abstract The chemistry of metal-carbon multiple bonds has grown into a major branch of organometallic chemistry since its beginning in 1963.1 Metal alkylidene and alkylidyne2 complexes, which originated from purely fundamental research efforts, are now used as building blocks for organometallic synthesis, and as catalytic and stoichiometric reagents for organic synthesis. The chemistry of metal alkylidenes has developed much further than the chemistry of metal alkylidynes. However, interest in alkylidyne complex chemistry has been rising in recent years as documented by several review article.3
Recurring Functional Interactions Predict Network Architecture of Interictal and Ictal States in Neocortical Epilepsy

Abstract Human epilepsy patients suffer from spontaneous seizures, which originate in brain regions that also subserve normal function. Prior studies demonstrate focal, neocortical epilepsy is associated with dysfunction, several hours before seizures. How does the epileptic network perpetuate dysfunction during baseline periods? To address this question, we developed an unsupervised machine learning technique to disentangle patterns of functional interactions between brain regions, or subgraphs, from dynamic functional networks constructed from approximately 100 h of intracranial recordings in each of 22 neocortical epilepsy patients. Using this approach, we found: (1) subgraphs from ictal (seizure) and interictal (baseline) epochs are topologically similar, (2) interictal subgraph topology and dynamics can predict brain regions that generate seizures, and (3) subgraphs undergo slower and more coordinated fluctuations during ictal epochs compared to interictal epochs. Our observations suggest that seizures mark a critical shift away from interictal states that is driven by changes in the dynamical expression of strongly interacting components of the epileptic network.
Inferring hidden structure in multilayered neural circuits.

A central challenge in sensory neuroscience involves understanding how neural circuits shape computations across cascaded cell layers. Here we attempt to reconstruct the response properties of experimentally unobserved neurons in the interior of a multilayered neural circuit, using cascaded linear-nonlinear (LN-LN) models. We combine non-smooth regularization with proximal consensus algorithms to overcome difficulties in fitting such models that arise from the high dimensionality of their parameter space. We apply this framework to retinal ganglion cell processing, learning LN-LN models of retinal circuitry consisting of thousands of parameters, using 40 minutes of responses to white noise. Our models demonstrate a 53% improvement in predicting ganglion cell spikes over classical linear-nonlinear (LN) models. Internal nonlinear subunits of the model match properties of retinal bipolar cells in both receptive field structure and number. Subunits have consistently high thresholds, supressing all but a small fraction of inputs, leading to sparse activity patterns in which only one subunit drives ganglion cell spiking at any time. From the model’s parameters, we predict that the removal of visual redundancies through stimulus decorrelation across space, a central tenet of efficient coding theory, originates primarily from bipolar cell synapses. Furthermore, the composite nonlinear computation performed by retinal circuitry corresponds to a boolean OR function applied to bipolar cell feature detectors. Our methods are statistically and computationally efficient, enabling us to rapidly learn hierarchical non-linear models as well as efficiently compute widely used descriptive statistics such as the spike triggered average (STA) and covariance (STC) for high dimensional stimuli. This general computational framework may aid in extracting principles of nonlinear hierarchical sensory processing across diverse modalities from limited data.
The Ground State Structure and Modular Transformations of Fractional Quantum Hall States on a Torus

The structure of ground states of generic FQH states on a torus is studied by using both effective theory and electron wavefunction. The relation between the effective theory and the wavefunction becomes transparent when one considers the ground state structure. We find that the non-abelian Berry’s phases of the abelian Hall states generated by twisting the mass matrix are identical to the modular transformation matrix for the characters of Gaussian conformal field theory. We also show that the Haldane-Rezayi spin singlet state has a ten fold ground state degeneracy on a torus which indicates such a state is a non-abelian Hall state.
Catalytic Ring Expansion Adventures

This account summarizes the Njardarson group ring expansion journey from early vinyl oxirane explorations to the latest vinyl oxetane ring expansion discoveries. The evolution of the program and incredible success of Cu(hfacac)2 as catalyst is detailed. Application of these new ring expansion reactions to natural product, pharmaceutical and commodity chemical targets is discussed as well as our intriguing mechanistic journey and interesting entry into the world of chiral counterion catalysis.
A mild method for selective cleavage of tetrahydropyranyl ethers in the presence of other acid-labile functionalities

Abstract A mild method for selective cleavage of tetrahydropyranyl ethers in the presence of other acid sensitive functionalities such as acetonides, methoxymethyl ethers, methylenedioxy ethers, mesitaldehyde acetals and t-butyldimethylsilyl ethers using Lewis acid-thiol system is described.
A novel alkaloid from the Indo-Pacific sponge Clathria basilana

Abstract One Indonesian collection of the massive orange marine sponge Clathria basilana yielded a new tetrahydroquinolizinium ion, clathryimine A (1), which on heating lost CO2 affording B (2).
Single crystal growth and structural characterization of four complex uranium oxides: CaUO4, β-Ca3UO6, K4CaU3O12, and K4SrU3O12

Abstract Single crystals of complex uranium oxides, CaUO4, β-Ca3UO6, K4CaU3O12 and K4SrU3O12 were grown from carbonate melts. The crystal structures of the four uranates were determined by single crystal X-ray diffraction. CaUO4 crystallizes in the hexagonal space group R-3m, with lattice parameters a = 6.2570(7) A and α = 36.04(2)°. The U6+ atom in CaUO4 is 8-coordinate and exhibits hexagonal bipyramidal geometry with six long and two short U–O bonds, typical of a uranyl species. β-Ca3UO6 forms in the monoclinic space group P21/n, with lattice parameters a = 5.728(1) A, b = 5.956(1) A, c = 8.298(2) A, and β = 90.55(3)°, and adopts a distorted double perovskite structure. K4CaU3O12 and K4SrU3O12 crystallize in the cubic space group Im-3m with lattice parameters a = 8.483(1) A and a = 8.582(1) A, respectively. In all three perovskite-type oxides, the U(VI) cation is located in an octahedral coordination environment and exhibits typical uranyl geometry with four long and two short U–O bonds.
A General N-Alkylation Procedure for Ethyl Pyroglutamate

Abstract Despite several reported procedures for coupling alkyl halides and 5-oxoproline esters (pyroglutamate derivatives), no general method has been described. The reaction of pyroglutamate with sodium hydride, in anhydrous THF in the presence of the halide, provides this general and practical alkylation method. Alkylation under phase transfer conditions is a useful, but less general, alternative.
Numerous recursive sites contribute to accuracy of splicing in long introns in flies

Recursive splicing, a process by which a single intron is removed from pre-mRNA transcripts in multiple distinct segments, has been observed in a small subset of Drosophila melanogaster introns. However, detection of recursive splicing requires observation of splicing intermediates that are inherently unstable, making it difficult to study. Here we developed new computational approaches to identify recursively spliced introns and applied them, in combination with existing methods, to nascent RNA sequencing data from Drosophila S2 cells. These approaches identified hundreds of novel sites of recursive splicing, expanding the catalog of recursively spliced fly introns by 4-fold. A subset of recursive sites were validated by RT-PCR and sequencing. Recursive sites occur in most very long (> 40 kb) fly introns, including many genes involved in morphogenesis and development, and tend to occur near the midpoints of introns. Suggesting a possible function for recursive splicing, we observe that fly introns with recursive sites are spliced more accurately than comparably sized non-recursive introns.
An alternative total synthesis of pentosidine

Pentosidine, a fluorescent advanced glycation endproduct that serves as a biomarker of diabetic complications, kidney dysfunction, oxidative stress, and aging and age-related diseases, was synthesized from 2,3-diaminopyridine and benzyloxycarbonyl (Cbz) protected chiral amino acids Nα-Cbz-lysine and Nδ-Cbz-ornithine. Regioselective alkylation of 2-(methylthio)imidazo[4,5-b]pyridine, chlorination of methylthio group, and amination of 2-chloro-imidazo[4,5-b]pyridine are the key steps. Hydantoin protection of amino acids was used and the deprotection under acidic condition was achieved in the presence of glycine. J. Heterocyclic Chem., (2011).
Addition of Transiently-Generated Methyl o-Lithiobenzoate to Imines. An Isoindolone Annulation.

Addition of phenyllithium to a mixture of an imine, methyl o-iodobenzoate, and BF(3).etherate at -105 degrees C gives good to excellent yields of isoindolones. The transient formation of methyl o-lithiobenzoate is proposed, which is formed by a rapid lithium/iodide exchange reaction of the phenyllithium with methyl o-iodobenzoate in the presence of the imine. The transiently generated anions can then be captured by the BF(3)-activated imines to form the isoindolones in good to high yield. The reactions conditions are sufficiently mild, and selective, to permit functional groups such carbmethoxy and aryl bromide, which could otherwise react with the added PhLi, to be tolerated.
Ba8Hg3U3S18: a complex uranium(+4)/uranium(+5) sulfide.

The compound Ba(8)Hg(3)U(3)S(18) was obtained from the solid-state reaction at 1123 K of U, HgS, BaS, and S, with BaBr(2)/KBr or BaCl(2) as a flux. This material crystallizes in a new structure type in space group P6 of the hexagonal system with three formula units in a cell of dimensions a = 27.08(1) A, c = 4.208(2) A, and V = 2673(2) A(3). The structure contains infinite chains of US(6) octahedra and nearly linear [S-Hg-S](2-) dithiomercurate anions, separated by Ba(2+) cations. In the temperature range 100-300 K, the paramagnetic behavior of Ba(8)Hg(3)U(3)S(18) can be fit to the Curie-Weiss law, resulting in μ(eff) = 5.40(4) μ(B), or 3.12(2) μ(B)/U. The compound displays an antiferromagnetic transition at T(N) = 59 K. Although the formal oxidation states of Ba, Hg, and S can be assigned as +2, +2, and -2, the oxidation state of U is less certain. On the basis of interatomic distance arguments and the magnetic susceptibility data, the compound is proposed to contain U in both +4 and +5 formal oxidation states.
A Potential Outcomes Calculus for Identifying Conditional Path-Specific Effects

The do-calculus is a well-known deductive system for deriving connections between interventional and observed distributions, and has been proven complete for a number of important identifiability problems in causal inference. Nevertheless, as it is currently defined, the do-calculus is inapplicable to causal problems that involve complex nested counterfactuals which cannot be expressed in terms of the “do” operator. Such problems include analyses of path-specific effects and dynamic treatment regimes. In this paper we present the potential outcome calculus (po-calculus), a natural generalization of do-calculus for arbitrary potential outcomes. We thereby provide a bridge between identification approaches which have their origins in artificial intelligence and statistics, respectively. We use po-calculus to give a complete identification algorithm for conditional path-specific effects with applications to problems in mediation analysis and algorithmic fairness.
Reactions of Aluminum Hydride Derivatives with Ammonia−Borane: A New Approach toward AlN/BN Materials

Preceramic precursors containing Al−N−B linkages were produced from the reactions of Me3NAlH3 with NH3BH3 in 1:1 and 1:2 ratios in toluene solutions followed by treatment with liquid ammonia. Both precursors were transformed into intimate ceramic mixtures of AlN and BN via pyrolysis under NH3 at 1000 °C. The AlN/BN ceramic composites were characterized by IR, XRD, and solid-state 27Al and 11B MAS NMR spectroscopies. SEM studies revealed that they were composed of nanosized composite particles of AlN and BN.
Sonogashira cross-coupling in a designer ionic liquid (IL) without copper, external base, or additive, and with recycling and reuse of the IL

Application of a piperidine-appended dimethyl-imidazolium-NTf2 ionic liquid as dual solvent and base in the Sonogashira cross-coupling reaction of aryl-iodides with terminal acetylenes under mild conditions has been demonstrated. The method employs PdCl2(PPh3)2 without copper and external base. It is applicable to the synthesis of SF5-substituted diaryl- and aryl-alkyl-acetylenes, and can also be utilized for efficient homo-coupling of terminal acetylenes under aerobic conditions. The potential for recycling and reuse of this designer-IL offers an added advantage.
Synthetic transformations of 1-cyanomethylbenzotriazole†

Lithiation of 1-cyanomethylbenzotriazole (4) with LDA and subsequent reactions with alkyl halides or carbonyl compounds afforded the corresponding 1-(α-cyanoalkyl)- and 1-(α-cyanoalkenyl)-benzotriazoles. Bromination of 4 with NBS formed 1-(bromocyanomethyl)benzotriazole. 1-Cyanoalkylbenzotriazoles condensed with hydrazine hydrate to give 4-amino-3,5-bis(benzotriazol-1-yl)triazoles which underwent deamination with sodium nitrite to yield 3,5-bis(benzotriazol-1-yl)triazoles.
Cycloaddition of Heteroatom-Substituted 2-Azaallyl Anions with Alkenes. Synthesis of 1-Pyrrolines and Bridged Azabicyclic Compounds

Nonstabilized 2-azaallyl anions bearing heteroatom substituents [R1CHNC(X)R2(−)Li(+), where R1 and R2 are hydrogen or alkyl groups and X = OMe, SPh, or NR2] were generated and found to undergo efficient [3 + 2] cycloadditions with alkenes to provide 1-pyrrolines after loss of LiX. The 2-azaallyl anions were generated by tin−lithium exchange on stannyl imidates, thioimidates, or amidines R1CH(SnBu3)NC(X)R2 with n-butyllithium. The initially formed 1-pyrrolines were found to be deprotonated under the reaction conditions to afford 1-metalloenamines, which could be quenched with alkyl halides, carbonyl compounds, or MeSSMe to provide further functionalized 1-pyrrolines. Cyclic methoxy-substituted 2-azaallyl anions were generated and were found to undergo cycloadditions with alkenes to afford bridged azabicyclic compounds (1-methoxy-7-azabicyclo[2.2.1]heptanes and 1-methoxy-8-azabicyclo[3.2.1]octanes). These are the first examples of cyclic nonstabilized 2-azaallyl anions.
Convergent total synthesis of squamostolide

Abstract A convergent total synthesis of the Annonaceous acetogenin squamostolide, in a longest linear sequence of nine steps from d -mannitol, is reported. Central to the efficiency of the synthesis is a highly selective tandem ring-closing/cross metathesis step in which lactone formation and fragment coupling are accomplished.
Heterogeneities in energy technological learning: Evidence from the U.S. electricity industry

Abstract While the role of organizational learning in improving firm performance is well documented, there are still questions on what drives technological learning. This is evident in the electricity industry where the growth of renewable energy technologies has been pervasive. Vicarious learning contributes to the adoption of emerging technologies through successful inter-firm knowledge sharing and transfer. However, there is hesitation to adoption that characterizes vicarious learning especially in the context of intra-firm learning. This paper investigates the differences in knowledge acquisition within and across electricity firms in the U.S. The learning curve model is applied to a longitudinal study of 5573 plants belonging to 1542 U.S. electricity firms between 1998 and 2010. This study finds: (i) The capacity growth of the solar photovoltaic technology is positively associated with intra-firm knowledge acquisition; (ii) The effect of financial incentives on the adoption of solar and wind technologies is higher under inter-firm learning; (iii) The higher the stringency of policy mandates, the more varied is the progress on technological change across technologies; (iv) Knowledge sharing between firms are higher for wind technology than for solar technology. These findings combine to show disparities in the learning trends of technologies across and within firms’ boundaries.
Viral-Mediated Optogenetic Stimulation of Peripheral Motor Nerves in Non-human Primates

Objective: Reanimation of muscles paralyzed by disease states such as spinal cord injury remains a highly sought therapeutic goal of neuroprosthetic research. Optogenetic stimulation of peripheral motor nerves expressing light-sensitive opsins is a promising approach to muscle reanimation that may overcome several drawbacks of traditional methods such as functional electrical stimulation (FES). However, the utility of these methods has only been demonstrated in rodents to date, while translation to clinical practice will likely first require demonstration and refinement of these gene therapy techniques in non-human primates. Approach: Three rhesus macaques were injected intramuscularly with either one or both of two optogenetic constructs (AAV6-hSyn-ChR2-eYFP and/or AAV6-hSyn-Chronos-eYFP) to transduce opsin expression in the corresponding nerves. Neuromuscular junctions were targeted for virus delivery using an electrical stimulating injection technique. Functional opsin expression was periodically evaluated up to 13 weeks post-injection by optically stimulating targeted nerves with a 472 nm fiber-coupled laser while recording electromyographic (EMG) responses. Main Results: One monkey demonstrated functional expression of ChR2 at 8 weeks post-injection in each of two injected muscles, while the second monkey briefly exhibited contractions coupled to optical stimulation in a muscle injected with the Chronos construct at 10 weeks. A third monkey injected only in one muscle with the ChR2 construct showed strong optically coupled contractions at 5 ½ weeks which then disappeared by 9 weeks. EMG responses to optical stimulation of ChR2-transduced nerves demonstrated graded recruitment relative to both stimulus pulse-width and light intensity, and followed stimulus trains up to 16 Hz. In addition, the EMG response to prolonged stimulation showed delayed fatigue over several minutes. Significance: These results demonstrate the feasibility of viral transduction of peripheral motor nerves for functional optical stimulation of motor activity in non-human primates, a variable timeline of opsin expression in a animal model closer to humans, and fundamental EMG response characteristics to optical nerve stimulation. Together, they represent an important step in translating these optogenetic techniques as a clinically viable gene therapy.
Asynchronous Delay-Aware Accelerated Proximal Coordinate Descent for Nonconvex Nonsmooth Problems

Nonconvex and nonsmooth problems have recently attracted considerable attention in machine learning. However, developing efficient methods for the nonconvex and nonsmooth optimization problems with certain performance guarantee remains a challenge. Proximal coordinate descent (PCD) has been widely used for solving optimization problems, but the knowledge of PCD methods in the nonconvex setting is very limited. On the other hand, the asynchronous proximal coordinate descent (APCD) recently have received much attention in order to solve large-scale problems. However, the accelerated variants of APCD algorithms are rarely studied. In this paper, we extend APCD method to the accelerated algorithm (AAPCD) for nonsmooth and nonconvex problems that satisfies the sufficient descent property, by comparing between the function values at proximal update and a linear extrapolated point using a delay-aware momentum value. To the best of our knowledge, we are the first to provide stochastic and deterministic accelerated extension of APCD algorithms for general nonconvex and nonsmooth problems ensuring that for both bounded delays and unbounded delays every limit point is a critical point. By leveraging Kurdyka-Łojasiewicz property, we will show linear and sublinear convergence rates for the deterministic AAPCD with bounded delays. Numerical results demonstrate the practical efficiency of our algorithm in speed.
Using Quantum Coherence to Enhance Gain in Atomic Physics

Quantum coherence and interference eects in atomic and molecular physics have been extensively studied because of intriguing counterintuitive physics and potential important applications. Here we present one such application, i.e. using quantum coherence to generate and enhance gain in the extreme ultra-violet (XUV)(@58.4nm in Helium) and infra-red (@794.76nm in Rubidium) regimes of electromagnetic radiation. We show that using moderate external coherent drive, a substantial enhancement in the output energy on the lasing transition can be achieved under optimal conditions. We also discuss the role of coherence. The present paper is intended to be pedagogical on this subject of coherence-enhanced lasing.
Differentially private chi-squared hypothesis testing: goodness of fit and independence testing

Hypothesis testing is a useful statistical tool in determining whether a given model should be rejected based on a sample from the population. Sample data may contain sensitive information about individuals, such as medical information. Thus it is important to design statistical tests that guarantee the privacy of subjects in the data. In this work, we study hypothesis testing subject to differential privacy, specifically chi-squared tests for goodness of fit for multinomial data and independence between two categorical variables.
A Solution to Time-Varying Markov Decision Processes

We consider a decision-making problem where the environment varies both in space and time. Such problems arise naturally when considering, e.g., the navigation of an underwater robot amidst ocean currents or the navigation of an aerial vehicle in wind. To model such spatiotemporal variation, we extend the standard Markov decision process (MDP) to a new framework called the time-varying Markov decision process (TVMDP). The TVMDP has a time-varying state transition model and transforms the standard MDP that considers only immediate and static uncertainty descriptions of state transitions, to a framework that is able to adapt to future time-varying transition dynamics over some horizon. We show how to solve a TVMDP via a redesign of the MDP value propagation mechanisms by incorporating the introduced dynamics along the temporal dimension. We validate our framework in a marine robotics navigation setting using spatiotemporal ocean data and show that it outperforms prior efforts.
Twisting, mutation and knot Floer homology

Let $\mathcal{L}$ be a knot with a fixed positive crossing and $\mathcal{L}_n$ the link obtained by replacing this crossing with $n$ positive twists. We prove that the knot Floer homology $\widehat{\text{HFK}}(\mathcal{L}_n)$ `stabilizes' as $n$ goes to infinity. This categorifies a similar stabilization phenomenon of the Alexander polynomial. As an application, we construct an infinite family of prime, positive mutant knots with isomorphic bigraded knot Floer homology groups. Moreover, given any pair of positive mutants, we describe how to derive a corresponding infinite family positive mutants with isomorphic bigraded $\widehat{\text{HFK}}$ groups, Seifert genera, and concordance invariant $\tau$.
Hierarchical and Matrix Structures in a Large Organizational Email Network: Visualization and Modeling Approaches

This paper presents findings from a study of the email network of a large scientific research organization, focusing on methods for visualizing and modeling organizational hierarchies within large, complex network datasets. In the first part of the paper, we find that visualization and interpretation of complex organizational network data is facilitated by integration of network data with information on formal organizational divisions and levels. By aggregating and visualizing email traffic between organizational units at various levels, we derive several insights into how large subdivisions of the organization interact with each other and with outside organizations. Our analysis shows that line and program management interactions in this organization systematically deviate from the idealized pattern of interaction prescribed by “matrix management”. In the second part of the paper, we propose a power law model for predicting degree distribution of organizational email traffic based on hierarchical relationships between managers and employees. This model considers the influence of global email announcements sent from managers to all employees under their supervision, and the role support staff play in generating email traffic, acting as agents for managers. We also analyze patterns in email traffic volume over the course of a work week.
Bearing the White Man’s Burden: American Empire and the Origin of Public Administration

There is an overlooked chapter in the history of American public administration: the experiment with colonial administration in the two decades following the Spanish-American War. Several scholars now identified as pioneers of American public administration were actively engaged in this project. They studied European empires closely to determine how the new American dependencies should be governed. This work was guided by beliefs about racial superiority and the duty of civilized nations to improve uncivilized peoples through colonization. This episode of administrative history provides insight into how American academics thought about race and public administration in the early decades of the twentieth century, both overseas and within the United States. It compels a reassessment of our understandings about their commitment to democracy, and about the supposed differences between American and European public administration at that time.
Multiplier transformations associated to convex domains in $\mathbb{R}^2$

We consider Fourier multipliers in $$\mathbb {R}^2$$ of the form $$m\circ \rho $$ where $$\rho $$ is the Minkowski functional associated with a convex set in $$\mathbb {R}^2$$ , and prove $$L^p$$ bounds for the corresponding multiplier operators. It is of interest to consider domains whose boundary is not smooth. Our results depend on a notion of Minkowski dimension introduced in Seeger and Ziesler (Math Z 236(4):643–676, 2001) that measures “flatness” of the boundary of the domain. Our methods analyze the case of oscillatory multipliers $$\frac{e^{i\rho (\xi )}}{(1+|\xi |)^{-a}}$$ associated with wave equations, which we use to derive results for more general multiplier transformations.
Efficient optimal joint channel estimation and data detection for massive MIMO systems

In this paper, we propose an efficient optimal joint channel estimation and data detection algorithm for massive MIMO wireless systems. Our algorithm is optimal in terms of the generalized likelihood ratio test (GLRT). For massive MIMO systems, we show that the expected complexity of our algorithm grows polynomially in the channel coherence time. Simulation results demonstrate significant performance gains of our algorithm compared with suboptimal non-coherent detection algorithms. To the best of our knowledge, this is the first algorithm which efficiently achieves GLRT-optimal non-coherent detections for massive MIMO systems with general constellations.